# Patent

## Title
Tungsten oxo alkylidene complexes for Zselective olefin metathesis

## Abstract

The current application describes tungsten oxo alkylidene complexes for olefin metathesis.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a Continuation of U.S. patent application Ser. No. 13/671,109, filed Nov. 7, 2012, now U.S. Pat. No. 9,085,595, which claims priority to U.S. Provisional Application Ser. No. 61/556,643, filed Nov. 7, 2011, the entirety of each of which is incorporated herein by reference.


STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
THIS INVENTION WAS MADE WITH GOVERNMENT SUPPORT UNDER GRANT NO. DE-FG02-86ER13564 AWARDED BY THE U.S. DEPARTMENT OF ENERGY AND UNDER GRANT NO. CHE-1111133 AWARDED BY THE NATIONAL SCIENCE FOUNDATION. THE GOVERNMENT HAS CERTAIN RIGHTS IN THIS INVENTION.


FIELD OF THE INVENTION
The present invention generally relates to olefin metathesis catalyst precursors.
BACKGROUND
Catalytic olefin metathesis has transformed chemical synthesis and offers exceptionally efficient pathways for synthesis of alkenes. A great number of commercially important molecules contain olefins. Such specialty chemicals include biologically active molecules, oleochemicals, renewables, fine chemicals, and polymeric materials, to name a few. Moreover, many reactions in organic chemistry require alkenes as starting materials. Accordingly, there remains an unmet need for improved methods and catalysts for metathesis reaction.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1. Thermal ellipsoid drawing of I-1.
FIG. 2. Thermal ellipsoid drawing (50% probability) of syn-W(O)(CH-t-Bu)(OHIPT) (Me2Pyr) (I-2). Hydrogen atoms have been omitted for clarity. Selected bond distances (Å) and angles (°): W1-C1=1.886(3), W1-O2=1.695(3), W1-O1=1.868(2), W1-N1=2.001(2), W1-O1-C21=166.9(2), W1-C1-C2=136.7(3).
FIG. 3. Thermal ellipsoid drawing (50% probability) of syn-W(O)(CH-t-Bu)(OHMT) (Me2Pyr)(PMe2Ph) (I-4). Hydrogen atoms have been omitted for clarity. Solvent molecules are not shown. Selected bond distances (Å) and angles (°): W1-C1=1.900(3), W1-O2=1.717(2), W1-O1=1.964(2), W1-N1=2.074(2), W1-P1=2.580(1), W1-O1-C21=159.8(2), W1-C1-C2=141.0(2).
FIG. 4. Typical 1H NMR spectrum of the product of 1-octene homocoupling mixture. Olefinic region of 1H NMR (in CDCl3) spectrum of a crude product of 1-octene homocoupling promoted by I-4. No trans-product (at  ̃5.38 ppm) can be observed. The asterisk denotes residual ethylene.
FIG. 5. Thermal ellipsoid drawing (50% probability) of W(O)(B(C6F5)3)(CH-t-Bu)(OHMT)(Me2Pyr) (I-6). Hydrogen atoms have been omitted for clarity. Selected bond distances (Å) and angles (°): W1-C1=1.868(2), W1-O2=1.759(2), W1-O1=1.860(2), W1-N1=1.968(2), B1-O2=1.571(3), W1-O1-C21=150.9(1), W1-C1-C2=155.4(2)
FIG. 6. 1H NMR spectra of WO(CH-t-Bu)(Me2Pyr)(HIPTO) solution in C6D6 after addition of 1 atm of ethylene. Signals attributed to proposed substituted and unsubstituted metallacycles are labeled * and #, respectively.
FIG. 7. Variable temperature 1H NMR spectra of I-2 and the mixture of I-2 and B(C6F5)3.
FIG. 8. Thermal ellipsoid plot (50% probability) of W(O)(CH-t-Bu)(Ph2Pyr)(OHMT). Hydrogen atoms have been omitted for clarity. Selected bond distances (Å) and angles (deg): W1-C1=1.895(2), W1-O1=1.690(1), W1-O2=1.894(1), W1-N1=2.037(2); W1-C1-C2=141.1(1), W1-O2-C6=143.1(1).
FIG. 9. Thermal ellipsoid plot (50% probability) of W(O)(CH-t-Bu)[N(C6F5)2](OHMT)(PMe2Ph). Hydrogen atoms have been omitted for clarity. Selected bond distances (Å) and angles (deg): W1-C1=1.898(2), W1-O1=1.710(2), W1-O2=1.965(1), W1-N1=2.127(2), W1-P1=2.564(1), W1-C1-C2=141(2), W1-O2-C6=154.0(1).
FIG. 10. Thermal ellipsoid plot (50% probability) of squarepyramidal W(O)(C3H6)(OHMT)(Silox). Hydrogen atoms, except for those on the metallacycle, have been omitted for clarity. Only the major component of disorder is shown. Selected bond distances (Å) and angles (deg): W1-C1=2.172(3), W1-C3=2.168(3), W1-O1=1.690(2), W1-O2=1.896(2), W1-O3=1.875(3), C1-C2=1.527(4), C2-C3=1.522(4); W1-C1-C2=95.0(2), W1-C3-C2=95.4(2), C1-C2-C3=95.6(2), C1-W1-C3=62.7(1), O2-W1-O3=103.3(1), O1-W1-O2=113.6(1), O1-W1-O3=113.4(1), W1-O2-C4=148.0(1), W1-O3-Si1=161.9(4).
FIG. 11. Thermal ellipsoid plot (50% probability) of tetrahedral W(O)(CH2)(OHMT)2. Hydrogen atoms, except for those on the methylidene, have been omitted for clarity. Only the major component of disorder is shown. Selected bond distances (Å) and angles (deg): W1-C1=1.895(8), W1-O1=1.694(5), W1-O2=1.881(2), W1-O3=1.917(2); W1-C1-H1A=109(3), W1-C1-H1B=127(3), H1A-C1-H1B=123(4), 01-W1-C1=103.1(3), W1-O2-C2=136.3(2), W1-O3-C26=138.6(2).



DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS
1. General Description of Certain Embodiments of the Invention
Early in the development of olefin metathesis catalysts that contain tungsten, it was shown that metathetically more active and reproducible systems were produced when tungsten oxo complexes were deliberately employed or were present as impurities in WCl6 (K. J. Ivin and J. C. Mol, Olefin Metathesis and Metathesis Polymerization; Academic Press: San Diego, 1997; K. J. Ivin, Olefin Metathesis; Academic Press, 1983; Calderon, N.; Ofstead, E. A.; Ward, J. P.; Judy, W. A.; Scott, K. W. J. Am. Chem. Soc. 1968, 90, 4133; Basset, J. M.; Coudurier, G.; Praliaud, H. J. Catal. 1974, 34, 152; Mocella, M. T.; Rovner, R.; Muetterties, E. L. J. Am. Chem. Soc. 1976, 98, 4689; Burwell, R. L., Jr.; Brenner, A. J. Mol. Catal. 1976, 1, 77; Kress, J. R. M.; Russell, M. J. M.; Wesolek, M. G.; Osborn, J. A. J. Chem. Soc. Chem. Comm. 1980, 431; Muetterties, E. L.; Band, E. 1980, 102, 6572; Kress, J. R. M.; Wesolek, M. G.; Le Ny; J.-P.; Osborn, J. A. J. Chem. Soc. Chem. Comm. 1981, 1039; Kress, J. R. M.; Wesolek, M. G.; Osborn, J. A. J. Chem. Soc. Chem. Comm. 1982, 514; Kress, J. R. M.; Osborn, J. A. J. Am. Chem. Soc. 1983, 105, 6346). The possibility that oxo alkylidene complexes, e.g., W(O)(CHR)X2 (where X is a chloride, alkoxide, etc.), are the true catalysts in at least some of the “classical” olefin metathesis systems became more likely when 1 (L=PMe3 and other phosphines) was prepared and isolated in good yield (Schrock, R. R.; Rocklage, S. M.; Wengrovius, J. H.; Rupprecht, G.; Fellmann, J. J. Molec. Catal. 1980, 8, 73; Wengrovius, J. H.; Schrock, R. R.; Churchill, M. R.; Missert, J. R.; Youngs, W. J. J. Am. Chem. Soc. 1980, 102, 4515; Wengrovius, J. H.; Schrock, R. R. Organometallics 1982, 1, 148). Compound 1 was the first high oxidation state tungsten alkylidene complex that would both (i) metathesize terminal and internal olefins (in the presence of a trace of AlCl3) and (ii) produce a new alkylidene that could be observed as a consequence of olefin metathesis. The three most likely possibilities for the role of AlCl3 are removal of halide to give monocationic or dicationic species, removal of a phosphine to give the 16 electron monophosphine adduct (Wengrovius, J. H.; Schrock, R. R.; Churchill, M. R.; Missert, J. R.; Youngs, W. J. J. Am. Chem. Soc. 1980, 102, 4515), or activation through addition of AlCl3 to the oxo ligand (Schrock, R. R.; Rocklage, S. M.; Wengrovius, J. H.; Rupprecht, G.; Fellmann, J. J. Molec. Catal. 1980, 8, 73; Wengrovius, J. H.; Schrock, R. R.; Churchill, M. R.; Missert, J. R.; Youngs, W. J. J. Am. Chem. Soc. 1980, 102, 4515; Wengrovius, J. H.; Schrock, R. R. Organometallics 1982, 1, 148).




By the time 1 was discovered, tantalum alkylidene complexes had been turned into functional olefin metathesis catalysts through use of alkoxides as ligands (Rocklage, S. M.; Fellmann, J. D.; Rupprecht, G. A.; Messerle, L. W.; Schrock, R. R. J. Am. Chem. Soc. 1981, 103, 1440; Schrock, R. R. Polyhedron 1995, 14, 3177). Therefore, some attempts were made to prepare a W(O)(CH-t-Bu)(OR)2 species from 1, but no such species were isolated and characterized. In view of the synthetic problems encountered upon attempted alkylation of oxo complexes, including removal of the oxo ligand entirely (Kress, J. R. M.; Wesolek, M. G.; Osborn, J. A. J. Chem. Soc. Chem. Comm. 1982, 514; Kress, J. R. M.; Osborn, J. A. J. Am. Chem. Soc. 1983, 105, 6346), and to protect alkylidenes against bimolecular decomposition, attention turned to the synthesis of imido alkylidene complexes of W and Mo, especially those containing a phenylimido ligand such as N(2,6-i-Pr2C6H3) (Schrock, R. R. Chem. Rev. 2002, 102, 145-180; Schrock, R. R. in Braterman, P. R., Ed. Reactions of Coordinated Ligands, Plenum: New York, 1986, p. 221). In the face of the success of imido alkylidene complexes in olefin metathesis, interest in oxo alkylidene complexes in the last 25 years has been sparce (Bryan, J. C.; Mayer, J. C. J. Am. Chem. Soc. 1990, 112, 2298; Blosch, L. L.; Abboud, K.; Boncella, J. M. J. Am. Chem. Soc. 1991, 113, 7066; Ahn, S.; Mayr, A. J. Am. Chem. Soc. 1996, 118, 7408; De la Mata, F. J.; Grubbs, R. H. Organometallics 1996, 15, 577; O'Donoghue, M. B.; Schrock, R. R.; LaPointe, A. M.; Davis. W. M. Organometallics 1996, 15, 1334; Crane, T. W.; White, P. S.; Templeton, J. L. Organometallics 1999, 18, 1897).
The most recent development in Mo and W imido alkylidene chemistry has been monoaryloxide monopyrrolide (MAP) complexes (Schrock, R. R. Chem. Rev. 2009, 109, 3211). One of the most interesting discoveries is the ability of some MAP catalysts to promote Z selective metathesis reactions as a consequence of the presence of a relatively “large” aryloxide and “small” imido group (Ibrahem, I; Yu, M.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc., 2009, 131, 3844; Flook, M. M.; Jiang, A. J.; Schrock, R. R.; Müller, P.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7962; Flook, M. M.; Gerber, L. C. H.; Debelouchina, G. T.; Schrock, R. R. Macromolecules 2010, 43, 7515; Flook, M. M.; Ng, V. W. L.; Schrock, R. R. J. Am. Chem. Soc. 2011, 133, 1784; Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 16630; Marinescu, S. C; Schrock, R. R.; Müller, P.; Takase, M. K.; Hoveyda, A. H. Organometallics, 2011, 30, 1780; Marinescu, S. C.; Levine, D. S.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 11512; Malcolmson, S. J.; Meek, S. J.; Sattely, E. S.; Schrock, R. R.; Hoveyda, A. H. Nature 2008, 456, 933; Meek, S. J.; O'Brien, R. V.; Llaveria, J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 471, 461; Yu, M.; Wang, C.; Kyle, A. F.; Jakubec, P.; Dixon, D. J.; Schrock, R. R.; Hoveyda, A. H. Nature 2011, 479, 88). The preferred metal for Z selective couplings of terminal olefins at this time appears to be tungsten and the most successful aryloxide ligand has been O-2,6-(2,4,6-triisopropylphenyl)2C6H3 or OHIPT. (The more active molybdenum complexes (Schrock, R. R., King, A. J.; Marinescu, S. C.; Simpson, J. H.; Müller, P. Organometallics 2010, 29, 5241) appear to isomerize the Z product to E.) It has been proposed that the unusual steric demands of the OHIPT ligand force all metallacyclobutane substituents to one side of the metallacycle ring, and therefore allow only Z products to form. Since an oxo ligand is smaller than any NR ligand (R not H), the question arose as to whether MAP versions of tungsten oxo alkylidene complexes would be useful Z selective catalysts.
In some embodiments, the present invention provides a compound of formula I:




    wherein:
    each of R1 and R2 is independently R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R;
    each R3 and R4 is halogen, R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
    each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
    
        two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
        two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur;
    
    
    n is 0, 1, or 2;
    each R5 is independently a monodentate ligand, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group; and
    two or more of R1, R2, R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand.


Further aspects of compounds of formula I are described in detail, infra.
2. Definitions
Compounds of the present invention include those described generally herein, and are further illustrated by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry”, 5th Ed., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.
The term “aliphatic” or “aliphatic group”, as used herein, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic hydrocarbon, bicyclic hydrocarbon, or tricyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as “carbocycle,” “cycloaliphatic” or “cycloalkyl”), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-30 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-20 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1-10 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1, 2, 3, or 4 aliphatic carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.
The term “cycloaliphatic,” as used herein, refers to saturated or partially unsaturated cyclic aliphatic monocyclic, bicyclic, or polycyclic ring systems, as described herein, having from 3 to 14 members, wherein the aliphatic ring system is optionally substituted as defined above and described herein. Cycloaliphatic groups include, without limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclopentenyl, cyclohexyl, cyclohexenyl, cycloheptyl, cycloheptenyl, cyclooctyl, cyclooctenyl, norbornyl, adamantyl, and cyclooctadienyl. In some embodiments, the cycloalkyl has 3-6 carbons. The terms “cycloaliphatic,” may also include aliphatic rings that are fused to one or more aromatic or nonaromatic rings, such as decahydronaphthyl or tetrahydronaphthyl, where the radical or point of attachment is on the aliphatic ring. In some embodiments, a carbocyclic group is bicyclic. In some embodiments, a carbocyclic group is tricyclic. In some embodiments, a carbocyclic group is polycyclic. In some embodiments, “cycloaliphatic” (or “carbocycle” or “cycloalkyl”) refers to a monocyclic C3-C6 hydrocarbon, or a C8-C10 bicyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule, or a C9-C16 tricyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule.
As used herein, the term “alkyl” is given its ordinary meaning in the art and may include saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. In certain embodiments, a straight chain or branched chain alkyl has about 1-20 carbon atoms in its backbone (e.g., C1-C20 for straight chain, C2-C20 for branched chain), and alternatively, about 1-10. In some embodiments, a cycloalkyl ring has from about 3-10 carbon atoms in their ring structure where such rings are monocyclic or bicyclic, and alternatively about 5, 6 or 7 carbons in the ring structure. In some embodiments, an alkyl group may be a lower alkyl group, wherein a lower alkyl group comprises 1-4 carbon atoms (e.g., C1-C4 for straight chain lower alkyls).
As used herein, the term “alkenyl” refers to an alkyl group, as defined herein, having one or more double bonds.
As used herein, the term “alkynyl” refers to an alkyl group, as defined herein, having one or more triple bonds.
The term “heteroalkyl” is given its ordinary meaning in the art and refers to alkyl groups as described herein in which one or more carbon atoms is replaced with a heteroatom (e.g., oxygen, nitrogen, sulfur, and the like). Examples of heteroalkyl groups include, but are not limited to, alkoxy, poly(ethylene glycol)-, alkyl-substituted amino, tetrahydrofuranyl, piperidinyl, morpholinyl, etc.
The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic or bicyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. The term “aryl” may be used interchangeably with the term “aryl ring.” In certain embodiments of the present invention, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, binaphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like.
The terms “heteroaryl” and “heteroar-,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms (i.e., monocyclic or bicyclic), in some embodiments 5, 6, 9, or 10 ring atoms. In some embodiments, such rings have 6, 10, or 14π electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. In some embodiments, a heteroaryl is a heterobiaryl group, such as bipyridyl and the like. The terms “heteroaryl” and “heteroar-”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. A heteroaryl group may be mono- or bicyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted.
As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7-10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term “nitrogen” includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or +NR (as in N-substituted pyrrolidinyl).
A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. A heterocyclyl group may be mono- or bicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted.
As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.
The term “heteroatom” means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quaternized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+ (as in N-substituted pyrrolidinyl)).
The term “unsaturated,” as used herein, means that a moiety has one or more units of unsaturation.
The term “halogen” means F, Cl, Br, or I.
As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.
Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; —(CH2)0-4R∘; —(CH2)0-4OR∘; —O(CH2)0-4R∘, —O—(CH2)0-4C(O)OR∘; —(CH2)0-4CH(OR∘)2; —(CH2)0-4Ph, which may be substituted with R∘; —(CH2)0-4O(CH2)0-1Ph which may be substituted with R∘; —CH═CHPh, which may be substituted with R∘; —(CH2)0-4O(CH2)0-1-pyridyl which may be substituted with R∘; —NO2; —CN; —N3; —(CH2)0-4N(R∘)2; —(CH2)0-4N(R∘)C(O)R∘; —N(R∘)C(S)R∘; —(CH2)0-4N(R∘)C(O)NR∘2; —N(R∘)C(S)NR∘2; —(CH2)0-4N(R∘)C(O)OR∘; —N(R∘)N(R∘)C(O)R∘; —N(R∘)N(R∘)C(O)NR∘2; —N(R∘)N(R∘)C(O)OR∘; —(CH2)0-4C(O)R∘; —C(S)R∘; —(CH2)0-4C(O)OR∘; —(CH2)0-4C(O)SR∘; —(CH2)0-44C(O)OSiR∘3; —(CH2)0-4C(O)R∘; —OC(O)(CH2)0-4SR—, SC(S)SR∘; —(CH2)0-4SC(O)R; —(CH2)0-4C(O)NR∘2; —C(S)NR∘2; —C(S)SR∘; —SC(S)SR∘, —(CH2)0-4OC(O)NR∘2; —C(O)N(OR)R∘; —C(O)C(O)R∘; —C(O)CH2C(O)R; —C(NOR∘)R∘; —(CH2)0-4SSR∘; —(CH2)0-4S(O)2R∘; —(CH2)0-4S(O)2OR∘; —(CH2)0-4OS(O)2R∘; —S(O)2NR∘2; —(CH2)0-4S(O)R; —N(R∘)S(O)2NR∘2; —N(R∘)S(O)2R; —N(OR)RO; —C(NH)NR∘2; —P(O)2R∘; —P(O)R∘2; —OP(O)R∘2; —OP(O)(OR∘)2; —SiR∘3; —OSiR∘3; —(C1-4 straight or branched alkylene)O—N(R∘)2; or —(C1-4 straight or branched alkylene)C(O)O—N(R∘)2, wherein each R∘ may be substituted as defined below and is independently hydrogen, C1-6 aliphatic, —CH2Ph, —O(CH2)0-1Ph, —CH2-(5-6 membered heteroaryl ring), or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R∘, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.
Suitable monovalent substituents on R∘ (or the ring formed by taking two independent occurrences of R∘ together with their intervening atoms), are independently halogen, —(CH2)0-2R●, -(haloR●), —(CH2)0-2OH, —(CH2)0-2OR●, —(CH2)0-2CH(OR●)2; —O(haloR●), —CN, —N3, —(CH2)0-2C(O)R●, —(CH2)0-2C(O)OH, —(CH2)0-2C(O)OR●, —(CH2)0-2SR●, —(CH2)0-2SH, —(CH2)0-2NH2, —(CH2)0-2NHR●, —(CH2)0-2NR2, —NO2, —SiR∘3, —OSiR∘3, —C(O)SR●, —(C1-4 straight or branched alkylene)C(O)OR●, or —SSR● wherein each R∘ is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C1-4 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R∘ include ═O and ═S.
Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: ═O, ═S, ═NNR*2, ═NNHC(O)R*, ═NNHC(O)OR*, ═NNHS(O)2R*, ═NR*, ═NOR*, —O(C(R*2))2-3O—, or —S(C(R*2))2-3S—, wherein each independent occurrence of R* is selected from hydrogen, C1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: —O(CR*2)2-3O—, wherein each independent occurrence of R* is selected from hydrogen, C1-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Suitable substituents on the aliphatic group of R* include halogen, —R●, -(haloR●), —OH, —OR●, —O(haloR●), —CN, —C(O)OH, —C(O)OR∘, —NH2, —NHR●, —NR●2, or —NO2, wherein each R● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1-4 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include —R†, —NR†2, —C(O)R†, —C(O)OR†, —C(O)C(O)R†, —C(O)CH2C(O)R†, —S(O)2R†, —S(O)2NR†2, —C(S)NR†2, —C(NH)NR†2, or —N(R†)S(O)2R†; wherein each R† is independently hydrogen, C1-6 aliphatic which may be substituted as defined below, unsubstituted —OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R†, taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
Suitable substituents on the aliphatic group of R† are independently halogen, —R●, -(haloR●), —OH, —OR●, —O(haloR●), —CN, —C(O)OH, —C(O)OR●, —NH2, —NHR●, —NR●2, or —NO2, wherein each R● is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1-4 aliphatic, —CH2Ph, —O(CH2)0-1Ph, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
As used herein, the term “stereogenic metal atom” is given its ordinary meaning, and refers to a metal atom coordinated by at least two ligands (e.g., at least four ligands), wherein the ligands are arranged about the metal atom such that the overall structure (e.g., metal complex) lacks a plane of symmetry with respect to the metal atom. In some cases, the stereogenic metal atom may be coordinated by at least three ligands, at least four ligands, at least five ligands, at least six ligands, or more. In certain embodiments, the stereogenic metal atom may be coordinated by four ligands. Metal complexes comprising a stereogenic metal center may provide sufficient space specificity at a reaction site of the metal complex, such that a molecular substrate having a plane of symmetry may be reacted at the reaction site to form a product that is free of a plane of symmetry. That is, the stereogenic metal center of the metal complex may impart sufficient shape specificity to induce stereogenicity effectively, producing a chiral product. Such metal complexes may exhibit improved catalytic activity and stereoselectivity, relative to previous systems, and may reduce undesired side reactions (e.g., dimerization or oligomerization of the metal complex).
The term “chiral” is given its ordinary meaning in the art and refers to a molecule that is not superimposable with its mirror image, wherein the resulting nonsuperimposable mirror images are known as “enantiomers” and are labeled as either an (R) enantiomer or an (S) enantiomer. Typically, chiral molecules lack a plane of symmetry.
The term “achiral” is given its ordinary meaning in the art and refers to a molecule that is superimposable with its mirror image. Typically, achiral molecules possess a plane of symmetry.
As used herein, a ligand may be either monodentate or polydentate. A ligand may have hapticity of more than 1. In some cases, the ligand has a hapticity of 1 to 10. For ligand with hapticity greater than 1, as sometimes done in the art, a single bond may be drawn between the ligand and the metal. In some cases, a ligand is alkylidene. In some cases, a ligand is nitrogen-containing ligand In some cases, a ligand is oxygen-containing ligand. In some cases, a ligand is phosphorus-containing ligand.
As used herein, a “nitrogen-containing ligand” may be any species comprising a nitrogen atom. In some cases, the nitrogen atom may bind to the metal atom. In some cases, the nitrogen-containing ligand may bind the metal center via a different atom. In some cases, the nitrogen atom may be a ring atom of a heteroaryl or heteroalkyl group. In some cases, the nitrogen atom may be a substituted amine group. It should be understood that, in catalyst precursors described herein, the nitrogen-containing ligand may have sufficiently ionic character to coordinate a metal center, such as a Mo or W metal center. Examples of nitrogen-containing ligands include, but are not limited to, pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, indolyl, indazolyl, carbazolyl, morpholinyl, piperidinyl, oxazinyl, substituted derivatives thereof, and the like. For example, the nitrogen-containing ligand may be pyrrolide or 2,5-dimethylpyrrolide. The nitrogen-containing ligand may be selected to interact with an oxygen-containing ligand such that the oxygen-containing ligand can readily replace the nitrogen-containing ligand in a precatalyst to generate a catalyst. In cases where the catalyst composition may be generated in situ in order to carry out a chemical reaction, the first, nitrogen-containing ligand may be selected such that, upon replacement by an oxygen-containing ligand, the nitrogen-containing ligands or protonated versions thereof do not interfere with the chemical reaction. In some embodiments, the nitrogen-containing ligand may be chiral and the precatalyst may be provided as a racemic mixture or a purified stereoisomer.
As used herein, the term “oxygen-containing ligand” may be used to refer to ligands comprising at least one oxygen atom. In some cases, the oxygen atom binds to the metal atom thereby forming an ether-linkage. In other cases, the oxygen-containing ligand may bind the metal center via a different atom. The term “oxygen-containing ligand” may also describe ligand precursors comprising at least one hydroxyl group (e.g., a hydroxyl-containing ligand), wherein deprotonation of the hydroxyl group results in a negatively charged oxygen atom, which may coordinate to a metal atom. The oxygen-containing ligand may be a heteroaryl or heteroalkyl group comprising at least one oxygen ring atom. In some cases, the oxygen atom may be positioned on a substituent of an alkyl, heteroalkyl, aryl, or heteroaryl group. For example, the oxygen-containing ligand may be a hydroxy-substituted aryl group, wherein the hydroxyl group is deprotonated upon coordination to the metal center.
As used herein, the term “phosphorus-containing ligand” may be used to refer to ligands comprising at least one phosphorus atom. In some cases, the phosphorus atom binds to the metal. In other cases, the phosphorus-containing ligand may bind to the metal center via a different atom (i.e., an atom other than the phosphorous). The phosphorus-containing ligand may have phosphorus atom of various oxidation states. In some cases the phosphorus-containing ligand is phosphine. In some cases the phosphorus-containing ligand is phosphite. In some cases the phosphorus-containing ligand is phosphate. The phosphorus-containing ligand may be either monodentate or polydentate. In some cases, two or more phosphorus atoms bind to the metal. In some cases, one or more phosphorus atoms together with one or more non-phosphorus atoms bind to the metal.
In may also describe ligand precursors comprising at least one hydroxyl group (e.g., a hydroxyl-containing ligand), wherein deprotonation of the hydroxyl group results in a negatively charged oxygen atom, which may coordinate to a metal atom. The oxygen-containing ligand may be a heteroaryl or heteroalkyl group comprising at least one oxygen ring atom. In some cases, the oxygen atom may be positioned on a substituent of an alkyl, heteroalkyl, aryl, or heteroaryl group. For example, the oxygen-containing ligand may be a hydroxy-substituted aryl group, wherein the hydroxyl group is deprotonated upon coordination to the metal center.
As defined herein, a “metal complex” is any complex used to form a provided precursor complex or any complex generated from a provided precursor complex (e.g., for use as a catalyst in a reaction such as a metathesis reaction).
The phrase “protecting group,” as used herein, refers to temporary substituents which protect a potentially reactive functional group from undesired chemical transformations. Examples of such protecting groups include esters of carboxylic acids, silyl ethers of alcohols, and acetals and ketals of aldehydes and ketones, respectively. A “Si protecting group” is a protecting group comprising a Si atom, such as Si-trialkyl (e.g., trimethylsilyl, tributylsilyl, t-butyldimethylsilyl), Si-triaryl, Si-alkyl-diphenyl (e.g., t-butyldiphenylsilyl), or Si-aryl-dialkyl (e.g., Si-phenyldialkyl). Generally, a Si protecting group is attached to an oxygen atom. The field of protecting group chemistry has been reviewed (Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). Such protecting groups (and associated protected moieties) are described in detail below.
Protected hydroxyl groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rd edition, John Wiley & Sons, 1999, the entirety of which is incorporated herein by reference. Examples of suitably protected hydroxyl groups further include, but are not limited to, esters, carbonates, sulfonates allyl ethers, ethers, silyl ethers, alkyl ethers, arylalkyl ethers, and alkoxyalkyl ethers. Examples of suitable esters include formates, acetates, proprionates, pentanoates, crotonates, and benzoates. Specific examples of suitable esters include formate, benzoyl formate, chloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate, 4,4-(ethylenedithio)pentanoate, pivaloate (trimethylacetate), crotonate, 4-methoxy-crotonate, benzoate, p-benylbenzoate, 2,4,6-trimethylbenzoate. Examples of suitable carbonates include 9-fluorenylmethyl, ethyl, 2,2,2-trichloroethyl, 2-(trimethylsilyl)ethyl, 2-(phenylsulfonyl)ethyl, vinyl, allyl, and p-nitrobenzyl carbonate. Examples of suitable silyl ethers include trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, triisopropylsilyl ether, and other trialkylsilyl ethers. Examples of suitable alkyl ethers include methyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, trityl, t-butyl, and allyl ether, or derivatives thereof. Alkoxyalkyl ethers include acetals such as methoxymethyl, methylthiomethyl, (2-methoxyethoxy)methyl, benzyloxymethyl, beta-(trimethylsilyl)ethoxymethyl, and tetrahydropyran-2-yl ether. Examples of suitable arylalkyl ethers include benzyl, p-methoxybenzyl (MPM), 3,4-dimethoxybenzyl, O-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, 2- and 4-picolyl ethers.
Protected amines are well known in the art and include those described in detail in Greene (1999). Suitable mono-protected amines further include, but are not limited to, aralkylamines, carbamates, allyl amines, amides, and the like. Examples of suitable mono-protected amino moieties include t-butyloxycarbonylamino (—NHBOC), ethyloxycarbonylamino, methyloxycarbonylamino, trichloroethyloxycarbonylamino, allyloxycarbonylamino (—NHAlloc), benzyloxocarbonylamino (—NHCBZ), allylamino, benzylamino (—NHBn), fluorenylmethylcarbonyl (—NHFmoc), formamido, acetamido, chloroacetamido, dichloroacetamido, trichloroacetamido, phenylacetamido, trifluoroacetamido, benzamido, t-butyldiphenylsilyl, and the like. Suitable di-protected amines include amines that are substituted with two substituents independently selected from those described above as mono-protected amines, and further include cyclic imides, such as phthalimide, maleimide, succinimide, and the like. Suitable di-protected amines also include pyrroles and the like, 2,2,5,5-tetramethyl-[1,2,5]azadisilolidine and the like, and azide.
Protected aldehydes are well known in the art and include those described in detail in Greene (1999). Suitable protected aldehydes further include, but are not limited to, acyclic acetals, cyclic acetals, hydrazones, imines, and the like. Examples of such groups include dimethyl acetal, diethyl acetal, diisopropyl acetal, dibenzyl acetal, bis(2-nitrobenzyl) acetal, 1,3-dioxanes, 1,3-dioxolanes, semicarbazones, and derivatives thereof.
Protected carboxylic acids are well known in the art and include those described in detail in Greene (1999). Suitable protected carboxylic acids further include, but are not limited to, optionally substituted C1-6 aliphatic esters, optionally substituted aryl esters, silyl esters, activated esters, amides, hydrazides, and the like. Examples of such ester groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, benzyl, and phenyl ester, wherein each group is optionally substituted. Additional suitable protected carboxylic acids include oxazolines and ortho esters.
Protected thiols are well known in the art and include those described in detail in Greene (1999). Suitable protected thiols further include, but are not limited to, disulfides, thioethers, silyl thioethers, thioesters, thiocarbonates, and thiocarbamates, and the like. Examples of such groups include, but are not limited to, alkyl thioethers, benzyl and substituted benzyl thioethers, triphenylmethyl thioethers, and trichloroethoxycarbonyl thioester, to name but a few.
3. Description of Certain Embodiments of the Invention
In some embodiments, the present invention provides complexes which serve as precursors to metathesis catalysts, including stereogenic-at-metal catalysts. In certain embodiments, provided precursor complexes are used in metathesis reactions, such as olefin metathesis reactions.
As used herein, the term “metathesis reaction” is given its ordinary meaning in the art and refers to a chemical reaction in which two reacting species exchange partners in the presence of a transition-metal catalyst. In some cases, a byproduct of a metathesis reaction may be ethylene. A metathesis reaction may involve reaction between species comprising, for example, olefins and/or alkynes. Examples of different kinds of metathesis reactions include cross metathesis, ring-closing metathesis, ring-opening metathesis, acyclic diene metathesis, alkyne metathesis, enyne metathesis, and the like. The metathesis reaction may occur between two substrates which are not joined by a bond (e.g., intermolecular metathesis reaction) or between two portions of a single substrate (e.g., intramolecular metathesis reaction). In some embodiments, complexes of the present invention are useful in the formation of a metathesis product with high enantioselectivity and/or high ratio of Z:E isomers, and/or high ratio of E:Z isomers.
In some embodiments, a compound is isolated as a Lewis base adduct. The terms “Lewis base” and “Lewis base adduct” are known in the art and refer to a chemical moiety capable of donating a pair of electrons to another chemical moiety. In some embodiments, the coordination of Lewis base molecules to a compound may result in a complex having a plane of symmetry with respect to the metal center. However, a stereogenic metal center may be formed by facile removal of the Lewis base molecules and/or replacement of one or more Lewis base molecules with one or more molecules that cause the complex to lose the plane of symmetry with respect to the metal center. For example, the provided compound may be formed and stored as a Lewis base adduct, and may be “activated” in a subsequent reaction step to generate a catalyst with a stereogenic metal center.
Some embodiments of the invention provide a composition comprising a provided precursor complex which, upon treatment to generate a metal complex, affords a catalyst suitable for use in reactions described herein. In some embodiments, treatment of the provided precursor complex generates a metal complex comprising a stereogenic metal atom and two or more ligands that bind the metal atom. In some embodiments, each ligand associated with the metal complex comprises an organic group. The ligands may be monodentate ligands, i.e., the ligands bind the stereogenic metal atom via one site of the ligand (e.g., a carbon atom or a heteroatom of the ligand). In some embodiments, a monodentate ligand may bind the metal center via a single bond or a multiple bond. In some embodiments, the metal complex comprises at least one ligand lacking a plane of symmetry. That is, at least one ligand bound to the stereogenic metal atom is a chiral ligand. In some embodiments, the metal complex comprises a nitrogen-containing ligand, including chiral and/or achiral nitrogen-containing ligands. For example, the ligand may be a chiral or achiral nitrogen heterocycle, such as a pyrrolide. In some embodiments, the metal complex comprises an oxygen-containing ligand, including chiral and/or achiral oxygen-containing ligands. For example, the ligand may be a chiral or achiral biphenyl group substituted with at least one oxygen-containing moiety, e.g., a phenol. In some cases, the metal atom may be bound to at least one carbon atom. In some embodiments, the metal complex comprises an phosphorus-containing ligand, including chiral and/or achiral oxygen-containing ligands.
Some aspects of the invention can be realized with provided precursor complexes comprising two or more ligands, wherein each ligand is a monodentate ligand, i.e., each ligand binds or coordinates the metal center via one coordination site of the metal only, or via one site of the ligand only. In some embodiments, a provided precursor complex comprises primarily monodentate ligands. In some embodiments, a provided precursor complex comprises at least one bidentate ligand, i.e., the ligand binds or coordinates the metal center via two coordination sites. In some embodiments, a provided precursor complex comprises a monodentate ligand and a bidentate ligand.
In some embodiments, methods of the present invention comprise use of a provided compound wherein, upon generation of a metal complex in situ, the metal complex is present in a diastereomeric ratio greater than 1:1. In some embodiments, the metal complex is present in a diastereomeric ratio greater than about 5:1, greater than about 7:1, greater than about 10:1, greater than about 20:1, or, in some cases, greater. In certain embodiments, the metal complex generated in situ is an active metal catalyst complex. Exemplary such active metal catalyst complexes include metal complexes described herein for use in, inter alia, olefin metathesis reactions.
In some embodiments, the present invention provides a compound of formula I:




    wherein:
    each of R1 and R2 is independently R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R;
    each of R3 and R4 is independently halogen, R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
    each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
    
        two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
        two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur;
    
    
    n is 0, 1, or 2;
    each R5 is independently a monodentate ligand, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group; and
    two or more of R1, R2, R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand.


As defined generally above, each of R1 and R2 is independently R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R, wherein R is hydrogen, or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, both of R1 and R2 are hydrogen. In some embodiments, one of R1 and R2 is hydrogen and the other is an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, the R1 group or the R2 group of formula I is optionally substituted C1-20 aliphatic. In some embodiments, R1 or R2 is optionally substituted C1-20 alkyl. In certain embodiments, R1 or R2 is C1-6 alkyl substituted with phenyl and one or two additional substituents. In certain embodiments, R1 or R2 is a lower alkyl group optionally substituted with one or two methyl groups and phenyl. In certain embodiments, R1 or R2 is —C(Me)2Ph. In certain embodiments, R1 or R2 is —C(Me)3. In some embodiments, R1 or R2 is selected from any of those R1 or R2 groups depicted or described herein.
In certain embodiments, R2 is hydrogen and R1 is R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R, wherein each R is independently as defined above and described herein. In certain embodiments, R2 is hydrogen and R1 is R, wherein R is as defined above and described herein. In certain embodiments, R2 is hydrogen and R1 is optionally substituted C1-20 aliphatic. In some embodiments, R2 is hydrogen and R1 is optionally substituted C1-20 alkyl. In certain embodiments, R2 is hydrogen and R1 is C1-6 alkyl substituted with phenyl and one or two additional substituents. In certain embodiments, R2 is hydrogen and R1 is a lower alkyl group optionally substituted with one or two methyl groups and phenyl. In certain embodiments, R2 is hydrogen and R1 is —C(Me)2Ph. In certain embodiments, R2 is hydrogen and R1 is —C(Me)3. In some embodiments, R2 is hydrogen and R1 is selected from any of those R1 or R2 groups depicted or described herein.
In some embodiments, the present invention provides a compound of formula I-a, below:




wherein each of n, R1, R3, R4, and R5 is as defined above and described in embodiments herein, both singly and in combination.

In some embodiments, both R1 and R2 are hydrogen.
As defined generally above, each R3 and R4 is halogen, R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each R is independently as defined above or described herein.
In some embodiments, at least one of R3 and R4 is halogen. In other embodiments, each R3 and R4 is independently R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each R is independently as defined above or described herein.
In certain embodiments, at least one of R3 and R4 is —N(R)2. In some embodiments, both of R3 and R4 are —N(R)2, wherein one R is hydrogen and the other is optionally substituted C1-20 aliphatic.
In other embodiments, R3 and R4 are —N(R)2, wherein the two R groups are taken together with the nitrogen to form an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-3 additional heteroatoms not including the N atom from N(R)2 independently selected from nitrogen, oxygen, or sulfur, wherein R3 and R4 are coordinated to W via a nitrogen. In some embodiments, the two R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 0-3 additional nitrogen atoms not including the N atom from N(R)2. Such rings include optionally substituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl. In some embodiments, such rings are unsubstituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl.
In some embodiments, at least one of R3 and R4 is an optionally substituted 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is an optionally substituted group selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazoly, oxadiazoyl, thiazolyl, and thiazolyl. In some embodiments, at least one of R3 and R4 is an unsubstituted group selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazoly, oxadiazoyl, thiazolyl, and thiazolyl. In some embodiments, at least one of R3 and R4 is a substituted group selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazoly, oxadiazoyl, thiazolyl, and thiazolyl. In some embodiments, at least one of R3 and R4 is an unsubstituted pyrrolyl. In some embodiments, each of R3 and R4 is an unsubstituted pyrrolyl. In some embodiments, at least one of R3 and R4 is a substituted pyrrolyl. In some embodiments, each of R3 and R4 is a substituted pyrrolyl.
In other embodiments, at least one of R3 and R4 is an optionally substituted 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is an optionally substituted group selected from indolyl, benzimidazolyl, and indazolyl. In some embodiments, at least one of R3 and R4 is an unsubstituted group selected from indolyl, benzimidazolyl, and indazolyl. In some embodiments, at least one of R3 and R4 is a substituted group selected from indolyl, benzimidazolyl, and indazolyl.
In certain embodiments, at least one of R3 and R4 is an optionally substituted group selected from




wherein each  represents the point of attachment to the metal. In some embodiments, at least one of R3 and R4 is an unsubstituted group selected from





In some embodiments, at least one of R3 and R4 is a substituted group selected from





In some embodiments, at least one of R3 and R4 is —OR wherein R is as defined above or described herein. In some embodiments, at least one of R3 and R4 is —OR wherein R is hydrogen. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted C1-20 aliphatic. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted phenyl. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted 8-10 membered bicyclic saturated, partially unsaturated or aryl ring. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, at least one of R3 and R4 is —OR wherein R is an optionally substituted phenyl. In some embodiments, at least one of R3 and R4 is phenoxide. In certain embodiments, at least one of R3 and R4 is —OR wherein R is a substituted phenyl. In certain embodiments, at least one of R3 and R4 is —OR wherein R is a phenyl substituted with one or more optionally substituted alkyl groups. In certain embodiments, at least one of R3 and R4 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted alkyl substituents. In certain embodiments, at least one of R3 and R4 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted alkyl substituents. In certain embodiments, at least one of R3 and R4 is —OR wherein R is a phenyl substituted with one or more optionally substituted aryl groups. In certain embodiments, at least one of R3 and R4 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted aryl substituents. In certain embodiments, at least one of R3 and R4 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted aryl substituents. In certain embodiments, at least one of R3 and R4 is —OR wherein R is a phenyl substituted with one or more optionally substituted phenyl groups. In certain embodiments, at least one of R3 and R4 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted phenyl substituents. In certain embodiments, at least one of R3 and R4 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted phenyl substituents. In certain embodiments at least one of R3 and R4 is O-2,6-dimesitylphenoxide (OHMT). In certain embodiments at least one of R3 and R4 is O-2,6-(2,4,6-triisopropylphenyl)2C6H3 (OHIPT). In certain embodiments at least one of R3 and R4 is 2,6-pentafluorophenylphenoxide (DFTO or decafluoroterphenoxide).
In certain embodiments at least one of R3 and R4 is O(R)2 wherein each R is independently as defined above or described herein.
In certain embodiments at least one of R3 and R4 is O(R)2 wherein each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments at least one of R3 and R4 is O(R)2 wherein two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, at least one of R3 and R4 is independently N(R)3 wherein each R is independently as defined above or described herein. In certain embodiments, at least one of R3 and R4 is independently N(R)3 wherein each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, one R group is hydrogen and the other two is independently an optionally substituted group selected from phenyl, napthyl, cyclohexyl, pyridyl, pyrimidinyl, cyclopentyl, methyl, ethyl, propyl, or butyl.
In certain embodiments, at least one of R3 and R4 is independently N(R)3, wherein the two or three R groups are taken together with the nitrogen atom to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the N atom from N(R)3 independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two or three R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 1-3 nitrogen atoms. Such rings include optionally substituted pyrrole, pyrazole, imidazole, and triazole.
In some embodiments, at least one of R3 and R4 is independently a phosphorus-containing ligand. In some embodiments, at least one of R3 and R4 is independently phosphorous-containing ligand capable of coordinating with W via the phosphorus atom. In some embodiments, at least one of R3 and R4 is independently —P(R′)2, P(R′)3, —P(O)(R′)2, P(O)(R′)3 wherein:

    each R′ is independently halogen, —R, —OR, —N(R)2, or two or three R′ are taken together with the phosphorus to form an optionally substituted 3-20 membered ring with 0-10 additional heteroatoms not including the phosphorus atom from —P(R′)2, P(R′)3, —P(O)(R′)2, or P(O)(R′)3, independently selected from nitrogen, oxygen, sulfur, or phosphorus; and
    each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
    
        two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
        two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur;
    
    


In some embodiments, at least one of R3 and R4 is independently P(R′)3, wherein each R′ is independently as defined above and described herein. In some embodiments, at least one of R3 and R4 is independently P(R′)3, wherein each R′ is R and wherein R is as defined above and described herein. In some embodiments, at least one of R3 and R4 is independently P(R′)3, wherein each R′ is an optionally substituted group selected from hydrogen, C1-20 aliphatic, phenyl, or ferrocene.
In some embodiments, at least one of R3 or R4 is partially dissociated.
In some embodiments, R3 is halogen, or —OR wherein R is as defined above and described herein. In some embodiments, R3 is halogen. In some embodiments, R3 is —OR wherein R is as defined above and described herein. In some embodiments, R3 is —OR wherein R is hydrogen. In some embodiments, R3 is —OR wherein R is an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3 is —OR wherein R is an optionally substituted C1-20 aliphatic. In some embodiments, R3 is —OR wherein R is an optionally substituted C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3 is —OR wherein R is an optionally substituted phenyl. In some embodiments, R3 is —OR wherein R is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R3 is —OR wherein R is an optionally substituted 8-10 membered bicyclic saturated, partially unsaturated or aryl ring. In some embodiments, R3 is —OR wherein R is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3 is —OR wherein R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3 is —OR wherein R is an optionally substituted 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3 is —OR wherein R is an optionally substituted 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, R3 is —OR wherein R is an optionally substituted phenyl. In some embodiments, R3 is phenoxide. In certain embodiments, R3 is —OR wherein R is a substituted phenyl. In certain embodiments, R3 is —OR wherein R is a phenyl substituted with one or more optionally substituted alkyl groups. In certain embodiments, R3 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted alkyl substituents. In certain embodiments, R3 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted alkyl substituents. In certain embodiments, R3 is —OR wherein R is a phenyl substituted with one or more optionally substituted aryl groups. In certain embodiments, R3 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted aryl substituents. In certain embodiments, R3 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted aryl substituents. In certain embodiments, R3 is —OR wherein R is a phenyl substituted with one or more optionally substituted phenyl groups. In certain embodiments, R3 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted phenyl substituents. In certain embodiments, R3 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted phenyl substituents. In certain embodiments R3 is O-2,6-dimesitylphenoxide (OHMT). In certain embodiments R3 is O-2,6-(2,4,6-triisopropylphenyl)2C6H3 (OHIPT). In some embodiments, R3 is not —O-2,6-Ph2C6H3. In some embodiments, R3 is 2,6-pentafluorophenylphenoxide (DFTO or decafluoroterphenoxide).
In some embodiments, R3 is an optionally substituted group selected from:




wherein each  represents the point of attachment to W.

In other embodiments, R3 is an optionally substituted





moiety. In some embodiments, R3 is optionally substituted with one or more electron-withdrawing groups. In some embodiments, R3 is optionally substituted with one or more halogen. In some embodiments, R3 is optionally substituted with one or more —F. In some embodiments, R3 is optionally substituted with one or more —Cl. In some embodiments, R3 is optionally substituted with one or more —Br. In some embodiments, R3 is optionally substituted with one or more —I.

Exemplary R3 groups are depicted below, wherein each  represents the point of attachment to the metal:




In some embodiments, R4 is halogen, R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each R is independently as defined above and described herein.
In some embodiments, R4 is —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, or —NROR, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each R is independently as defined above and described herein.
In certain embodiments, R4 is halogen. In some embodiments, R4 is —N(R)2. In some embodiments, R4 is an optionally substituted 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is an optionally substituted 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is an optionally substituted 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, at least one of R3 and R4 is halogen. In some embodiments, none of R3 and R4 is halogen.
In certain embodiments, R4 is —N(R)2. In some embodiments, R4 is —N(R)2 wherein each R is hydrogen. In some embodiments, R4 is —N(R)2 wherein only one R is hydrogen. In some embodiments, R4 is —N(R)2 wherein neither R is hydrogen.
In other embodiments, R4 is —N(R)2, wherein the two R groups are taken together with the nitrogen to form an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-3 additional heteroatoms not including the N atom from N(R)2 independently selected from nitrogen, oxygen, or sulfur, wherein R4 is coordinated to W via a nitrogen. In some embodiments, the two R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 0-3 additional nitrogen atoms not including the N atom from N(R)2. Such rings include optionally substituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl. In some embodiments, such rings are unsubstituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl.
In some embodiments, R4 is an optionally substituted 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is an optionally substituted group selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazoly, oxadiazoyl, thiazolyl, and thiazolyl. In some embodiments, R4 is an unsubstituted group selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazoly, oxadiazoyl, thiazolyl, and thiazolyl. In some embodiments, R4 is a substituted group selected from pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyl, isoxazoly, oxadiazoyl, thiazolyl, and thiazolyl. In some embodiments, R4 is unsubstituted pyrrolyl. In some embodiments, R4 is substituted pyrrolyl.
In other embodiments, R4 is an optionally substituted 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is an optionally substituted group selected from indolyl, benzimidazolyl, and indazolyl. In some embodiments, R4 is an unsubstituted group selected from indolyl, benzimidazolyl, and indazolyl. In some embodiments, R4 is a substituted group selected from indolyl, benzimidazolyl, and indazolyl.
In certain embodiments, the hapticity of R4 is 1. In certain embodiments, the hapticity of R4 is more than 1. In certain embodiments, the hapticity of R4 is 2-8. In certain embodiments, the hapticity of R4 is 2. In certain embodiments, the hapticity of R4 is 3. In certain embodiments, the hapticity of R4 is 4. In certain embodiments, the hapticity of R4 is 5. In certain embodiments, the hapticity of R4 is 6. In certain embodiments, the hapticity of R4 is 7. In certain embodiments, the hapticity of R4 is 8.
In certain embodiments, R4 is an optionally substituted group selected from




wherein each  represents the point of attachment to the metal.

In some embodiments, R4 is —OR wherein R is as defined above and described herein. In some embodiments, R4 is —OR wherein R is hydrogen. In some embodiments, R4 is —OR wherein R is an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is —OR wherein R is an optionally substituted C1-20 aliphatic. In some embodiments, R4 is —OR wherein R is an optionally substituted C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is —OR wherein R is an optionally substituted phenyl. In some embodiments, R4 is —OR wherein R is an optionally substituted 3-7 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R4 is —OR wherein R is an optionally substituted 8-10 membered bicyclic saturated, partially unsaturated or aryl ring. In some embodiments, R4 is —OR wherein R is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is —OR wherein R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is —OR wherein R is an optionally substituted 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R4 is —OR wherein R is an optionally substituted 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, R4 is —OR wherein R is an optionally substituted phenyl. In some embodiments, R4 is phenoxide. In certain embodiments, R4 is —OR wherein R is a substituted phenyl. In certain embodiments, R4 is —OR wherein R is a phenyl substituted with one or more optionally substituted alkyl groups. In certain embodiments, R4 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted alkyl substituents. In certain embodiments, R4 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted alkyl substituents. In certain embodiments, R4 is —OR wherein R is a phenyl substituted with one or more optionally substituted aryl groups. In certain embodiments, R4 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted aryl substituents. In certain embodiments, R4 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted aryl substituents. In certain embodiments, R4 is —OR wherein R is a phenyl substituted with one or more optionally substituted phenyl groups. In certain embodiments, R4 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted phenyl substituents. In certain embodiments, R4 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted phenyl substituents. In certain embodiments R4 is O-2,6-dimesitylphenoxide (OHMT). In certain embodiments R4 is O-2,6-(2,4,6-triisopropylphenyl)2C6H3 (OHIPT). In some embodiments, R4 is not —O-2,6-Ph2C6H3. In some embodiments, R4 is 2,6-pentafluorophenylphenoxide (DFTO or decafluoroterphenoxide).
In some embodiments, R4 is an optionally substituted group selected from:




wherein each  represents the point of attachment to W.

In other embodiments, —OR4 is an optionally substituted





moiety. In some embodiments, R3 is optionally substituted with one or more electron-withdrawing groups. In some embodiments, R3 is optionally substituted with one or more halogen. In some embodiments, R3 is optionally substituted with one or more —F. In some embodiments, R3 is optionally substituted with one or more —Cl. In some embodiments, R3 is optionally substituted with one or more —Br. In some embodiments, R3 is optionally substituted with one or more —I.

Exemplary R3 groups are depicted below, wherein each  represents the point of attachment to the metal:




Exemplary R4 groups are depicted below, wherein each  represents the point of attachment to the metal:




As defined generally above, n is 0, 1, or 2.
In some embodiments, n is 0. In some embodiments, n is 1. In some embodiments, n is 2.
In certain embodiments, n is 0 and the present invention provides a compound of formula II:




wherein each of R1, R2, R3, and R4 is as defined above and described in embodiments herein, both singly and in combination.

In some embodiments, the present invention provides a compound of formula II-a, below:




wherein each of R1, R3, and R4 is as defined above and described in embodiments herein, both singly and in combination.

In certain embodiments, n is 1 and the present invention provides a compound of formula III:




wherein each of R1, R2, R3, R4, and R5 is as defined above and described in embodiments herein, both singly and in combination.

In some embodiments, the present invention provides a compound of formula III-a:




wherein each of R1, R3, R4, and R5 is as defined above and described in embodiments herein, both singly and in combination.

In certain embodiments, n is 2 and the present invention provides a compound of formula IV:




wherein each of R1, R2, R3, R4, and R5 is as defined above and described in embodiments both singly and in combination.

In certain embodiments, the present invention provides a compound of formula IV-a:




wherein each of R1, R3, R4, and R5 is as defined above and described in embodiments herein, both singly and in combination.

As defined generally above, each R5 is independently a monodentate ligand, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group. In some embodiments, each R5 is independently halogen, nitrogen-containing ligand, oxygen-containing ligand, or phosphorus-containing ligand. In some embodiments, two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group. One of ordinary skill in the art will appreciate that R5 can be any suitable ligand capable of coordinating with W. In some embodiments, such ligands are depicted herein.
In certain embodiments, the hapticity of R5 is 1. In certain embodiments, the hapticity of R5 is more than 1. In certain embodiments, the hapticity of R5 is 2-8. In certain embodiments, the hapticity of R5 is 2. In certain embodiments, the hapticity of R5 is 3. In certain embodiments, the hapticity of R5 is 4. In certain embodiments, the hapticity of R5 is 5. In certain embodiments, the hapticity of R5 is 6. In certain embodiments, the hapticity of R5 is 7. In certain embodiments, the hapticity of R5 is 8.
In some embodiments, each R5 is independently nitrogen-containing ligand capable of coordinating with W via the nitrogen atom. Accordingly, in some embodiments, each R5 is independently —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, N(R)3, a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen atom and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen atom and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen atom and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having at least one nitrogen atom and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group, wherein each R is independently as defined above or described herein.
In some embodiments, at least one of R5 is independently selected from an optionally substituted 6-membered heteroaryl ring having 1-3 nitrogens. Such R5 includes optionally substituted pyridine, pyrimidine, or triazine groups.
In certain embodiments, each R5 is independently optionally substituted pyridine. In some embodiments, each R5 is independently optionally substituted pyridine.
In other embodiments, each R5 is independently selected from an optionally substituted 5-membered heteroaryl ring having one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such R5 groups include optionally substituted pyrrole, pyrazole, imidazole, triazole, oxazole, isoxazole, oxadiazole, thiazole, and thiadiazole rings.
In some embodiments, at least one of R5 is independently —N(R)2, —NHC(O)R, —NHC(O)OR, —NHC(O)N(R)2, N(R)3, or —NHSO2R wherein each R is independently as defined above or described herein. In some embodiments, at least one of R5 is —N(R)2 wherein each R is independently as defined above or described herein.
In certain embodiments, each R5 is independently —N(R)2 wherein each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, one R group is hydrogen and the other is and optionally substituted group selected from phenyl, napthyl, cyclohexyl, pyridyl, pyrimidinyl, cyclopentyl, methyl, ethyl, propyl, or butyl.
In certain embodiments, each R5 is independently —N(R)2, wherein the two R groups are taken together with the nitrogen atom to form an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-3 additional heteroatoms not including the N atom from N(R)2 independently selected from nitrogen, oxygen, or sulfur. In some embodiments, the two R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 1-3 nitrogen atoms. Such rings include optionally substituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl.
In certain embodiments, each R5 is independently N(R)3 wherein each R is independently as defined above or described herein. In certain embodiments, each R5 is independently N(R)3 wherein each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, one R group is hydrogen and the other is and optionally substituted group selected from phenyl, napthyl, cyclohexyl, pyridyl, pyrimidinyl, cyclopentyl, methyl, ethyl, propyl, or butyl.
In certain embodiments, each R5 is independently N(R)3, wherein the two or three R groups are taken together with the nitrogen atom to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the N atom from N(R)3 independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two or three R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 1-3 nitrogen atoms. Such rings include optionally substituted pyrrole, pyrazole, imidazole, and triazole.
In certain embodiments, each R5 is independently —NHC(O)R wherein R is as defined above or described herein. In some embodiments, each R5 is independently —NHC(O)R, wherein R is an optionally substituted group selected from C1-20 aliphatic, phenyl, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R is an optionally substituted group selected from phenyl, napthyl, cyclohexyl, pyridyl, pyrimidinyl, cyclopentyl, methyl, ethyl, propyl, or butyl.
In some embodiments, two R5 are taken together with their intervening atoms to form an optionally substituted bidentate moiety. In certain embodiments, two R5 are taken together to form optionally substituted bipyridyl. In certain embodiments, two R5 are taken together to form:




In some embodiments, two R5 are taken together with their intervening atoms to form a bidentate optionally substituted bicyclic or tricyclic heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In certain embodiments, two R5 are taken together to form optionally substituted phenanthroline. In certain embodiments, two R5 are taken together to form




In some embodiments, each R5 is independently oxygen-containing ligand. In some embodiments, each R5 is independently oxygen-containing ligand capable of coordinating with W via the oxygen atom. In some embodiments, each R5 is independently —OR, O(R)2, a 5-6 membered monocyclic heteroaryl ring having at least one oxygen atom and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one oxygen atom and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one oxygen atom and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having at least one oxygen atom and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group, wherein each R is independently as defined above or described herein.
In certain embodiments, each R5 is independently —OR, wherein each R is independently as defined above or described herein. In certain embodiments, each R5 is independently —OR, wherein each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, one R group is hydrogen and the other is and optionally substituted group selected from phenyl, napthyl, cyclohexyl, pyridyl, pyrimidinyl, cyclopentyl, methyl, ethyl, propyl, or butyl.
In certain embodiments, each R5 is independently O(R)2, wherein each R is independently as defined above or described herein. In certain embodiments, each R5 is independently O(R)2, wherein each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-14 membered bicyclic or tricyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, one R group is hydrogen and the other is and optionally substituted group selected from phenyl, napthyl, cyclohexyl, pyridyl, pyrimidinyl, cyclopentyl, methyl, ethyl, propyl, or butyl.
In certain embodiments, each R5 is independently O(R)2, wherein the two R groups are taken together with the oxygen atom to form an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-3 additional heteroatoms not including the oxygen atom from O(R)2 independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, each R5 is independently a phosphorus-containing ligand. In some embodiments, each R5 is independently a phosphorous-containing ligand capable of coordinating with W via the phosphorus atom. In some embodiments, each R5 is independently —P(R′)2, P(R′)3, —P(O)(R′)2, P(O)(R′)3 wherein:

    each R′ is independently halogen, —R, —OR, —N(R)2, or two or three R′ are taken together with the phosphorus to form an optionally substituted 3-20 membered ring with 0-10 additional heteroatoms not including the phosphorus atom from —P(R′)2, P(R′)3, —P(O)(R′)2, or P(O)(R′)3, independently selected from nitrogen, oxygen, sulfur, or phosphorus; and
    each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
    
        two R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
        two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur.
    
    


In some embodiments, each R5 is independently P(R′)3, wherein each R′ is independently as defined above and described herein. In some embodiments, each R5 is independently P(R′)3, wherein each R′ is R and wherein R is as defined above and described herein. In some embodiments, each R5 is independently P(R′)3, wherein each R′ is an optionally substituted group selected from hydrogen, C1-20 aliphatic, phenyl, or ferrocene.
In some embodiments, one or two R5 are partially dissociated.
Exemplary monodentate and bidentate R5 groups are depicted below:




In some embodiments, two or more of R1, R2, R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand. In some embodiments, two or more of R1, R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand. In some embodiments, two or more of R1, R2, R3 and R4 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand. In some embodiments, two or more of R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand. In some embodiments, R3 and R4 are taken together with their intervening atoms to form an optionally substituted polydentate ligand.
As defined general above, each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:

    
    
        two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
        two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur.
    
    


In some embodiments, R is hydrogen. In some embodiments, R is not hydrogen.
In some embodiments, R is optionally substituted C1-20 aliphatic. In some embodiments, R is C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R is an optionally substituted a 3-7 membered saturated or partially unsaturated carbocyclic ring. In some embodiments, R is an optionally substituted 8-10 membered bicyclic saturated or partially unsaturated ring. In some embodiments, R is an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R is an optionally substituted 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, R is independently an optionally substituted group selected from phenyl, an 8-10 membered bicyclic aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, R is optionally substituted phenyl. In some embodiments, R is phenyl substituted with one or more optionally substituted alkyl groups. In some embodiments, R is 2,6 di-substituted phenyl with two optionally substituted alkyl substituents. In some embodiments, R is 2, 4, 6 tri-substituted phenyl with three optionally substituted alkyl substituents. In some embodiments, R is a phenyl substituted with one or more optionally substituted aryl groups. In some embodiments, R is a phenyl substituted with one or more optionally substituted phenyl groups. In some embodiments, R is 2,6 di-substituted phenyl with two optionally substituted aryl substituents. In some embodiments, R is 2, 4, 6 tri-substituted phenyl with three optionally substituted aryl substituents. In some embodiments, R is a phenyl substituted with one or more optionally substituted phenyl groups. In some embodiments, R is 2,6 di-substituted phenyl with two optionally substituted phenyl substituents. In some embodiments, R is 2, 4, 6 tri-substituted phenyl with three optionally substituted phenyl substituents.
In some embodiments, R is optionally substituted




In some embodiments, R is optionally substituted with one or more electron-withdrawing groups. In some embodiments, R is optionally substituted with one or more halogen. In some embodiments, R is optionally substituted with one or more —F. In some embodiments, R is optionally substituted with one or more —Cl. In some embodiments, R is optionally substituted with one or more —Br. In some embodiments, R is optionally substituted with one or more —I. In some embodiments, R is 2,6-dimesitylphenyl (HMT). In some embodiments, R is 2,6-(2,4,6-triisopropylphenyl)2C6H3 (HIPT). In some embodiments, R is 2,6-pentafluorophenylphenoxide (DFT).

In some embodiments, R is an optionally substituted 8-10 membered aryl ring. In some embodiments, R is a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R is an optionally substituted 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, R is an optionally substituted group selected from:




Exemplary optional substituents, as described above and herein, include but not limited to alkyl, halogen, —OSiR3 groups.

In some embodiments, two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur. In some embodiments, two R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 0-3 additional nitrogen atoms not including the N atom from —N(R)2. Such rings include optionally substituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl. In some embodiments, such rings are unsubstituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl.
More embodiments of R include but are not limited to those described in the embodiments of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12.
Exemplary compounds of formula I are set forth in Table 1, below.







TABLE 1





Exemplary Compounds.






















I-1


 







I-2


 







I-3


 







I-4


 







I-5


 







I-6


 







I-7


 







I-8


 







I-9


 







I-10


 







I-11


 



W(O)(CH—t-Bu)
I-12



(Ph2Pyr)(OHMT)




W(O)(CH—t-Bu)
I-13



(Ph2Pyr)(OHIPT)




W(O)(CH—t-Bu)
I-14



[N(C6F5)2](OHMT)(PPhMe2)




W(O)(CH—t-Bu)
I-15



(PMe3)2Cl2




W(O)(CH—t-Bu)
I-16



(O-2,6-Ph2C6H3)2(PMe3)




W(O)(CH—t-Bu)
I-17



(Cl)(OHIPT)




W(O)(CH—t-Bu)
I-18



(PMe2Ph)2Cl2




W(O)(CHCMe2Ph)
I-19



Cl2(PMe2Ph)2




W[OB(C6F5)3](CH—t-Bu)
I-20



(Me2Pyr)(OHMT)




W(O)(CH—t-Bu)
I-21



[N—(C6F5)2](OHMT)




W(O)(CH—t-Bu)(OHMT)2
I-22



W(O)(CH—t-Bu)(OHIPT)2
I-23



W(O)(CH—t-Bu)
I-24



(Me2Pyr)(DFTO)(PPhMe2)




W(O)(CH—t-Bu)
I-25



(Me2Pyr)(DFTO)




W(O)(CHCMe2Ph)
I-26



(Me2Pyr)(DFTO)(PPhMe2)




W(O)(CHCMe2Ph)
I-27



(Me2Pyr)(DFTO)




W(O)(CH—t-Bu)
I-28



[N—(C6F5)2](DFTO)




W(O)(CH—t-Bu)(DFTO)2
I-29









In some embodiments, the present invention provides a compound of formula V:




    wherein:
    each of R6 and R7 is independently halogen, —OR or a phosphorus-containing ligand;
    each R8 is independently a monodentate ligand, or two R8 are taken together with their intervening atoms to form an optionally substituted bidentate group; and
    each of R1, R2, and n is independently as defined above and described herein.


In some embodiments, n=2.
In some embodiments, R8 is independently a monodentate ligand, or two R8 are taken together with their intervening atoms to form an optionally substituted bidentate group. In some embodiments, R8 is R5, wherein R5 is as defined above and described herein.
In some embodiments, each of R6, R7 and R8 is independently selected from halogen and P(R′)3, wherein each R′ is independently as defined above or described herein. In some embodiments, each of R6 and R7 is independently halogen and each of R8 is independently P(R′)3. In some embodiments, n=2, each of R6 and R7 is independently halogen, and each of R8 is independently P(R′)3. In some embodiments, each of R6 and R7 is independently halogen, n is 2, and R8 is PR3, wherein each of R is independently as defined above and described herein.
In some embodiments, a compound of formula V is WO(CHR1R2)(P(R)3)2Cl2, or WO(CHR1R2)(P(R)3)2Br2, wherein each of R1 and R2 is independently as defined above or described herein, and each R is independently an optionally substituted group selected from C1-20 aliphatic or phenyl. In some embodiments, a compound of formula V is WO(CH-t-Bu)(PMe2Ph)2Cl2. In some embodiments, a compound of formula V is WO(CH-t-Bu)(PMe3)2Cl2. In some embodiments, a compound of formula V is W(O)(CH-t-Bu)(OHMT)(PMe2Ph)Cl. In some embodiments, a compound of formula V is W(O)(CH-t-Bu)(OHIPT)(PMe2Ph)Cl. In some embodiments, a compound of formula V is W(O)(CH-t-Bu)(DFTO)(PMe2Ph)Cl.
In some embodiments, a compound of formula V has the structure of formula V-a:




    wherein:
    each of R9 and R10 is independently halogen; and
    each of R1, R2, R8 and n is independently as defined above and described herein.


In some embodiments, R9 is —F. In some embodiments, R9 is —Cl. In some embodiments, R9 is —Br. In some embodiments, R9 is —I. In some embodiments, R10 is —F. In some embodiments, R10 is —Cl. In some embodiments, R10 is —Br. In some embodiments, R10 is —I.
In some embodiments, both R9 and R10 are —Cl. In some embodiments, n=2 and both R8 are monodentate phosphine ligands. In some embodiments, n=2 and both R8 are monodentate phosphine ligands having the structure of PR3, wherein each of R is independently as defined above and described herein. In some embodiments, two R8 are taken together to form a bidentate phosphine ligand.
In some embodiments, a compound of structure V or V-a has the structure of W(O)(CHR1)Cl2(R8)2, wherein R8 is a monodentate phosphine ligand having the structure of PR3, wherein each R is independently as defined above and described herein. In some embodiments, PR3 is PMe2Ph. In some embodiments, a compound of structure V or V-a is W(O)(CHt-Bu)Cl2(PMe2Ph)2. In some embodiments, a compound of structure V or V-a is W(O)(CHCMe2Ph)Cl2(PMe2Ph)2.
In some embodiments, the present invention provides a compound of formula V having the structure of formula V-b:




    wherein:
    R11 is —OR; and
    each of R1, R2, R8, R9, R10, R and n is independently as defined above and described herein.


Exemplary —OR for R11 is extensively described in the specification, for example but not limited to the embodiments described for R3 and R4. In some embodiments, R1 is —OR, wherein R is not hydrogen. In some embodiments, R1 is —OR, wherein R is an optionally substituted group selected from C1-20 aliphatic or phenyl. In certain embodiments, R11 is —OR wherein R is optionally substituted phenyl. In certain embodiments, R11 is —OR wherein R is substituted phenyl. In certain embodiments, R11 is —OR wherein R is phenyl substituted with one or more optionally substituted alkyl groups. In certain embodiments, R11 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted alkyl substituents. In certain embodiments, R11 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted alkyl substituents. In certain embodiments, R11 is —OR wherein R is a phenyl substituted with one or more optionally substituted aryl groups. In certain embodiments, R11 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted aryl substituents. In certain embodiments, R11 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted aryl substituents. In certain embodiments, R11 is —OR wherein R is a phenyl substituted with one or more optionally substituted phenyl groups. In certain embodiments, R11 is —OR wherein R is 2,6 di-substituted phenyl with two optionally substituted phenyl substituents. In certain embodiments, R11 is —OR wherein R is 2, 4, 6 tri-substituted phenyl with three optionally substituted phenyl substituents. In certain embodiments R11 is O-2,6-dimesitylphenoxide (OHMT). In certain embodiments, R11 is O-2,6-(2,4,6-triisopropylphenyl)2C6H3 (OHIPT). In certain embodiments, R11 is 2,6-pentafluorophenylphenoxide (DFTO or decafluoroterphenoxide). In some embodiments, —OR is —OHMT. In some embodiments, —OR is OHIPT. In some embodiments, —OR is DFTO. In some embodiments, at least one of R3 and R4 is not —O-2,6-Ph2C6H3.
In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(OHMT)(PMe2Ph)Cl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(OHIPT)(PMe2Ph)Cl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(DFTO)(PMe2Ph)Cl.
In some embodiments, the present invention provides a compound of formula VI:




wherein each of R1, R2, n and R5 is independently as defined above and described herein. In some embodiments, the two R1 in formula VI are the same. In some embodiments, the two R2 in formula VI are the same. In some embodiments, the two R1 in formula VI are the same and the two R2 in formula VI are the same.

In some embodiments, a compound of formula VI has the structure of formula VI-a:




wherein each of R1, n and R5 is independently as defined above and described herein. In some embodiments, the two R1 in formula VI-a are the same.

In some embodiments, each R1 in formula VI or VI-a is R. In some embodiments, each R1 in formula VI or VI-a is optionally substituted C1-20 aliphatic. In some embodiments, each R1 in formula VI or VI-a is optionally substituted tert-butyl.
In some embodiments, each R5 in formula VI or VI-a is independently a monodentate ligand. In some embodiments, each R5 in formula VI or VI-a is independently a monodentate nitrogen-containing ligand. In some embodiments, each R5 in formula VI or VI-a is independently a monodentate phosphorus-containing ligand.
In some embodiments, two R5 in formula VI-a are taken together with their intervening atoms to form an optionally substituted bidentate moiety. In certain embodiments, two R5 are taken together to form optionally substituted bidentate bipyridyl.
In some embodiments, a compound of formula VI is WO(CH2t-Bu)(bipy) (bipy=2,2′pyridine). In some embodiments, a compound of formula VI is WO(CH2CMe2Ph)(bipy) (bipy=2, 2′pyridine).
In some embodiments, the present invention provides a compound of formula VII:




wherein each R9 is independently as defined above and described herein. In some embodiments, a compound of formula VII is W(O)2(Cl)2(bipy). In some embodiments, a compound of formula VII is W(O)2(Br)2(bipy).

In some embodiments, the present invention provides a compound of formula VIII:




wherein:

R12′ is —OR or —OSiR3; and

each of R1, R2, R8, R11, R and n is independently as defined above and described herein. In some embodiments, a compound of formula VIII is other than WO(CH-t-Bu)(O-2,6-Ph2C6H3)2(R8)n. In some embodiments, at least one of R11 and R12′ is not —O-2,6-Ph2C6H3. In some embodiments, n=0. In some embodiments, n=1.

In some embodiments, the present invention provides a compound of formula VIII-a,




wherein R11′ is —OR;

each of R1, R2, R8, R11, R and n is independently as defined above and described herein. In some embodiments, both R11 and R11′ are the same. In some embodiments, R11 and R11′ are different. Exemplary —OR embodiments for R11 and R11′ are extensively described above and herein, including but not limited to those described for R3 and R4. In some embodiments, at least one of R11 and R11′ is not —O-2,6-Ph2C6H3. In some embodiments, a compound of formula VIII-a is other than WO(CH-t-Bu)(O-2,6-Ph2C6H3)2(R8)n. In some embodiments, n=0. In some embodiments, n=1.

In some embodiments, a compound of formula VIII-a is W(O)(CH-t-Bu)(OHMT)2. In some embodiments, a compound of formula VIII-a is W(O)(CH2)(OHMT)2. In some embodiments, a compound of formula VIII-a is W(O)(CH2)(DFTO)2.
In some embodiments, the present invention provides a compound of formula VIII-b,




wherein R12 is —OSiR3, and each of R1, R2, R8, R11, R and n is independently as defined above and described herein. In some embodiments, n=0.

In some embodiments, R12 is —OSiR3 wherein at least one R is not hydrogen. In some embodiments, R12 is —OSiR3 wherein at least two R are not hydrogen. In some embodiments, R12 is —OSiR3 wherein none of R is hydrogen. In some embodiments, R12 is —OSiR3 wherein each R is independently an optionally substituted group selected from C1-20 aliphatic and phenyl. In some embodiments, R12 is —OSiR3 wherein at least one R is optionally substituted C1-20 aliphatic. In some embodiments, R12 is —OSiR3 wherein at least one R is optionally substituted phenyl. In some embodiments, R12 is —OSi(t-Bu)3. In some embodiments, a compound of formula VIII-b is WO(CH-t-Bu)[OSi(t-Bu)3](OHMT). In some embodiments, a compound of formula VIII-b is WO(CH-t-Bu)[OSi(t-Bu)3](OHIPT). In some embodiments, a compound of formula VIII-b is WO(CH-t-Bu)[OSi(t-Bu)3](DFTO).
In some embodiments, a compound of formula VIII is W(O)(CH-t-Bu)(OHMT)2. In some embodiments, a compound of formula VIII is W(O)(CH2)(OHMT)2. In some embodiments, a compound of formula VIII is WO(CH-t-Bu)[OSi(t-Bu)3](OHMT). In some embodiments, a compound of formula VIII-b is WO(CH-t-Bu)[OSi(t-Bu)3](OHIPT). In some embodiments, a compound of formula VIII-b is WO(CH-t-Bu)[OSi(t-Bu)3](DFTO).
In some embodiments, the present invention provides a compound of formula IX:




    wherein:
    R1 and R2′ are taken together with W to form an optionally substituted 3-8 membered saturated or partially unsaturated ring having, in addition to the intervening metal atom, 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
    R3′ is R3 or —OSiR3; and
    each of R3, R4, R5 and n is independently as defined above and described herein.


In some embodiments, R1′ and R2′ are taken together with W to form an optionally substituted 4 membered metallacyclobutane. In some embodiments, R1′ and R2′ are taken together with W to form a substituted 4 membered metallacyclobutane. In some embodiments, R1′ and R2′ are taken together with W to form an unsubstituted 4 membered metallacyclobutane.
In some embodiments, R3′ is R3, wherein R3 is as defined above and described herein. In some embodiments, R3′ is —OSiR3, wherein each R is independently as defined above and described herein. In some embodiments, R3′ is —OSiR3 wherein at least one R is not hydrogen. In some embodiments, R3′ is —OSiR3 wherein at least two R are not hydrogen. In some embodiments, R3′ is —OSiR3 wherein none of R is hydrogen. In some embodiments, R3′ is —OSiR3 wherein at least one R is optionally substituted C1-20 aliphatic. In some embodiments, R3′ is —OSiR3 wherein at least one R is optionally substituted phenyl. In some embodiments, R3′ is —OSi(t-Bu)3.
In some embodiments, R3′ is —OR, wherein R is optionally substituted phenyl; or R3′ is —OSiR3. In some embodiments, R3′ is —OR, wherein R is optionally substituted phenyl; or R3′ is —OSiR3, wherein each R is independently optionally substituted C1-20 aliphatic or phenyl.
In some embodiments, R3′ is not —O-2,6-Ph2C6H3.
In some embodiments, each of R3′ and R4 is independently —OR, wherein R is independently optionally substituted phenyl. In some embodiments, R3′ is —OSiR3, wherein each R is independently optionally substituted C1-20 aliphatic or phenyl; and R4 is —OR, wherein R is optionally substituted phenyl. In some embodiments, R3′ is —OR, wherein R is optionally substituted phenyl; or R3′ is —OSiR3, wherein each R is independently optionally substituted C1-20 aliphatic or phenyl.
In some embodiments, a compound of formula IX is W(O)(CH2CH2CH2)(OHMT)(Silox) (Silox=-OSi(t-Bu)3). In some embodiments, a compound of formula IX is W(O)(C3H6)(OHMT)2. In some embodiments, a compound of formula IX is W(O)(C3H6)(OHIPT)2. In some embodiments, a compound of formula IX is W(O)(C3H6)(DFTO)2.
In some embodiments, the present invention provides novel ligands their corresponding protonated compounds or salts thereof. In some embodiments, the present invention provides methods for preparing novel ligands and their corresponding protonated compounds or salts thereof. In some embodiments, a novel ligand is 2,6-pentafluorophenylphenoxide (DFTO or decafluoroterphenoxide). In some embodiments, a protonated compound of DFTO is DFTOH. In some embodiments, a salt of DFTO is LiODFT. In some embodiments, the present invention provides a method for preparing DFTOH or its salts thereof.
A provided novel ligand can be utilized to prepare novel compound or metal complexes. In some embodiments, the present invention provides a compound or metal complex comprising a novel ligand. In some embodiments, the present invention provides a compound or metal complex comprising one or more DFTO ligands. In some embodiments, the present invention provides a compound or metal complex comprising one or more DFTOH ligands. In some embodiments, the present invention provides a compound having the structure of formula I, II, III, IV, V, VI, VII, VIII, or IX, and comprising one or more DFTO ligands. In some embodiments, the present invention provides a compound having the structure of formula I, II, III, IV, V, VI, VII, VIII, or IX, and comprising one or more DFTOH ligands.
In some embodiments, a provided compound in this invention forms a complex with a Lewis acid. In some embodiments, a Lewis acid comprises a boron atom. In some embodiments, a Lewis acid is of the structure of B(R′)3. In some embodiments, a Lewis acid is of the structure of B(R)3. In some embodiments, a Lewis acid is of the structure of B(R)3, wherein R is not hydrogen. In some embodiments, a Lewis acid is of the structure of B(R)3, wherein R is an optionally substituted C1-20 aliphatic or phenyl. In some embodiments, a Lewis acid is of the structure of B(R)3, wherein R is an optionally substituted phenyl. In some embodiments, a Lewis acid is B(C6F5)3.
In some embodiments, the present invention provides a compound having the structure of any of the formulae described herein, wherein the compound is a 14e tungsten oxo alkylidene complex. In some embodiments, the present invention provides a compound having the structure of any of the formulae described herein, wherein the compound is a 14e tungsten oxo alkylidene complex and the complex is a syn isomer. In some embodiments, the present invention provides a compound having the structure of any of the formulae described herein, wherein the compound is a 16e tungsten oxo alkylidene complex.
In some embodiments, the present invention provides a compound having the structure of any of the formulae described herein, wherein at least one ligand is an optionally substituted phenoxide. In some embodiments, the present invention provides a compound having the structure of any of the formulae described herein, wherein at least one ligand is an optionally substituted 2,6-terphenoxide. In some embodiments, an optionally substituted 2,6-terphenoxide is OHMT. In some embodiments, an optionally substituted 2,6-terphenoxide is OHIPT. In some embodiments, an optionally substituted 2,6-terphenoxide is DFTO. In some embodiments, such a compound has good stability. In some embodiments, the existence of optionally substituted 2,6-terphenoxide ligand contribute to decrease composition. In some embodiments, the existence of optionally substituted 2,6-terphenoxide ligand contribute to decrease bimolecular composition.
Methods of Making Compounds
The present invention recognizes the importance of improved methods to prepare tungsten oxo alkylidene complexes. It has been known in the art that it is a challenge to make relatively stable and reactive versions of tungsten oxo alkylidene complexes in good yield.
In certain embodiments, the present invention further provides methods of making provided compounds. In some embodiments, a provided compound is synthesized from a synthetically accessible or commercially available metal complex and one or more suitable ligands.
In some embodiments, the present invention provides a method of preparing a compound of formula I, comprising reacting a metal compound of formula V:




    
    
        wherein:
        each of R1 and R2 is independently R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R;
        each R6 and R7 is halogen, —OR or a phosphorus-containing ligand;
        each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
        
            two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
            two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur;
        
        
        n is 0, 1, or 2;
        each R8 is independently a monodentate ligand, or two R8 are taken together with their intervening atoms to form an optionally substituted bidentate group; and
        two or more of R1, R2, R6 R7 and R8 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand;

with one or more suitable ligands to form a compound of formula I:

    
    






wherein each of n, R1, R2, R3 R4 and R5 is independently as defined above or described herein.

In some embodiments, each of R6, R7 and R8 is independently selected from halogen and P(R′)3, wherein each R′ is independently as defined above or described herein. In some embodiments, each of R6 and R7 is independently halogen and each of R8 is independently P(R′)3. In some embodiments, n=2, each of R6 and R7 is independently halogen, and each of R8 is independently P(R′)3. In some embodiments, n=2, each of R6 and R7 is independently halogen, and each of R8 is independently P(R)3.
In some embodiments, a compound of formula V is WO(CHR1R2)(P(R)3)2Cl2, or WO(CHR1R2)(P(R)3)2Br2, wherein each of R1 and R2 is independently as defined above or described herein, and each R is independently an optionally substituted group selected from C1-20 aliphatic or phenyl. In some embodiments, a compound of formula V is WO(CH-t-Bu)(PMe2Ph)2Cl2. In some embodiments, a compound of formula V is WO(CH-t-Bu)(PMe3)2Cl2.
In some embodiments, the present invention provides simplified method for preparing tungsten oxo alkylidene complexes having the structure of formulae V, V-a, and V-b. In some embodiments, a compound of formula V has the structure of formula V-a:




wherein:

each of R9 and R10 is independently halogen; and

each of R1, R2, R8 and n is independently as defined above and described herein.

In some embodiments, the present invention provides a method of making a tungsten oxo alkylidene complex, wherein the alkylidene is prepared on tungsten. Such methods differ from those in which the alkylidene group is “transferred” from another metal, for example, in the transformation below (L=PMe2Ph):




Exemplary methods in which the alkylidene group is prepared on tungsten are described herein.

In some embodiments, the present invention provides a method of making a compound of formula V-a:




comprising the use of a compound of formula VI:





wherein each of R1, R2, R5, R8, R9, R10 and n is independently as defined above and described herein. In some embodiments, the two R1 in formula VI are the same. In some embodiments, the two R2 in formula VI are the same. In some embodiments, the two R1 in formula VI are the same and the two R2 in formula VI are the same.

In some embodiments, a compound of formula VI has the structure of formula VI-a:




wherein each of R1, n and R5 is independently as defined above and described herein. In some embodiments, the two R1 in formula VI-a are the same.

In some embodiments, each R1 in formula VI or VI-a is R. In some embodiments, each R1 in formula VI or VI-a is optionally substituted C1-20 aliphatic. In some embodiments, each R1 in formula VI or VI-a is optionally substituted tert-butyl.
In some embodiments, each R5 in formula VI or VI-a is independently a monodentate ligand. In some embodiments, each R5 in formula VI or VI-a is independently a monodentate nitrogen-containing ligand. In some embodiments, each R5 in formula VI or VI-a is independently a monodentate phosphorus-containing ligand.
In some embodiments, two R5 in formula VI-a are taken together with their intervening atoms to form an optionally substituted bidentate moiety. In certain embodiments, two R5 are taken together to form optionally substituted bidentate bipyridyl.
In some embodiments, a compound of formula VI is WO(CH2t-Bu)(bipy) (bipy=2, 2′pyridine). In some embodiments, a compound of formula VI is WO(CH2CMe2Ph)(bipy) (bipy=2, 2′pyridine).
In some embodiments, the above method of preparing a compound of formula V or V-a further comprises the use of a Lewis acid. In some embodiments, the above method of preparing a compound of formula V or V-a further comprises the use of a salt of zinc. In some embodiments, the above method of preparing a compound of formula V or V-a further comprises the use of ZnCl2(dioxane).
In some embodiments, the above method of preparing a compound of formula V or V-a further comprises the use of R3SiR9, wherein each of R and R9 is independently as defined above and described herein. In some embodiments, R3SiR9 is TMSCl.
In some embodiments, the above method of preparing a compound of formula V or V-a further comprises the use of R8, wherein R8 is as defined above and described herein. In some embodiments, R8 is PR3, wherein each R is independently as defined above and described herein. In some embodiments, R8 is PMe2Ph.
In some embodiments, a provided method involves formation of the alkylidene ligand on tungsten through α hydrogen atom abstraction in the corresponding dialkyl precursor. In some embodiments, the alkylidene ligand is ═CH(t-Bu) and the two corresponding alkyl groups are —CH2t-Bu.
In some embodiments, the present invention provides a method of preparing a compound of formula V-b:




comprising reacting a first compound of formula V-a:





with a second compound having the structure of R11H or its salt thereof, wherein:

R11 is —OR; and each of R1, R2, R8, R9, R10, R and n is independently as defined above and described herein.

In some embodiments, a second compound in the above method is R11H. In some embodiments, a second compound in the above method is the alkoxide or aryloxide salt of R11H. In some embodiments, a second compound is R11Li. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(OHMT)(PMe2Ph)Cl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(OHIPT)(PMe2Ph)Cl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(DFTO)(PMe2Ph)Cl.
In some embodiments, the present invention provides a method of preparing a compound having the structure of formula VI:




comprising the use of a compound having the formula VII:





wherein each of R1, R2, R5, R9 and n is independently as defined above and described herein.

In some embodiments, a compound of formula VII is W(O)2(Cl)2(bipy). In some embodiments, a compound of formula VII is W(O)2(Br)2(bipy).
In some embodiments, the present invention provides a method of preparing a compound having the structure of formula VI




comprising reacting a first compound having the structure of formula VII:





with a second compound comprising a





moiety directly bonded to a metal,

wherein each of R1, R2, R5, R9 and n is independently as defined above and described herein, and the two





moieties in formula VI and the second compound are the same.

In some embodiments, the present invention provides a method of preparing a compound having the structure of formula VI-a:




comprising reacting a first compound having the structure of formula VII:





with a second compound comprising a





moiety directly bonded to a metal,

wherein each of R1, R2, R5, R9 and n is independently as defined above and described herein, and the two R1 in formula VI-a and the second compound are the same.

In some embodiments, a second compound in the provided methods is a Grignard reagent. In some embodiments, a second compound in the provided methods is a Grignard reagent having the formula of R1CH(R2)MgR10. In some embodiments, a second compound in the provided methods is a Grignard reagent having the formula of R1CH(R2)MgR10. In some embodiments, a second compound in the provided methods is a Grignard reagent having the formula of R1CH2MgR10. In some embodiments, such a Grignard reagent is t-BuCH2MgCl. In some embodiments, such a Grignard reagent is PhC(Me)2CH2MgCl.
In some embodiments, the present invention provides a method of preparing a compound having the structure of formula VII:




comprising the use of W(R9)6. In some embodiments, such a method further comprises the use of R5. In some embodiments, a provided method further optionally comprises the use of dimethoxyethane (DME). In some embodiments, a provided method further comprises the use of TMS2O. In some embodiments, W(R9)6 is WCl6.

In some embodiments, the present invention provides methods to prepare multiple types of oxo alkylidene species from a compound of formula V-b, including but not limited to compounds having the structure of formula I. Exemplary compounds and methods are described below.
In some embodiments, the present invention provides a method of making a compound of formula I, wherein R3 is —OR and R4 is —N(R)2, comprising reacting a first compound of formula V-b, wherein R11 is —R3,
with a second compound of formula R2NH or its anionic amide salt thereof;
wherein each variable is independently as defined above and described herein.
In some embodiments, R3 and R11 in the above method are —OR, wherein R is optionally substituted phenyl. Exemplary optionally substituted phenyl is extensive described in the specification including but not limited to the embodiments for R3, R4 and R11. In some embodiments, —OR is —OHMT. In some embodiments, —OR is OHIPT. In some embodiments, —OR is DFTO.
In some embodiments, a second compound in the above method is the anionic amide salt of R2NH. In some embodiments, a second compound in the above method is LiNR2. Exemplary embodiments of R or —NR2 are extensively and independently defined above and described herein, including but not limited to the embodiments for R3 and R4. In some embodiments, two R groups are taken together with the nitrogen to form an optionally substituted 5-membered heteroaryl ring having 0-3 additional nitrogen atoms not including the N atom from —N(R)2. Such rings include optionally substituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl. In some embodiments, such rings are unsubstituted pyrrol-1-yl, pyrazol-1-yl, imidazol-1-yl, and triazol-1-yl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(OHMT)(PMe2Ph)Cl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(OHIPT)(PMe2Ph)Cl. In some embodiments, a compound of formula V-b is W(O)(CH-t-Bu)(DFTO)(PMe2Ph)Cl. In some embodiments, a second compound is LiPh2Pyr. In some embodiments, a second compound is LiMe2Pyr. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(Ph2Pyr)(OHMT). In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(Ph2Pyr)(OHIPT). In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(Ph2Pyr)(DFTO). In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(Me2Pyr)(OHMT)(PMe2Ph). In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(Me2Pyr)(OHIPT). In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(Me2Pyr)(DFTO). As used herein, Ph2Pyr is




and Me2Pyr is





In some embodiments, a second compound is LiN(C6F5)2, and a compound of formula I is W(O)(CH-t-Bu)[N(C6F5)2](OHMT)(PPhMe2).

In some embodiments, the present invention provides a method of making a compound of formula I, wherein each of R3 and R4 is independently —OR, comprising: reacting a first compound of formula V-b, wherein R11 is R4 in formula I, with a second compound of formula R3H or its salt thereof, wherein R3 is the same as R3 of formula I,
wherein each variable is independently as defined above and described herein.
In some embodiments, the present invention provides a method of making a compound of formula I, wherein R3 and R4 are the same and are —OR, comprising: reacting a first compound of formula V-a with a second compound of formula R3H or its salt thereof; wherein each variable is independently as defined above and described herein.
In some embodiments, a second compound is the salt of R3H. In some embodiments, a second compound is R3Li. Exemplary —OR for R3, R4 and R11 is extensively described above and herein. In some embodiments, R is optionally substituted phenyl. In some embodiments, R3 and R4 are the same. In some embodiments, R3 and R4 are different. In some embodiments, one of R3 and R4 is —OHMT. In some embodiments, one of R3 and R4 is —OHIPT. In some embodiments, one of R3 and R4 is -DFTO. In some embodiments, both of R3 and R4 are —OHMT. In some embodiments, both of R3 and R4 are —OHIPT. In some embodiments, both of R3 and R4 are -DFTO. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(OHMT)2. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(OHIPT)2. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(DFTO)2. In some embodiments, at least one of R3 and R4 is not —O-2,6-Ph2C6H3.
In some embodiments, R3Li is LiOHMT. In some embodiments, R3Li is LiOHIPT. In some embodiments, R3Li is LiODFT.
In some embodiments, the present invention provides a method of making a compound of formula VIII-a:




comprising reacting a first compound of formula V-b:





with a second compound of formula R11H or its salt thereof,

wherein each variable is independently as defined above and described herein.

In some embodiments, a second compound is the salt of R11′H. In some embodiments, a second compound is R11′Li. Exemplary —OR for R11′ and R11 is extensively described above and herein. In some embodiments, R is optionally substituted phenyl. In some embodiments, R11 and R11′ are the same. In some embodiments, R11 and R11′ are different. In some embodiments, one of R11 and R11′ is —OHMT. In some embodiments, one of R11 and R11′ is —OHIPT. In some embodiments, one of R11 and R11′ is -DFTO. In some embodiments, both of R11 and R11′ are —OHMT. In some embodiments, both of R11 and R11′ are —OHIPT. In some embodiments, both of R11 and R11′ are -DFTO. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(OHMT)2. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(OHIPT)2. In some embodiments, a compound of formula I is W(O)(CH-t-Bu)(DFTO)2. In some embodiments, at least one of R11 and R11′ is not —O-2,6-Ph2C6H3.
In some embodiments, R11′Li is LiOHMT. In some embodiments, R11′Li is LiOHIPT. In some embodiments, R11 Li is LiODFT.
In some embodiments, the present invention provides a method of making a compound of formula VIII-b,




comprising reacting a first compound of formula V-b:





with a second compound of formula R12H or its salt thereof;

wherein R12 is —OSiR3, and each of R1, R2, R8, R11, R and n is independently as defined above and described herein.

In some embodiments, a second compound is a salt of R12H. In some embodiments, a second compound is R12Na. In some embodiments, a second compound is NaOSi(t-Bu)3.
As described above, in some embodiments, neutral ligands, such as neutral nitrogen-, oxygen-, and/or phosphorus-containing ligands for R5 and R8 (e.g., bipyr and phosphine ligands) can be partially associated with W. In some embodiments, such association can be detected by NMR. In some embodiments, while not wishing to be bound by any theory, dissociation is caused by the greater steric demand of ligands other than the neutral ligands. In some embodiments, a compound is detected or isolated without the neutral ligand, for example, without R5 or R8 (n=0). In some embodiments, such a compound comprises OHIPT. In other embodiments, a compound is detected or isolated with one or more neutral ligand, for example, with R5 and/or R8 (n=1 or n=2). In some embodiments, such a compound comprises OHMT. In some embodiments, such a compound comprises OHIPT. In some embodiments, such a compound comprises DFTO. The present invention recognizes that in the provided methods, the neutral ligands (e.g., R5 or R8) may dissociate due to the association of new ligands. A non-limiting example is when W(O)(CH-t-Bu)(OHMT)2 is formed by reacting W(O)(CH-t-Bu)(OHMT)(PMe2Ph)Cl with LiOHMT.
In some embodiments, the present invention provides a method of making a compound of formula IX:




comprising reacting a first compound of formula I-c:





with a second compound comprising a double bond,

wherein each variable is independently as defined above and described herein.

In some embodiments, each of R3′ and R4 is independently —OR. In some embodiments, R3′ is —OSiR3 and R4 is independently —OR.
In some embodiments, a second compound comprising a double bond in the above method is a terminal olefin. In some embodiments, a second compound comprising a double bond is ethylene.
In some embodiments, the provided methods would be beneficial to the preparation and application of oxo alkylidene compounds. For example, among other benefits, the provided methods for uses cheaper and widely available starting material (e.g., WCl6), and/or simpler reaction and/or purification procedures. In some embodiments, the provided methods also produce compound with higher purity and/or activity.
In some embodiments, a ligand is provided in a molar ratio of about 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, or 1:1 relative to the metal complex. In some embodiments, a ligand is provided in a molar ratio of about 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, 0.2:1, or 0.1:1 relative to the metal complex. In certain embodiments, a ligand is provided in a molar ratio of about 1:1 relative to the metal complex. One of skill in the art will appreciate that the optimal molar ratio of ligand to metal complex will depend on, inter alia, whether the ligand is mono- or polydentate.
In some embodiments, a ligand is provided in a molar ratio of about 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1, 3:1, 2:1, or 1:1 relative to the metal complex of formula III. In some embodiments, a ligand is provided in a molar ratio of about 0.9:1, 0.8:1, 0.7:1, 0.6:1, 0.5:1, 0.4:1, 0.3:1, 0.2:1, or 0.1:1 relative to the metal complex of formula III. In certain embodiments, a ligand is provided in a molar ratio of about 1:1 relative to the metal complex of formula III. One of skill in the art will appreciate that the optimal molar ratio of ligand to metal complex will depend on, inter alia, whether the ligand is mono- or polydentate.
Suitable conditions for performing provided methods generally employ one or more solvents. In certain embodiments, one or more organic solvents are used. Examples of such organic solvents include, but are not limited to, hydrocarbons such as benzene, toluene, and pentane, halogenated hydrocarbons such as dichloromethane, or polar aprotic solvents, such as ethereal solvents including ether, tetrahydrofuran (THF), or dioxanes, or mixtures thereof. In certain embodiments, one or more solvents are deuterated.
In some embodiments, a single solvent is used. In certain embodiments, the solvent is benzene. In certain embodiments, the solvent is ether.
In some embodiments, mixtures of two or more solvents are used, and in some cases may be preferred to a single solvent. In certain embodiments, the solvent mixture is a mixture of an ethereal solvent and a hydrocarbon. Exemplary such mixtures include, for instance, an ether/benzene mixture. Solvent mixtures may be comprised of equal volumes of each solvent or may contain one solvent in excess of the other solvent or solvents. In certain embodiments wherein a solvent mixture is comprised of two solvents, the solvents may be present in a ratio of about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1. In certain embodiments wherein a solvent mixture comprises an ethereal solvent and a hydrocarbon, the solvents may be present in a ratio of about 20:1, about 10:1, about 9:1, about 8:1, about 7:1, about 6:1, about 5:1, about 4:1, about 3:1, about 2:1, or about 1:1 ethereal solvent:hydrocarbon. In certain embodiments, the solvent mixture comprises a mixture of ether and benzene in a ratio of about 5:1. One of skill in the art would appreciate that other solvent mixtures and/or ratios are contemplated herein, that the selection of such other solvent mixtures and/or ratios will depend on the solubility of species present in the reaction (e.g., substrates, additives, etc.), and that experimentation required to optimized the solvent mixture and/or ratio would be routine in the art and not undue.
Suitable conditions for forming a provided precursor complex or a compound typically employ ambient reaction temperatures. In some embodiments, a suitable reaction temperature is about 15° C., about 20° C., about 25° C., or about 30° C. In some embodiments, a suitable reaction temperature is from about 15° C. to about 25° C. In certain embodiments, a suitable reaction temperature is about 20° C., 21° C., 22° C., 23° C., 24° C., or 25° C.
In certain embodiments, a provided method for preparing a provided precursor complex or a compound is performed at elevated temperature. In some embodiments, a suitable reaction temperature is from about 25° C. to about 110° C. In certain embodiments, a suitable reaction temperature is from about 40° C. to about 100° C., from about 50° C. to about 100° C., from about 60° C. to about 100° C., from about 70° C. to about 100° C., from about 80° C. to about 100° C., or from about 90° C. to about 100° C.
In certain embodiments, a provided method for preparing a provided precursor complex or a compound is performed at temperature lower than ambient temperatures. In some embodiments, a suitable reaction temperature is from about −100° C. to about 10° C. In certain embodiments, a suitable reaction temperature is from about −80° C. to about 0° C., from about −70° C. to about 0° C., from about −60° C. to about 0° C., from about −50° C. to about 0° C., from about −40° C. to about 0° C., or from about −30° C. to about 0° C.
In some embodiments, a provided method is performed at different temperatures. In some embodiments, the reaction temperature changes in a provided method. In some embodiments, a provided method involves temperature increase from a lower temperature to a higher temperature. In some embodiments, a provided method comprises temperature increase from about −80° C., about −70° C., about −60° C., about −50° C., about −40° C., about −30° C., about −20° C., about −10° C., and about 0° C. to about 0° C., about 10° C., about 20° C., ambient temperature, about 22° C., about 25° C., about 30° C., about 40° C., about 50° C., about 60° C., about 70° C., about 80° C., about 90° C., about 100° C. and about 110° C. In some embodiments, a provided method comprises temperature increase from about −30° C. to 22° C. In some embodiments, a provided method comprises temperature decrease from a higher temperature to a lower temperature. In some embodiments, a provided method comprises temperature increase from about 110° C., about 100° C., about 90° C., about 80° C., about 70° C., about 60° C., about 50° C., about 40° C., about 30° C., about 25° C., about 22° C., ambient temperature, about 20° C., about 10° C., and about 0° C. to about 0° C., about −10° C., about −20° C., about −30° C., about −40° C., about −50° C., about −60° C., about −70° C., about −80° C., about −90° C., and about −100° C.
Suitable conditions for forming a provided precursor complex or a compound typically involve reaction times of about 1 minute to about 1 day. In some embodiments, the reaction time ranges from about 0.5 hour to about 20 hours. In some embodiments, the reaction time ranges from about 0.5 hour to about 15 hours. In some embodiments, the reaction time ranges from about 1.0 hour to about 12 hours. In some embodiments, the reaction time ranges from about 1 hour to about 10 hours. In some embodiments, the reaction time ranges from about 1 hour to about 8 hours. In some embodiments, the reaction time ranges from about 1 hour to about 6 hours. In some embodiments, the reaction time ranges from about 1 hour to about 4 hours. In some embodiments, the reaction time ranges from about 1 hour to about 2 hours. In some embodiments, the reaction time ranges from about 2 hours to about 8 hours. In some embodiments, the reaction time ranges from about 2 hours to about 4 hours. In some embodiments, the reaction time ranges from about 2 hours to about 3 hours. In certain embodiments, the reaction time is about 1 hour. In certain embodiments, the reaction time is about 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12 hours. In some embodiments, the reaction time is about 12 hours. In certain embodiments, the reaction time is less than about 1 hour. In certain embodiments, the reaction time is about 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, or 55 minutes. In some embodiments, the reaction time is about 30 minutes.
Exemplary Uses of Provided Compounds
As described herein, provided compounds of formula I are particularly useful for metathesis reactions.
In some embodiments, methods using provided compounds involve reacting a first species and a second species to form a product comprising a double bond, wherein the double bond comprises an atom of the first species and an atom of the second species. In some embodiments, the first species and the second species are different. In some embodiments, the first species and the second species are the same. In some embodiments, the double bond may comprise a carbon atom from the first species and a carbon atom from the second species. The double bond produced may have a Z (e.g., cis) or E (e.g., trans) configuration. Those of ordinary skill in the art would understand the meaning of the terms “cis” or “Z” and “trans” or “E,” as used within the context of the invention.
Some embodiments may provide the ability to selectively synthesize, via a metathesis reaction, products having a Z or E configuration about a double bond. In some embodiments, methods using compounds of formula I of the present invention may provide the ability to synthesize compounds comprising a Z-disubstituted olefin. In some embodiments, such methods are useful when applied to a wide range of olefin substrates, including those having sterically small or large groups adjacent the olefin. In some embodiments, the substrate olefins are terminal olefins. In some embodiments, complexes of the present invention are useful in methods for synthesizing Z-disubstituted enol ethers. In some embodiments, complexes of the present invention are useful in methods for synthesizing Z-disubstituted allylic amines. In some embodiments, complexes of the present invention are useful in methods for synthesizing Z-disubstituted allylic amides.
In some embodiments, a compound of formula I promotes Z-selective olefin metathesis reactions. In some embodiments, a compound of formula I promotes E-selective olefin metathesis reactions.
In some embodiments, a metathesis reaction using a compound of formula I produces a double bond in a Z:E ratio greater than about 1:1, greater than about 2:1, greater than about 3:1, greater than about 4:1, greater than about 5:1, greater than about 6:1, greater than about 7:1, greater than about 8:1, greater than about 9:1, greater than about 95:5, greater than about 96:4, greater than about 97:3, greater than about 98:2, or, in some cases, greater than about 99:1, as determined using methods described herein (e.g., HPLC). In some cases, about 100% of the double bond produced in the metathesis reaction may have a Z configuration. The Z or cis selectivity may also be expressed as a percentage of product formed. In some cases, the product may be greater than about 50% Z, greater than about 60% Z, greater than about 70% Z, greater than about 80% Z, greater than about 90% Z, greater than about 95% Z, greater than about 96% Z, greater than about 97% Z, greater than about 98% Z, greater than about 99% Z, or, in some cases, greater than about 99.5% Z.
In some embodiments, a metathesis reaction using a compound of formula I produces a double bond in an E:Z ratio greater than about 1:1, greater than about 2:1, greater than about 3:1, greater than about 4:1, greater than about 5:1, greater than about 6:1, greater than about 7:1, greater than about 8:1, greater than about 9:1, greater than about 95:5, greater than about 96:4, greater than about 97:3, greater than about 98:2, or, in some cases, greater than about 99:1, as determined using methods described herein (e.g., HPLC). In some cases, about 100% of the double bond produced in the metathesis reaction may have an E configuration. The E or trans selectivity may also be expressed as a percentage of product formed. In some cases, the product may be greater than about 50% E, greater than about 60% E, greater than about 70% E, greater than about 80% E, greater than about 90% E, greater than about 95% E, greater than about 96% E, greater than about 97% E, greater than about 98% E, greater than about 99% E, or, in some cases, greater than about 99.5% E.
Without wishing to be bound by any particular theory, it is believed that the Z-selectivity is due, at least in part, to the small size of the oxo ligand relative to R3, wherein R3 is as defined above and described herein.
In some embodiments, a compound of formula I isomerizes a product. In some embodiments, a compound of formula I isomerizes a Z product. In some embodiments, a compound of formula I isomerizes a Z product slower than the formation of the product. In some embodiments, a compound of formula I isomerizes a E product. In some embodiments, a compound of formula I isomerizes a E product slower than the formation of the product.
In some embodiments, a compound of formula I does not isomerizes a product. In some embodiments, a compound of formula I does not isomerizes a Z product. In some embodiments, a compound of formula I does not isomerizes a E product.
In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, is stable under metathesis condition. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 1 hour. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 2 hours. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 6 hours. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 12 hours. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 24 hours. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 48 hours. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes under metathesis condition within about 96 hours.
In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes prior to isomerization of a product. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, partially decomposes prior to isomerization of a product. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes prior to isomerization of a Z product. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, partially decomposes prior to isomerization of a Z product. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, decomposes prior to isomerization of a E product. In some embodiments, a compound of formula I, or the active catalyst formed from a compound of formula I, partially decomposes prior to isomerization of a E product.
In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >50% cis, >50% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >60% cis, >60% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >70% cis, >70% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is 80% cis, >80% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >90% cis, 90% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >95% cis, 90% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >99% cis, 90% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >90% cis, >90% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >95% cis, >90% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >99% cis, >90% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >99% cis, >95% synditactic. In some embodiments, a metathesis reaction using a compound of the present invention produces a polymer wherein the polymer is >99% cis, >97% synditactic.
In some embodiments, a metathesis reaction using a compound of formula I is further accelerated by the addition of a Lewis acid. In some embodiments, such a Lewis acid is B(C6F5)3.
As mentioned above, provided compounds are useful for metathesis reactions. Exemplary such methods and reactions are described below.
It will be appreciated that, in certain embodiments, each variable recited for the above method is as defined above and described in embodiments, herein, singly and in combination.
EXEMPLIFICATION
General Comments.
All manipulations were done either in a nitrogen-filled drybox or on an air free dual-manifold Schlenk line. The solvents were sparged with nitrogen, passed through activated alumina, and stored over activated 4 Å Linde-type molecular sieves. Methylene chloride-d2, chloroform-d3, and benzene-d6 were distilled from calcium hydride (CD2Cl2, CDCl3) or sodium ketyl (C6D6), and stored over activated 4 Å Linde-type molecular sieves. NMR spectra were recorded using Varian spectrometers at 500 (1H), 125 (13C), 121 (31P), 471 (19F), and 161 (11B) MHz, reported in δ (parts per million) relative to tetramethylsilane (1H, 13C), 85% phosphoric acid (31P), CFCl3 (19F), or BF3.Et2O (11B), and referenced to the residual 1H/13C signals of the deuterated solvent (1H (δ): benzene 7.16; methylene chloride 5.32, chloroform 7.26; 13C (δ): benzene 128.06; methylene chloride 53.84, chloroform 77.16), or external 85% phosphoric acid (31P (δ): 0.0), C6F6 (19F (δ): −169.4), and BF3.Et2O (11B (δ): 0.0) standards. Midwest Microlab, Indianapolis, Ind. provided the elemental analysis results.
WO(CH-t-Bu)Cl2(PMe2Ph)2 (Wengrovius, J. H.; Schrock, R. R. Organometallics 1982, 1, 148-155), Li(Me2Pyr) (Jiang, A. J.; Simpson, J. H.; Müller, P.; Schrock, R. R. J. Am. Chem. Soc. 2009, 131, 7770-7780), HIPTOH (Stanciu, C.; Olmstead, M. M.; Phillips, A. D.; Stender, M.; Power, P. P. Eur. J. Inorg. Chem. 2003, 2003, 3495-3500), HIPTOLi (Stanciu, C.; Olmstead, M. M.; Phillips, A. D.; Stender, M.; Power, P. P. Eur. J Inorg. Chem. 2003, 2003, 3495-3500), HMTOH (Dickie, D. A.; MacIntosh, I. S.; Ino, D. D.; He, Q.; Labeodan, O. A.; Jennings, M. C.; Schatte, G.; Walsby, C. J.; Clyburne, J. A. C. Can. J. Chem. 2008, 86, 20-31), HMTOLi (Dickie, D. A.; MacIntosh, I. S.; Ino, D. D.; He, Q.; Labeodan, O. A.; Jennings, M. C.; Schatte, G.; Walsby, C. J.; Clyburne, J. A. C. Can. J. Chem. 2008, 86, 20-31), DCMNBD (Tabor, D. C.; White, F.; Collier, L. W.; Evans, S. A. J. Org. Chem. 1983, 48, 1638-1643) were prepared according to reported procedures. The substrates for olefin homocoupling reactions were distilled from CaH2 and stored in a glovebox over molecular sieves. All other reagents were used as received unless noted otherwise.
X-Ray Crystal Structure Determination Details.
Low-temperature diffraction data (φ- and ω-scans) were collected on a Bruker-AXS X8 Kappa Duo diffractometer coupled to a Smart APEX 2 CCD detector with Mo Kα radiation (λ=0.71073 Å) from an IμS micro-source. Absorption and other corrections were applied using SADABS (Sheldrick, G. M. SADABS, v. 2.10 —A program for area detector absorption corrections; Bruker AXS: Madison, Wis., 2003). All structures were solved by direct methods using SHELXS (Sheldrick, G. M. Acta Cryst. 1990, A46, 467-473) and refined against F2 on all data by full-matrix least squares with SHELXL-97 (Sheldrick, G. M. Acta Cryst. 2008, A64, 112-122) using established refinement approaches (Müller, P. Crystallography Reviews 2009, 15, 57-83). All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were included in the models at geometrically calculated positions and refined using a riding model except for alkylidene protons. Coordinates for the alkylidene hydrogen atoms were taken from the difference Fourier synthesis and the hydrogen atoms were subsequently refined semi-freely with the help of a distance restraint, unless otherwise noted. The isotropic displacement parameters of all hydrogen atoms were fixed to 1.2 times the Ueq value of the atoms they are linked to (1.5 times for methyl groups). All disordered atoms were refined with the help of similarity restraints on the 1,2- and 1,3-distances and displacement parameters as well as rigid bond restraints for anisotropic displacement parameters.
The compound W(O)(CH-t-Bu)(OHIPT)Cl(PMe2Ph) (I-1) crystallizes in the monoclinic space group P21/c with one molecule in the asymmetric unit. The tungsten atom, chloride, oxo, and alkylidene ligands were modeled as a two component disorder and the ratio of the occupancies refined to 0.9130(18). One of the iPr groups was also found to be disordered over two positions, the ratio of occupancies refined to 0.694(17). The anisotropic displacement parameters for the chloride (Cl1, Cl1A), oxo (O2, O2A), and one carbon (C1, C1A) on the alkylidene were constrained to be equivalent, pairwise. Coordinates for the hydrogen atom bound to C1 was taken from the difference Fourier synthesis as noted above. However, the hydrogen atom bound to C1A, the minor component of the disorder, could not be found in the difference Fourier synthesis and was included in the model at a geometrically calculated position and refined using a riding model.
The compound W(O)(OHIPT)(Me2Pyr) (I-2) crystallizes in the monoclinic space group P21/n with one molecule in the asymmetric unit. One of the aryl groups on the alkoxide ligand was modeled as a two component disorder and the ratio of the occupancies of the two components refined to 0.637(5). The anisotropic displacement parameters of all of atoms in this disorder were constrained to be equivalent, pairwise. The largest residual electron density was modeled as a second tungsten position and the relative occupancy of the two components refined to 0.9787(4). The anisotropic displacement parameters of the two components were constrained to be equivalent. The oxo, pyrrolide, and alkylidene were observed in the difference Fourier synthesis but refinement of these ligands as a disorder was unstable, therefore an alternative site was modeled only for the tungsten.
The compound W(O)(CH-t-Bu)(OHMT)(Me2Pyr)(PMe2Ph) (I-4) crystallizes in the triclinic space group P-1 with one molecule in the asymmetric unit along with one and a half molecules of pentane. One half of a pentane molecule is located near a crystallographic inversion center and disordered accordingly which leads to a non-integer value for carbon.
The compound W(O)(B(C6F5)3(OHMT)(Me2Pyr) (I-6) crystallizes in the monoclinic space group P21/n with one molecule in the asymmetric unit.
We prepared W(O)(CH-t-Bu)(OHIPT)(Me2Pyr) (where Me2Pyr=2,5-dimethylpyrrolide) from W(O)(CH-t-Bu)(PMe2Ph)2Cl2 as the starting material. The reaction between WO(CH-t-Bu)Cl2(PMe2Ph)2 and LiOHIPT in benzene at 22° C. for 14 h led to isolation of off-white WO(CH-t-Bu)Cl(OHIPT)(PMe2Ph) (I-1) in 60% yield. Two isomers of I-1 are present in a 3:2 ratio according to 1H, 13C, and 31P NMR spectra. Both are syn alkylidenes on the basis of JCαH values for the alkylidene of 123 Hz (major isomer) and 117 Hz (minor isomer). The phosphine remains bound to tungsten on the NMR time scale (JPW=420 Hz and 379 Hz, respectively) at 22° C. An X-ray crystal structure (FIG. 1) revealed a distorted square-pyramidal geometry with the neopentylidene ligand in the apical position and the phosphine ligand trans to chloride. The alkylidene was found to be disordered over syn and anti orientations in 91:9 ratio. One possibility is that the other isomer has a similar structure in which the OHIPT and C1 ligands have switched positions.




Synthesis of WO(CH-t-Bu)(OHIPT)Cl(PMe2Ph) (I-1).
A solution of WO(CH-t-Bu)Cl2(PMe2Ph) (300.0 mg, 0.486 mmol) in 10 mL of benzene was mixed with a solution of HIPTOLi (247.1 mg, 0.489 mmol, 1.01 eq) in 5 mL of benzene. The cloudy, yellow reaction mixture was stirred at room temperature for 14 h. The solvent was removed in vacuo to give a yellow solid. The product was extracted to toluene (5 mL) and LiCl was removed by filtration through a bed of Celite. Toluene was removed in vacuo to yield a pale yellow crystalline solid. The product was triturated with pentane (5 mL) and the resulting suspension was filtered. Off-white solid was collected (280.2 mg, 60% yield). Two isomers in 61:39 ratio formed according to NMR spectra; only non-overlapping alkylidene signals are listed: Major isomer 1H NMR (C6D6) δ 9.36 (d, 1, WCH-t-Bu, 3JHP=3 Hz, 2JHW=11 Hz); 13C NMR (C6D6) δ 292.4 (d, WCH-t-Bu, 1JCH=123 Hz, 2JCP=12 Hz, 1JCW=163 Hz); 31P NMR (C6D6): δ 12.89 (s, 1JPW=420 Hz). Minor isomer: 1H NMR (C6D6): δ 8.89 (d, 1, WCH-t-Bu, 3JHP=3 Hz, 2JHW=13 Hz); 13C{1H}NMR (C6D6): δ 278.7 (d, WCH-t-Bu, 1JCH=117 Hz, 2JCP=16 Hz, 1JCW=188 Hz); 31P NMR (C6D6): δ 16.15 (s, 1JPW=379 Hz). Anal. Calcd for C49H70ClO2PW: C, 62.52; H, 7.50. Found: C, 62.31; H, 7.49.







TABLE 2





Crystal data and structure refinement details for W(O)(CH—t-


Bu)(OHIPT)Cl(PMe2Ph) (I-1).
















Identification code
x11139


Empirical formula
C49H70ClO2PW


Formula weight
941.32


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Monoclinic


Space group
P21/c









Unit cell dimensions
a = 22.6931(16) Å
α = 90°.



b = 8.9674(6) Å
β = 104.2850(10)°.



c = 23.7379(17) Å
γ = 90°.








Volume
4681.3(6) Å3


Z
4


Density (calculated)
1.336 Mg/m3


Absorption coefficient
2.594 mm−1


F(000)
1944


Crystal size
0.20 × 0.05 × 0.05 mm3


Theta range for data collection
1.77 to 30.32°.


Index ranges
−32 <= h <= 32, −12 <= k <= 12,



−33 <= l <= 33


Reflections collected
108649


Independent reflections
14056 [R(int) = 0.0492]


Completeness to
100.0%


theta = 30.32°



Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.8812 and 0.6250


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
14056/267/576


Goodness-of-fit on F2
1.022


Final R indices
R1 = 0.0197, wR2 = 0.0403


[I > 2sigma(I)]



R indices (all data)
R1 = 0.0264, wR2 = 0.0422


Largest diff. peak and hole
0.656 and −0.972 e · Å−3









Reaction of I-1 with ethylene resulted in formation of methylidene complex WO(CH2)(HIPTO)Cl(PMe2Ph) (I-10) as confirmed by in situ 1H NMR (two doublets of doublets, δ=8.64 and 10.44 ppm, 2JHH=10 Hz, 3JHp=4 Hz) data. The methylidene complex decomposes in solution in 24 h.




Treatment of I-1 with Li(Me2Pyr) in benzene at 60° C. for 16 h led to formation of yellow W(O)(CH-t-Bu)(OHIPT)(Me2Pyr) (I-2) in 80% isolated yield. An X-ray structure (FIG. 2) showed I-2 to have a pseudotetrahedral geometry, a syn alkylidene, and an η1-Me2Pyr ligand.
Synthesis of WO(CH-t-Bu)(Me2Pyr)(HIPTO) (I-2).
A portion of Li(Me2Pyr) (56.4 mg, 0.558 mmol, 1.02 eq.) was added as a solid to a solution of WO(CH-t-Bu)(HIPTO)Cl(PMe2Ph) (515.0 mg, 0.547 mmol) in 10 mL of benzene. The reaction mixture was transferred to a solvent Schlenk-type flask equipped with a Teflon valve, degassed, and heated at 60° C. for 16 h with rapid stirring. The color of the solution changed from pale- to bright-yellow. The volatiles were removed by heating at 60° C. in vacuo. Resulting yellow solid was triturated with 5 mL of benzene and LiCl was removed by filtration through a bed of Celite. Benzene was removed in vacuo leaving a bright-yellow solid. The product was triturated with 5 mL of pentane and filtered. The filtrate was left in a refrigerator at −30° C. for 1 day to give yellow crystalline solid. Two crops were combined (378.2 mg, 80% yield): 1H NMR (C6D6) δ 9.40 (s, 1, WCH-t-Bu, 2JHW=10 Hz), 7.25 (m, 2, Ar—H), 7.20 (m, 2, Ar—H), 7.12 (d, 2, Ar—H), 6.91 (t, 1, Ar—H), 5.99 (s, 2, Pyr-H), 2.85 (overlapping sept, 6, CHMe2), 1.94 (s, 6, Pyr-Me), 1.30 (d, 6, CHMe2), 1.29 (d, 6, CHMe2), 1.29 (d, 6, CHMe2), 1.21 (s, 9, WCH-t-Bu), 1.17 (overlapping d, 12, CHMe2), 1.10 (d, 6, CHMe2); 13C{1H}NMR (C6D6) δ 274.4 (WCH-t-Bu, 1JCH=125 Hz, 1JCW=155 Hz), 158.1, 149.1, 147.3, 146.9, 132.9, 131.9, 131.1, 123.2, 121.9, 121.7, 110.8, 43.1, 33.9, 31.4, 31.3, 25.7, 24.5, 24.5, 24.4, 24.3, 18.4. Anal. Calcd for C47H67NO2W: C, 65.50; H, 7.84; N, 1.63. Found: C, 65.30; H, 7.78; N, 1.60.







TABLE 3





Crystal data and structure refinement data for WO(CH—t-


Bu)(Me2Pyr)(HIPTO) (I-2).
















Identification code
x11080


Empirical formula
C47H67NO2W


Formula weight
861.87


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Monoclinic


Space group
P21/n









Unit cell dimensions
a = 14.7275(18) Å
α = 90°.



b = 15.986(2) Å
β = 110.046(2)°.



c = 19.325(2) Å
γ = 90°.








Volume
4274.1(9) Å3


Z
4


Density (calculated)
1.339 Mg/m3


Absorption coefficient
2.739 mm−1


F(000)
1784


Crystal size
0.30 × 0.20 × 0.05 mm3


Theta range for data collection
1.51 to 30.32°.


Index ranges
−20 <= h <= 20, −22 <= k <= 22,



−26 <= l <= 27


Reflections collected
89374


Independent reflections
12819 [R(int) = 0.0624]


Completeness to theta = 30.32°
100.0%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.8752 and 0.4938


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
12819/739/524


Goodness-of-fit on F2
1.076


Final R indices [I > 2sigma(I)]
R1 = 0.0333, wR2 = 0.0754


R indices (all data)
R1 = 0.0413, wR2 = 0.0775


Largest diff. peak and hole
1.917 and −1.870 e · Å−3









The analogous reaction between W(O)(CH-t-Bu)(PMe2Ph)2Cl2 and LiOHMT (OHMT=O-2,6-dimesitylphenoxide) in benzene at 22° C. for 3 h led to isolation of off-white WO(CH-t-Bu)Cl(OHMT)(PMe2Ph) (I-3) in 70% yield. As with I-1, the 1H NMR spectrum of the product contains two alkylidene doublet resonances that correspond to two isomers of I-3 in 87:13 ratio. The values of 1JCH, 122 and 116 Hz, suggest that both isomers are syn alkylidenes.
Synthesis of WO(CH-t-Bu)(HMTO)Cl(PMe2Ph) (I-3).
A solution of WO(CH-t-Bu)Cl2(PMe2Ph) (1000.0 mg, 1.620 mmol) in 15 mL of benzene was added to a portion of solid HMTOLi (572.3 mg, 1.701 mmol, 1.05 eq). The cloudy, yellow reaction mixture was stirred at room temperature for 3 h. The solvent was removed in vacuo to give a yellow solid. The product was extracted to toluene (10 mL) and LiCl was removed by filtration through a bed of Celite. Toluene was removed in vacuo to produce a yellow crystalline solid. The product was triturated with pentane (10 mL) and the resulting suspension was filtered. Yellow solid product was collected (872.0 mg, 1.128 mmol, 70% yield). Two isomers in a 87:13 ratio formed according to NMR spectra; only non-overlapping alkylidene signals are listed: Major isomer 1H NMR (C6D6) δ 9.34 (d, 1, WCH-t-Bu, 3JHP=3 Hz, 2JHW=8 Hz); 13C NMR (C6D6): δ 295.1 (d, WCH-t-Bu, 1JCH=122 Hz, 2JCP=11 Hz, 1JCW=168 Hz); 31P NMR (C6D6): δ 13.40 (s, 1JPW=416 Hz). Minor isomer 1H NMR (C6D6) δ 9.03 (d, 1, WCH-t-Bu, 3JHP=3 Hz, 2JHW=13 Hz); 13C{1H}NMR (C6D6): δ 278.6 (d, WCH-t-Bu, 1JCH=116 Hz, 2JCP=15 Hz, 1JCW=187 Hz); 31P NMR (C6D6): δ 15.64 (s, 1JPW=386 Hz). Anal. Calcd for C37H46ClO2PW: C, 57.49; H, 6.00. Found: C, 57.52; H, 5.99.
In some embodiments, synthesis of WO(CH-t-Bu)(HMTO)Cl(PMe2Ph) (I-3) can also be performed by reacting compound WO(CH-t-Bu)Cl2(PMe2Ph) with one equivalent of HMTOLi (HMTO=hexamethylterphenoxide) in toluene at room temperature to yield WO(CH-t-Bu)(HMTO)Cl(PMe2Ph). The 1H NMR spectrum of the product contains two alkylidene proton doublets that correspond to two isomers of I-3 in 87:13 ratio. The values of 1JCH, 122 and 166 Hz, suggest that both species are syn alkylidenes.
Addition of Li(Me2Pyr) to I-3 in toluene at −30° C. with subsequent stirring at 22° C. for 10 h led to yellow W(O)(CH-t-Bu)(OHMT)(Me2Pyr)(PMe2Ph) (I-4) in 70% isolated yield. An X-ray structure of I-4 (FIG. 3) showed it to be a square pyramid with the syn neopentylidene in the apical position and the phosphine bound trans to the pyrrolide.
Synthesis of WO(CH-t-Bu)(Me2Pyr)(HMTO)(PMe2Ph) (I-4).
A portion of Li(Me2Pyr) (86.3 mg, 0.854 mmol, 1.1 eq.) was added as a solid to a cold (−30° C.) solution of WO(CH-t-Bu)(HMTO)Cl(PMe2Ph) (600.0 mg, 0.776 mmol) in 15 mL of toluene. The reaction mixture was stirred at room temperature for 10 h. Toluene was removed in vacuo. Resulting brown oil was triturated with 5 mL of toluene and LiCl was removed by filtration through a bed of Celite. Toluene was removed in vacuo leaving brown oil. The product was triturated with 5 mL of pentane causing precipitation of pale yellow solid. The product was filtered and washed with 5 mL of cold pentane. The filtrate was reduced in volume to ca. 3 mL and left in a refrigerator at −30° C. for 1 day giving yellow crystals. Two crops were combined (452 mg, 70% yield): 1H NMR (48 mM in C6D6) δ 9.14 (broad s, 1, WCH-t-Bu), 7.30 (m, 2, PMe2Ph), 7.05 (m, 3, PMe2Ph), 7.00 (m, 2, Ar—H), 6.88 (m, 5, Ar—H), 6.10 (s, 2, Pyr-H), 2.20 (s, 6, Pyr-Me), 2.08 (overlapping singlets, 18, Ar-Me), 1.11 (s, 6, PMe2Ph), 1.02 (s, 9, WCH-t-Bu); 13C{1H}NMR (48 mM C6D6): δ 278.9 (broad, WCH-t-Bu), 158.5, 140.1, 137.6, 137.1, 136.7, 134.6, 131.9, 131.0, 130.9, 130.6, 129.3, 129.0, 128.6, 128.5, 128.4, 125.4, 125.2, 125.0, 122.5, 109.9, 43.6, 32.6, 21.4, 21.2, 20.7, 17.5. 31P NMR (48 mM C6D6): δ −25.5 (broad s); 1H NMR (20 mM in CD2Cl2, −30° C.) δ 9.92 (broadened s, 1, WCH-t-Bu), 7.48 (m, 2, PMe2Ph), 7.41 (m, 3, PMe2Ph), 6.94 (m, 7, Ar—H), 5.70 (s, 1, Pyr-H), 5.66 (s, 1 Pyr-H), 2.37 (s, 3, Ar-Me), 2.34 (s, 3, Ar-Me), 2.29 (s, 3, Ar-Me), 2.23 (s, 3, Ar-Me), 1.93 (s, 3, Ar-Me), 1.88 (s, 3, Ar-Me), 1.62 (s, 3, Pyr-Me), 1.54 (m, 6, PMe2Ph), 1.30 (s, 3, Pyr-Me), 0.52 (s, 9, WCH-t-Bu); 13C{1H}NMR (20 mM in CD2Cl2, −30° C.): δ 293.16 (WCH-t-Bu, 1JCH=125 Hz), 160.0, 139.3, 138.6, 136.7 (d), 135.0, 134.8, 134.3, 134.0, 133.5, 131.8, 131.6, 131.2, 130.6, 130.5 (d), 130.4, 130.1, 129.4, 129.2, 128.6 (d), 128.2, 120.0, 107.3, 105.8, 44.0, 30.8, 21.9, 21.6, 21.4, 21.0, 20.6, 18.7, 18.8, 13.9 (d), 11.0 (d). 31P NMR (20 mM in CD2Cl2, −30° C.): δ −1.80 (s, 1JPW=289 Hz). Anal. Calcd for C43H54NO2PW: C, 62.10; H, 6.54; N, 1.68. Found: C, 61.95; H, 6.73; N, 1.43.







TABLE 4





Crystal data and structure refinement details for W(O)(OHMT)(CH—t-


Bu)(Me2Pyr)(PMe2Ph) (I-4).
















Identification code
x11146


Empirical formula
C50.50H72NO2PW


Formula weight
939.91


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Triclinic


Space group
P-1









Unit cell dimensions
a = 13.4162(7) Å
α = 71.8330(10)°.



b = 13.5775(7) Å
β = 65.5150(10)°.



c = 14.7782(8) Å
γ = 83.6550(10)°.








Volume
2327.2(2) Å3


Z
2


Density (calculated)
1.341 Mg/m3


Absorption coefficient
2.554 mm−1


F(000)
974


Crystal size
0.07 × 0.02 × 0.02 mm3


Theta range for data collection
1.58 to 30.32°.


Index ranges
−19 <= h <= 19, −19 <= k <= 19,



−20 <= l <= 20


Reflections collected
105170


Independent reflections
13947 [R(int) = 0.0684]


Completeness to theta = 30.32°
99.9%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.9507 and 0.8415


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
13947/75/541


Goodness-of-fit on F2
1.032


Final R indices [I > 2sigma(I)]
R1 = 0.0287, wR2 = 0.0576


R indices (all data)
R1 = 0.0380, wR2 = 0.0609


Largest diff. peak and hole
2.589 and −1.184 e · Å−3









The PMe2Ph ligand in I-4 is partially dissociated at room temperature and rapidly exchanging on and off the metal. The alkylidene resonance is broad and its chemical shift is concentration dependent (8.57-9.14 ppm for 4 mM-48 mM solutions in C6D6). Variable temperature 1H and 31P NMR studies of a 20 mM solution of I-4 in CD2Cl2 showed that the phosphine is “bound” below −30° C. as indicated by a sharp 31P signal corresponding to the coordinated ligand (1.80 ppm, 1JPW=289 Hz). On the basis of the chemical shift for free and coordinated phosphine the value of the equilibrium constant for phosphine dissociation can be estimated as 0.015 M at room temperature. This value corresponds to 57% dissociation of phosphine in a 20 mM solution of I-4 in C6D6.
Both I-2 and I-4 react with ethylene to give an unsubstituted metallacyclobutane complex (and t-butylethylene) that has a square pyramidal structure (presumably with the oxo ligand in the apical position) on the basis of chemical shifts of metallacycle protons in the range 0.7-4.5 ppm (Feldman J.; Schrock, R. R. Prog. Inorg. Chem. 1991, 39, 1). With I-2 the reaction with ethylene is relatively slow and what we propose is an intermediate square pyramidal β-t-butylmetallacyclobutane complex can be observed before t-butylethylene is formed. In the case of compound I-4, a mixture of an unsubstituted square pyramidal metallacycle and a methylidene are readily formed upon addition of ethylene. In both systems the metallacycles slowly decompose over a period of 24 h to unidentified products. A square pyramidal metallacyclobutane made from imido alkylidenes has been proposed to be further away from the transition state for olefin loss than is the alternative TBP metallacycle (Feldman, J.; Davis, W. M.; Thomas, J. K.; Schrock, R. R. Organometallics 1990, 9, 2535).
Compound I-2 (0.01 M solution in C6D6) reacts with 1 atm of ethylene with a quick color change of the solution from yellow to red. In 10 min. approximately 50% of I-2 is converted to a square pyramidal metallacycle as evidenced by the appearance of multiplets in 4.6-1.8 ppm region (FIG. 6, bottom) (Feldman, J.; Davis, W. M.; Thomas, J. K.; Schrock, R. R. Organometallics 1990, 9, 2535). At the same time, no signal from 3,3-dimethyl-1-butene was observed. Therefore, it can be proposed that the substituted metallacycle is formed in the early stage of the reaction. The 1H NMR spectrum recorded after 1 h (FIG. 6, middle) showed almost complete disappearance of the metallacycle multiplets that were observed in the 10 min. spectrum and formation of 3,3-dimethyl-1-butene and the unsubstituted square pyramidal metallacyclobutane.
ROMP of DCMNBD.
In a nitrogen-filled glovebox, a solution of monomer (50.0 mg, 50 equiv) in 1.0 mL of toluene was added to a solution of a catalyst in 0.2 mL of toluene. The mixture was stirred for 4 h. Aliquots were taken and diluted with CDCl3 to monitor reaction progress. After reaction completion, 0.5 mL of benzaldehyde was added on air and stirred for 30 min. The mixture was added dropwise to 50 mL of methanol with rapid stirring. A fine white solid formed immediately, and the mixture was stirred for 10 h. The polymer was filtered off on a glass frit and dried under vacuum.
Both I-2 and I-4 serve as initiators for the polymerization of 5,6-dicarbomethoxynorbornadiene (DCMNBD). The polymerization of 50 equiv of DCMNBD is relatively slow with I-2 and propagation is faster than initiation. The resulting polymer is >99% cis, 90% syndiotactic. The polymerization of 50 equiv of DCMNBD with I-4 is relatively fast and all initiator is consumed. The resulting polymer is >99% cis, 98% syndiotactic (Schrock, R. R.; Müller, P.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131, 7962).
Compound I-2 reacts with DCMNBD in toluene slowly to yield >99% cis, 90% syndiotactic poly-DCMNBD. The polymerization of 50 equivalents of the monomer was complete in 90 min. Monitoring the reaction progress of in situ in CD2Cl2 by 1H NMR revealed that only 20% of the starting neopentylidene was consumed in 40 min.
Compound I-4 readily reacts with ethylene in benzene to form a metallacycle along with a methylidene complex in 1:1 ratio after 10 min. The metallacycle resonances are in 0.-4.5 ppm range, which suggests a square-pyramidal geometry. In case of I-4, however, 3.3-dimethylbutene formed rapidly, indicating that only the unsubstituted tungstacyclobutane was present. Both the metallacycle and the methylidene decomposed within 1 h in benzene.
Terminal Olefin Homocoupling.
In a nitrogen-filled glovebox, neat substrate (200 mg) was added to a solid catalyst in 1 dram vial. The vial was placed in 20 mL scintillation vial and sealed. The reaction mixture was stirred at 22° C. and aliquots were sampled. The aliquots were quenched outside a box by exposure to air and addition of CDCl3. The conversion and selectivity of the reactions were monitored by 1H NMR.
Homocoupling of neat terminal olefins with I-2 takes place slowly (hours) at room temperature. In contrast, I-4 was found to be a highly active and highly Z-selective (Table 5). A catalyst loading as low as 0.2 mol % yielded up to 88% conversion in 6 h for several of the six chosen substrates. No trans product could be observed in 1H NMR spectra of the Z products.







TABLE 5







Conversions to Z-selective Metathesis Homocoupling Products of Neat


Terminal Olefins Promoted by I-4.a









substrate/cat loading (mol %);



>99% Z product in each case.
















S1/
S2/
S3/
S4/
S5/
S6/



time
0.2%
0.2%
0.2%
0.2%
0.2%
1%







10 min
28%
44%
65%
—
28%
—



30 min
39%
67%
75%
—
39%
—



 1 h
47%
79%
75%
 2%
47%
10%



 6 h
66%
86%
—
—
73%b
—



24 h
72%
88%
—
11%
—
59%







aS1 = 1-octene, S2 = allylbenzene, S3 = allylboronic acid pinacolate ester, S4 = allylSiMe3, S5 = 1-decene, S6 = Methyl-10-undecenoate.



bThe aliquot was taken after 7 h.






Clearly formation of the Z product is highly selective. Only a small increase in conversion was found for longer (>6 h) reaction times, which suggests that the majority of the catalyst has decomposed at this stage. Decomposition of a catalyst prior to isomerization of the Z product to E can be a desirable feature of the coupling reaction. The reactions were run on a 200 mg scale in a closed vessel with a volume of  ̃20 mL. Homocoupling of 1-decene under 0.5 Torr vacuum did not show a significant increase in turnover compared to the reaction carried out under 1 atm of nitrogen. Without wishing to be bound by any particular theory, we ascribe the relatively low turnover in the case of allylTMS (S4) to steric issues, and in the case of methyl-10-undecenoate (S6, at 1% catalyst loading) to ester binding to W.
Results of homocoupling (HC) of 1-octene to 5-decene catalyzed by I-2 are shown in Table 6. The rate of the reaction is higher in comparison to the recently reported analogous W(NAr)(C3H6)(3,5-Me2Pyr)(HIPTO) catalyst (32% conversion in 16 h, 4 mol % catalyst loading) (Marinescu, S. C; Schrock, R. R.; Müller, P.; Takase, M. K.; Hoveyda, A. H. Organometallics, 2011, 30, 1780). Z-selectivity was found to be only 70-72% and declined as the reaction progressed.







TABLE 6







Homocoupling of l-octene in the presence of I-2.











solution in benzene,




time, h
4 mol % cat.
neat, 2 mol % cat.
neat, 0.2 mol % cat.













0.67
—
2% conv., 75% cis.
<1% conv., 75% cis


2
15% conv., 70% cis
—
—


4
26% conv., 72% cis
24% conv., 57% cis.
4% conv., 70% cis


8
34% conv., 70% cis
—
—


48
68% conv., 52% cis
—
—









Compound I-4 was found to be an excellent catalyst for ROMP and HC of terminal olefins reactions. For instance, polymerization of 50 equivalents of DCMNBD was complete in less than 10 min and the isolated polymer for found to be all-cis and 98% syndiotactic. The results of homocoupling of terminal olefins at room temperature with 4 mol % catalyst loading are listed in Table 7. The reactions are rapid with high conversion being achieved within 3 h. The products are >98% cis, i.e., no trans product could be observed in 1H NMR spectra. Little change in conversion was found after longer (>10 h) reaction times, which suggests that the catalyst decomposes with time. Without wishing to be bound by any particular theory, since isomerization of a Z-product is believed to be the main reason for a decay of 2-selectivity with reaction time for tungsten imido alkylidenes (Jiang, A. J.; Zhao, Y.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009 131 16630), decomposition of a catalyst prior to the point when such side reaction is likely to occur can be, in fact, desirable.







TABLE 7







Homocoupling of terminal olefins in benzene in presence of 4 mol % of I-


4.











substrate
catalyst
time
% cis
% conv.















l-octene
I-4
1
min
>98
32




10
min
>98
41




1
h
>98
66




4
h
>98
81




10
h
>98
88



I-4 + 2 B(C6F5)3
1
min
33
82




10
min
21
93


Allylboronic acid
I-4
10
min
>98
19


pinacol ester

1
h
>98
41




3
h
>98
49



I-4 + 2 B(C6F5)3
10
min
71
80




1
h
53
93


Allyltrimethylsilane
I-4
14
h
>98
32


Allylbenzene
I-4
1
h
>98
85




3
h
>98
91


Methyl-10-undecenoate
I-4
1
h
>98
79




3
h
>98
91


Allylcyclohexane
I-4
1
h
94
24




3
h
87
42









The homocoupling of neat 1-octene catalyzed by I-4 led to analogously high conversion and Z-selectivity for lower catalyst loadings (as low as 0.2 mol %, see Table 8). For example, 72% conversion was achieved in 24 h.







TABLE 8







Homocoupling of neat l-octene in presence of I-4.









time, h
neat, 1 mol % cat.
neat, 0.2 mol % cat.












0.17
62% conv., >98% cis
28% conv., >98% cis


0.5
63% conv., >98% cis
39% conv., >98% cis


1
69% conv., >98% cis
47% conv., >98% cis


6
—
66% conv., >98% cis


24
—
72% conv., >98% cis









The reactivity of I-2 in both HC and ROMP reactions in presence of Lewis acids was studied. It was found that the presence of either B(C6H5)3 or B(C6F5)3 greatly improve the reaction rates. The results of the homocoupling of 1-octene in benzene solution as well as in the neat substrate are summarized in Tables 9 and 10. Addition of one equivalent of strong Lewis acid B(C6F5)3 dramatically increases the reactivity of tungsten oxo alkylidene complex (78% conversion in 15 min with 4 mol % catalyst loading: compare to 15% conversion for I-2 in 2 h in similar conditions). The Z-selectivity declined. At the same time, addition of one equivalent of milder Lewis acid B(C6H5)3 led to increased reactivity while Z-selectivity of the catalyst was preserved.







TABLE 9







Homocoupling of l-octene solution in benzene in the presence of I-2


with a Lewis acid added.









time, h
I-2 + B(C6H5)3, 4 mol %
I-2 + B(C6F5)3, 4 mol %












0.25
—
78% conv., 48% cis


0.67
23% conv., 72% cis
—


2
29% conv., 70% cis
—


4
38% conv., 57% cis
—
















TABLE 10







Homocoupling of neat l-octene in the presence of I-2 with one


equivalent of a Lewis acid added.











I-2 + B(C6F5)3,
I-2 + B(C6H5)3,
I-2 + B(C6F5)3,


time, h
2 mol %
0.2 mol %
0.2 mol %













0.67
82% conv., 35% cis
18% conv., 68% cis
56% conv., 59% cis


4
90% conv., 20% cis
38% conv., 60% cis
88% conv., 44% cis









ROMP of DCMNBD catalyzed by I-2 is significantly accelerated in presence of Lewis acids. Polymerization of 50 equivalents of the monomer was found to be complete in less than 25 min with 40 equivalents of DCMNBD consumed in 10 min when one equivalent of B(C6F5)3 was added to I-2. In the same conditions, only six equivalents of the monomer reacted with I-2 without presence of LA. The initiation reaction remains slow in the presence of B(C6F5)3 (it was found that only 8-10% of starting neopentylidene reacted with the monomer); however, the rate of propagation increases dramatically. It is possible that a stronger Lewis acid adduct is formed with the insertion product than with the sterically crowded neopentylidene initiator, thus increasing the rate of propagation. Interestingly, high activity of I-2+B(C6F5)3 was observed even in the presence of a large excess of monomer bearing Lewis base sites, probably due to higher basicity of tungsten oxo alkylidene.
Similar results were obtained when B(C6H5)3 was used as an additive. In the first 10 min of the reaction, 10 equivalents of the monomer were consumed. It was found that 20-25% of I-2 reacted in 60 min.
Variable temperature (VT)1H NMR study of the mixture of I-2 and 0.5 equivalents of B(C6F5)3 in CD2Cl2 showed that the LA adduct formation can be observed at low temperatures (FIG. 7). The alkylidene peak broadens and shifts downfield with cooling from 22° C. to −30° C. At −50° C., two peaks, one broad at 10.38 ppm and one sharper at 8.86 ppm, are observed in alkylidene region. The two alkylidene peaks become sharper at −80° C. This change is accompanied by the appearance of eight peaks in the aromatic pyrrolide region. The 1H NMR of I-2 in CD2Cl2 at −80° C. showed that the alkylidene signal at 8.86 ppm as well as two pyrrolide proton signals belong to the LA-free MAP (FIG. 7 bottom). It is possible that formation of the LA adduct can lead to the stabilization of η5 coordination mode of pyrrolide at low temperatures to compensate for electron density deficiency on the metal center.
Addition of Lewis acids to I-4 significantly speeds up metathesis reactions. For example, addition of B(C6F5)3 to I-4 resulted in a 90% conversion in 1 h for 1-octene homocoupling with 0.2 mol % catalyst loading. The homocoupling metathesis reaction yields the thermodynamic mixture (20% Z). Table 7 presented more data.
Addition of two equivalents of B(C6F5)3 to I-4 led to formation of (Me2PhP)(B(C6F5)3) and I-6. The Lewis acid in I-6 is labile at room temperature as demonstrated by a broadened alkylidene signal in the 1H NMR spectrum at 7.30 ppm. The 1H NMR spectrum of 45 mM adduct solution at −60° C. shows a sharp alkylidene resonance at 7.06 ppm. An X-ray structure of I-6 showed that B(C6F5)3 is coordinated to the oxo ligand (FIG. 5). The W1-O2-B1 unit is bent (W1-O2-B1 angle is 159.9(1)°). The W1-O2 distance is elongated (1.759(2) Å) relative to that in I-4 (1.717(2) Å) or in I-2 (1.695(3) Å) and is slightly shorter than in reported B(C6F5)3 adducts of tungsten oxo complexes (Barrado, G.; Doerrer, L.; Green, M. L. H.; Leech, M. A. J. Chem. Soc., Dalton Trans. 1999, 1061; Galsworthy, J. R.; Green, J. C.; Green, M. L. H.; Müller, M. J. Chem. Soc., Dalton Trans. 1998, 15; Wolff, F.; Choukroun, R.; Lorber, C.; Donnadieu, B. Eur. J. Inorg. Chem. 2003, 628; Sinchez Nieves, J.; Royo, P.; Mosquera, M. E. G. Eur. J. Inorg. Chem. 2006, 127). A relatively weak coordination of B(C6F5)3 to the oxo is also indicated by the B1-O2 bond length (1.571(3) Å), which is longer than in any B(C6F5)3 adducts of transition metal oxo complexes (1.484(3)-1.558(2) Å) in the literature. The average values of the C-B-C and O-B-C angles (112.6° and 106.1°, respectively) also suggest that B(C6F5)3 is relatively weakly coordinated to the oxo.
Synthesis of W(O)(B(C6F5)3)(CH-t-Bu)(OHMT)(Me2Pyr) (I-6).
A cold (−30° C.) suspension of B(C6F5)3 (37.3 mg, 0.073 mmol, 2.02 eq.) in 2 mL pentane was added to a cold (−30° C.) suspension of WO(CH-t-Bu)(Me2Pyr)(HMTO)(PMe2Ph) (30.0 mg, 0.036 mmol) in 5 mL of pentane with rapid stirring. The color of the mixture changed from yellow to orange and white precipitate gradually formed. The solvent volume was reduced to ca. 3 mL and the mixture was filtered. The volume of orange filtrate was reduced to ca. 1 mL and the solution was placed in the freezer at −30° C. In three days, orange crystals formed. NMR signals are listed for 45 mM solution of I-4.B(C6F5)3 in CD2Cl2 at −60° C., generated in situ from WO(CH-t-Bu)(Me2Pyr)(HMTO)(PMe2Ph) and 2.02 equiv B(C6F5)3): 1H NMR δ 7.06 (s, 1, WCH-t-Bu, 3JWH=17 Hz), 7.26 (t, 1, Ar—H), 7.12 (d, 2, Ar—H), 6.93 (s, 2, Ar—H), 6.57 (s, 2, Ar—H), 5.76 (broadened s, 1, Pyr-H), 5.44 (broadened s, 1, Pyr-H), 2,11 (s, 6, Ar-Me), 2.05 (s, 6, Ar-Me), 1.89 (s, 6, Ar-Me), 1.86 (s, 3, Pyr-Me), 1.54 (s, 3, Pyr-Me), 0.89 (s, 9, WCH-t-Bu); 13C{1H}NMR: δ 274.2 (WCH-t-Bu, 1JCH=115 Hz), 157.8, 147.8, 145.9, 137.3, 135.5, 135.3, 131.4, 130.9, 128.3, 128.2, 125.8, 115.0, 112.3, 110.7, 49.7, 31.7, 21.2, 20.7, 20.6, 17.4, 12.8. 19F NMR: −135.2 (broad, 1), −136.3 (broad, 1), −161.1 (broad, 1), −165.6 (broad, 1), −166.7 (broad, 1). 11B NMR: −3 (very broad).







TABLE 11





Crystal data and structure refinement details for W(O)(CH—t-


Bu)(B(C6F5)3(OHMT)(Me2Pyr) (I-6).
















Identification code
x11151


Empirical formula
C53H43BF15NO2W


Formula weight
1205.54


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Monoclinic


Space group
P21/n









Unit cell dimensions
a = 13.2954(11) Å
α = 90°.



b = 21.6218(18) Å
β = 93.976(2)°.



c = 16.9582(15) Å
γ = 90°.








Volume
4863.2(7) Å3


Z
4


Density (calculated)
1.647 Mg/m3


Absorption coefficient
2.476 mm−1


F(000)
2392


Crystal size
0.21 × 0.05 × 0.04 mm3


Theta range for data collection
1.80 to 30.32°


Index ranges
−18 <= h <= 18, −30 <= k <= 30,



−24 <= l <= 24


Reflections collected
116266


Independent reflections
14569 [R(int) = 0.0508]


Completeness to theta = 30.32i
99.9%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.9184 and 0.6244


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
14569/1/672


Goodness-of-fit on F2
1.027


Final R indices [I > 2sigma(I)]
R1 = 0.0262, wR2 = 0.0529


R indices (all data)
R1 = 0.0391, wR2 = 0.0574


Largest diff. peak and hole
0.800 and −1.005 e · Å−3









In some embodiments, compounds I-7, I-8, and I-9 are prepared from reacting WO(CH-t-Bu)Cl2(PMe2Ph)2 with lithium pyrrolides:




We conclude that tungsten oxo alkylidene complexes are viable catalysts for the Z-selective metathesis coupling of terminal olefins. Without wishing to be bound by any particular theory, it is believed that the resulting selectivity is due to the small size of the oxo ligand relative to OHMT, the low rate of isomerization of the initial Z product relative to coupling of terminal olefins, and decomposition of the active catalyst under the conditions employed.
New Synthesis of Oxo Alkylidene Complexes of Tungsten
The original synthesis of W(O)(CH-t-Bu)Cl2(PMe2Ph)2 and related bis-phosphine complexes was based on synthesis of a tantalum neopentylidene complex and transfer of the neopentylidene ligand from tantalum to tungsten, as shown below (L is PMe2Ph):




Ta(CH-t-Bu)Cl2(PMe2Ph)2 is prepared form Ta(CH2-t-Bu)3Cl2, which is synthesized from TaCl5 and Zn(CH2t-Bu)2 in pentane. For this synthesis, Zn(CH2t-Bu)2 must be prepared and purified extensively before use. W(O)(O-t-Bu)4 can be synthesized in modest yield in a reaction between W(O)Cl4 and LiO-t-Bu and isolated through sublimation, but again the process is lengthy and indirect: i.e., the alkylidene is not prepared on tungsten. Other methods have been tried, including through alkylation of W(O)Cl4. However, direct alkylation of W(O)Cl4 with lithium, magnesium, aluminum, or zinc alkyls has been found to lead to complex mixtures that contain complexes in which the oxo group has been removed from the metal and/or the metal has been reduced. The several tungsten d0 oxo alkyl complexes that are known generally cannot be synthesized in pure form and good yield through direct alkylation of tungsten oxo complexes.

The present invention provides new and better methods of making tungsten oxo alkylidene complexes from readily available starting material. Non-limiting examples are described herein.
In some embodiments, W(O)2Cl2 is prepared on a large scale in a reaction between tungsten hexachloride and hexamethyldisiloxane in dichloromethane. Pale yellow W(O)2Cl2(bipy) can be prepared on a large scale in essentially one step from WCl6 through addition of bipyridine to a dichloromethane solution of W(O)2Cl2(DME) (DME=demethoxyethane). Addition of 3.7 equiv of neopentylmagnesium chloride to a solution of 2 in THF results in the formation of dark red solutions. After aqueous aerobic workup analogous to that reported by Schrauzer (Zhang, C.; Schlemper, E. O.; Schrauzer, G. N. Organometallics 1990, 9, 1016), yellow W(O)2(CH2-t-Bu)2(bipy) (3a) can be isolated in 70% yield. Similar reactions employing PhMe2CH2MgCl led to W(O)2(CH2CMe2Ph)2(bipy) (3b) in 67% yield. Proton NMR spectra are consistent with 3a,b having C2v symmetry with the two oxo ligands cis to each other and trans to bipy. Treatment of 3a with a mixture containing one equivalent of ZnCl2(dioxane), slightly less than two equivalents of PMe2Ph, and two equivalents of trimethylsilyl chloride (TMSCl) in toluene at 100° C. for two hours led to the formation of the tungsten oxo alkylidene complex, W(O)(CH-t-Bu)Cl2(PMe2Ph)2, hexamethyldisiloxane (TMS2O), neopentane, and ZnCl2(bipy). Double recrystallization of the crude product from a mixture of ether and tetrahydrofuran gave 1a in 45% isolated yield. The neophylidene analog, W(O)(CHCMe2Ph)Cl2(PMe2Ph)2 (1b), was prepared in a similar manner and isolated in 39% yield as a yellow solid. Like 1a, 1b is a syn alkylidene on the basis of the JCHα value for the alkylidene (126 Hz). The two phosphine ligands are equivalent and remain bound to tungsten on the NMR time scale at 22° C. with JPW=333 Hz. The new synthesis of W(O)(CHR)Cl2(PMe2Ph)2 complexes 1a and 1b consists of three relatively simple steps starting from tungsten hexachloride, which is a significant improvement over the existing method.




Without the intention to be limited by any theory, a mechanism is proposed for the above transformation. The mechanism of formation of the alkylidene in 1a,b is proposed to involve attack on one of the oxo ligands in W(O)2(CH2R)2(bipy) (R=t-Bu, CMe2Ph) successively by 2 equiv of TMSCl to give TMS2O and a W(O)Cl2(CH2R)2(bipy) intermediate, from which CH3R is lost to give W(O)(CHR)Cl2(bipy). Intramolecular abstraction of an α proton in the alkyl group becomes possible after one oxo ligand is replaced by two chlorides, especially in the presence of a ligand that could promote a abstraction in an 18-electron, seven-coordinate intermediate. There is a possibility that a abstraction takes place in an intermediate W(O)Cl(OSiMe3)(CH2R)2(bipy) species followed by replacement of the trimethylsiloxide with chloride upon further reaction with TMSCl. Treatment of W(O)2(CH2-t-Bu)2(bipy) with only 2 equiv of TMSCl leads to a product mixture whose NMR spectra are consistent with the major product being W(O)(CH-t-Bu)Cl2(bipy).
Synthesis of Oxo Alkylidene Derivatives
The reaction between 1a and LiOR (LiOR=LiOHIPT, LiOHMT) in benzene at 22° C. led to formation of the off-white W(O)(CHt-Bu)Cl(OR)(PMe2Ph) complexes 4a (OR=OHMT) and 4b (OR=OHIPT), each as a mixture of two syn alkylidene isomers. The phosphine remains bound to tungsten on the NMR time scale at 22° C. in both 4a and 4b. Addition of LiMe2Pyr to 4a,b led to isolation of W(O)(CH-t-Bu)(η1-Me2Pyr)(OHMT)(PMe2Ph) (5a) and W(O)(CH-t-Bu)(η1-Me2Pyr)(OHIPT) (5b), both of which were characterized through X-ray studies.11 Phosphine-free 5b is formed as a consequence of the greater steric demand of the OHIPT versus that of the OHMT ligand. The structure of 5a is a square pyramid with a syn neopentylidene in the apical position and the phosphine bound trans to the pyrrolide. The equilibrium constant for phosphine dissociation in 5a was estimated to be 0.015 M at room temperature through NMR studies, a value that corresponds to 57% dissociation of phosphine-free W(O)(CH-t-Bu)(η1-Me2Pyr)(OHMT) being present in a 20 mM solution of 5a in C6D6.
In some embodiments, the present invention provides methods to prepare tungsten oxo alkylidene species from a compound having the structure of formula V-b. In some embodiments, the compounds are obtained as 14 e species. In some embodiments, the compounds are obtained as 14 e species without R8. In some embodiments, a compound of formula V-b is 4a. Exemplary methods and compounds prepared are described herein.
4a can be used to prepare other oxo alkylidene species, in addition to 5a, as shown in Scheme 1. Some of the prepared compounds are obtained as 14e without phosphine ligand.




Addition of 1 equiv of lithium 2,5-diphenylpyrrolide to a toluene solution of W(O)(CH-t-Bu)(OHMT)Cl(PMe2Ph) at room temperature led to the formation of yellow W(O)(CH-t-Bu)(Ph2Pyr)(OHMT) (6) in 57% isolated yield. The α proton resonance for the alkylidene resonance in the 1H NMR spectrum of 6 is found at 9.99 ppm (cf. 9.14 ppm in 5a) with JCH=124 Hz, which is characteristic of a syn orientation of the alkylidene. Although the alkylidene resonance is broadened slightly, the 183W satellites are discernible (JHW=10 Hz). The resonances for the two protons on the pyrrolide ring are broad at room temperature, which, without the intention to be limited by any theory, suggests either hindered rotation of the diphenylpyrrolide ligand or an equilibrium between η1 and η5 coordination modes.

Single crystals of 6 were grown from toluene/pentane solution at −30° C. A thermal ellipsoid drawing of the structure is shown in FIG. 8. The W═O distance (1.690(1) Å) is comparable to the W═O bond length in 5b (1.695(3) Å). The pyrrolide ligand is coordinated in ill fashion with an W—Npyr distance of 2.037(2) Å, versus the W—Npyr bond length in 5b (2.001(2) Å). In Mo(NAr)(CH-t-Bu)(η1-2,5-Ph2Pyr)(η5-2,5-Ph2Pyr), the Mo—Npyr bond length for the ill pyrrolide is slightly longer (2.1145(10) Å) than in 5b. The W—Npyr vector in 6 does not lie in the plane of the pyrrolide ligand: i.e., the pyrrolide is tipped so that the angle between the W—Npyr vector and the plane is 161.7°.
Treatment of 4a with LiN(C6F5)2 in CH2Cl2 led to formation of W(O)(CH-t-Bu)[N(C6F5)2](OHMT)(PMe2Ph) (7) in 60% isolated yield. The X-ray structure 7 showed it to be essentially a square pyramid with the syn alkylidene ligand in the apical position and the phosphine ligand trans to the amide (FIG. 9). The amido nitrogen atom is not planar (the three angles sum to 349.7(2)°) and one of the ortho fluorides could be interacting weakly with the metal trans to the alkylidene (W1-F1=2.758(1) Å), which is not unusual in complexes that contain the perfluorodiphenylamido ligand. The amido ligand could also be said to be “tipped” out of planarity, as found for the diphenylpyrrolide in 6. The broad alkylidene resonance in 7 results from the phosphine dissociating in solution at room temperature. A variable temperature 1H and 31P NMR study of a 74 mM solution of 7 in toluene-ds showed that the phosphine is bound on the NMR time scale below −20° C. (a sharp resonance is found at 2.69 ppm with JPW=347 Hz), but in toluene at 22° C. Keq is  ̃0.002 M, i.e.,  ̃50% of 7 is converted into W(O)(CH-t-Bu)[N—(C6F5)2](OHMT) at 74 mM concentration. At −20° C., 10 broadened 19F resonances are observed for 7, which suggests that the N(C6F5)2 ligand is not rotating freely at −20° C.
Addition of one equivalent of NaOSi(t-Bu)3 to 4a at room temperature resulted in formation of phosphine-free W(O)(CH-t-Bu)(OHMT)(Silox) (8) as the only product, according to 1H and 31P NMR data. 8 was very soluble in pentane. 8 was prepared from 250 mg of 4 and a solution of it in pentane was exposed to one atmosphere of ethylene; the metallacyclobutane complex, W(O)(CH2CH2CH2)(OHMT)(Silox) (9), crystallized out as light yellow crystals in 25% isolated yield. A 0.018 M solution of 9 in C6D6 under dinitrogen was found to consist of 98% 9 and 2% of what is proposed to be the methylidene complex, W(O)(CH2)(OHMT)(Silox) (δCH2 at 7.77 and 8.93 ppm), formed through loss of ethylene from 9. Heating a solution of 9 in C6D6 to 70° C. led to broadening of the metallacycle proton signals and the appearance of free ethylene and broadened methylidene signals, consistent with facile exchange of ethylene in the WC3 ring on the NMR time scale. Only three metallacycle resonances are observed for W(O)(C3H6)(OHMT)(Silox) in C6D6 (4.10, 2.54, and 1.93 ppm, 1:1:1 ratio); presumably three other resonances are obscured. Three 13C resonances can be attributed to the metallacycle at 43.8, 41.5, and 22.3 ppm. The range of chemical shifts of metallacycle protons and carbons is indicative of squarepyramidal (SP) coordination of the metal center found for W(NAr)[CH2CH(t-Bu)CH2](O-t-Bu)2.




Single crystals of 9 were grown from a mixture of toluene and pentane at −30° C. An X-ray structural study confirmed the proposed SP configuration of 9 in which the oxo ligand is in the apical position (FIG. 10). To our knowledge, 9 is the first structurally characterized metallacyclobutane derived from an oxo alkylidene and the first unsubstituted high oxidation state molybdacyclobutane or tungstacyclobutane that has a square pyramidal geometry. (All unsubstituted Mo or W imido metallacyclobutane complexes have TBP geometries.) The bond lengths and bond angles in the WC3 ring in 9 are identical to those in W(NAr)[CH2CH(t-Bu)CH2][OCMe2(CF3)]2 (within 3σ), as shown below. The WC3 ring in 9 is bent with a 33.8° dihedral angle between the C1-W-C3 and C1-C2-C3 planes compared to a 33.4° angle in W(NAr)[CH2CH(t-Bu)CH2][OCMe2(CF3)]2. Relatively long W—Cβ distances in SP metallacyclobutane complexes of W (W . . . C2=2.762(3) Å in 9) have led to the proposal that SP metallacyclobutane complexes are further from the transition state for loss of olefin to give an alkylidene than are TBP metallacycles.




Addition of one equivalent of LiOHMT to W(O)(CH-t-Bu)(OHMT)Cl(PMe2Ph) (100° C., toluene) leads to formation of W(O)(CH-t-Bu)(OHMT)2 (10) in good yield. 10 is also prepared in 41% isolated yield by treating W(O)(CH-t-Bu)Cl2(PMe2Ph)2 with two equivalents of LiOHMT at 100° C. in toluene for 48 h. The resonance for the alkylidene proton in the proton NMR spectrum of 10 is found at 7.34 ppm with 1JHW=14 Hz. Three mesityl methyl resonances were observed for the OHMT ligands in the proton NMR spectrum at 22° C., consistent with the OHMT ligands being equivalent, free rotation about the W—O bonds, and no rotation about the C—C bonds to the central phenyl ring. The two sets of ortho mesityl methyl groups arise from the fact that no symmetry plane bisects the C═W═O angle in 10.
When a pentane solution of 10 was placed under 1 atm of ethylene, a yellow precipitate can be isolated whose proton NMR spectrum in C6D6 shows that a mixture of W(O)(C3H6)(OHMT)2 (11) and W(O)(CH2)(OHMT)2 (12) in a 3:1 ratio is present. We propose that the precipitate is pure 11, but upon dissolution in benzene some ethylene is lost from 11 to give the mixture of 11 and 12 in solution. Only 11 is sufficiently insoluble to precipitate in the manner described. Compound 12 can be isolated in pure form through repeated dissolution of mixtures of 11 and 12 in toluene followed by slow removal of the solvent in vacuo:




Two methylidene doublet resonances are observed in 1H NMR spectra of 12 in C6D6 at 8.90 ppm (Hsyn, 1JCH=160 Hz, 2JHH=10 Hz) and 7.85 ppm (Hanti, 1JCH=140 Hz). The lower JCH value for Hanti is consistent with a C—Hanti agostic interaction with the metal center. Three mesityl methyl resonances are found in the proton NMR spectrum at 22° C., as noted above for 10. Compound 12 was found to be stable in solution for at least 24 h at room temperature at a concentration of  ̃20 mM.

An X-ray structural determination of 12 confirms that it is a monomeric tetrahedral 14-electron species in the solid state (FIG. 11). To our knowledge, this is the first X-ray structural study of an oxo methylidene complex. The oxo and methylidene ligands were found to be mutually disordered in a ratio of 71:29. The disorder could be resolved and the methylidene protons located in the major component; they were refined semifreely with appropriate bond length restraints (see Supporting Information). The W═C bond length (1.895(8) Å) is similar to the M=C distances in two structurally-characterized 14e imido methylidene complexes of Mo (1.892(5) Å) and W (1.908(4) Å) (Schrock, R. R., King, A. J.; Marinescu, S. C.; Simpson, J. H.; Müller, P. Organometallics 2010, 29, 5241). The CH2 plane is tilted  ̃9° relative to O═W═C plane, as is also found in the two Mo and W imido methylidene complexes (by 8°). The W═C1-H1a (Hanti) angle (109(3)°) is smaller than the W═C1-H1b (Hsyn) angle (127(3)°), consistent with an agostic interaction between the CHanti bond and the metal center, and with the lower 2JCHanti values relative to 2JCHsyn values. The W═O bond length (1.694(5) Å) is comparable to that in W(O)(CH-t-Bu)(Me2Pyr)(HIPTO) (1.695(3) Å, Peryshkov, D. V.; Schrock, R. R.; Takase, M. K.; Müller, P.; Hoveyda, A. H. J. Am. Chem. Soc. 2011, 133, 20754). The planes of two phenolate rings of the terphenoxides intersect at an angle of 81.5° with respect to each other. The nearly “perpendicular” relationship of the two OHMT ligands resembles a baseball cover and, without the intention to be limited by any theory, must hinder formation of the bis-μ-methylidene intermediate required for bimolecular decomposition yet must not block access of ethylene to the metal and formation of square pyramidal metallacyclobutane complex 11. Without the intention to be limited by theory, the 2,6-terphenoxide ligand contributes to discourage bimolecular decomposition.
EXPERIMENTAL
General Comments.
All manipulations were done either in a nitrogen-filled drybox or on an air-free dual-manifold Schlenk line. The solvents were sparged with nitrogen, passed through activated alumina, and stored over activated 4 Å Linde-type molecular sieves. Methylene chloride-d2, benzene-d6, and toluene-d8 were distilled from calcium hydride (CD2Cl2) or sodium ketyl (C6D6, C7D8), and stored over activated 4 Å Linde-type molecular sieves. NMR spectra were recorded using Varian spectrometers at 500 (1H), 125 (13C) and 121 (31P) MHz, reported in δ (parts per million) relative to tetramethylsilane (1H, 13C) or 85% phosphoric acid (31P), and referenced to the residual 1H/13C signals of the deuterated solvent (1H (δ): benzene 7.16; methylene chloride 5.32, chloroform 7.26, toluene 7.09, 7.01, 6.97, 2.08; 13C (δ): benzene 128.06; methylene chloride 53.84, chloroform 77.16, toluene 20.43) or external 85% phosphoric acid standard (31P (δ): 0) and hexafluorobenzene (19F (δ): −164.9). Midwest Microlab, Indianapolis, Ind. provided the elemental analysis results.
W(O)(CHCMe3)Cl(HMTO)(PMe2Ph), H(2,5-Ph2Pyr), NH(C6F5)2 were prepared according to reported procedures. H(Silox) was received as a generous gift from Professor Pete Wolczanski. NaSilox was prepared in the reaction of H(Silox) and NaH in THF. All other reagents were used as received unless noted otherwise.
Synthesis of W(O)2Cl2(Bipy).
The compound was prepared by a modification of the published procedure. A solution of hexamethyldisiloxane (21.482 g, 132 mmol, 2.1 eq) was added dropwise to the solution of tungsten hexachloride (25.000 g, 63.0 mmol) in 250 mL of dichloromethane. A solution of dimethoxyethane (13.058 g, 144.9 mmol, 2.3 eq) was added. The mixture was stirred for 2 h at room temperature during which time it became dark blue and contained a suspended precipitate. A pale blue solution was obtained after filtration of the mixture through Celite. A solution of 2,2′-bipyridine (10.330 g, 66.1 mmol, 1.05 eq) in 30 ml of dichloromethane was added and the mixture was stirred for 30 min. The precipitate was isolated by filtration, washed twice with 50 mL of dichloromethane, and dried under vacuum. The pale yellow powder was collected (25.824 g, 58.3 mmol, 92% yield). Anal. Calcd for C10H8Cl2N2O2W: C, 27.10; H, 1.82; N, 6.32. Found: C, 26.27; H, 1.86; N, 5.97.
Synthesis of W(O)2(CH2CMe3)2(Bipy) (3a).
Compound 3a was prepared in a manner similar to the published procedure using W(O)2Cl2(bipy) instead of W(O)2Br2(bipy) as a starting material. A cold (−30° C.) solution of (CH3)3CCH2MgCl in ether (40 mL, 1.66M, 3.7 eq.) was added to a cold (−30° C.) suspension of W(O)2Cl2(bipy) (8.000 g, 18.06 mmol) in 150 mL of THF. The reaction mixture was stirred at room temperature for 1 h. Volatiles were removed under vacuum leaving dark red residue. After addition of water (300 mL) the mixture was periodically shaken with CH2Cl2 (200 mL) in air. The organic fraction gradually changed color from green to yellow to orange. The mixture was filtered through Celite. The aqueous layer was separated and discarded. The organic layer was washed five times with portions of water (150 mL), dried with anhydrous MgSO4, and concentrated to 20 mL volume, causing formation of a yellow solid. A portion of hexane (200 mL) was added and the mixture was filtered. The precipitate was recrystallized from dichloromethane/hexane. The solid product was isolated by filtration and dried under vacuum (6.464 g, 12.57 mmol, 70% yield): 1H NMR (CD2Cl2) δ 9.55 (m, 2, bipy H), 8.39 (m, 2, bipy H), 8.15 (m, 2, bipy H), 7.58 (m, 2, bipy H), 0.94 (s, 18, CH2CMe3), 0.81 (s, 4, CH2CMe3, JWH=8 Hz); 13C NMR (CD2Cl2) δ 196.3, 152.0, 150.4, 139.2, 125.8, 123.6, 68.1, 34.9, 33.5. Anal. Calcd for C20H30N2O2W: C, 46.71; H, 5.88; N, 5.45. Found: C, 46.79; H, 5.91; N, 5.47.
Synthesis of W(O)2(CH2CMe2Ph)2(Bipy) (3b).
The compound was prepared in a manner analogous to that employed to prepare 3a. A cold (−30° C.) solution of (CH3)2PhCCH2MgCl in ether (100 mL, 0.5 M, 3.7 equiv) was added to a cold (−30° C.) suspension of W(O)2Cl2(bipy) (6.000 g, 13.55 mmol) in 80 mL of THF. The reaction mixture was stirred at room temperature for 1 h. Volatiles were removed under vacuum, leaving a dark red residue. After addition of water (300 mL) the mixture was periodically shaken with CH2Cl2 (200 mL) in air. The organic fraction gradually changed color from green to yellow. The mixture was filtered through Celite. The aqueous layer was separated and discarded. The organic layer was washed five times with portions of water (150 mL), dried with anhydrous MgSO4, and concentrated to 20 mL volume, causing formation of a pale yellow solid. A portion of hexane (150 mL) was added, and the mixture was filtered. The precipitate was recrystallized from chloroform/hexane. The solid product was isolated by filtration and dried under vacuum (5.85 g, 9.16 mmol, 67% yield): 1H NMR (CD2Cl2) δ 8.95 (m, 2, bipy H), 8.24 (m, 2, bipy H), 8.03 (m, 2, bipy H), 7.35 (m, 2, bipy H), 7.05 (m, 10, CH2CMe2Ph), 1.38 (s, 12, CH2CMe2Ph), 1.06 (s, 4, CH2CMe2Ph, JWH=8 Hz); 13C NMR (CD2Cl2) δ 154.1, 152.0, 149.9, 138.9, 127.7, 126.0, 125.8, 124.8, 123.6, 68.2, 41.3, 32.2. Anal. Calcd for C30H34N2O2W: C, 56.44; H, 5.37; N, 4.39. Found: C, 56.42; H, 5.44; N, 4.35.
Synthesis of W(O)(CHCMe3)Cl2(PMe2Ph)2 (La).
Compound 3a (3.80 g, 7.39 mmol) was mixed with ZnCl2(dioxane) (1.74 g, 7.76 mmol, 1.05 equiv) and PMe2Ph (1.94 g, 14.04 mmol, 1.9 equiv) in 40 mL of toluene. The mixture was cooled to −30° C., and TMSCl (1.77 g, 16.26 mmol, 2.2 equiv) was added. The mixture was stirred at room temperature for 30 min and then heated to 100° C. for 2 h, during which time the color darkened and a precipitate formed. All the volatiles were removed under vacuum at 50° C. Benzene (40 mL) was added to the dark residue, and the mixture was filtered through Celite. Solvent was evaporated from the filtrate in vacuo, leaving a yellow solid and a brown oil. The residue was stirred with 40 mL of ether for 3 h, during which time the oil disappeared and a yellow solid remained. The solid was recrystallized twice from a mixture of ether and tetrahydrofuran at −30° C. to produce a yellow crystalline solid (2.03 g, 45% yield). The 1H NMR spectrum of the product is identical with that reported: 1H NMR (C6D6) δ 12.10 (t, 1, WCHCMe3, 1JCH=125 Hz, 3JPH=4 Hz), 7.65 (m, 4), 6.97 (m, 6), 1.92 (m, 12, PMe2Ph), 0.82 (s, 9, WCHCMe3). Anal. Calcd for C21H32Cl2OP2W: C, 40.87; H, 5.23. Found: C, 40.90; H, 5.12.
Synthesis of W(O)(CHCMe2Ph)Cl2(PMe2Ph)2 (1b).
The compound was prepared in a manner analogous to that described for 1a. Compound 3b (2.99 g, 4.68 mmol) was mixed with ZnCl2(dioxane) (1.10 g, 4.91 mmol, 1.05 equiv) and PMe2Ph (1.22 g, 8.85 mmol, 1.8 equiv) in 40 mL of toluene. The mixture was cooled to −30° C., and TMSCl (1.17 g, 10.76 mmol, 2.3 equiv) was added. The mixture was stirred at room temperature for 30 min and was heated at 100° C. for 2 h, during which time the color darkened and a precipitate formed. The solvent volume was reduced to approximately 30 mL in vacuo, and 10 mL of pentane was added. The solution was filtered through Celite, and the volatiles were removed in vacuo, leaving a brown oil. The residue was recrystallized twice from a mixture of ether and tetrahydrofuran at −30° C. to give a yellow crystalline solid (1.24 g, 39% yield): 1H NMR (C6D6) δ 12.01 (t, 1, WCHCMe2Ph, 1JCH=126 Hz, 3JPH=4 Hz), 7.68 (m, 4), 7.03 (m, 8), 6.96 (m, 3), 1.94 (t, 6, PMe2Ph), 1.58 (t, 6, PMe2Ph), 1.27 (s, 6, WCHCMe2Ph); 13C NMR (C6D6) δ 315.8 (t, WCHCMe2Ph, JPC=11 Hz), 150.6, 135.1 (t), 131.4 (t), 130.6, 128.75, 128.70, 128.65, 126.8, 126.1, 51.9, 30.9, 14.7 (td); 31P NMR (C6D6) δ 4.02 (JPW=333 Hz). Anal. Calcd for C26H34Cl2OP2W: C, 45.97; H, 5.05. Found: C, 46.23; H, 4.99.
Synthesis of W(O)(CHCMe3)(Ph2Pyr)(OHMT). Synthesis of W(O)(CHCMe3)(Ph2Pyr)(OHMT) (6).
A solution of W(O)(CHCMe3)Cl(OHMT)(PMe2Ph) (300.0 mg, 0.388 mmol) in 10 mL of benzene was added to a portion of solid Li(Ph2Pyr) (105.0 mg, 0.466 mmol, 1.2 equiv). The cloudy reaction mixture was stirred at room temperature for 24 h. The solvent was removed in vacuo to give brown oil. The product was extracted to toluene (5 mL) and the mixture was filtered through a bed of Celite. Toluene was removed in vacuo to produce brown oil. Yellow solid precipitated upon addition of pentane (4 mL) and the resulting suspension was filtered and washed with 5 mL of pentane. Yellow solid was recrystallized from toluene/pentane at −30° C.: yield 182.0 mg, 57%; 1H NMR (C6D6) δ 9.99 (s, 1, WCH-t-Bu, 1JCH=124 Hz, 2JWH=11 Hz), 7.24-6.94 (m, 12), 6.89 (s, 2), 6.65 (s, 2), 6.61 (d, 1), 6.46-6.14 (br., 2), 2.22 (s, 6, Ar Me), 2.18 (s, 6, Ar Me), 2.04 (s, 6, Ar Me), 0.71 (s, 9, WCH-t-Bu); 13C NMR (C6D6) δ 279.7 (WCH-t-Bu, 1JCW=201 Hz), 157.4, 137.8, 137.5, 137.3, 136.2, 133.8, 133.5, 133.1, 131.5, 130.7, 129.4, 129.2, 129.1, 127.1, 126.4, 124.3, 123.1, 113.1, 111.4, 108.6, 42.9, 32.1, 21.4, 21.2, 21.1. Anal. Calcd for C45H77NO2W: C, 66.10; H, 5.79; N, 1.71. Found: C, 65.93; H, 5.90; N, 1.76.
Synthesis of W(O)(CHCMe3)[N(C6F5)2](OHMT)(PMe2Ph) (7)
A solution of W(O)(CH-t-Bu)Cl(OHMT)(PMe2Ph) (252 mg, 0.326 mmol) in 10 mL of dichloromethane was added to a portion of solid LiN(C6F5)2 (127 mg, 0.358 mmol, 1.1 equiv). The reaction mixture was stirred at room temperature for 8 h, during which time a white precipitate formed. The solvent was removed in vacuo to give a brown oil. The product was extracted into toluene (5 mL), and the solvent was filtered through a bed of Celite. Toluene was removed in vacuo to produce a yellow oil. The oil was dissolved in a 1⁄4 mixture of ether and pentane and cooled to −30° C. The product was collected as an off-white solid: yield 230 mg, 65%; 1H NMR (74 mM in C6D5CD3, 22° C.) δ 10.21 (br, 1, WCH-t-Bu), 7.25 (m, 2), 7.00 (m, 3), 6.82 (m, 6), 6.64 (br, 2), 2.23 (br, 6, Ar Me), 2.10 (br, 6, Ar Me), 2.04 (br, 6, Ar Me), 1.20 (br, 6, PMe2Ph) 0.60 (br, 9, WCH-t-Bu); 31P NMR (74 mM in C6D5CD3, 22° C.) δ 2.44 (br); 1H NMR (74 mM in PMe2Ph, −20° C.) δ 10.37 (br, 1, WCH-t-Bu), 7.20 (m, 2), 6.95 (m, 3), 6.81 (m, 6), 6.72 (br, 1), 6.54 (br, 1), 2.35 (br, 3, Ar Me), 2.22 (br, 3, Ar Me), 2.17 (br, 6, Ar Me) 2.03 (br, 3, Ar Me), 2.00 (br, 3, Ar Me), 1.17 (d, 6, PMe2Ph) 0.52 (br, 9, WCH-t-Bu); 13C NMR (74 mM in C6D5CD3, −20° C., C—F are expected to be weak) δ 297.3 (WCH-t-Bu), 160.1, 139.1, 138.5, 138.0, 137.6, 137.1, 136.8, 136.5, 135.0, 134.7, 133.8, 133.4, 133.0, 132.7, 131.9, 130.9, 130.8, 130.6, 129.7, 128.5, 128.4, 128.2, 120.9, 44.3, 29.8, 22.1, 21.8, 21.4, 21.1, 21.0, 20.9, 14.3 (d), 11.4 (d); 31P NMR (74 mM in C6D5CD3, −20° C.) δ 2.69 (s, JPW=347 Hz); 19F NMR (74 mM in C6D5CD3, −20° C.) δ −146.18 (br, 1), −146.62 (br, 1), −152.04 (br, 1), −160.78 (br, 1), −165.66 (br, 1), −167.58 (br, 2), −168.91 (br, 1), −169.09 (br, 1), −174.82 (br, 1). Anal. Calcd for C49H46F10NO2PW: C, 54.21; H, 4.27; N, 1.29. Found: C, 54.50; H, 4.32; N, 1.59.
Synthesis of W(O)(C3H6)(OHMT)(Silox) (9).
A cold (−30° C.) solution of W(O)(CH-t-Bu)(OHMT)Cl(PMe2Ph) (250.0 mg, 0.323 mmol) in 10 mL of toluene was added to a portion of solid NaSilox (85.2 mg, 0.357 mmol, 1.1 equiv). The brown reaction mixture was stirred at room temperature for 3 h. The solvent was removed in vacuo to give brown oil. The product was extracted to toluene (5 mL), and the mixture was filtered through a bed of Celite. Toluene was removed in vacuo to produce a brown oil. Pentane (3 mL) was added to the oil. The solution was degassed by three successive freeze-pump-thaw cycles, and 1 atm of ethylene was added. The mixture was stirred at 0° C. for 1 h, during which time a yellow crystalline precipitate formed. The precipitate was filtered off, washed with 0.5 mL of cold pentane, and collected: yield 64 mg, 25%. A 0.018 M solution in C6D6 contained 98% of 4 and 2% of the corresponding methylidene along with the equivalent amount of ethylene: 1H NMR (C6D6) δ 7.02-6.90 (m, 7, Ar H), 4.10 (m, 1, WC3H6), 2.54 (m, 1, WC3H6), 2.26 (br s, 12, Ar Me), 2.20 (s, 6, Ar Me), 1.93 (m, 1, WC3H6), 1.05 (s, 27, SiCMe3); 13C NMR (C6D6) δ 156.6, 136.8 (br), 136.4 (br), 135.0 (br), 134.4 (br), 130.6, 129.2, 128.7, 124.0, 43.8 (WC3H6), 41.4 (WC3H6), 30.0 (SiCMe3), 23.9 (SiCMe3), 22.3 (WC3H6), 21.4 (br, Ar Me), 21.2 (Ar Me). Anal. Calcd for C39H58O3SiW: C, 59.42; H, 7.43. Found: C, 59.20; H, 7.11.
Synthesis of W(O)(CHCMe3)(OHMT)2 (10).
A solution of W(O)(CHCMe3)Cl2(PMe2Ph) (200.0 mg, 0.324 mmol) in 10 mL of toluene was added to a solution of LiOHMT (261.6 mg, 0.778 mmol, 2.4 equiv). The reaction mixture was stirred at 100° C. for 48 h, and the volatiles were removed in vacuo to give a brown oil. The product was extracted into toluene (5 mL), and the mixture was filtered through a bed of Celite. The toluene was removed in vacuo to give a brown oil. Addition of 4 mL of pentane caused a yellow solid to precipitate. The solid was filtered off and washed with 3 mL of cold pentane: yield 124 mg, 41%; 1H NMR (C6D6) δ 7.34 (s, 1, WCH-t-Bu, 1JCH=122 Hz, 2JWH=14 Hz), 6.90 (br s, 4, Ar H), 6.87-6.85 (m, 8, Ar H), 6.83-6.80 (m, 2, Ar H), 2.26 (s, 12, Ar Me), 2.08 (s, 12, Ar Me), 2.03 (s, 12, Ar Me), 0.92 (s, 9, WCH-t-Bu); 13C NMR (C6D6) δ 253.6 (WCH-t-Bu), 158.5, 137.0, 136.7, 136.5, 134.9, 131.7, 130.7, 128.9, 128.8, 123.0, 41.1, 33.2, 21.6, 21.3, 20.8. Anal. Calcd for C53H60O3W: C, 68.53; H, 6.51. Found: C, 68.22; H, 6.53.
Synthesis of W(O)(CH2)(OHMT)2 (12).
A sample of 11 (60 mg, 0.067 mmol) was dissolved in 1 mL of toluene, and the solvent was removed in vacuo at room temperature. After two additional dissolution/evacuation cycles, a brown oil was obtained. Toluene (0.1-0.2 mL) and pentane (0.3-0.5 mL) were added, and the sample was placed in a freezer at −30° C. for 2 days. Yellow crystals formed and were separated from the brown mother liquor by decantation: yield 32 mg, 55%; 1H NMR (C6D6) δ 8.90 (d, 1, WCHsyn, 2JHH=10 Hz, 1JCH=160 Hz), 7.85 (d, 1, WCHanti, 2JHH=10 Hz, 1JCH=140 Hz), 6.90 (br s, 4, Ar H), 6.89-6.85 (m, 8, Ar H), 6.84-6.80 (m, 2, Ar H), 2.22 (s, 12, Ar Me), 2.00 (s, 12, Ar Me), 1.96 (s, 12, Ar Me); 13C NMR (C6D6) δ 225.8 (WCH2), 158.1, 137.2, 136.9, 136.7, 134.4, 131.5, 130.0, 128.3, 123.4, 123.0, 21.3, 20.9, 20.8. Anal. Calcd for C49H52O3W: C, 67.43; H, 6.01. Found: C, 67.74; H, 6.12.
Synthesis of 1-MeO-2,6-(C6F5)2—C6H3.
1-MeO-2,6-[B(OH)2]2-C6H3 (700 mg, 3.58 mmol), Pd(PPh3)4 (165 mg, 0.143 mmol) and K2CO3 (2.47 g, 17.9 mmol) were suspended in a mixture of toluene (12 mL) and ethanol (8 mL). C6F5Br (1.33 mL, 10.73 mmol) was added at room temperature. After refluxing for 1 day, the mixture was cooled to room temperature and filtered through silica plug and washed with CH2Cl2. Removal of the solvent gave a light yellow oil that was dissolved in a mixture of CH2Cl2 and hexane; colorless crystals formed at −35° C.; yield 1.021 g (65%): 1H NMR (300 MHz, acetone-d6, 20° C.) δ 7.63 (d, 3JHH=5 Hz, 2H), 7.48 (t, 3JHH=5 Hz, 1H), 3.38 (s, 3H, Me); 19F NMR (282 MHz, acetone-d6, 20° C.) δ −141.9 (m, 4F, o-F), −157.6 (t, 3JFF=21 Hz, 2F, p-F), −165.0 (m, 4F, m-F); 13C{1H}NMR (125 MHz, acetone-d6, 20° C.) δ 158.3 (s, 1C), 145.8 (d, 1JCF=298 Hz, 4C), 142.1 (d, 1JCF=252 Hz, 2C), 138.8 (d, 1JCF=250 Hz, 4C), 128.6 (s, 2C), 125.4 (s, 1C), 121.6 (s, 2C), 113.5 (t, 2JCF=19 Hz, 2C). HRMS (ESI/[M+Na]+) Calcd for C19H6F10NaO: 643.0151. Found: 643.0149.
Synthesis of HO-2,6-(C6F5)2—C6H3.
1-MeO-2,6-(C6F5)2C6H3 (552 mg, 1.25 mmol) was dissolved in CH2Cl2 (20 mL). BBr3 (0.238 mL, 2.51 mmol) was added at 0° C. The mixture was warmed up to room temperature. After 16 hours, water (10 mL) was added to quench the reaction. The organic layer was separated from the aqueous layer and the aqueous layer was extracted with diethyl ether. The organic parts were combined and dried with MgSO4. Removal of the solvent in vacuo gave a white solid that was recrystallized from hexanes to give colorless crystals; yield 482 mg (90%): 1H NMR (300 MHz, CDCl3, 20° C.) δ 7.42 (d, 3JHH=8 Hz, 2H), 7.28 (t, 3JHH=7 Hz, 1H), 4.92 (br, 1H, OH); 19F NMR (282 MHz, CDCl3, 20° C.) δ −139.9 (m, 4F, o-F), −154.3 (t, 3JFF=21 Hz, 2F, p-F), −165.0 (m, 4F, m-F); 13C{1H}NMR (125 MHz, CDCl3, 20° C.) δ 151.3 (s, 1C), 145.0 (d, 1JCF=250 Hz, 4C), 141.4 (d, 1JCF=242 Hz, 2C), 138.2 (d, 1JCF=253 Hz, 4C), 133.6 (s, 2C), 121.7 (s, 1C), 115.0 (s, 2C), 111.2 (t, 2JCF=19 Hz, 2C). Anal. Calcd for C14H4F10O: C, 50.72; H, 0.95. Found: C, 50.96; H, 1.06.
X-Ray Crystal Structure Determination Details.
Low-temperature diffraction data (φ- and ω-scans) were collected on a Bruker-AXS X8 Kappa Duo diffractometer coupled to a Smart APEX 2 CCD detector with Mo Kα radiation (λ=0.71073 Å) from an IμS micro-source. Absorption and other corrections were applied using SADABS. All structures were solved by direct methods using SHELXS and refined against F2 on all data by full-matrix least squares with SHELXL-97 using established refinement approaches. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms were included in the models at geometrically calculated positions and refined using a riding model, except for alkylidene, metallacycle, and methylidene protons. Coordinates for these hydrogen atoms were taken from the difference Fourier synthesis, and the hydrogen atoms were subsequently refined semi-freely with the help of distance restraints. The isotropic displacement parameters of all hydrogen atoms were fixed to 1.2 times the Ueq value of the atoms they are linked to (1.5 times for methyl groups). All disordered atoms were refined with the help of similarity restraints on the 1,2- and 1,3-distances and displacement parameters as well as rigid bond restraints for anisotropic displacement parameters.
W(O)(CH-t-Bu)(Ph2Pyr)(OHMT) (6) crystallizes in the triclinic space group with P1 one molecule in the asymmetric unit. Coordinates for the hydrogen atom bound to C1 were taken from the difference Fourier synthesis as noted above.
W(O)(CH-t-Bu)(N(C6F5)2)(OHMT)(PMe2Ph) (7) crystallizes in monoclinic space group P21/c with one molecule in the asymmetric unit. Coordinates for the hydrogen atom bound to C1 were taken from the difference Fourier synthesis as noted above.
W(O)(C3H6)(OHMT)(Silox) (9) crystallizes in the triclinic space group P1 with one molecule in the asymmetric unit. The tungsten atom and oxo ligand were modeled as a two-component disorder, and the ratio of the occupancies was refined to 0.9687(6):0.0313(6). The Silox ligand was also found to be disordered over two positions, and the ratio of occupancies was refined to 0.521(8):0.479(8). The anisotropic displacement parameters for silicon and carbon atoms of the Silox group were constrained to be equivalent, pairwise.
W(O)(CH2)(OHMT)2 (12) crystallizes in the monoclinic space group P21/n with one molecule in the asymmetric unit. The tungsten atom, oxo, and methylidene ligand were modeled as a two-component disorder, and the ratio of the occupancies was refined to 0.711(1):0.289(1). The anisotropic displacement parameters for the tungsten (W1, W1 Å), oxo, and chloride ligands (C1, O1A and C1A, O1) were constrained to be equivalent, pairwise. Coordinates of the hydrogen atoms bound to C1 were taken from the difference Fourier synthesis as noted above. The hydrogen atoms bound to C1A, the minor component of the disorder, could not be found in the difference Fourier synthesis and were not included in the model.
Crystal data were presented below.







TABLE 12





Crystal data and structure refinement


for W(O)(CHCMe3)(Ph2Pyr) (OHMT).
















Identification code
X8_12012


Empirical formula
C45 H47 N O2 W


Formula weight
817.69


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Triclinic


Space group
P1









Unit cell dimensions
a = 9.6557(8) Å
α = 83.319(2)°



b = 10.7803(9) Å
β = 79.010(2)°



c = 19.4906(17) Å
γ = 73.730(2)°








Volume
1907.6(3) Å3


Z
2


Density (calculated)
1.424 Mg/m3


Absorption coefficient
3.065 mm−1


F(000)
828


Crystal size
0.10 × 0.09 × 0.05 mm3


Theta range for data collection
1.07 to 31.00°.


Index ranges
−13 <= h <= 13, −15 <=



k <= 15, −28 <= l <= 27


Reflections collected
82590


Independent reflections
12148 [R(int) = 0.0414]


Completeness to theta = 31.00°
99.9%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.8668 and 0.7492


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
12148/1/454


Goodness-of-fit on F2
1.028


Final R indices [I > 2sigma(I)]
R1 = 0.0209, wR2 = 0.0463


R indices (all data)
R1 = 0.0254, wR2 = 0.0479


Largest diff. peak and hole
1.277 and −0.764 e.Å−3
















TABLE 13





Crystal data and structure refinement for


W(O)(CHCMe3)[N(C6F5)2](OHMT)(PMe2Ph).
















Identification code
X8_12046


Empirical formula
C49 H46 F10 N O2 P W


Formula weight
1085.69


Temperature
100(2) K


Wavelength
0.71073 ≈


Crystal system
Monoclinic


Space group
P2(1)/c









Unit cell dimensions
a = 12.0498(5) Å
a = 90°



b = 21.0063(10) Å
b = 95.3650(10)°



c = 17.9963(8) Å
g = 90°








Volume
4535.3(4) Å3


Z
4


Density (calculated)
1.590 Mg/m3


Absorption coefficient
2.664 mm−1


F(000)
2168


Crystal size
0.168 × 0.095 × 0.068 mm3


Theta range for data collection
1.49 to 30.62°.


Index ranges
−17 <= h <= 17, −12 <=



k <= 30, −25 <= l <= 25


Reflections collected
120239


Independent reflections
13947 [R(int) = 0.0367]


Completeness to theta = 30.62°
99.8%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.878 and 0.722


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
13947/1/591


Goodness-of-fit on F2
1.066


Final R indices [I > 2sigma(I)]
R1 = 0.0259, wR2 = 0.0559


R indices (all data)
R1 = 0.0297, wR2 = 0.0573


Largest diff. peak and hole
1.809 and −0.862 e.Å−3
















TABLE 14





Crystal data and structure refinement


for W(O)(C3H6)(OHMT)(Silox).
















Identification code
X8_12002


Empirical formula
C39 H58 O3 Si W


Formula weight
786.79


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Triclinic


Space group
P1









Unit cell dimensions
a = 9.3385(10) Å
α = 91.207(2)°



b = 12.9036(14) Å
β = 92.359(2)°



c = 15.7140(18) Å
γ = 99.810(2)°








Volume
1863.5(4) Å3


Z
2


Density (calculated)
1.402 Mg/m3


Absorption coefficient
3.165 mm−1


F(000)
808


Crystal size
0.12 × 0.12 × 0.05 mm3


Theta range for data collection
1.30 to 30.52°.


Index ranges
−13 <= h <= 13, −18 <=



k <= 18, −22 <= l <= 22


Reflections collected
82344


Independent reflections
11320 [R(int) = 0.0611]


Completeness to theta = 30.52°
99.2%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.8578 and 0.7026


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
11320/288/489


Goodness-of-fit on F2
1.028


Final R indices [I > 2sigma(I)]
R1 = 0.0255, wR2 = 0.0506


R indices (all data)
R1 = 0.0338, wR2 = 0.0531


Largest diff. peak and hole
0.775 and −0.795 e.Å−3
















TABLE 15





Crystal data and structure refinement for W(O)(CH2)(OHMT)2.
















Identification code
X8_12011


Empirical formula
C49 H53 O3 W


Formula weight
873.76


Temperature
100(2) K


Wavelength
0.71073 Å


Crystal system
Monoclinic


Space group
P2(1)/n









Unit cell dimensions
a = 15.1114(7) Å
α = 90°



b = 15.4585(7) Å
β = 96.5350(10)°



c = 17.5246(8) Å
γ = 90°








Volume
4067.1(3) Å3


Z
4


Density (calculated)
1.427 Mg/m3


Absorption coefficient
2.881 mm−1


F(000)
1780


Crystal size
0.04 × 0.01 × 0.01 mm3


Theta range for data collection
1.69 to 29.57°.


Index ranges
−20 <= h <= 20, −21 <=



k <= 21, −24 <= l <= 24


Reflections collected
91677


Independent reflections
11396 [R(int) = 0.0458]


Completeness to theta = 29.57°
100.0%


Absorption correction
Semi-empirical from equivalents


Max. and min. transmission
0.9718 and 0.9059


Refinement method
Full-matrix least-squares on F2


Data/restraints/parameters
11396/10/506


Goodness-of-fit on F2
1.210


Final R indices [I > 2sigma(I)]
R1 = 0.0409, wR2 = 0.0803


R indices (all data)
R1 = 0.0481, wR2 = 0.0824


Largest diff. peak and hole
2.698 and −1.329 e.Å−3









While several embodiments of the present invention have been described and illustrated herein, those of ordinary skill in the art will readily envision a variety of other means and/or structures for performing the functions and/or obtaining the results and/or one or more of the advantages described herein, and each of such variations and/or modifications is deemed to be within the scope of the present invention. More generally, those skilled in the art will readily appreciate that all parameters, dimensions, materials, and configurations described herein are meant to be exemplary and that the actual parameters, dimensions, materials, and/or configurations will depend upon the specific application or applications for which the teachings of the present invention is/are used. Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. It is, therefore, to be understood that the foregoing embodiments are presented by way of example only and that, within the scope of the appended claims and equivalents thereto, the invention may be practiced otherwise than as specifically described and claimed. The present invention is directed to each individual feature, system, article, material, kit, and/or method described herein. In addition, any combination of two or more such features, systems, articles, materials, kits, and/or methods, if such features, systems, articles, materials, kits, and/or methods are not mutually inconsistent, is included within the scope of the present invention.

## Claims

1. A method for performing an olefin metathesis reaction, comprising providing a compound of formula I-c:



wherein:
each of R1 and R2 is independently R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R;
R3′ is R3 or —OSi(R)3;
R3 is R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
R4 is halogen, R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur;

n is 0, 1, or 2;
each R5 is independently a monodentate ligand, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group; and
two or more of R1, R2, R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand;
wherein the compound is other than WO(CH-t-Bu)(O-2,6-Ph2C6H3)2(R5)n, WO(CH-t-Bu)(O-t-Bu)2(R5)n, W(O)(CHCMe3)(Me2Pyr)2(PMe2Ph)n, and
WO(CH—CH═C(Ph)2)(OC(CH3)(CF3)2)2(R5), wherein Me2Pyr is 2,5-dimethylpyrrolyl.

2. The method of claim 1, wherein:
R3′ is —OR or —OSi(R)3;
R4 is —N(R)2, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur.

3. The method of claim 1, wherein the compound of formula I-c promotes Z-selective olefin metathesis.

4. The method of claim 1, wherein R3′ is —OR, wherein R is optionally substituted phenyl.

5. The method of claim 4, wherein R3′ is

6. The method of claim 2, wherein R4 is —N(R)2, wherein the two R groups are taken together with the nitrogen to form an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-3 additional heteroatoms not including the N atom from —N(R)2 independently selected from nitrogen, oxygen, or sulfur.

7. The method of claim 6, wherein R4 is

8. The method of claim 2, wherein the compound of formula I-c is selected from:




W(O)(CH-t-Bu)(Ph2Pyr)(OHMT), W(O)(CH-t-Bu)(Ph2Pyr)(OHIPT), W(O)(CH-t-Bu)[N(C6F5)2](OHMT)(PPhMe2), W(O)(CH-t-Bu)[N—(C6F5)2](OHMT), W(O)(CH-t-Bu)(Me2Pyr)(DFTO)(PPhMe2), W(O)(CH-t-Bu)(Me2Pyr)(DFTO), W(O)(CHCMe2Ph)(Me2Pyr)(DFTO)(PPhMe2), W(O)(CHCMe2Ph)(Me2Pyr)(DFTO), and W(O)(CH-t-Bu)[N—(C6F5)2](DFTO).

9. The method of claim 1, wherein:
R3′ is —OR; and
R4 is —OR.

10. The method of claim 1, wherein:
R3′ is —OSi(R)3; and
R4 is —OR.

11. The method of claim 1, wherein the compound of formula I-c is W(O)(CH-t-Bu)(OHMT)2, W(O)(CH-t-Bu)(OHIPT)2, W(O)(CH-t-Bu)(DFTO)2, or WO(CH-t-Bu)[OSi(t-Bu)3](OHMT).

12. The method of claim 1, wherein n is 0.

13. The method of claim 1, further comprising providing Lewis acid.

14. The method of claim 1, wherein:
R3′ is R3;
R3 is —OR; and
R4 is —N(R)2.

15. The method of claim 1, wherein:
R3 is an optionally substituted group selected from:





and
R4 is —N(R)2, wherein the two R groups are taken together with the nitrogen to form an optionally substituted 3-8 membered saturated, partially unsaturated, or aryl ring having 0-3 additional heteroatoms not including the N atom from —N(R)2 independently selected from nitrogen, oxygen, or sulfur.

16. The method of claim 1, wherein R4 is optionally substituted pyrrolyl.

17. A method for performing an olefin metathesis reaction, comprising providing a compound of formula IX:



wherein R1′ and R2′ are taken together with W to form an optionally substituted 3-8 membered saturated or partially unsaturated ring having, in addition to the intervening metal atom, 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein both R1′ and R2′ are directly bonded to W through carbon atoms;
R3′ is R3 or —OSi(R)3;
each of R3 and R4 is independently halogen, R, —N(R)2, —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)2, —NRSO2R, —NRSO2N(R)2, —NROR, NR3, —OR, O(R)2, a phosphorus-containing ligand, or an optionally substituted group selected from a 5-6 membered monocyclic heteroaryl ring having at least one nitrogen and 0-3 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having at least one nitrogen and 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur;

n is 0, 1, or 2;
each R5 is independently a monodentate ligand, or two R5 are taken together with their intervening atoms to form an optionally substituted bidentate group; and
two or more of R1′, R2′, R3, R4 and R5 may be taken together with their intervening atoms to form an optionally substituted polydentate ligand; and
wherein the compound is other than





wherein —ORf6 is —OC(CH3)(CF3)2.

18. The method of claim 17, wherein R1′ and R2′ are taken together with W to form an optionally substituted 4-membered metallacyclobutane.

19. A method of preparing a compound of formula V-a:



comprising providing a compound of formula VI:




wherein:
n is 0, 1, or 2;
each of R1 and R2 is independently R, —OR, —SR, —N(R)2, —OC(O)R, —SOR, —SO2R, —SO2N(R)2, —C(O)N(R)2, —NRC(O)R, or —NRSO2R;
each of R5 and R8 is independently a monodentate ligand, or two R5 or two R8 are taken together with their intervening atoms to form an optionally substituted bidentate group;
each of R9 and R10 is independently halogen; and
each R is independently hydrogen or an optionally substituted group selected from C1-20 aliphatic, C1-20 heteroaliphatic having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, phenyl, ferrocene, a 3-7 membered saturated or partially unsaturated carbocyclic ring, an 8-10 membered bicyclic saturated, partially unsaturated or aryl ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-10 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or:
two or three R groups on the same nitrogen atom are taken together with the nitrogen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same nitrogen atom independently selected from nitrogen, oxygen, or sulfur; or:
two R groups on the same oxygen atom are taken together with the oxygen to form an optionally substituted 3-12 membered saturated, partially unsaturated, or aryl ring having 0-5 additional heteroatoms not including the same oxygen atom independently selected from nitrogen, oxygen, or sulfur.

20. The method of claim 19, wherein n is 2.