# Patent

## Title
Catalysts and methods for polymer synthesis

## Abstract

The present invention provides unimolecular metal complexes having increased activity in the copolymerization of carbon dioxide and epoxides. Also provided are methods of using such metal complexes in the synthesis of polymers. According to one aspect, the present invention provides metal complexes comprising an activating species with co-catalytic activity tethered to a multidentate ligand that is coordinated to the active metal center of the complex.

## Background
PRIORITY CLAIM
This application is a divisional of U.S. patent application Ser. No. 13/059,967, filed Feb. 18, 2011 now U.S. Pat. No. 8,633,123 which is a national phase application under 35 U.S.C. 371 of International PCT Application PCT/US09/54773, filed Aug. 24, 2009 which claims priority to U.S. Provisional Patent Application Ser. No. 61/091,013, filed Aug. 22, 2008; U.S. Provisional Patent Application Ser. No. 61/096,313, filed Sep. 11, 2008 and U.S. Provisional Patent Application Ser. No. 61/098,739, filed Sep. 19, 2008. The entire contents of each of these priority applications are incorporated herein by reference.


BACKGROUND
Catalysts capable of effecting the copolymerization of epoxides and carbon dioxide to form aliphatic polycarbonates (APCs) have been known in the art since the 1960s. The early catalysts were based on heterogeneous zinc compounds and suffered from low reactivity, a lack of selectivity for polymer formation vs. cyclic carbonate formation, and a tendency to produce polycarbonates contaminated with ether linkages.
Improved catalysts based on transition metals have been discovered over the past decade or so. These newer catalysts have increased reactivity and improved selectivity. Nevertheless, even using highly active catalysts such as those disclosed in U.S. Pat. No. 7,304,172, the reaction times required to make high molecular weight polymer are typically quite long. In addition, the best-performing catalysts disclosed in the '172 patent require the addition of a separate co-catalyst to achieve optimum activity.
Attempts to address these shortcomings have been made. Catalysts described by Nozaki and co-workers (Angew. Chem. Int. Ed. 2006, 45, 7274-7277) tether an amine co-catalyst to a ligand of the catalyst. These next-generation catalytic systems suffer from lengthy and complicated syntheses and undesirable induction times prior to onset of polymerization. There remains a need for catalysts that have increased activity that will further reduce the polymerization time required to produce high molecular weight APCs.
SUMMARY
The present invention provides, among other things, unimolecular catalyst systems having activity in the copolymerization of carbon dioxide and epoxides and methods of using the same. In some embodiments, the present invention provides metal complexes having an activating species with co-catalytic activity tethered to a multidentate ligand that is coordinated to an active metal center of a metal complex.
In certain embodiments, the present invention provides unimolecular metal complexes and methods for using the same in the copolymerization of carbon dioxide and epoxides. In some embodiments, provided metal complexes have the structure:




wherein:

    
    
        M is a metal atom;
    
    






comprises a multidentate ligand;

    
    
        (Z)m represents one or more activating moieties attached to the multidentate ligand, where  is a linker moiety covalently coupled to the ligand, each Z is an activating functional group; and m is an integer from 1 to 4 representing the number of Z groups present on an individual linker moiety.
    
    


In some embodiments, tethered activating functional groups (Z) are neutral nitrogen-containing moieties. In certain embodiments, neutral nitrogen-containing moieties are selected from the group consisting of:




or a combination of two or more of these,

wherein:

    
    
        each occurrence of R1, and R2 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein R1 and R2 groups can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more additional heteroatoms;
        each occurrence of R5 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein an R5 group can be taken with an R1 or R2 group to form one or more optionally substituted rings; and
        each occurrence of R7 is independently hydrogen, a hydroxyl protecting group, or an optionally substituted radical selected from the group consisting of C1-20 acyl; C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
    
    


In some embodiments, tethered activating functional groups (Z) are cationic moieties. In certain embodiments, cationic moieties are selected from the group consisting of:










or a combination of two or more of these,

wherein:

    
    
        each occurrence of R1, R2, and R3 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein any two or more R1, R2, and R3 groups can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more additional heteroatoms;
        R4 is hydrogen or —OR7;
        R4′ is hydrogen, hydroxyl, or optionally substituted C1-20 aliphatic;
        each occurrence of R5 and R6 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein R5 and R6 can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more heteroatoms, and an R5 or R6 group can be taken with an R1 or R2 group to form one or more optionally substituted rings;
        each occurrence of R7 is independently hydrogen, a hydroxyl protecting group, or an optionally substituted radical selected from the group consisting of C1-20 acyl; C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
        each occurrence of R8, R9, and R10 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein any two or more R8, R9 and R10 groups can be taken together with intervening atoms to form one or more optionally substituted rings;
        each occurrence of R11 is independently selected from the group consisting of: halogen, —NO2, —CN, —SRy, —S(O)Ry, —S(O)2Ry, —NRyC(O)Ry, —OC(O)Ry, —CO2Ry, —NCO, —N3, —OR7, —OC(O)N(Ry)2, —N(Ry)2, —NRyC(O)Ry, —NRyC(O)ORy; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; where each occurrence of Ry is independently —H, or an optionally substituted radical selected from the group consisting of C1-6 aliphatic, 3- to 7-membered heterocyclic, phenyl, and 8- to 10-membered aryl, and where two or more adjacent R11 groups can be taken together to form an optionally substituted saturated, partially unsaturated, or aromatic 5- to 12-membered ring containing 0 to 4 heteroatoms;
        X− is any anion, and
        Ring A is an optionally substituted, 5- to 10-membered heteroaryl group.
    
    


In some embodiments, an activating functional group (Z) is a phosphorous-containing functional group.
In certain embodiments, a phosphorous-containing functional group is chosen from the group consisting of: phosphines (—PRy2); Phosphine oxides —P(O)Ry2; phosphinites P(OR7)Ry2; phosphonites P(OR7)2Ry; phosphites P(OR7)3; phosphinates OP(OR7)Ry2; phosphonates; OP(OR7)2Ry; phosphates —OP(OR7)3; phosphonium salts ([—PRy3]+) where the phosphorous-containing functional group may be linked to a metal complex through any available position (e.g. direct linkage via the phosphorous atom, or in some cases via an oxygen atom).
In certain embodiments, a phosphorous-containing functional group is chosen from the group consisting of:




or a combination of two or more of these

    
    
        wherein R1 and R2, are as defined above; and
        each R7′ is independently hydrogen, a hydroxyl protecting group, or an optionally substituted radical selected from the group consisting of C1-20 acyl; C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and where two R7′ groups can be taken together with intervening atoms to form an optionally substituted ring optionally containing one or more heteroatoms, and an R7′ group can be taken with an R1 or R2 group to an optionally substituted ring;
    
    


In some embodiments, phosphorous containing functional groups include those disclosed in The Chemistry of Organophosphorus Compounds. Volume 4. Ter- and Quinquevalent Phosphorus Acids and their Derivatives. The Chemistry of Functional Group Series Edited by Frank R. Hartley (Cranfield University, Cranfield, U.K.). Wiley: New York. 1996. ISBN 0-471-95706-2, the entirety of which is hereby incorporated herein by reference.
In certain embodiments, a phosphorous-containing functional group has the structure

*—(X)b-[(R6R7R8P)+]nQn−, wherein:

    X is —O—, —N═, or —NRz—,
    b is 1 or 0,
    each of R6, R7 and R8 are independently present or absent and, if present, are independently selected from the group consisting of optionally substituted C1-C20 aliphatic, optionally substituted C6-C14 aryl, optionally substituted 3- to 14-membered heterocyclic, optionally substituted 5- to 14-membered heteroaryl, halogen, ═O, —ORz, ═NRz, and N(Rz)2 where Rz is hydrogen, or an optionally substituted C1-C20 aliphatic, optionally substituted 6- to 14-membered aryl, optionally substituted 3- to 14-membered heterocyclic, or optionally substituted 5- to 14-membered heteroaryl,
    Q is any anion, and
    n is an integer between 1 and 4.


In some embodiments, the present disclosure encompasses methods for the copolymerization of epoxides and carbon dioxide, such methods comprising contacting one or more epoxides with a catalyst described above in the presence of carbon dioxide.
In some embodiments, the present disclosure encompasses methods for the formation of cyclic carbonates from epoxides and carbon dioxide, such methods comprising contacting one or more epoxides with a catalyst described above in the presence of carbon dioxide.
In some embodiments, the present disclosure encompasses methods for the formation of polyethers, such methods comprising contacting one or more epoxides with a catalyst described above.
DEFINITIONS
Definitions of specific functional groups and chemical terms are described in more detail below. 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., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March's Advanced Organic Chemistry, 5th Edition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3rd Edition, Cambridge University Press, Cambridge, 1987; the entire contents of each of which are incorporated herein by reference.
Certain compounds of the present invention can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and/or diastereomers. Thus, inventive compounds and compositions thereof may be in the form of an individual enantiomer, diastereomer or geometric isomer, or may be in the form of a mixture of stereoisomers. In certain embodiments, the compounds of the invention are enantiopure compounds. In certain embodiments, mixtures of enantiomers or diastereomers are provided.
Furthermore, certain compounds, as described herein may have one or more double bonds that can exist as either a Z or E isomer, unless otherwise indicated. The invention additionally encompasses the compounds as individual isomers substantially free of other isomers and alternatively, as mixtures of various isomers, e.g., racemic mixtures of enantiomers. In addition to the above-mentioned compounds per se, this invention also encompasses compositions comprising one or more compounds.
As used herein, the term “isomers” includes any and all geometric isomers and stereoisomers. For example, “isomers” include cis- and trans-isomers, E- and Z-isomers, R- and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention. For instance, a compound may, in some embodiments, be provided substantially free of one or more corresponding stereoisomers, and may also be referred to as “stereochemically enriched.”
Where a particular enantiomer is preferred, it may, in some embodiments be provided substantially free of the opposite enantiomer, and may also be referred to as “optically enriched.” “Optically enriched,” as used herein, means that the compound is made up of a significantly greater proportion of one enantiomer. In certain embodiments the compound is made up of at least about 90% by weight of an enantiomer. In some embodiments the compound is made up of at least about 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9% by weight of an enantiomer. In some embodiments the enantiomeric excess of provided compounds is at least about 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%. In some embodiments, enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by asymmetric syntheses. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S. H., et al., Tetrahedron 33:2725 (1977); Eliel, E. L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, S. H. Tables of Resolving Agents and Optical Resolutions p. 268 (E. L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, Ind. 1972).
The terms “halo” and “halogen” as used herein refer to an atom selected from fluorine (fluoro, —F), chlorine (chloro, —Cl), bromine (bromo, —Br), and iodine (iodo, —I).
The term “aliphatic” or “aliphatic group”, as used herein, denotes a hydrocarbon moiety that may be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spiro-fused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1-30 carbon atoms. In certain embodiments, aliphatic groups contain 1-12 carbon atoms. In certain embodiments, aliphatic groups contain 1-8 carbon atoms. In certain embodiments, aliphatic groups contain 1-6 carbon atoms. In some embodiments, aliphatic groups contain 1-5 carbon atoms, in some embodiments, aliphatic groups contain 1-4 carbon atoms, in yet other embodiments aliphatic groups contain 1-3 carbon atoms, and in yet other embodiments aliphatic groups contain 1-2 carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl. In certain embodiments, the term aliphatic group encompasses aliphatic groups wherein one or more hydrogen atoms are replaced with a halogen atom. In certain embodiments, the term aliphatic group encompasses chlorinated or fluorinated aliphatic groups including perfluorinated compounds.
The term “epoxide”, as used herein, refers to a substituted or unsubstituted oxirane. Such substituted oxiranes include monosubstituted oxiranes, disubstituted oxiranes, trisubstituted oxiranes, and tetrasubstituted oxiranes. Such epoxides may be further optionally substituted as defined herein. In certain embodiments, epoxides comprise a single oxirane moiety. In certain embodiments, epoxides comprise two or more oxirane moieties.
The term “polymer”, as used herein, refers to a molecule of high relative molecular mass, the structure of which comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass. In certain embodiments, a polymer is comprised of only one monomer species (e.g., polyethylene oxide). In certain embodiments, a polymer of the present invention is a copolymer, terpolymer, heteropolymer, block copolymer, or tapered heteropolymer of one or more epoxides.
The term “unsaturated”, as used herein, means that a moiety has one or more double or triple bonds.
The terms “cycloaliphatic”, “carbocycle”, or “carbocyclic”, used alone or as part of a larger moiety, refer to a saturated or partially unsaturated cyclic aliphatic monocyclic, bicyclic, or polycyclic ring systems, as described herein, having from 3 to 12 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, and cyclooctadienyl. In some embodiments, the cycloalkyl has 3-6 carbons. The terms “cycloaliphatic”, “carbocycle” or “carbocyclic” 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 groups is bicyclic. In some embodiments, a carbocyclic group is tricyclic. In some embodiments, a carbocyclic group is polycyclic.
The term “alkyl,” as used herein, refers to saturated, straight- or branched-chain hydrocarbon radicals derived by removal of a single hydrogen atom from an aliphatic moiety. Unless otherwise specified, alkyl groups contain 1-12 carbon atoms. In certain embodiments, alkyl groups contain 1-8 carbon atoms. In certain embodiments, alkyl groups contain 1-6 carbon atoms. In some embodiments, alkyl groups contain 1-5 carbon atoms, in some embodiments, alkyl groups contain 1-4 carbon atoms, in yet other embodiments alkyl groups contain 1-3 carbon atoms, and in yet other embodiments alkyl groups contain 1-2 carbon atoms. Examples of alkyl radicals include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, sec-pentyl, iso-pentyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl, dodecyl, and the like.
The term “alkenyl,” as used herein, denotes a monovalent group derived by the removal of a single hydrogen atom from a straight- or branched-chain aliphatic moiety having at least one carbon-carbon double bond. Unless otherwise specified, alkenyl groups contain 2-12 carbon atoms. In certain embodiments, alkenyl groups contain 2-8 carbon atoms. In certain embodiments, alkenyl groups contain 2-6 carbon atoms. In some embodiments, alkenyl groups contain 2-5 carbon atoms, in some embodiments, alkenyl groups contain 2-4 carbon atoms, in yet other embodiments alkenyl groups contain 2-3 carbon atoms, and in yet other embodiments alkenyl groups contain 2 carbon atoms. Alkenyl groups include, for example, ethenyl, propenyl, allyl, 1,3-butadienyl, butenyl, 1-methyl-2-buten-1-yl, allyl, 1,3-butadienyl, allenyl, and the like.
The term “alkynyl,” as used herein, refers to a monovalent group derived by the removal of a single hydrogen atom from a straight- or branched-chain aliphatic moiety having at least one carbon-carbon triple bond. Unless otherwise specified, alkynyl groups contain 2-12 carbon atoms. In certain embodiments, alkynyl groups contain 2-8 carbon atoms. In certain embodiments, alkynyl groups contain 2-6 carbon atoms. In some embodiments, alkynyl groups contain 2-5 carbon atoms, in some embodiments, alkynyl groups contain 2-4 carbon atoms, in yet other embodiments alkynyl groups contain 2-3 carbon atoms, and in yet other embodiments alkynyl groups contain 2 carbon atoms. Representative alkynyl groups include, but are not limited to, ethynyl, 2-propynyl (propargyl), 1-propynyl, and the like.
The term “carbocycle” and “carbocyclic ring” as used herein, refer to monocyclic and polycyclic moieties wherein the rings contain only carbon atoms. Unless otherwise specified, carbocycles may be saturated, partially unsaturated or aromatic, and contain 3 to 20 carbon atoms. Representative carbocycles include cyclopropane, cyclobutane, cyclopentane, cyclohexane, bicyclo[2,2,1]heptane, norbornene, phenyl, cyclohexene, naphthalene, and spiro[4.5]decane, to name but a few.
The term “aryl” used alone or as part of a larger moiety as in “aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic and polycyclic ring systems having a total of six to 20 ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains three to twelve 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 is not limited to, phenyl, biphenyl, naphthyl, 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 additional rings, such as benzofuranyl, indanyl, phthalimidyl, naphthimidyl, phenantriidinyl, or tetrahydronaphthyl, and the like.
The term “heteroaliphatic,” as used herein, refers to aliphatic groups wherein one or more carbon atoms are independently replaced by one or more atoms selected from the group consisting of oxygen, sulfur, nitrogen, phosphorus, or boron. In certain embodiments, one to six carbon atoms are independently replaced by one or more of oxygen, sulfur, nitrogen, or phosphorus. Heteroaliphatic groups may be substituted or unsubstituted, branched or unbranched, cyclic or acyclic, and include saturated, unsaturated or partially unsaturated groups.
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 14 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 it 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, benzofuranyl and pteridinyl. 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 polycyclic. 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 7-14-membered bicyclic heterocyclic moiety that is saturated, partially unsaturated, or aromatic 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, tetrahydrothienyl, pyrrolidinyl, pyrrolidonyl, 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, where the radical or point of attachment is on the heterocyclyl ring. 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.
The term “acyl” as used herein refers to a group having a formula —C(O)R where R is hydrogen or an optionally substituted aliphatic, aryl, or heterocyclic group.
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.
One of ordinary skill in the art will appreciate that the synthetic methods, as described herein, utilize a variety of protecting groups. By the term “protecting group,” as used herein, it is meant that a particular functional moiety, e.g., O, S, or N, is masked or blocked, permitting, if desired, a reaction to be carried out selectively at another reactive site in a multifunctional compound. In preferred embodiments, a protecting group reacts selectively in good yield to give a protected substrate that is stable to the projected reactions; the protecting group is preferably selectively removable by readily available, preferably non-toxic reagents that do not attack the other functional groups; the protecting group forms a separable derivative (more preferably without the generation of new stereogenic centers); and the protecting group will preferably have a minimum of additional functionality to avoid further sites of reaction. As detailed herein, oxygen, sulfur, nitrogen, and carbon protecting groups may be utilized. By way of non-limiting example, hydroxyl protecting groups include methyl, methoxylmethyl (MOM), methylthiomethyl (MTM), t-butylthiomethyl, (phenyldimethylsilyl)methoxymethyl (SMOM), benzyloxymethyl (BOM), p-methoxybenzyloxymethyl (PMBM), (4-methoxyphenoxy)methyl (p-AOM), guaiacolmethyl (GUM), t-butoxymethyl, 4-pentenyloxymethyl (POM), siloxymethyl, 2-methoxyethoxymethyl (MEM), 2,2,2-trichloroethoxymethyl, bis(2-chloroethoxy)methyl, 2-(trimethylsilyl)ethoxymethyl (SEMOR), tetrahydropyranyl (THP), 3-bromotetrahydropyranyl, tetrahydrothiopyranyl, 1-methoxycyclohexyl, 4-methoxytetrahydropyranyl (MTHP), 4-methoxytetrahydrothiopyranyl, 4-methoxytetrahydrothiopyranyl S,S-dioxide, 1-[(2-chloro-4-methyl)phenyl]-4-methoxypiperidin-4-yl (CTMP), 1,4-dioxan-2-yl, tetrahydrofuranyl, tetrahydrothiofuranyl, 2,3,3a,4,5,6,7,7a-octahydro-7,8,8-trimethyl-4,7-methanobenzofuran-2-yl, 1-ethoxyethyl, 1-(2-chloroethoxy)ethyl, 1-methyl-1-methoxyethyl, 1-methyl-1-benzyloxyethyl, 1-methyl-1-benzyloxy-2-fluoroethyl, 2,2,2-trichloroethyl, 2-trimethylsilylethyl, 2-(phenylselenyl)ethyl, t-butyl, allyl, p-chlorophenyl, p-methoxyphenyl, 2,4-dinitrophenyl, benzyl, p-methoxybenzyl, 3,4-dimethoxybenzyl, o-nitrobenzyl, p-nitrobenzyl, p-halobenzyl, 2,6-dichlorobenzyl, p-cyanobenzyl, p-phenylbenzyl, 2-picolyl, 4-picolyl, 3-methyl-2-picolyl N-oxido, diphenylmethyl, p,p′-dinitrobenzhydryl, 5-dibenzosuberyl, triphenylmethyl, α-naphthyldiphenylmethyl, p-methoxyphenyldiphenylmethyl, di(p-methoxyphenyl)phenylmethyl, tri(p-methoxyphenyl)methyl, 4-(4′-bromophenacyloxyphenyl)diphenylmethyl, 4,4′,4′′-tris(4,5-dichlorophthalimidophenyl)methyl, 4,4′,4′′-tris(levulinoyloxyphenyl)methyl, 4,4′,4′′-tris(benzoyloxyphenyl)methyl, 3-(imidazol-1-yl)bis(4′,4′′-dimethoxyphenyl)methyl, 1,1-bis(4-methoxyphenyl)-1′-pyrenylmethyl, 9-anthryl, 9-(9-phenyl)xanthenyl, 9-(9-phenyl-10-oxo)anthryl, 1,3-benzodithiolan-2-yl, benzisothiazolyl S,S-dioxido, trimethylsilyl (TMS), triethylsilyl (TES), triisopropylsilyl (TIPS), dimethylisopropylsilyl (IPDMS), diethylisopropylsilyl (DEIPS), dimethylthexylsilyl, t-butyldimethylsilyl (TBDMS), t-butyldiphenylsilyl (TBDPS), tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl (DPMS), t-butylmethoxyphenylsilyl (TBMPS), formate, benzoylformate, acetate, chloroacetate, dichloroacetate, trichloroacetate, trifluoroacetate, methoxyacetate, triphenylmethoxyacetate, phenoxyacetate, p-chlorophenoxyacetate, 3-phenylpropionate, 4-oxopentanoate (levulinate), 4,4-(ethylenedithio)pentanoate (levulinoyldithioacetal), pivaloate, adamantoate, crotonate, 4-methoxycrotonate, benzoate, p-phenylbenzoate, 2,4,6-trimethylbenzoate (mesitoate), alkyl methyl carbonate, 9-fluorenylmethyl carbonate (Fmoc), alkyl ethyl carbonate, alkyl 2,2,2-trichloroethyl carbonate (Troc), 2-(trimethylsilyl)ethyl carbonate (TMSEC), 2-(phenylsulfonyl)ethyl carbonate (Psec), 2-(triphenylphosphonio) ethyl carbonate (Peoc), alkyl isobutyl carbonate, alkyl vinyl carbonate alkyl allyl carbonate, alkyl p-nitrophenyl carbonate, alkyl benzyl carbonate, alkyl p-methoxybenzyl carbonate, alkyl 3,4-dimethoxybenzyl carbonate, alkyl o-nitrobenzyl carbonate, alkyl p-nitrobenzyl carbonate, alkyl S-benzyl thiocarbonate, 4-ethoxy-1-napththyl carbonate, methyl dithiocarbonate, 2-iodobenzoate, 4-azidobutyrate, 4-nitro-4-methylpentanoate, o-(dibromomethyl)benzoate, 2-formylbenzenesulfonate, 2-(methylthiomethoxy)ethyl, 4-(methylthiomethoxy)butyrate, 2-(methylthiomethoxymethyl)benzoate, 2,6-dichloro-4-methylphenoxyacetate, 2,6-dichloro-4-(1,1,3,3-tetramethylbutyl)phenoxyacetate, 2,4-bis(1,1-dimethylpropyl)phenoxyacetate, chlorodiphenylacetate, isobutyrate, monosuccinoate, (E)-2-methyl-2-butenoate, o-(methoxycarbonyl)benzoate, α-naphthoate, nitrate, alkyl N,N,N′,N′-tetramethylphosphorodiamidate, alkyl N-phenylcarbamate, borate, dimethylphosphinothioyl, alkyl 2,4-dinitrophenylsulfenate, sulfate, methanesulfonate (mesylate), benzylsulfonate, and tosylate (Ts). For protecting 1,2- or 1,3-diols, the protecting groups include methylene acetal, ethylidene acetal, 1-t-butylethylidene ketal, 1-phenylethylidene ketal, (4-methoxyphenyl)ethylidene acetal, 2,2,2-trichloroethylidene acetal, acetonide, cyclopentylidene ketal, cyclohexylidene ketal, cycloheptylidene ketal, benzylidene acetal, p-methoxybenzylidene acetal, 2,4-dimethoxybenzylidene ketal, 3,4-dimethoxybenzylidene acetal, 2-nitrobenzylidene acetal, methoxymethylene acetal, ethoxymethylene acetal, dimethoxymethylene ortho ester, 1-methoxyethylidene ortho ester, 1-ethoxyethylidine ortho ester, 1,2-dimethoxyethylidene ortho ester, α-methoxybenzylidene ortho ester, 1-(N,N-dimethylamino)ethylidene derivative, α-(N,N′-dimethylamino)benzylidene derivative, 2-oxacyclopentylidene ortho ester, di-t-butylsilylene group (DTBS), 1,3-(1,1,3,3-tetraisopropyldisiloxanylidene) derivative (TIPDS), tetra-t-butoxydisiloxane-1,3-diylidene derivative (TBDS), cyclic carbonates, cyclic boronates, ethyl boronate, and phenyl boronate Amino-protecting groups include methyl carbamate, ethyl carbamante, 9-fluorenylmethyl carbamate (Fmoc), 9-(2-sulfo)fluorenylmethyl carbamate, 9-(2,7-dibromo)fluoroenylmethyl carbamate, 2,7-di-t-butyl-[9-(10,10-dioxo-10,10,10,10-tetrahydrothioxanthyl)]methyl carbamate (DBD-Tmoc), 4-methoxyphenacyl carbamate (Phenoc), 2,2,2-trichloroethyl carbamate (Troc), 2-trimethylsilylethyl carbamate (Teoc), 2-phenylethyl carbamate (hZ), 1-(1-adamantyl)-1-methylethyl carbamate (Adpoc), 1,1-dimethyl-2-haloethyl carbamate, 1,1-dimethyl-2,2-dibromoethyl carbamate (DB-t-BOC), 1,1-dimethyl-2,2,2-trichloroethyl carbamate (TCBOC), 1-methyl-1-(4-biphenylyl)ethyl carbamate (Bpoc), 1-(3,5-di-t-butylphenyl)-1-methylethyl carbamate (t-Bumeoc), 2-(2′- and 4′-pyridyl)ethyl carbamate (Pyoc), 2-(N,N-dicyclohexylcarboxamido)ethyl carbamate, t-butyl carbamate (BOC), 1-adamantyl carbamate (Adoc), vinyl carbamate (Voc), allyl carbamate (Alloc), 1-isopropylallyl carbamate (Ipaoc), cinnamyl carbamate (Coc), 4-nitrocinnamyl carbamate (Noc), 8-quinolyl carbamate, N-hydroxypiperidinyl carbamate, alkyldithio carbamate, benzyl carbamate (Cbz), p-methoxybenzyl carbamate (Moz), p-nitrobenzyl carbamate, p-bromobenzyl carbamate, p-chlorobenzyl carbamate, 2,4-dichlorobenzyl carbamate, 4-methylsulfinylbenzyl carbamate (Msz), 9-anthrylmethyl carbamate, diphenylmethyl carbamate, 2-methylthioethyl carbamate, 2-methylsulfonylethyl carbamate, 2-(p-toluenesulfonyl)ethyl carbamate, [2-(1,3-dithianyl)]methyl carbamate (Dmoc), 4-methylthiophenyl carbamate (Mtpc), 2,4-dimethylthiophenyl carbamate (Bmpc), 2-phosphonioethyl carbamate (Peoc), 2-triphenylphosphonioisopropyl carbamate (Ppoc), 1,1-dimethyl-2-cyanoethyl carbamate, m-chloro-p-acyloxybenzyl carbamate, p-(dihydroxyboryl)benzyl carbamate, 5-benzisoxazolylmethyl carbamate, 2-(trifluoromethyl)-6-chromonylmethyl carbamate (Tcroc), m-nitrophenyl carbamate, 3,5-dimethoxybenzyl carbamate, o-nitrobenzyl carbamate, 3,4-dimethoxy-6-nitrobenzyl carbamate, phenyl(o-nitrophenyl)methyl carbamate, phenothiazinyl-(10)-carbonyl derivative, N′-p-toluenesulfonylaminocarbonyl derivative, N′-phenylaminothiocarbonyl derivative, t-amyl carbamate, S-benzyl thiocarbamate, p-cyanobenzyl carbamate, cyclobutyl carbamate, cyclohexyl carbamate, cyclopentyl carbamate, cyclopropylmethyl carbamate, p-decyloxybenzyl carbamate, 2,2-dimethoxycarbonylvinyl carbamate, o-(N,N-dimethylcarboxamido)benzyl carbamate, 1,1-dimethyl-3-(N,N-dimethylcarboxamido)propyl carbamate, 1,1-dimethylpropynyl carbamate, di(2-pyridyl)methyl carbamate, 2-furanylmethyl carbamate, 2-iodoethyl carbamate, isoborynl carbamate, isobutyl carbamate, isonicotinyl carbamate, p-(p′-methoxyphenylazo)benzyl carbamate, 1-methylcyclobutyl carbamate, 1-methylcyclohexyl carbamate, 1-methyl-1-cyclopropylmethyl carbamate, 1-methyl-1-(3,5-dimethoxyphenyl)ethyl carbamate, 1-methyl-1-(p-phenylazophenyl)ethyl carbamate, 1-methyl-1-phenylethyl carbamate, 1-methyl-1-(4-pyridyl)ethyl carbamate, phenyl carbamate, p-(phenylazo)benzyl carbamate, 2,4,6-tri-t-butylphenyl carbamate, 4-(trimethylammonium)benzyl carbamate, 2,4,6-trimethylbenzyl carbamate, formamide, acetamide, chloroacetamide, trichloroacetamide, trifluoroacetamide, phenylacetamide, 3-phenylpropanamide, picolinamide, 3-pyridylcarboxamide, N-benzoylphenylalanyl derivative, benzamide, p-phenylbenzamide, o-nitophenylacetamide, o-nitrophenoxyacetamide, acetoacetamide, (N′-dithiobenzyloxycarbonylamino)acetamide, 3-(p-hydroxyphenyl)propanamide, 3-(o-nitrophenyl)propanamide, 2-methyl-2-(o-nitrophenoxy)propanamide, 2-methyl-2-(o-phenylazophenoxy)propanamide, 4-chlorobutanamide, 3-methyl-3-nitrobutanamide, o-nitrocinnamide, N-acetylmethionine derivative, o-nitrobenzamide, o-(benzoyloxymethyl)benzamide, 4,5-diphenyl-3-oxazolin-2-one, N-phthalimide, N-dithiasuccinimide (Dts), N-2,3-diphenylmaleimide, N-2,5-dimethylpyrrole, N-1,1,4,4-tetramethyldisilylazacyclopentane adduct (STABASE), 5-substituted 1,3-dimethyl-1,3,5-triazacyclohexan-2-one, 5-substituted 1,3-dibenzyl-1,3,5-triazacyclohexan-2-one, 1-substituted 3,5-dinitro-4-pyridone, N-methylamine, N-allylamine, N-[2-(trimethylsilyl)ethoxy]methylamine (SEM), N-3-acetoxypropylamine, N-(1-isopropyl-4-nitro-2-oxo-3-pyroolin-3-yl)amine, quaternary ammonium salts, N-benzylamine, N-di(4-methoxyphenyl)methylamine, N-5-dibenzosuberylamine, N-triphenylmethylamine (Tr), N-[(4-methoxyphenyl)diphenylmethyl]amine (MMTr), N-9-phenylfluorenylamine (PhF), N-2,7-dichloro-9-fluorenylmethyleneamine, N-ferrocenylmethylamino (Fcm), N-2-picolylamino N′-oxide, N-1,1-dimethylthiomethyleneamine, N-benzylideneamine, N-p-methoxybenzylideneamine, N-diphenylmethyleneamine, N-[(2-pyridyl)mesityl]methyleneamine, N—(N′,N′-dimethylaminomethylene)amine, N,N′-isopropylidenediamine, N-p-nitrobenzylideneamine, N-salicylideneamine, N-5-chlorosalicylideneamine, N-(5-chloro-2-hydroxyphenyl)phenylmethyleneamine, N-cyclohexylideneamine, N-(5,5-dimethyl-3-oxo-1-cyclohexenyl)amine, N-borane derivative, N-diphenylborinic acid derivative, N-[phenyl(pentacarbonylchromium- or tungsten)carbonyl]amine, N-copper chelate, N-zinc chelate, N-nitroamine, N-nitrosoamine, amine N-oxide, diphenylphosphinamide (Dpp), dimethylthiophosphinamide (Mpt), diphenylthiophosphinamide (Ppt), dialkyl phosphoramidates, dibenzyl phosphoramidate, diphenyl phosphoramidate, benzenesulfenamide, o-nitrobenzenesulfenamide (Nps), 2,4-dinitrobenzenesulfenamide, pentachlorobenzenesulfenamide, 2-nitro-4-methoxybenzenesulfenamide, triphenylmethylsulfenamide, 3-nitropyridinesulfenamide (Npys), p-toluenesulfonamide (Ts), benzenesulfonamide, 2,3,6-trimethyl-4-methoxybenzenesulfonamide (Mtr), 2,4,6-trimethoxybenzenesulfonamide (Mtb), 2,6-dimethyl-4-methoxybenzenesulfonamide (Pme), 2,3,5,6-tetramethyl-4-methoxybenzenesulfonamide (Mte), 4-methoxybenzenesulfonamide (Mbs), 2,4,6-trimethylbenzenesulfonamide (Mts), 2,6-dimethoxy-4-methylbenzenesulfonamide (iMds), 2,2,5,7,8-pentamethylchroman-6-sulfonamide (Pmc), methanesulfonamide (Ms), β-trimethylsilylethanesulfonamide (SES), 9-anthracenesulfonamide, 4-(4′,8′-dimethoxynaphthylmethyl)benzenesulfonamide (DNMBS), benzylsulfonamide, trifluoromethylsulfonamide, and phenacylsulfonamide. Exemplary protecting groups are detailed herein, however, it will be appreciated that the present invention is not intended to be limited to these protecting groups; rather, a variety of additional equivalent protecting groups can be readily identified using the above criteria and utilized in the method of the present invention. Additionally, a variety of protecting groups are described 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.
When substituents are described herein, the term “radical” or “optionally substituted radical” is sometimes used. In this context, “radical” means a moiety or functional group having an available position for attachment to the structure on which the substituent is bound. In general the point of attachment would bear a hydrogen atom if the substituent were an independent neutral molecule rather than a substituent. The terms “radical” or “optionally-substituted radical” in this context are thus interchangeable with “group” or “optionally-substituted group”.
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” or “optionally substituted radical” 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.
In some chemical structures herein, substituents are shown attached to a bond that crosses a bond in a ring of the depicted molecule. This convention indicates that one or more of the substituents may be attached to the ring at any available position (usually in place of a hydrogen atom of the parent structure). In cases where an atom of a ring so substituted has two substitutable positions, two groups may be present on the same ring atom. Unless otherwise indicated, when more than one substituent is present, each is defined independently of the others, and each may have a different structure. In cases where the substituent shown crossing a bond of the ring is —R, this has the same meaning as if the ring were said to be “optionally substituted” as described in the preceding paragraph.
Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; —(CH2)0-4Ro; —(CH2)0-4ORo; —O—(CH2)0-4C(O)ORo; —(CH2)0-4CH(ORo)2; —(CH2)0-4SRo; —(CH2)0-4Ph, which may be substituted with Ro; —(CH2)0-4O(CH2)0-1Ph which may be substituted with Ro; —CH═CHPh, which may be substituted with Ro; —NO2; —CN; —N3; —(CH2)0-4N(Ro)2; —(CH2)0-4N(RoC(O)Ro; —N(Ro)C(S)Ro; —(CH2)0-4N(Ro)C(O)NRo2; —N(Ro)C(S)NRo2; —(CH2)0-4N(RoC(O)ORo; —N(Ro)N(Ro)C(O)Ro; —N(Ro)N(Ro)C(O)NRo2; —N(Ro)N(Ro)C(O)ORo; —(CH2)0-4C(O)Ro; —C(S)Ro; —(CH2)0-4C(O)ORo; —(CH2)0-4C(O)N(Ro)2; —(CH2)0-4C(O)SRo; —(CH2)0-4C(O)OSiRo3; —(CH2)0-4OC(O)Ro; —OC(O)(CH2)0-4SR—, SC(S)SRo; —(CH2)0-4SC(O)Ro; —(CH2)0-4C(O)NRo2; —C(S)NRo2; —C(S)SRo; —SC(S)SRo, —(CH2)0-4OC(O)NRo2; —C(O)N(ORo)Ro; —C(O)C(O)Ro; —C(O)CH2C(O)Ro; —C(NORo)Ro; —(CH2)0-4SSRo; —(CH2)0-4S(O)2Ro; —(CH2)0-4S(O)2ORo; —(CH2)0-4OS(O)2Ro; —S(O)2NRo2; —(CH2)0-4S(O)Ro; —N(Ro)S(O)2NRo2; —N(Ro)S(O)2Ro; —N(ORo)Ro; —C(NH)NRo2; —P(O)2Ro; —P(O)Ro2; —OP(O)Ro2; —OP(O)(ORo)2; SiRo3; —(C1-4 straight or branched)alkylene)O—N(Ro)2; or —(C1-4 straight or branched) alkylene)C(O)O—N(Ro)2, wherein each Ro may be substituted as defined below and is independently hydrogen, C1-8 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, or, notwithstanding the definition above, two independent occurrences of Ro, taken together with intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or polycyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.
Suitable monovalent substituents on Ro (or the ring formed by taking two independent occurrences of Ro 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)0-4C(O)N(Ro)2; —(CH2)0-2SR., —(CH2)0-2SH, —(CH2)0-2NH2, —(CH2)0-2NHR., —(CH2)0-2NR.2, —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 Ro 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 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. A substitutable nitrogen may be substituted with three R† substituents to provide a charged ammonium moiety —N+(R†)3, wherein the ammonium moiety is further complexed with a suitable counterion.
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 “catalyst” refers to a substance the presence of which increases the rate and/or extent of a chemical reaction, while not being consumed or undergoing a permanent chemical change itself.
As used herein, the term “multidentate” refers to ligands having multiple sites capable of coordinating to a single metal center.
As used herein, the term “activating moiety” refers to a moiety comprising one or more activating functional groups. In certain embodiments, an activating moiety improves the catalytic activity of a metal complex. In some embodiments, such improved catalytic activity is characterized by higher conversion of starting materials compared to a metal complex lacking an activating moiety. In some embodiments, such improved catalytic activity is characterized by higher rate of conversion of starting materials compared to a metal complex lacking an activating moiety. In some embodiments, such improved catalytic activity is characterized by higher yield of product compared to a metal complex lacking an activating moiety.


DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS
The present invention provides, among other things, unimolecular metal complexes for the copolymerization of carbon dioxide and epoxides and methods of using the same. In certain embodiments, provided metal complexes contain a metal-ligand moiety tethered to one or more activating moieties. In some embodiments, an activating moiety comprises a linker and one or more activating functional groups. In some embodiments, provided metal complexes act as polymerization catalysts. In certain embodiments, at least one activating functional group present on the tethered moiety can act as a polymerization co-catalyst and thereby increase the rate of the copolymerization.
In certain embodiments, provided metal complexes include a metal atom coordinated to a multidentate ligand and at least one activating moiety tethered to the multidentate ligand. In certain embodiments, provided metal complexes have the structure:




wherein:

    
    
        M is a metal atom;
    
    






comprises a multidentate ligand;

    
    
        (Z)m represents one or more activating moieties attached to the multidentate ligand, where  is a linker moiety covalently coupled to the ligand, each Z is an activating functional group; and m is an integer from 1 to 4 representing the number of Z groups present on an individual linker moiety.
    
    


In certain embodiments, provided metal complexes include a metal atom coordinated to a multidentate ligand and at least one activating moiety tethered to the multidentate ligand. In some embodiments, there are 1 to 10 activating moieties (Z)m tethered to the multidentate ligand. In certain embodiments, there are 1 to 8 such activating moieties tethered to the multidentate ligand. In certain embodiments, there are 1 to 4 such activating moieties tethered to the multidentate ligand.
I. Activating Functional Groups
In some embodiments, an activating functional group is selected from the group consisting of neutral nitrogen-containing functional groups, cationic moieties, phosphorous-containing functional groups, and combinations of two or more of these.
I.a. Neutral Nitrogen-Containing Activating Groups
In some embodiments, one or more tethered activating functional groups on provided metal complexes are neutral nitrogen-containing moieties. In some embodiments, such moieties include one or more of the structures in Table Z-1:







TABLE Z-1













 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 















or a combination of two or more of these,

wherein:

    
    
        each occurrence of R1, and R2 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein two or more R1 and R2 groups can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more additional heteroatoms;
        each occurrence of R5 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein an R5 group can be taken with an R1 or R2 group to form one or more optionally substituted rings;
        each occurrence of R7 is independently hydrogen, a hydroxyl protecting group, or an optionally substituted radical selected from the group consisting of C1-20 acyl; C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
    
    


In some embodiments, an activating functional group is an N-linked amino group:




where R1 and R2 are as defined above.
In certain embodiments, R1 and R2 are both hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In specific embodiments, an N-linked amine activating functional group is selected from the group consisting of:










In some embodiments, one or more activating functional groups is an N-linked hydroxyl amine derivative:




wherein R1 and R7 are as defined above.
In certain embodiments, R7 is hydrogen. In some embodiments, R7 is an optionally substituted radical selected from the group consisting of C1-12 aliphatic, phenyl, 8- to 10-membered aryl, and 3- to 7-membered heterocyclic. In certain embodiments, R7 is a C1-12 aliphatic. In certain embodiments, R7 is a C1-6 aliphatic. In some embodiments, R7 is an optionally substituted 8- to 10-membered aryl group. In certain embodiments, R7 is an optionally substituted phenyl. In some embodiments, R7 is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl.
In certain embodiments, R1 is hydrogen. In some embodiments, R1 is an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In some embodiments, R1 is an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In some embodiments, R1 is an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, R1 is an optionally substituted C1-20 aliphatic. In certain embodiments, R1 is an optionally substituted C1-12 aliphatic. In some embodiments, R1 is an optionally substituted C1-6 aliphatic. In some embodiments, R1 is an optionally substituted C1-12 heteroaliphatic. In some embodiments, R1 is an optionally substituted 8- to 10-membered aryl. In certain embodiments, R1 is an optionally substituted phenyl. In some embodiments, R1 is an optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R1 is an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 is butyl. In some embodiments, R1 is isopropyl. In some embodiments, R1 is phenyl. In some embodiments, R1 is benzyl. In some embodiments, R1 is perfluoro. In some embodiments, R1 is —CF2CF3.
In certain embodiments, R1 and R7 are taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more additional heteroatoms.
In certain embodiments, one or more N-linked hydroxyl amine activating functional groups are selected from the group consisting of:




In some embodiments, an activating functional group in a provided metal complex is an amidine. In certain embodiments, such amidine activating functional groups are selected from:




where each occurrence of R1, R2 and R5 are as defined above.
In certain embodiments, each R1 and R2 is hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, each R1 and R2 is independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In some embodiments, each R1 and R2 is independently an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In certain embodiments, R5 is H. In certain embodiments, R5 is optionally substituted C1-20 aliphatic. In some embodiments, R5 is optionally substituted 6- to 14-membered aryl. In certain embodiments, R5 is optionally substituted C1-12 aliphatic. In some embodiments, R5 is optionally substituted C1-6 aliphatic. In certain embodiments, R5 is optionally substituted phenyl.
In some embodiments, one or more R1 or R2 groups are taken together with R5 and intervening atoms to form an optionally substituted ring. In certain embodiments, R1 and R5 are taken together to form an optionally substituted 5- or 6-membered ring. In some embodiments, R2 and R5 are taken together to form an optionally substituted 5- or 6-membered ring optionally containing one or more additional heteroatoms. In some embodiments, R1, R2 and R5 are taken together to form an optionally substituted fused ring system. In some embodiments such rings formed by combinations of any of R1, R2 and R5 are partially unsaturated or aromatic.
In certain embodiments, an activating functional group is an N-linked amidine:




In certain embodiments, N-linked amidine groups are selected from the group consisting of:





In certain embodiments, activating functional groups are amidine moieties linked through the imine nitrogen:




In certain embodiments, imine-linked amidine activating functional groups are selected from the group consisting of:







In certain embodiments, activating functional groups are amidine moieties linked through a carbon atom:




In certain embodiments, carbon-linked amidine activating groups are selected from the group consisting of:








In some embodiments, one or more activating functional groups is a carbamate. In certain embodiments, a carbamate is N-linked:




where R1 and R2 are as defined above. In some embodiments, a carbamate is O-linked:





where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are both hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In some embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle. In some embodiments, R2 is selected from the group consisting of: methyl, t-butyl, t-amyl, benzyl, adamantyl, allyl, 4-methoxycarbonylphenyl, 2-(methylsulfonyl)ethyl, 2-(4-biphenylyl)-prop-2-yl, 2-(trimethylsilyl)ethyl, 2-bromoethyl, and 9-fluorenylmethyl.
In some embodiments, an activating functional group is a guanidine or bis-guanidine group:




    
    
        where each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein any two or more R1, R1′, R2, R2′, R2′′, R3, and R3′ groups can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more additional heteroatoms;
    
    


In certain embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is hydrogen. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; 3- to 7-membered heterocyclic, phenyl, and 8- to 10-membered aryl. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is hydrogen or an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In certain embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic, phenyl, and 8- to 10-membered aryl. In certain embodiments, each occurrence of R1 and R2 is independently an optionally hydrogen or an optionally substituted C1-8 aliphatic, phenyl, or 8- to 10-membered aryl group. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen or an optionally substituted C1-20 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently hydrogen an optionally substituted aryl group or an optionally substituted C1-8 aliphatic group. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen or an optionally substituted C1-6 aliphatic group. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen or an optionally substituted C1-4 aliphatic group. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1, R1′, R2, R2′, R2′′, R3, and R3′ are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1, R1′, R2, R2′, R2′′, R3, and R3′ are each independently optionally substituted C1-6 aliphatic. In some embodiments, one or more occurrence of R1′, R2, R2′, R2′′, R3, and R3′ is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, one or more occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen or an optionally substituted phenyl or 8- to 10-membered aryl. In some embodiments, one or more occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen, or an optionally substituted 5- to 10-membered heteroaryl.
In some embodiments, R1 is optionally substituted C1-6 aliphatic. In certain embodiments, R1′ is optionally substituted C1-6 aliphatic. In certain embodiments, R2 is optionally substituted C1-6 aliphatic. In certain embodiments, R2′ is optionally substituted C1-6 aliphatic. In certain embodiments, R2′′ is optionally substituted C1-6 aliphatic. In certain embodiments, R3 is optionally substituted C1-6 aliphatic. In certain embodiments, R3′ is optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1, R1′, R2, R2′, R2′′, R3, and R3′ is independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In certain embodiments, R1, R1′, R2, R2′, R2′′, R3, and R3′ are each methyl or ethyl. In some embodiments, one or more R1, R1′, R2, R2′, R2′′, R3, and R3′ is perfluoro.
In some embodiments, any two or more R1, R1′, R2, R2′, R2′′, R3, and R3′ groups are taken together with intervening atoms to form one or more optionally substituted rings.
In certain embodiments, R1 and R2 are taken together with intervening atoms to form an optionally substituted ring optionally containing one or more additional heteroatoms. In some embodiments, R2 and R2′ are taken together with intervening atoms to form an optionally substituted ring optionally containing one or more additional heteroatoms. In certain embodiments, R1 and R3 are taken together with intervening atoms to form an optionally substituted ring optionally containing one or more additional heteroatoms. In some embodiments, [R2 and R2′] and [R1 and R3] are taken together with intervening atoms to form an optionally substituted ring optionally containing one or more additional heteroatoms. In some embodiments, three or more R1, R1′, R2, R2′, R2′′, R3, and R3′ groups are taken together with any intervening atoms to form optionally substituted rings. In certain embodiments, R1 and R2 groups are taken together to form an optionally substituted 5- or 6-membered ring. In some embodiments, three or more R1 and/or R2 groups are taken together to form an optionally substituted fused ring system.
In certain embodiments where an activating functional group is a guanidine or bis guanidine moiety, it is chosen from the group consisting of:










In some embodiments, an activating functional group is a urea:




where R1, and R2 are as defined above.

In certain embodiments, R1 and R2 are each hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In certain embodiments, activating functional groups are oxime or hydrazone groups:




where R1, R2, R5, and R7 are as defined above.
In certain embodiments, R1 and R2 are both hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In certain embodiments, R5 is H. In certain embodiments, R5 is optionally substituted C1-20 aliphatic, and in some embodiments R5 is optionally substituted 6- to 14-membered aryl. In certain embodiments, R5 is optionally substituted C1-12 aliphatic and in some embodiments, optionally substituted C1-6 aliphatic. In certain embodiments, R5 is optionally substituted phenyl.
In some embodiments, one or more R1 or R2 groups are taken together with R5 and intervening atoms to form an optionally substituted ring. In certain embodiments, R1 and R5 are taken together to form an optionally substituted 5- or 6-membered ring. In some embodiments, R2 and R5 are taken together to form an optionally substituted 5- or 6-membered ring optionally containing one or more additional heteroatoms. In some embodiments, R1, R2 and R5 are taken together to form an optionally substituted fused ring system. In some embodiments such rings formed by combinations of any of R1, R2 and R5 are partially unsaturated or aromatic.
In certain embodiments, R7 is —H. In certain embodiments, R7 is optionally substituted C1-20 aliphatic, while in some embodiments R5 is optionally substituted 6- to 14-membered aryl. In certain embodiments, R7 is optionally substituted C1-12 aliphatic or in some embodiments, optionally substituted C1-6 aliphatic. In certain embodiments, R7 is optionally substituted C1-12 acyl or in some embodiments, optionally substituted C1-6 acyl. In certain embodiments, R7 is optionally substituted phenyl. In some embodiments, R7 is a hydroxyl protecting group. In some embodiments, R7 is a silyl protecting group.
In some embodiments, an activating functional group is an N-oxide derivative:




where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are both hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, or 8- to 10-membered aryl and 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In specific embodiments, an N-oxide activating functional group is selected from the group consisting of:







I.b. Cationic Activating Groups

In some embodiments, one or more tethered activating functional groups on provided metal complexes are cationic moieties include cationic moieties. In some embodiments, such moieties include one or more of the structures in Table Z-2:







TABLE Z-2













 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 















or a combination of two or more of these,

wherein:

    
    
        each occurrence of R1, R2, and R3 is as previously defined;
        R4′ is hydrogen, hydroxyl, optionally substituted C1-20 aliphatic;
        each occurrence of R5 and R6 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein R5 and R6 can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more heteroatoms, and an R5 or R6 group can be taken with an R1 or R2 group to form one or more optionally substituted rings;
        each occurrence of R8, R9, and R10 is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein any two or more R8, R9 and R10 groups can be taken together with intervening atoms to form one or more optionally substituted rings;
        each occurrence of R11 is independently selected from the group consisting of: halogen, —NO2, —CN, —SRy, —S(O)Ry, —S(O)2Ry, —NRyC(O)Ry, —OC(O)Ry, —CO2Ry, —NCO, —N3, —OR7, —OC(O)N(Ry)2, —N(Ry)2, —NRyC(O)Ry, —NRyC(O)ORy; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, where each occurrence of Ry is independently hydrogen or an optionally substituted C1-6 aliphatic group, and where two or more adjacent R11 groups can be taken together to form an optionally substituted saturated, partially unsaturated, or aromatic 5- to 12-membered ring containing 0 to 4 heteroatoms;
        X− is any anion, and
        Ring A is an optionally substituted, 5- to 10-membered heteroaryl group.
    
    


In certain embodiments, a cationic activating functional group is a protonated amine:




where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are both hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, or 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In specific embodiments, a protonated amine activating functional group is selected from the group consisting of:







In certain embodiments, an activating functional group is a guanidinium group:




In some embodiments, each of R4, R5, R6, R7, and R8 is hydrogen. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or C1-20 aliphatic. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or C1-12 aliphatic. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or C1-20 heteroaliphatic. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or phenyl. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or 8- to 10-membered aryl. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or 5- to 10-membered heteroaryl. In some embodiments, each occurrence of R4, R5, R6, R7, and R8 is independently hydrogen or 3- to 7-membered heterocyclic. In some embodiments, one or more of R4, R5, R6, and R7 is optionally substituted C1-12 aliphatic. In certain embodiments, any of (R4 and R5), (R5 and R6), (R6 and R7), (R7 and R8), and (R4 and R7) can be taken together with intervening atoms to form one or more optionally substituted rings. In some embodiments, (R4 and R5) and (R6 and R7) are taken together to form rings.

It will be appreciated that when a guanidinium cation is depicted as




all such resonance forms are contemplated and encompassed by the present disclosure. For example, such groups can also be depicted as





In specific embodiments, a guanidinium activating functional group is selected from the group consisting of:




In some embodiments, an activating functional group is a sulfonium group or an arsonium group:




where R8, R9, and R10 are as defined above.

In certain embodiments, each occurrence of R8, R9, and R10 is independently optionally substituted C1-20 aliphatic. In some embodiments, each occurrence of R8, R9, and R10 is independently hydrogen or optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R9, R10, and R11 is independently hydrogen or optionally substituted phenyl. In some embodiments, each occurrence of R9, R10, and R11 is independently hydrogen or optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R8, R9, and R10 is independently hydrogen or optionally substituted 5- to 10-membered heteroaryl. In some embodiments, each occurrence of R9, R10, and R11 is independently hydrogen or optionally substituted 3- to 7-membered heterocyclic. In some embodiments, R8 and R9 are taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted 3- to 14-membered heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl.
In certain embodiments, R8, R9 and R10 are each methyl. In certain embodiments, R8, R9 and R10 are each phenyl.
In specific embodiments, an arsonium activating functional group is selected from the group consisting of:




In some embodiments, an activating functional group is an optionally substituted nitrogen-containing heterocycle. In certain embodiments, the nitrogen-containing heterocycle is an aromatic heterocycle. In certain embodiments, the optionally substituted nitrogen-containing heterocycle is selected from the group consisting of: pyridine, imidazole, pyrrolidine, pyrazole, quinoline, thiazole, dithiazole, oxazole, triazole, pyrazolem, isoxazole, isothiazole, tetrazole, pyrazine, thiazine, and triazine.
In some embodiments, a nitrogen-containing heterocycle includes a quaternarized nitrogen atom. In certain embodiments, a nitrogen-containing heterocycle includes an iminium moiety such as




In certain embodiments, the optionally substituted nitrogen-containing heterocycle is selected from the group consisting of pyridinium, imidazolium, pyrrolidinium, pyrazolium, quinolinium, thiazolium, dithiazolium, oxazolium, triazolium, isoxazolium, isothiazolium, tetrazolium, pyrazinium, thiazinium, and triazinium.

In certain embodiments, a nitrogen-containing heterocycle is linked to a metal complex via a ring nitrogen atom. In some embodiments, a ring nitrogen to which the attachment is made is thereby quaternized, and in some embodiments, linkage to a metal complex takes the place of an N—H bond and the nitrogen atom thereby remains neutral. In certain embodiments, an optionally substituted N-linked nitrogen-containing heterocycle is a pyridinium derivative. In certain embodiments, optionally substituted N-linked nitrogen-containing heterocycle is an imidazolium derivative. In certain embodiments, optionally substituted N-linked nitrogen-containing heterocycle is a thiazolium derivative. In certain embodiments, optionally substituted N-linked nitrogen-containing heterocycle is a pyridinium derivative.
In some embodiments, an activating functional group is




In certain embodiments, ring A is an optionally substituted, 5- to 10-membered heteroaryl group. In some embodiments, Ring A is an optionally substituted, 6-membered heteroaryl group. In some embodiments, Ring A is a ring of a fused heterocycle. In some embodiments, Ring A is an optionally substituted pyridyl group.

In some embodiments, R12 is hydrogen. In some embodiments, R12 is an optionally substituted C1-20 aliphatic group. In some embodiments, R12 is C1-20 heteroaliphatic. In some embodiments, R12 is optionally substituted phenyl, 8- to 10-membered aryl; 5- to 10-membered heteroaryl. In some embodiments, R12 is 3- to 7-membered heterocyclic. In some embodiments, R12 is an optionally substituted C1-12 aliphatic group. In some embodiments, R12 is neopentyl. In some embodiments, R12 is oxide or hydroxyl.
In some embodiments, when Z is




ring A is other than an imidazole, an oxazole, or a thiazole.

In specific embodiments, a nitrogen-containing heterocycle activating functional group is selected from the group consisting of:







In some embodiments, an activating functional group is




where R1, R2 and R5 are as defined above.

In certain embodiments, R1 and R2 are each hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, 5- to 14-membered heteroaryl, phenyl, 8- to 10-membered aryl and 3- to 7-membered heterocyclic. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In certain embodiments, R5 is H. In certain embodiments, R5 is optionally substituted C1-20 aliphatic, and in some embodiments R5 is optionally substituted 6- to 14-membered aryl. In certain embodiments, R5 is optionally substituted C1-12 aliphatic and in some embodiments, optionally substituted C1-6 aliphatic. In certain embodiments, R5 is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R5 is perfluoro. In some embodiments, R5 is —CF2CF3. In certain embodiments, R5 is optionally substituted phenyl.
In some embodiments, one or more R1 or R2 groups are taken together with R5 and intervening atoms to form an optionally substituted ring. In certain embodiments, R1 and R5 are taken together to form an optionally substituted 5- or 6-membered ring. In some embodiments, R2 and R5 are taken together to form an optionally substituted 5- or 6-membered ring optionally containing one or more additional heteroatoms. In some embodiments, R1, R2 and R5 are taken together to form an optionally substituted fused ring system. In some embodiments such rings formed by combinations of any of R1, R2 and R5 are partially unsaturated or aromatic.
In some embodiments, an activating functional group is




where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In some embodiments, R1 and R2 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R1 and R2 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In some embodiments, each occurrence of R1 and R2 is independently perfluoro. In some embodiments, each occurrence of R1 and R2 is independently —CF2CF3.
In some embodiments, an activating functional group is




where R1, R2, R3, and R5 are as defined above.

In certain embodiments, R1, R2, and R3 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In certain embodiments, R1, R2, and R3 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In certain embodiments, R1, R2, and R3 are each independently an optionally substituted C1-6 aliphatic. In certain embodiments, R1, R2, and R3 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In certain embodiments, R1, R2, and R3 are each independently perfluoro. In some embodiments, R1, R2, and R3 are each independently —CF2CF3.
In certain embodiments, R5 is hydrogen. In certain embodiments R5 is an optionally substituted group selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, R5 is an optionally substituted C1-12 aliphatic. In some embodiments, R5 is optionally substituted C1-6 aliphatic.
In some embodiments, an activating functional group is




In certain embodiments, R1 and R2 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In some embodiments, R1 and R2 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R1 and R2 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In some embodiments, each occurrence of R1 and R2 is independently perfluoro. In some embodiments, each occurrence of R1 and R2 is independently —CF2CF3.

In certain embodiments, R5 and R6 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl, and 8-10-membered aryl. In some embodiments, R5 and R6 are each independently an optionally substituted C1-20 aliphatic. In some embodiments, R5 and R6 are each independently an optionally substituted C1-20 heteroaliphatic having. In some embodiments, R5 and R6 are each independently an optionally substituted phenyl or 8-10-membered aryl. In some embodiments, R5 and R6 are each independently an optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R3 and R4 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R5 and R6 are each independently an optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R5 and R6 is independently methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In some embodiments, each occurrence of R5 and R6 is independently perfluoro. In some embodiments, each occurrence of R5 and R6 is independently —CF2CF3.
In some embodiments, an activating functional group is




where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are each hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl or 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In some embodiments, an activating functional group is




In certain embodiments, R1, R2, and R3 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In certain embodiments, R1, R2, and R3 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In certain embodiments, R1, R2, and R3 are each independently an optionally substituted C1-6 aliphatic. In certain embodiments, R1, R2, and R3 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In certain embodiments, R1, R2, and R3 are each independently perfluoro. In some embodiments, R1, R2, and R3 are each independently —CF2CF3.

In some embodiments, an activating functional group is




where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are each hydrogen. In some embodiments, only one of R1 and R2 is hydrogen. In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic, phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
In certain embodiments, R1 and R2 are each independently an optionally substituted radical selected from the group consisting of C1-12 aliphatic and C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-12 aliphatic. In some embodiments, R1 and R2 are each independently optionally substituted C1-6 aliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-20 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted C1-12 heteroaliphatic. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 8- to 10-membered aryl. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted phenyl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 5- to 10-membered heteroaryl group. In some embodiments, each occurrence of R1 and R2 is independently an optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, R1 and R2 are each independently hydrogen, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, optionally substituted phenyl, or optionally substituted benzyl. In certain embodiments, R1 and R2 are both methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, phenyl or benzyl. In some embodiments, R1 and R2 are each butyl. In some embodiments, R1 and R2 are each isopropyl. In some embodiments, R1 and R2 are perfluoro. In some embodiments, R1 and R2 are —CF2CF3. In some embodiments, R1 and R2 are each phenyl. In some embodiments, R1 and R2 are each benzyl.
In some embodiments, R1 and R2 are taken together with intervening atoms to form one or more optionally substituted rings. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —C(Ry)2—, —C(Ry)2C(Ry)2—, —C(Ry)2C(Ry)2C(Ry)2—, —C(Ry)2OC(Ry)2—, and —C(Ry)2NRyC(Ry)2—. In certain embodiments, R1 and R2 are taken together to form a ring fragment selected from the group consisting of: —CH2—, —CH2CH2—, —CH2CH2CH2—, —CH2OCH2—, and —CH2NRyCH2—. In some embodiments, R1 and R2 are taken together to form an unsaturated linker moiety optionally containing one or more additional heteroatoms. In some embodiments, the resulting nitrogen-containing ring is partially unsaturated. In certain embodiments, the resulting nitrogen-containing ring comprises a fused polycyclic heterocycle.
In some embodiments, an activating functional group is




In certain embodiments, R1 and R2 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In some embodiments, R1 and R2 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R1 and R2 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In some embodiments, each occurrence of R1 and R2 is independently perfluoro. In some embodiments, each occurrence of R1 and R2 is independently —CF2CF3.

In some embodiments, an activating functional group is




In certain embodiments, R1, R2, and R3 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In certain embodiments, R1, R2, and R3 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In certain embodiments, R1, R2, and R3 are each independently an optionally substituted C1-6 aliphatic. In certain embodiments, R1, R2, and R3 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In certain embodiments, R1, R2, and R3 are each independently perfluoro. In some embodiments, R1, R2, and R3 are each independently —CF2CF3.

In some embodiments, an activating functional group is




where R1 and R2 are as defined above.

In certain embodiments, R1 and R2 are each independently an optionally substituted group selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; and 8-10-membered aryl. In some embodiments, R1 and R2 are each independently an optionally substituted 4-7-membered heterocyclic. In some embodiments, R1 and R2 can be taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted C3-C14 heterocycle, optionally substituted C6-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl. In some embodiments, R1 and R2 are each independently selected from the group consisting of methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, or benzyl. In some embodiments, each occurrence of R1 and R2 is independently perfluoro. In some embodiments, each occurrence of R1 and R2 is independently —CF2CF3.
In certain embodiments, X is any anion. In certain embodiments, X is a nucleophile. In some embodiments, X is a nucleophile capable of ring opening an epoxide. In certain embodiments, X is absent. In certain embodiments, X is a nucleophilic ligand. Exemplary nucleophilic ligands include, but are not limited to, —ORx, —SRx, —O(C═O)Rx, —O(C═O)ORx, —O(C═O)N(Rx)2, —N(Rx)(C═O)Rx, —NC, —CN, halo (e.g., —Br, —I, —Cl), —N3, —O(SO2)Rx and —OPRx3, wherein each Rx is, independently, selected from hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl and optionally substituted heteroaryl.
In certain embodiments, X is —O(C═O)Rx, wherein Rx is selected from optionally substituted aliphatic, fluorinated aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, fluorinated aryl, and optionally substituted heteroaryl.
For example, in certain embodiments, X is —O(C═O)Rx, wherein Rx is optionally substituted aliphatic. In certain embodiments, X is —O(C═O)Rx, wherein Rx is optionally substituted alkyl and fluoroalkyl. In certain embodiments, X is —O(C═O)CH3 or —O(C═O)CF3.
Furthermore, in certain embodiments, X is —O(C═O)Rx, wherein Rx is optionally substituted aryl, fluoroaryl, or heteroaryl. In certain embodiments, X is —O(C═O)Rx, wherein Rx is optionally substituted aryl. In certain embodiments, X is —O(C═O)Rx, wherein Rx is optionally substituted phenyl. In certain embodiments, X is —O(C═O)C6H5 or —O(C═O)C6F5.
In certain embodiments, X is —ORx, wherein Rx is selected from optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, and optionally substituted heteroaryl.
For example, in certain embodiments, X is —ORx, wherein Rx is optionally substituted aryl. In certain embodiments, X is —ORx, wherein Rx is optionally substituted phenyl. In certain embodiments, X is —OC6H5 or —OC6H2(2,4-NO2).
In certain embodiments, X is halo. In certain embodiments, X is —Br. In certain embodiments, X is —Cl. In certain embodiments, X is —I.
In certain embodiments, X is —O(SO2)Rx. In certain embodiments X is —OTs. In certain embodiments X is —OSO2Me. In certain embodiments X is —OSO2CF3. In some embodiments, X is a 2,4-dinitrophenolate anion.
I.c. Phosphorous-Containing Activating Groups
In some embodiments, activating functional groups Z are phosphorous containing groups.
In certain embodiments, a phosphorous-containing functional group is chosen from the group consisting of: phosphines (—PRy2); Phosphine oxides —P(O)Ry2; phosphinites P(OR7)Ry2; phosphonites P(OR7)2Ry; phosphites P(OR7)3; phosphinates OP(OR7)Ry2; phosphonates; OP(OR7)2Ry; phosphates —OP(OR7)3; phosphonium salts ([—PRy3]+) where a phosphorous-containing functional group may be linked to a metal complex through any available position (e.g. direct linkage via the phosphorous atom, or in some cases via an oxygen atom).
In certain embodiments, a phosphorous-containing functional group is chosen from the group consisting of:




or a combination of two or more of these

    
    
        wherein R1 and R2, are as defined above; and
        each R7′, is independently hydrogen, a hydroxyl protecting group, or an optionally substituted radical selected from the group consisting of C1-20 acyl; C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and where two R7′ groups can be taken together with intervening atoms to form an optionally substituted ring optionally containing one or more heteroatoms, and an R7 group can be taken with an R1 or R2 group to an optionally substituted ring;
    
    


In some embodiments, phosphorous containing functional groups include those disclosed in The Chemistry of Organophosphorus Compounds. Volume 4. Ter- and Quinquevalent Phosphorus Acids and their Derivatives. The Chemistry of Functional Group Series Edited by Frank R. Hartley (Cranfield University, Cranfield, U.K.). Wiley: New York. 1996. ISBN 0-471-95706-2, the entirety of which is hereby incorporated herein by reference.

*—(X)b-[(R6R7R8P)+]nQn−, wherein:

    X is —O—, —N═, or —NRz—,
    b is 1 or 0,
    each of R6, R7 and R8 are independently present or absent and, if present, are independently selected from the group consisting of optionally substituted C1-C20 aliphatic, optionally substituted phenyl, optionally substituted C8-C14 aryl, optionally substituted 3- to 14-membered heterocyclic, optionally substituted 5- to 14-membered heteroaryl, halogen, ═O, —ORz, ═NRz, and N(Rz)2 where Rz is hydrogen, or an optionally substituted C1-C20 aliphatic, optionally substituted phenyl, optionally substituted 8- to 14-membered aryl, optionally substituted 3- to 14-membered heterocyclic, or optionally substituted 5- to 14-membered heteroaryl,
    Q is any anion, and
    n is an integer between 1 and 4.


In some embodiments, an activating functional group is a phosphonate group:




wherein R1, R2, and R7′ is as defined above.

In specific embodiments, a phosphonate activating functional group is selected from the group consisting of:




In some embodiments, an activating functional group is a phosphonic diamide group:




wherein R1, R2, and R7′ are as defined above. In certain embodiments, each R1 and R2 group in a phosphonic diamide is methyl.

In some embodiments, an activating functional group is a phosphine group:




wherein R1, and R2 are as defined above.

In specific embodiments, a phosphine activating functional group is selected from the group consisting of:




II. Linker Moieties

As described above, each activating moiety (Z)m comprises a linker “” coupled to at least one activating functional group Z as described above, with m denoting the number of activating functional groups present on a single linker moiety.
As noted above there may be one or more activating moiety (Z)m tethered to a given metal complex, similarly, each activating moiety itself may contain more than one activating functional group Z. In certain embodiments, each activating moiety contains only one activating functional group (i.e. m=1). In some embodiments, each activating moiety contains more than one activating functional groups (i.e. m>1). In certain embodiments, an activating moiety contains two activating functional groups (i.e. m=2). In certain embodiments, an activating moiety contains three activating functional groups (i.e. m=3). In certain embodiments, an activating moiety contains four activating functional groups (i.e. m=4). In certain embodiments where more than one activating functional group is present on an activating moiety, they are all the same functional group. In some embodiments where more than one activating functional group is present on an activating moiety, two or more of the activating functional groups are different.
In certain embodiments, each linker moiety  contains 1-30 atoms including at least one carbon atom, and optionally one or more atoms selected from the group consisting of N, O, S, Si, B, and P.
In certain embodiments, the linker is an optionally substituted C2-30 aliphatic group wherein one or more methylene units are optionally and independently replaced by —NRy—, —N(Ry)C(O)—, —C(O)N(Ry)—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S —, —SO—, —SO2—, —C(═S)—, —C(═NRy)—, or —N═N—, where each occurrence of Ry is independently —H, or an optionally substituted radical selected from the group consisting of C1-6 aliphatic 3- to 7-membered heterocyclic, phenyl, and 8- to 10-membered aryl. In certain embodiments, a linker moiety is a C4-C12 aliphatic group substituted with one or more moieties selected from the group consisting of halogen, —NO2, —CN, —SRy, —S(O)Ry, —S(O)2Ry, —NRyC(O)Ry, —OC(O)Ry, —CO2Ry, —NCO, —N3, —OR7, —OC(O)N(Ry)2, —N(Ry)2, —NRyC(O)Ry, and —NRyC(O)ORy, where Ry is —H, or an optionally substituted radical selected from the group consisting of C1-6 aliphatic 3- to 7-membered heterocyclic, phenyl, and 8- to 10-membered aryl.
In certain embodiments, a linker moiety is an optionally substituted C3-C30 aliphatic group. In certain embodiments, a linker is an optionally substituted C4-24 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C4-C20 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C4-C12 aliphatic group. In certain embodiments, a linker is an optionally substituted C4-10 aliphatic group. In certain embodiments, a linker is an optionally substituted C4-8 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C4-C6 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C6-C12 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C8 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C7 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C6 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C5 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C4 aliphatic group. In certain embodiments, a linker moiety is an optionally substituted C3 aliphatic group. In certain embodiments, a aliphatic group in the linker moiety is an optionally substituted straight alkyl chain. In certain embodiments, the aliphatic group is an optionally substituted branched alkyl chain. In some embodiments, a linker moiety is a C4 to C20 alkyl group having one or more methylene groups replaced by —C(RaRb)— where Ra and Rb are each, independently C1-C4 alkyl groups. In certain embodiments, a linker moiety consists of an aliphatic group having 4 to 30 carbons including one or more gem-dimethyl substituted carbon atoms.
In certain embodiments, a linker moiety includes one or more optionally substituted cyclic elements selected from the group consisting of saturated or partially unsaturated carbocyclic, aryl, heterocyclic, or heteroaryl. In certain embodiments, a linker moiety consists of the substituted cyclic element, in some embodiments the cyclic element is part of a linker with one or more non-ring heteroatoms or optionally substituted aliphatic groups comprising other parts of the linker moiety.
In some embodiments, a linker moiety is of sufficient length to allow one or more activating functional groups to be positioned near a metal atom of a metal complex. In certain embodiments, structural constraints are built into a linker moiety to control the disposition and orientation of one or more activating functional groups near a metal center of a metal complex. In certain embodiments such structural constraints are selected from the group consisting of cyclic moieties, bicyclic moieties, bridged cyclic moieties and tricyclic moieties. In some embodiments, such structural constraints are the result of acyclic steric interactions. In certain embodiments such structural constraints are selected from the group consisting of cis double bonds, trans double bonds, cis allenes, trans allenes, and triple bonds. In some embodiments, such structural constraints are selected from the group consisting of substituted carbons including geminally disubstituted groups such as sprirocyclic rings, gem dimethyl groups, gem diethyl groups and gem diphenyl groups. In certain embodiments such structural constraints are selected from the group consisting of heteroatom-containing functional groups such as sulfoxides, amides, and oximes.
In certain embodiments, linker moieties are selected from the group consisting of:







where s=0-6 and t=1-4

where * represents the site of attachment to a ligand, and each # represents a site of attachment of an activating functional group.
In some embodiments, s is 0. In some embodiments, s is 1. In some embodiments, s is 2. In some embodiments, s is 3. In some embodiments, s is 4. In some embodiments, s is 5. In some embodiments, s is 6.
In some embodiments, t is 1. In some embodiments, t is 2. In some embodiments, t is 3. In some embodiments, t is 4.
III. Metal Complexes
As noted above, the present invention encompasses metal complexes that include a metal atom coordinated to a multidentate ligand and at least one activating moiety tethered to a multidentate ligand. In certain embodiments, provided metal complexes have the structure:




where





represents a metal atom coordinated to a multidentate ligand.

III.a. Metal Atoms

In certain embodiments, M is a metal atom selected from periodic table groups 3-13, inclusive. In certain embodiments, M is a transition metal selected from periodic table groups 5-12, inclusive. In certain embodiments, M is a transition metal selected from periodic table groups 4-11, inclusive. In certain embodiments, M is a transition metal selected from periodic table groups 5-10, inclusive. In certain embodiments, M is a transition metal selected from periodic table groups 7-9, inclusive. In some embodiments, M is selected from the group consisting of Cr, Mn, V, Fe, Co, Mo, W, Ru, Al, and Ni. In some embodiments, M is a metal atom selected from the group consisting of: cobalt; chromium; aluminum; titanium; ruthenium, and manganese. In some embodiments, M is cobalt. In some embodiments, M is chromium. In some embodiments, M is aluminum.
In certain embodiments, a metal complex is a zinc, cobalt, chromium, aluminum, titanium, ruthenium, or manganese complex. In certain embodiments, a metal complex is an aluminum complex. In some embodiments, a metal complex is a chromium complex. In some embodiments, a metal complex is a zinc complex. In certain some embodiments, a metal complex is a titanium complex. In some embodiments, a metal complex is a ruthenium complex. In certain embodiments, a metal complex is a manganese complex. In certain embodiments, a metal complex is cobalt complex. In certain embodiments where the metal complex is a cobalt complex, the cobalt metal has an oxidation state of 3+ (i.e., Co(III)). In some embodiments, the cobalt metal has an oxidation state of 2+.
III.b. Ligands
In some embodiments, a metal complex




comprises a metal atom coordinated to a single tetradentate ligand and in some embodiments, the metal complex comprises a chelate containing a plurality of individual ligands. In certain embodiments, a metal complex contains two bidentate ligands. In some embodiments, a metal complex contains a tridentate ligand.

In various embodiments, tetradentate ligands suitable for metal complexes of the present invention may include, but are not limited to: salen derivatives 1, derivatives of salan ligands 2, bis-2-hydroxybenzamido derivatives 3, derivatives of the Trost ligand 4, porphyrin derivatives 5, derivatives of tetrabenzoporphyrin ligands 6, derivatives of corrole ligands 7, phthalocyaninate derivatives 8, and dibenzotetramethyltetraaza[14]annulene (tmtaa) derivatives 9 or 9′.







In some embodiments, a metal multidentate ligand coordinated with a metal complex may comprise a plurality of discrete ligands. In some embodiments, metal complexes include two bidentate ligands. In certain embodiments, such bidentate ligands may have the structure




where Rd and R1 are as defined above. Metal complexes having two such ligands may adopt one of several geometries, and the present disclosure encompasses such variations.

In certain embodiments, metal complexes including two bidentate ligands may have structures selected from the group consisting of:




where each





represents a ligand:





In certain embodiments, a tetradentate ligand is a salen ligand. In certain embodiments, a metal complex is a metallosalenate. In certain embodiments, a metal complex is a cobalt salen complex. In certain embodiments, a metal complex is a chromium salen complex. In some embodiments, a metal complex is an aluminum salen complex.
In certain embodiments, at least one activating moiety is tethered to a carbon atom of a phenyl ring of the salicylaldehyde-derived portions of a salen ligand. In certain embodiments, at least one activating moiety is tethered to a carbon atom of a porphyrin ligand. In certain embodiments, at least one activating moiety is tethered to a pyrrole-carbon atom of a porphyrin ligand. In certain embodiments, at least one activating moiety is tethered to a carbon atom forming the bridge between the pyrrole rings of a porphyrin ligand.
In certain embodiments, at least one activating moiety is tethered to one or more carbon atoms of only one phenyl ring of the salicylaldehyde-derived portions of a salen ligand, as shown in formula I:




wherein:

    
    
        M is a metal atom;
        X is a nucleophile capable of ring opening an epoxide;
        k is an integer from 0-2 inclusive;
        R′ represents one or more substituents optionally present on the phenyl rings and each R′ is independently selected from the group consisting of: halogen, —NO2, —CN, —SW, —S(O)Ry, —S(O)2Ry, —NRyC(O)Ry, —OC(O)Ry, —CO2Ry, —NCO, —N3, —OR7, —OC(O)N(Ry)2, —N(Ry)2, —NRyC(O)Ry, —NRyC(O)ORy; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, where two or more adjacent R′ groups can be taken together to form an optionally substituted saturated, partially unsaturated, or aromatic 5- to 12-membered ring containing 0 to 4 heteroatoms;
        Ry is —H, or an optionally substituted radical selected from the group consisting of C1-6 aliphatic, 3- to 7-membered heterocyclic, phenyl, and 8- to 10-membered aryl;
    
    






represents is an optionally substituted moiety linking the two nitrogen atoms of the diamine portion of the salen ligand, where





is selected from the group consisting of phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an optionally substituted C2-20 aliphatic group, wherein one or more methylene units are optionally and independently replaced by —NRy—, —N(Ry)C(O)—, —C(O)N(Ry)—, —OC(O)N(Ry)—, —N(Ry)C(O)O—, —OC(O)O—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO2—, —C(═S)—, —C(═NRy)—, —C(═NORy)— or —N═N—;

    
    
        (Z)m represents one or more activating moieties, where “” is a covalent linker containing one or more atoms selected from the group consisting of C, O, N, S, and Si; Z is a activating functional group and m is an integer from 1 to 4 indicating the number of individual activating functional groups present in each activating moiety.
    
    


In certain embodiments, both salicylaldehyde-derived portions of a salen ligand bear one or more activating moieties:




wherein M, X, k, R′,




and (Z)m are as defined above.

In some embodiments, provided metal complexes comprise a




moiety that has the structure:





wherein:

    
    
        M is a metal atom,
        R1a, R1a′, R2a, R2a′, R3a, and R3a′ are independently a (Z)m group, hydrogen, halogen, —OR, —NR2, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2; —CNO, —NRSO2R, —NCO, —N1, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
        each R is independently hydrogen, an optionally substituted radical selected the group consisting of acyl; carbamoyl; arylalkyl; phenyl, 8- to 10-membered aryl; C1-12 aliphatic; C1-12 heteroaliphatic; 5- to 10-membered heteroaryl; 4- to 7-membered heterocyclyl; an oxygen protecting group; and a nitrogen protecting group; or:
        
            two R on the same nitrogen atom are taken with the nitrogen to form a 3- to 7-membered heterocyclic ring;
        
        
        wherein any of [R2a′ and R3a′], [R2a and R3a], [R1a and R2a], and [R1a′ and R2a′] may optionally be taken together with the carbon atoms to which they are attached to form one or more rings which may in turn be substituted with one or more R20a groups; and
        R4a is selected from the group consisting of:
    
    






where

    
    
        Rc at each occurrence is independently a  group, hydrogen, halogen, —OR, —NR2, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2; —CNO, —NRSO2R, —NCO, —N3, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
        where:
        
            two or more Rc groups may be taken together with the carbon atoms to which they are attached and any intervening atoms to form one or more rings;
            when two Rc groups are attached to the same carbon atom, they may be taken together along with the carbon atom to which they are attached to form a moiety selected from the group consisting of: a 3- to 8-membered spirocyclic ring, a carbonyl, an oxime, a hydrazone, an imine;
        
        
        X is a nucleophile capable of ring opening an epoxide;
        Y is a divalent linker selected from the group consisting of: —NR—, —N(R)C(O)—, —C(O)NR—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO2—, —C(═S)—, —C(═NR)—, or —N═N—; a polyether; a C3 to C8 substituted or unsubstituted carbocycle; and a C1 to C8 substituted or unsubstituted heterocycle;
        m′ is 0 or an integer from 1 to 4, inclusive;
        q is 0 or an integer from 1 to 4, inclusive; and
        x is 0, 1, or 2.
    
    


In some embodiments, at least one of [R2a and R3a] and [R2a′ and R3a′] are taken together to form a ring. In some embodiments, both [R2a and R3a] and [R2a′ and R3a′] are taken together to form rings. In some embodiments, the rings formed by [R2a and R3a] and [R2a′ and R3a′] are substituted phenyl rings.
In certain embodiments, one or more of R1a, R1a′, R2a, R2a′, R3a, and R3a′ are independently a Z group.
In certain embodiments of provided metal complexes, a




moiety has a structure selected from the group consisting of:





wherein:

    
    
        M is a metal atom;
        R4a, R4a′, R5a, R5a′, R6a, R6a′, R7a, and R7a′ are each independently a Z group, hydrogen, halogen, —OR, —NRz, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2;
        —CNO, —NRSO2R, —NCO, —N1, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
        wherein [R1a and R4a], [R1a′ and R4a′] and any two adjacent R4a, R4a′, R5a, R5a′, R6a, R6a′, R7a, and R7a′ groups can be taken together with intervening atoms to form one or more optionally substituted rings;
        n is 0 or an integer from 1 to 8, inclusive; and
        p is 0 or an integer from 1 to 4, inclusive.
    
    


In some embodiments, M is Co.
In some embodiments, R1a, R1a′, R4a, R4a′, R6a, and R6a′ are each H. In some embodiments, R5a, R5a′, R7a and R7a′ are each optionally substituted C1-C12 aliphatic. In some embodiments, R4a, R4a′, R5a, R5a′, R6a, R6a′, R7a, and R7a′ are each independently selected from the group consisting of: —H, —SiR3; methyl, ethyl, n-propyl, i-propyl, n-butyl, sec-butyl, t-butyl, isoamyl, t-amyl, thexyl, and trityl. In some embodiments, R1a, R1a′, R4a, R4a′, R6a, and R6a′ are each —H. In some embodiments, R7a is selected from the group consisting of —H; methyl; ethyl; n-propyl; i-propyl; n-butyl; sec-butyl; t-butyl; isoamyl; t-amyl; thexyl; and trityl. In some embodiments, R5a and R7a are independently selected from the group consisting of —H; methyl; ethyl; n-propyl; i-propyl; n-butyl; sec-butyl; t-butyl; isoamyl; t-amyl; thexyl; and trityl. In certain embodiments, one or more of R5a, R5a′, R7a and R7a′ is a Z group. In some embodiments, R5a and R5a′ are a Z group.
In certain embodiments of provided metal complexes, a




moiety has a structure selected from the group consisting of:





In certain embodiments of complexes having formulae described above, at least one of the phenyl rings comprising a salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:













where (Z)m represents one or more independently-defined activating moieties which may be bonded to any one or more unsubstituted positions of a salicylaldehyde-derived phenyl ring.
In certain embodiments, there is an activating moiety tethered to the position ortho to a metal-bound oxygen substituent of one or both of the salicylaldehyde-derived phenyl rings of a salen ligand as in formulae IIIa and IIIb:




wherein:

    
    
        M, X, k, R′,
    
    






and (Z)m are as defined above, and

    
    
        R4a, R4a′, R5a, R5a′, R6a, and R6a′ are each independently a Z group, hydrogen, halogen, —OR, —NR2, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2; —CNO, —NRSO2R, —NCO, —N3, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
        wherein any two adjacent R4a, R4a′, R5a, R5a′, R6a, and R6a′ groups can be taken together with intervening atoms to form one or more optionally substituted rings.
    
    


In certain embodiments of compounds having formulae IIIa or IIIb, R4a, R4a′, R6a, and R6a′ are each hydrogen, and R5a, R5a′ are, independently, optionally substituted C1-C20 aliphatic.
In certain embodiments of complexes IIIa and IIIb, at least one of the phenyl rings comprising a salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:







In certain embodiments, there is an activating moiety tethered to the position para to the phenolic oxygen of one or both of a salicylaldehyde-derived phenyl rings of the salen ligand as in structures IVa and IVb:




where M, X, k, R′, R4a, R4a′, R6a, R6a′, R7a, R7a′,




and

(Z)m are as defined above.
In certain embodiments of compounds having formulae IVa or IVb, R4a, R4a′, R6a, and R6a′ are hydrogen, and each R7a, R7a′ is, independently, optionally substituted C1-C20 aliphatic.
In certain embodiments of catalysts IVa and IVb, at least one of the phenyl rings comprising a salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:







In some embodiments, there is an activating moiety tethered to the position para to the imine substituent of one or both of the salicylaldehyde-derived phenyl rings of a salen ligand as in formulae Va or Vb:




where M, X, k, R′, R4a, R4a′, R5a, R5a′, R7a, R7a′,





and (Z)m are as defined above.

In certain embodiments of compounds having formulae Va or Vb, each R4 and R4a is hydrogen, and each R5a, R5a′, R7a, R7a′ is, independently, hydrogen or optionally substituted C1-C20 aliphatic.
In certain embodiments of catalysts Va and Vb, at least one of the phenyl rings comprising a salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:










In some embodiments, there is an activating moiety tethered to the position ortho to the imine substituent of one or both of the salicylaldehyde-derived phenyl rings of a salen ligand as in formulae VIa and VIb:




where X, k, M, R′, R5a, R5a′, R6a, R6a′, R7a, R7a′,





and (Z)m are as defined above.

In certain embodiments of compounds having formulae VIa or VIb, each R6a and R6a′ is hydrogen, and each R5a, R5a′, R7a, and R7a′ is, independently, hydrogen or optionally substituted C1-C20 aliphatic.
In certain embodiments of catalysts VIa and VIb, at least one of the phenyl rings comprising a salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:










In some embodiments, there are activating moieties tethered to the positions ortho and para to the phenolic oxygen of one or both of the salicylaldehyde-derived phenyl rings of a salen ligand as in formulae VIIa and VIIb:




where M, X, k, R′, R4a, R4a′, R6a, R6a′,





and (Z)m are as defined above.

In certain embodiments of compounds having formulae VIa or VIb, each R6a, R6a′, R4a, and R4a′ is, independently, hydrogen or optionally substituted C1-C20 aliphatic.
In certain embodiments of compounds having formulae VIIa or VIIb, each R6a, R6a′, R4a, and R4a′ is hydrogen.
In some embodiments, there are activating moieties tethered to the positions ortho and para to the imine substituent of one or both of the salicylaldehyde-derived phenyl rings of a salen ligand as in formulae VIIIa and VIIIb:




where X, k, M, R′, R5a, R5a′, R7a, R7a′,





and (Z)m are as defined above.

In certain embodiments of compounds having formulae VIIIa or VIIIb, each R5a, R5a′, R7a, and R7a′ is, independently, optionally, hydrogen or substituted C1-C20 aliphatic.
In certain embodiments of the present invention, catalysts of structures VIIIa or VIIIb above, at least one of the phenyl rings comprising the salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:













In some embodiments, there is an activating moiety tethered to the imine carbon of a salen ligand as in formulae IXa and IXb:




where

M, X, k, R4a, R4a′, R5a, R5a′, R6a, R6a′, R7a, R7a′,





and (Z)m are as defined above with the proviso that the atom of the activating moiety attached to the salen ligand is a carbon atom.

In certain embodiments of compounds having formulae IXa or IXb, each R4a, R4a′, R6a, and R6a′ is hydrogen, and each R5a, R5a′, R7a, and R7a′ is, independently, hydrogen or optionally substituted C1-C20 aliphatic.
In certain embodiments of the present invention, metal complexes of structures IXa or IXb above, at least one of the phenyl rings comprising a salicylaldehyde-derived portion of a catalyst is independently selected from the group consisting of:










As shown above, the two phenyl rings derived from salicylaldehyde in the core salen structures need not be the same. Though not explicitly shown in formulae Ia through IXb above, it is to be understood that a catalyst may have an activating moiety attached to different positions on each of the two rings, and such compounds are specifically encompassed within the scope of the present invention. Furthermore, activating moieties can be present on multiple parts of the ligand, for instance activating moieties can be present on the diamine bridge and on one or both phenyl rings in the same catalyst.
In certain embodiments, the salen ligand cores of catalysts Ia through IXb above are selected from the group shown below wherein any available position may be independently substituted with one or more R-groups or one or more activating moieties as described above.




where M, X, and k, are as defined above.
In some embodiments, at least one activating moiety is tethered to the diamine-derived portion of the salen ligand, as shown in formula X:




where M, X, k, R′,





and (Z)m are as defined above.

In certain embodiments, salen ligands of formula X are selected from an optionally substituted moiety consisting of:







where M, X, k, R′, and (Z)m are as defined above.

In certain embodiments, the diamine bridge of catalysts of formula Xa an optionally substituted moiety selected from the group consisting of:







where M and (Z)m is as defined above.

In certain embodiments, metallosalenate complexes of the present invention include, but are not limited to those in Table 1 below:










Table 1 ⊥













 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 















In certain embodiments, for complexes of Table 1, M is Co—X, where X is as defined above. In certain embodiments, for complexes of Table 1, M is Co—OC(O)CF3. In certain embodiments, for complexes of Table 1, M is Co—OAc. In certain embodiments, for complexes of Table 1, M is Co—OC(O)C6F5. In certain embodiments, for complexes of Table 1, M is Co—N3. In certain embodiments, for complexes of Table 1, M is Co—Cl. In certain embodiments, for complexes of Table 1, M is Co-nitrophenoxy. In certain embodiments, for complexes of Table 1, M is Co-dinitrophenoxy.
In some embodiments, for complexes of Table 1, M is Cr—X, where X is as defined above.
In certain embodiments, a tetradentate ligand is a porphyrin ligand. In some embodiments, a metal complex is a cobalt porphyrin complex. In certain embodiments, a metal complex is a chromium porphyrin complex. In some embodiments, a metal complex is an aluminum porphyrin complex.
Examples of porphyrin containing metal complexes of the present invention include, but are not limited to:







wherein each of M, X, k, R′, and (Z)m is as defined above.
In certain embodiments, a multidentate ligand is an optionally substituted tetrabenzoporphyrin. Suitable examples include, but are not limited to:







wherein M, R′, and (Z)m are as previously defined.

In certain embodiments of porphyrin and phthalocyanine-based complexes described herein, M is aluminum. In certain embodiments of porphyrin and phthalocyanine-based complexes described herein, M is cobalt. In certain embodiments of porphyrin and phthalocyanine-based complexes described herein, M is manganese.
In certain embodiments, porphyrin complexes of the present invention include, but are not limited to those in Table 2 below:







TABLE 2













 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 








 















In certain embodiments, for complexes of Table 2, M is Co—X, where X is as defined above. In certain embodiments, for complexes of Table 2, M is Co—OC(O)CF3. In certain embodiments, for complexes of Table 2, M is Co—OAc. In certain embodiments, for complexes of Table 1, M is Co—OC(O)C6F5. In certain embodiments, for complexes of Table 2, M is Co—N3. In certain embodiments, for complexes of Table 2, M is Co—Cl. In certain embodiments, for complexes of Table 2, M is Co-nitrophenoxy. In certain embodiments, for complexes of Table 2, M is Co-dinitrophenoxy.
In certain embodiments, for complexes of Table 2, M is Al—X, where X is as defined above. In certain embodiments, for complexes of Table 2, M is Cr—X, where X is as defined above.
In certain embodiments, porphyrin complexes of the present invention are synthesized as shown in the following schemes:










In some embodiments, the present disclosure provides methods of polymerization comprising contacting an epoxide with carbon dioxide in the presence of a provided metal complex to form a polycarbonate. In some embodiments, the present invention provides a method of polymerization, the method comprising:

    
    
        a) providing an epoxide of formula:
    
    






    
    
        
        
            wherein:
            Ra′ is hydrogen or an optionally substituted radical selected from the group consisting of C1-30 aliphatic; C1-30 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and
            each of Rb′, Rc′, and Rd′ is independently hydrogen or an optionally substituted radical selected from the group consisting of C1-12 aliphatic; C1-12 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
            wherein any of (Ra′ and Rc′), (Rc′ and Rd′), and (Ra′ and Rb′) can be taken together with intervening atoms to form one or more optionally substituted rings;
        
        
        b) contacting the epoxide and carbon dioxide in the presence of a metal complex as described herein to provide a polymer having a formula selected from the group consisting of:
    
    






In some embodiments, a provided polymer has a formula:




In some embodiments, a provided polymer has a formula:





In some embodiments, carbon dioxide is optional and a provided polymer has a formula:





In certain embodiments, Rb′, Rc′, and Rd′ are each hydrogen. In some embodiments, Ra′ is optionally substituted C1-12 aliphatic. In some embodiments, Ra′ is optionally substituted C1-12 heteroaliphatic. In some embodiments, the epoxide is ethylene oxide, propylene oxide, or cyclohexene oxide.
In certain embodiments, one of Ra′, Rb′, Rc′, and leis hydrogen. In certain embodiments, two of Ra′, Rb′, Rc′, and Rd′ are hydrogen. In certain embodiments, three of Ra′, Rb′, Rc′, and Rd′ are hydrogen.
In certain embodiments, Ra′ is hydrogen. In certain embodiments, Rb′ is hydrogen. In certain embodiments, Rc′ is hydrogen. In certain embodiments, Rd′ is hydrogen.
In certain embodiments, Ra′, Rb′, Rc′, and Rd′ are each independently an optionally substituted C1-30 aliphatic group. In certain embodiments, Ra′, Rb′, Rc′, and Rd′ are each independently an optionally substituted C1-20 aliphatic group. In certain embodiments, Ra′, Rb′, Rc′, and Rd′ are each independently an optionally substituted C1-12 aliphatic group. In certain embodiments, Ra′, Rb′, Rc′, and Rd′ are each independently an optionally substituted C1-8 aliphatic group. In certain embodiments, Ra′, Rb′, Rc′, and Rd′ are each independently an optionally substituted C3-8 aliphatic group. In certain embodiments, Ra′, Rb′, Rc′, and Rd′ are each independently an optionally substituted C3-12 aliphatic group.
In certain embodiments, Ra′ is an optionally substituted C1-30 aliphatic group. In certain embodiments, Rb′ is an optionally substituted C1-30 aliphatic group. In certain embodiments, Rc′ is an optionally substituted C1-30 aliphatic group. In certain embodiments, Rd′ is an optionally substituted C1-30 aliphatic group.
In some embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form one or more optionally substituted 3-12-membered carbocyclic rings. In some embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form a polycyclic carbocycle comprising two or more optionally substituted 3-8-membered carbocyclic rings. In some embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form a polycyclic carbocycle comprising two or more optionally substituted 5-7-membered carbocyclic rings.
In some embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form a bicyclic carbocycle comprising two optionally substituted 3-12-membered carbocyclic rings. In some embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form a bicyclic carbocycle comprising two optionally substituted 3-8-membered carbocyclic rings. In some embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form a bicyclic carbocycle comprising two optionally substituted 5-7-membered carbocyclic rings.
In certain embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form an optionally substituted 3-12-membered carbocyclic ring. In certain embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form an optionally substituted 3-8-membered carbocyclic ring. In certain embodiments, an Ra′ and an Rb′ attached to the same carbon are taken together to form an optionally substituted 5-7-membered carbocyclic ring.
In some embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form one or more optionally substituted 3-12-membered carbocyclic rings. In some embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form a polycyclic carbocycle comprising two or more optionally substituted 3-8-membered carbocyclic rings. In some embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form a polycyclic carbocycle comprising two or more optionally substituted 5-7-membered carbocyclic rings.
In some embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form a bicyclic carbocycle comprising two optionally substituted 3-12-membered carbocyclic rings. In some embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form a bicyclic carbocycle comprising two optionally substituted 3-8-membered carbocyclic rings. In some embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form a bicyclic carbocycle comprising two optionally substituted 5-7-membered carbocyclic rings.
In certain embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form an optionally substituted 3-12-membered carbocyclic ring. In certain embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form an optionally substituted 3-8-membered carbocyclic ring. In certain embodiments, an Rb′ and an Rc′ attached to adjacent carbons are taken together to form an optionally substituted 5-7-membered carbocyclic ring.
In certain embodiments, the polymer comprises a copolymer of two different repeating units where Ra′, Rb′, and Rc′ of the two different repeating units are not all the same. In some embodiments, a polymer comprises a copolymer of three or more different repeating units wherein Ra′, Rb′, and Rc′ of each of the different repeating units are not all the same as Ra′, Rb′, and Rc′ of any of the other different repeating units. In some embodiments, a polymer is a random copolymer. In some embodiments, a polymer is a tapered copolymer.
In some embodiments, a polymer contains a metal complex as described herein. In some embodiments, a polymer comprises residue of a metal complex as described herein. In some embodiments, a polymer comprises a salt of an organic cation and X, wherein X is a nucleophile or counterion. In some embodiments, X is 2,4-dinitrophenolate anion.
In some embodiments, Ra′ is optionally substituted C1-12 aliphatic. In some embodiments, Ra′ is optionally substituted C1-12 heteroaliphatic. In some embodiments, Ra′ is optionally substituted phenyl. In some embodiments, Ra′ is optionally substituted 8- to 10-membered aryl. In some embodiments, Ra′ is optionally substituted 5- to 10-membered heteroaryl. In some embodiments, Ra′ is optionally substituted 3- to 7-membered heterocyclic.
In certain embodiments, Ra′ is selected from methyl, ethyl, propyl, butyl, vinyl, allyl, phenyl, trifluoromethyl,




or any two or more of the above. In certain embodiments, Ra′ is methyl. In certain embodiments, Ra′ is ethyl. In certain embodiments, Ra′ is propyl. In certain embodiments, Ra′ is butyl. In certain embodiments, Ra′ is vinyl. In certain embodiments, Ra′ is allyl. In certain embodiments, Ra′ is phenyl. In certain embodiments, Ra′ is trifluoromethyl. In certain embodiments, Ra′ is





In certain embodiments, Ra′ is





In certain embodiments, Ra′ is





In certain embodiments, Ra′ is





In certain embodiments, Ra′ is





In certain embodiments, Ra′ is





In certain embodiments, Ra′ is





In some embodiments, Rb′ is hydrogen. In some embodiments, Rb′ is optionally substituted C1-12 aliphatic. In some embodiments, Rb′ is optionally substituted C1-12 heteroaliphatic. In some embodiments, Rb′ is optionally substituted phenyl. In some embodiments, Rb′ is optionally substituted 8- to 10-membered aryl. In some embodiments, Rb′ is optionally substituted 5- to 10-membered heteroaryl. In some embodiments, Rb′ is optionally substituted 3- to 7-membered heterocyclic.
In some embodiments, Rc′ is hydrogen. In some embodiments, Rc′ is optionally substituted C1-12 aliphatic. In some embodiments, Rc′ is optionally substituted C1-12 heteroaliphatic. In some embodiments, Rc′ is optionally substituted phenyl. In some embodiments, Rc′ is optionally substituted 8- to 10-membered aryl. In some embodiments, Rc′ is optionally substituted 5- to 10-membered heteroaryl. In some embodiments, Rc′ is optionally substituted 3- to 7-membered heterocyclic.
In some embodiments, Ra′ and Rc′ are taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted 3- to 14-membered heterocycle, optionally substituted phenyl, optionally substituted C8-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl.
In some embodiments, Rb′ and Rc′ are taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted 3- to 14-membered heterocycle, optionally substituted phenyl, optionally substituted C8-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl.
In some embodiments, Ra′ and Rb′ are taken together with intervening atoms to form one or more rings selected from the group consisting of: optionally substituted C3-C14 carbocycle, optionally substituted 3- to 14-membered heterocycle, optionally substituted phenyl, optionally substituted C8-C10 aryl, and optionally substituted 5- to 10-membered heteroaryl.
In some embodiments, the invention includes methods for synthesizing polyethers from epoxides. Suitable methods of performing these reactions are disclosed in U.S. Pat. No. 7,399,822, the entire contents of which are hereby incorporated herein by reference.
In some embodiments, the invention includes methods for synthesizing cyclic carbonates from carbon dioxide and epoxides using catalysts described above, suitable methods of performing this reaction are disclosed in U.S. Pat. No. 6,870,004 which is incorporated herein by reference.
EXAMPLES
Example 1
A general route to a symmetric cobalt (III) salen ligand of the present invention is shown in Schemes E1 and E2, below:




As shown in Scheme E1, disubstituted phenol E1-a is formylated to provide salicylaldehyde derivative E1-b. Two equivalents of this aldehyde are then reacted with a diamine (in this case 1,2-diamino cyclohexane) to afford Schiff base E1-c. This compound is then reacted with cobalt (II) acetate to give the Co(II)-salen complex (not shown) which is oxidized by air in the presence of trifluoroacetic acid to afford the active cobalt (III) catalyst. Similar chemistries can be applied to synthesis of the catalysts described hereinabove. One skilled in the art of organic synthesis can adapt this chemistry as needed to provide the specific catalysts described herein.
Example 2
A typical route to an asymmetric cobalt (III) salen ligand is shown in Scheme E2:




As shown in Scheme E2, disubstituted salicylaldehyde derivative E1-b is treated with one equivalent of a monohydrochloride salt of 1,2 cyclohexanediamine the resulting Schiff base E2-a is then neutralized and a second different salicylaldehyde derivative is added. This compound is then reacted with cobalt (II) acetate to give the Co(II)-salen complex which is oxidized by air in the presence of trifluoroacetic acid to afford the active cobalt (III) catalyst. Similar chemistries can be applied to synthesis of the catalysts described hereinabove. One skilled in the art of organic synthesis can adapt this chemistry as needed to provide the specific catalysts described herein.
Example 3
Example 3 describes the synthesis of a catalyst




where M is Co(III),





is salcy,  is





Z is a P-linked phosphorimine moiety





and m is 1, wherein there are one or two (Z)m groups present (Scheme E4 and E3, respectively).





As shown in Scheme E3, triol E3-a is protected as a ketal to afford monohydric alcohol E3-b, this compound is then alkylated with bromide E3-c to afford benzyl ether E3-d. Deprotection and oxidation of the other benzylic alcohol affords salicylaldehyde E3-e which is condensed with cyclohexanediamine as described above to give ligand E3-f. The phosphorimine nitrogen is then quaternized and the metal complex formed as before to provide catalyst E3-h. In an alternative route not shown here the metal is first inserted and then quarternization is performed.







As shown in Scheme E3b, salicyladedyde E3-e (described above) is condensed with cyclohexanediamine monohydrochloride to afford the mono-Schiff base hydrochloride E4a. This salt is then neutralized, condensed with di-t-butyl salicaldehyde, and methylated to give E4-b. The resulting ligand is metallated and oxidized as described above for Scheme E3 to give catalyst E4-c.
Example 4
Example 4 describes the synthesis of catalysts where M is Co(III),




is salcy,  is





Z is a 1-[4-dimethylamino-pyridinium]





or 1-[N-methylimidazolium],





and m is 1, wherein there are one or two (Z)m groups present (Scheme E5 and E6, respectively).





Scheme E4 shows the synthesis of compounds CS-6 and CS-7. For each compound trans-1,2-Diaminocyclohexane (2.0 mol) is slowly added to an anhydrous ethanol solution of benzyl chloride CS-4 (1.0 mol). The reaction is stirred and heated to reflux for 3 h, then cooled to rt and diluted with water. This mixture is cooled overnight in the freezer and solids are collected by filtration to afford dichloride CS-5. The dichloride CS-5 (1.0 mol) is reacted with N,N-Dimethylamino pyridine (2.0 mol) or N-methyl imidazole in acetonitrile. The reactions are heated at 80° C. for 18 h and then the solvent is removed in vacuo to provide the respective ammonium salts. These salts are metallated and oxidized as described previously to provide catalysts CS-6 and CS-7.
Example 5
Example 5 describes the synthesis of catalysts where M is Co(III),




is salcy,  is





Z is a 1-[N-methylimidazolium] (CS-8), or dimethylamino (CS-9) and m is 1, wherein there are two (Z)m groups present (Scheme E5 and E6, respectively).





Scheme E5 shows the synthesis of compounds CS-8 and CS-9 using conditions similar to those described above. Synthesis of CS-8: The known compound 1-(2-methylaminoethyl)-3-methylimidazole (2.0 mol) is combined with CS-5 (1.0 mol) in acetonitrile. The reaction is heated to 80° C. for 18 h and then the solvent is removed in vacuo, metallation with Co(OAc)2 and oxidation in TFA are then performed as described above to afford catalyst CS-8. Synthesis of CS-9: N,N,N′-Trimethyl-1,2-ethanediamine (4.0 mol) is combined with CS-5 (1.0 mol) in acetonitrile. The reaction is heated to 80° C. for 18 h, cooled, and the solvent is removed in vacuo. The crude product is diluted with ether, filtered to remove amine salts, and concentrated in vacuo. The residue is dissolved in degassed methanol and combined with Co(OAc)2 (1.0 mol). After stirring for 3 h the residue is filtered and washed with methanol. Trifluoroacetic acid (1.0 mol) is added slowly to a stirring solution of the solid residue in dichloromethane. After stirring open to air for 3 h, the solids are filtered and dried in vacuo to produce CS-9.
Example 6
Example 6 and Scheme E6 describe the synthesis of catalysts where M is Co(III),




is salcy,  is





Z is dibutylamino and m is 1, wherein there are two (Z)m groups present.





Synthesis of CS-10:
Ligand CS-5 (1.0 mol), 3-(dibutylamino)-1-propanol (2.0 mol), a 50% NaOH solution (10 mol), tetrabutylammonium bisulphate (4 mol %), and dichloromethane are combined and heated at 65° C. overnight. The reaction mixture is concentrated in vacuo to remove the bulk of the solvent and the aqueous layer is extracted with ethyl acetate. The organic layer is separated, dried with magnesium sulfate, filtered, and concentrated in vacuo. After purification using silica gel the product is dissolved in degassed methanol and combined with Co(OAc)2 (1.0 mol). After stirring for 3 h, the residue is filtered and washed with methanol. Trifluoroacetic acid (1.0 mol) is added slowly to a dichloromethane solution of the solid residue. After stirring open to air for 3 h, the solids are filtered and dried in vacuo to produce CS-10.
Example 7
Example 7 and Scheme E7 describe the synthesis of catalysts where M is Co(III),




is salcy,  includes two





groups taken together to form a ring including the Z group, Z is 3-[N-methylpyridinium] and m is 1, wherein there is one (Z)m group present.





Synthesis of CS-11.
Ligand CS-5 (1.0 mol), 3,5-bis(hydroxymethyl)-N-methylpyridinium iodide (2.0 mol), a 50% NaOH solution (10 mol), tetrabutylammonium bisulphate (4 mol %), and dichloromethane are combined and heated at 65° C. overnight. The reaction mixture is concentrated in vacuo to remove the bulk of the solvent and the aqueous layer is extracted with ethyl acetate. The organic layer is separated, dried with magnesium sulfate, filtered, and concentrated in vacuo. The procedure detailed above for the metallation and oxidation is followed to produce CS-11.
Example 8
Example 8 and Scheme E8 describe the synthesis of catalysts where M is Co(III),




is salcy,  is





Z is 1-[4-t-butylpyridinium], and m is 2, wherein there are two (Z)m groups present.





Synthesis of AC-2.
Intermediate AC-1 (0.37 g, 0.35 mmol), 4-tbutylpyridine (0.21 mL, 1.41 mmol), and AcCN (4 mL) were combined in a sealed vial and heated to 80° C. with stirring for 18 h. The solvent was removed in vacuo, leaving a yellow residue (0.61 g, 110% yield, AcCN present). 1H NMR (400 MHz, CDCl3, δ): 9.53 (t, 8H), 8.21 (s, 2H), 7.94 (t, 8H), 7.08 (s, 2H), 6.83 (s, 2H), 4.81 (m, 8H), 3.29 (m, 2H), 2.78 (m, 2H), 2.15 (s, 6H), 1.5-2.0 (m, 24H), 1.36 (s, 36H); IR (ATR, film cast from AcCN): νC—N=1637 cm−1. A solution of the residue (0.30 g, 0.19 mmol) in dry EtOH (5 mL) was added to AgBF4 (0.19 g, 0.85 mmol) in a schlenk tube and stirred overnight shielded from the light. The solution was filtered through Celite and the solvent was removed in vacuo, giving a solid residue. This residue was flashed over a small plug of silica gel with 5:1 CH2Cl2:EtOH as eluant. The solvent was removed to give a solid residue (0.18 g, 67% yield). 1H NMR (400 MHz, CDCl3, δ): 8.75 (t, 8H), 7.98 (d, 2H), 7.92 (t, 8H), 7.1-7.3 (m, 4H), 4.52 (m, 8H), 3.6 (m, 2H), 2.7 (m, 2H), 2.19 (s, 6H), 1.5-2.0 (m, 24H), 1.38 (s, 36H); IR (ATR, film cast from CH2Cl2): νC—N=1641 cm−1, νBF4=1050 cm−1. A solution of the residue (0.18 g, 0.12 mmol) in dry EtOH (4 mL) was added to Co(OAc)2 (0.022 g, 0.12 mmol) in a schlenk tube under N2. The solution was stirred for 3 h at room temperature, and the solvent was removed in vacuo. The residue was triturated with ether, dried in vacuo, and redissolved in CH2Cl2. A solution of CF3CO2H (9 μL, 0.12 mmol) in CH2Cl2 (80 μL) was added and the solution stirred for 3 h open to air. Solid NaO2CCF3 (0.067 g, 0.49 mmol) was added, and the solution was stirred under N2 for 2 days. The solution was filtered through Celite and the solvent was removed in vacuo to leave a brown residue (0.071 g, 37% yield). 1H NMR (400 MHz, DMSO-d6, δ): 8.86 (t, 8H), 8.08 (t, 8H), 8.07 (s, 2H), 7.30 (m, 4H), 4.44 (m, 8H), 3.54 (m, 2H), 2.9 (m, 2H), 2.47 (s, 6H), 1.5-2.0 (m, 24H), 1.29 (s, 36H); IR (ATR): νC═O=1682 cm−1, νC═N=1641 cm−1.
Additional ligands AC-6 through AC-11 were synthesized using the conditions described for compound AC-2 and are summarized in Scheme E8b and Table E8:














TABLE E8






Q
1H NMR spectraa
IRb


Compound
(Scheme E8b)
(δ, ppm)
(cm−1)







AC-6c




9.0 (d, 8H), 8.6 (t, 4H),  8.5 (s, 2H), 8.1 (t, 8H), 6.9  (s, 2H), 6.8 (s, 2H), 4.5 (t, 8H), 3.4 (m, 2H), 2.1 (s,  6H), 1.4-2.9 (m, 24H).
νC═N = 1629


 


AC-7




8.61 (d, 8H), 8.29 (s, 2H),  6.99 (s, 2H), 6.92 (d, 8H),  6.85 (s, 2H), 4.30 (t, 8H),  3.34 (m, 2H), 3.23 (s,  24H), 2.65 (m, 2H), 2.18  (s, 6H), 1.4-2.9 (m, 16H).
νC═N = 1649


 


AC-8





νC═N = 1627


 


AC-9





νC═N = 1610


 


AC-10





νC═N = 1627


 


AC-11





νC═N = 1628





a400 MHz, CDCl3.


bAll compounds exhibited the loss of a peak at 1213 cm−1 attributed to the CH2I group in AC-1.


cNMR spectrum is in DMSO-d6.






Example 9
Example 9 and Scheme E9 describe the synthesis of catalysts where M is Co(III),




is salcy,  is





Z is N,N-bis-(3-dimethylaminopropyl)amino (AC-4), tetramethyl guanidino (AC-5), N-linked morpholino (AC-6), or N-linked piperidino (AC-14), and m is 2, wherein there are two (Z)m groups present.





Synthesis of AC-4.
Intermediate AC-3 (0.45 g, 0.63 mmol), 3,3′-iminobis(N,N′-dimethylpropylamine) (0.28 mL, 1.26 mmol), K2CO3 (0.35 g, 2.52 mmol) and AcCN (5 mL) were combined in a sealed vial and heated to 80° C. with stirring for 18 h. The solution was filtered and the solvent was removed in vacuo, triturated with ether, and dried in vacuo to leave a yellow residue (0.48 g, 91% yield). 1H NMR (400 MHz, CDCl3, δ): 8.21 (m, 2H), 6.8-7.2 (m, 4H), 3.75 (m, 2H), 3.0-3.4 (m, 20H), 2.0-2.8 (m, 28H), 2.18 (s, 6H), 1.4-2.0 (m, 24H); IR (ATR): νC═N=1600 cm−1. A solution of the residue (0.21 g, 0.25 mmol) in dry EtOH (10 mL) was added to Co(OAc)2 (0.045 g, 0.25 mmol) in a schlenk tube under N2. CH2Cl2 (3 mL) was added to completely dissolve the solution. The solution was stirred for 18 h at room temperature, and the solvent was removed in vacuo. The residue was triturated with ether, dried in vacuo, and redissolved in CH2Cl2 (10 mL). CF3CO2H (20 μL, 0.25 mmol) was added and the solution stirred for 3.5 h open to air. The solvent was removed in vacuo, triturated with ether, and dried in vacuo to leave a brown residue (0.28 g, 108% yield, residual CH2Cl2). 1H NMR (400 MHz, DMSO-d6, δ): 7.92 (m, 2H), 7.1-7.4 (m, 4H), 3.58 (m, 2H), 3.0-3.4 (m, 20H), 2.0-2.8 (m, 28H), 2.3 (s, 6H), 1.4-2.0 (m, 24H); IR (ATR): νC═O=1688 cm−1, νC═N=1616 cm−1.
Synthesis of AC-5.
Intermediate AC-3 (0.20 g, 0.29 mmol), 1,1,3,3-tetramethylguanidine (0.21 mL, 1.71 mmol), K2CO3 (0.39 g, 2.85 mmol) and AcCN (2 mL) were combined in a sealed vial and reacted as in AC-4, except that the residue was also washed with hexanes. 1H NMR (400 MHz, CDCl3, δ): 8.23 (d, 2H), 6.95 (s, 2H), 6.80 (s, 2H), 3.35 (m, 2H), 3.1 (m, 4H), 2.7-2.8 (m, 24H), 2.48 (m, 4H), 2.20 (s, 6H), 1.4-2.0 (m, 16H); IR (ATR): νC═N=1594 cm−1. The residue was reacted as in AC-4. IR (ATR): νC═O=1690 cm−1, νC═N=1610 cm−1.
Synthesis of AC-6.
Intermediate AC-3 (0.32 g, 0.44 mmol), morpholine (0.16 mL, 1.77 mmol), K2CO3 (0.61 g, 4.4 mmol) and AcCN (4 mL) were combined in a sealed vial and reacted as in AC-4, except that the residue was also washed with a NaOAc buffer (pH=4) solution to remove residual morpholine. 1H NMR (400 MHz, CDCl3, δ): 8.22 (s, 2H), 6.92 (s, 2H), 6.79 (s, 2H), 3.69 (m, 8H), 3.28 (m, 2H), 2.2-2.5 (m, 16H), 2.19 (s, 6H), 1.4-2.0 (m, 16H). The residue was reacted as in AC-4. 1H NMR (400 MHz, DMSO-d6, δ): 7.91 (s, 2H), 7.23 (s, 2H), 7.14 (s, 2H), 3.6 (m, 2H), 3.52 (m, 8H), 2.99 (m, 2H), 2.57 (s, 6H), 2.47 (m, 4H), 2.2-2.5 (m, 12H), 1.4-2.0 (m, 16H); IR (ATR): νC═O=1671 cm−1, νC═N=1630 cm−1.
Additional ligands AC-13 and AC-14 were synthesized using the conditions described for compounds AC-4 through AC-6 and are summarized in Scheme E9b and Table E9:














TABLE E9






Q
1H NMR spectraa
IRb


Compound
(Scheme E9b)
(δ, ppm)
(cm−1)







AC-13




8.25 (s, 2H), 7.02 (d,  2H), 6.77 (d, 2H), 3.7  (m, 8H), 3.3 (m, 2H),  2.2-2.6 (m, 12H), 1.3- 2.0 (m, 20H), 1.37 (s,  18H)
νC═N = 1628


 


AC-14





νC═N = 1629





a400 MHz, CDCl3.


bAll compounds exhibited the loss of a peak at 1213 cm−1 attributed to the CH2I group in AC-1.






Example 10
Confirmation of inventive concepts, processes, methods, and compositions described herein has been provided, among other ways, through publication by others after the priority date of the present case. For example, Examples 10-27 describe working Examples presented in Chinese Patent Application No. 200810229276.1, published as CN 101412809A. Additional experimental and characterization data are described by Lu and co-workers, J. Am. Chem. Soc., 2009, 131, 11509-11518, and supporting information available at www.pubs.acs.org, the entirety each of which is hereby incorporated by reference.
In certain embodiments, provided catalysts and/or methods for the preparation of polycarbonate are characterized by one or more of the following: retaining high catalytic activity at low catalyst concentration; reaction conditions that are relatively mild; high catalytic activity with high selectivity for polymer product; alternate structure in the polycarbonate product higher than 97% with relatively narrow distribution of molecular weight; retaining high catalytic activity for copolymerization of carbon dioxide and epoxides at higher reaction temperatures (e.g., above 50° C., above 75° C., or above 100° C.); and catalysts that can be used to catalyze the polymerization of carbon dioxide with two or more alkylene oxides for the synthesis of polycarbonate polymer.
The following materials were added sequentially into a stainless steel high pressure reactor of effective volume of 200 mL at ambient temperature: 0.1 mmole of cobalt complex I-a (R1 is cyclohexyl diamine, X is NO3−1 anion; R2═H; R3, R4 and R5 are tertiary butyl; group containing organic base group is at position 3 of the benzene ring in the ligand, n is 2) and one mole of propylene oxide. The reactor was then filled with carbon dioxide and the pressure is maintained constant at 2.0 MPa. The temperature was controlled at 25° C. The content was stirred with a magnetic stirring bar for 6 hours and the remaining carbon dioxide was slowly released. The remaining alkylene oxide was collected in −20° C. cold trap and a certain amount of mixture of methanol/chloroform was added to dissolve the high polymer. Then a large amount of diethyl ether was added to precipitate the polycarbonate. The precipitate was filtered and washed several times with diethyl ether and dried in vacuum to constant weight to afford 27 grams of polycarbonate as a white solid. The average molecular weight of the polymer was determined by gel permeation chromatography to be 101,000 g/mol with a molecular weight distribution of 1.24. A Varian INOVA-400 MHz Nuclear Magnetic Resonance spectrometer was used to determine its 1H-NMR and the result showed that the alternate structure is over 99%.




Example 11
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the molar ratio of catalyst to propylene oxide was changed from 1:10000 to 1:50000 (0.02 mmole of catalyst and 1 mole of propylene oxide were used). The reaction was carried out at 25° C. for 24 hours to afford 21 grams of poly(propylene carbonate) with a molecular weight of 223,000 g/mol and a molecular weight distribution of 1.29. The polymer formed contained more than 99% carbonate linkages.
Example 12
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the molar ratio of catalyst to propylene oxide was changed from 1:10000 to 1:200000 (0.008 mmole of catalyst and 1.6 mole of propylene oxide were used). The reaction was carried out at 50° C. for 10 hours to afford 19 grams of poly(propylene carbonate) with a molecular weight of 318,000 g/mol and a molecular weight distribution of 1.37. The polymer formed contained more than 99% carbonate linkages.
Example 13
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the molar ratio of catalyst to propylene oxide was changed from 1:10000 to 1:2000 (0.5 mmole of catalyst and 1 mole of propylene oxide were used). The reaction was carried out at 25° C. for 3 hours to afford 48 grams of poly(propylene carbonate) with a molecular weight of 52,800 g/mol and a molecular weight distribution of 1.30. The polymer formed contained more than 99% carbonate linkages.
Example 14
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the reaction temperature was changed from 25° C. to 100° C. and the reaction was carried out for 0.5 hours to afford 34 grams of poly(propylene carbonate) with a molecular weight of 112,400 g/mol and a molecular weight distribution of 1.38. The polymer formed contained more than 99% carbonate linkages.
Example 15
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the reaction temperature was changed from 25° C. to 10° C. and the reaction was carried out for 10 hours to afford 18 grams of poly(propylene carbonate) with a molecular weight of 914,000 g/mol and a molecular weight distribution of 1.38. The polymer formed contained more than 99% carbonate linkages.
Example 16
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the propylene oxide was replaced with 1,2-butylene oxide. The reaction was carried out at 25° C. for 6 hours to afford 31 grams of poly(butylene carbonate) with a molecular weight of 127,000 g/mol and a molecular weight distribution of 1.21. The polymer formed contained more than 99% carbonate linkages.
Example 17
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the propylene oxide was replaced with 1,2-octylene oxide. The reaction was carried out at 25° C. for 10 hours to afford 34 grams of poly(octylene carbonate) with a molecular weight of 109,000 g/mol and a molecular weight distribution of 1.38. The polymer formed contained more than 99% carbonate linkages.
Example 18
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the propylene oxide was replaced with a mixture of propylene oxide and cyclohexylene oxide (the molar ratio of the catalyst to propylene oxide and cyclohexylene oxide was 1:5000:5000). The reaction was carried out at 50° C. for 6 hours to afford 59 grams of poly(propylene-co-cyclohexene carbonate) with a molecular weight of 187,000 g/mol and a molecular weight distribution of 1.29. The polymer formed contained more than 99% carbonate linkages.
Example 19
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the axial anion in the cobalt complex I-a was changed from nitrate radical to acetate moiety. The reaction was carried out at 25° C. for 6 hours to afford 34 grams of poly(propylene carbonate) with a molecular weight of 95,000 g/mol and a molecular weight distribution of 1.28. The polymer formed contained more than 99% carbonate linkages.
Example 20
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the diamine skeleton in the cobalt complex I-a was changed from cyclohexane diamine to ethylene diamine. The reaction was carried out at 25° C. for 6 hours to afford 29 grams of poly(propylene carbonate) with a molecular weight of 112,000 g/mol and a molecular weight distribution of 1.20. The polymer formed contained more than 99% carbonate linkages.
Example 21
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the diamine skeleton in the cobalt complex I-a was changed from cyclohexane diamine to o-phenylene diamine. The reaction was carried out at 25° C. for 6 hours to afford 25 grams of poly(propylene carbonate) with a molecular weight of 92,000 g/mol and a molecular weight distribution of 1.15. The polymer formed contained more than 99% carbonate linkages.
Example 22
The following materials were added sequentially into a stainless steel high pressure reactor of volume of 200 mL at ambient temperature: 0.1 mmole of cobalt complex I-b (R1 is 1,2-propylene diamine, X is dinitrophenyl anion; R2═H; R1 is tertiary butyl; there are organic base groups at position 5 of the two benzene rings in the ligand, n is 0) and 1 mole of propylene oxide. The reactor was then filled with carbon dioxide and the pressure was maintained constant at 2.0 MPa. The reaction was carried out at 25° C. for 6 hours to afford 23 grams of polycarbonate as a white solid. The average molecular weight of the polymer was determined by gel permeation chromatography to be 81,000 g/mol with a molecular weight distribution of 1.34. The polymer formed contained more than 99% carbonate linkages.




Example 23
The following materials were added sequentially into a stainless steel high pressure reactor of volume of 200 mL at ambient temperature: 0.1 mmole of cobalt complex I-c (R1 is ethylene diamine, X is dinitrophenyl anion; R2=H; R3 is tertiary butyl; there are organic base groups at position 3 and position 5 of one of the benzene rings in the ligand, n is 0) and 1 mole of propylene oxide. The reactor was then filled with carbon dioxide and the pressure was maintained constant at 2.0 MPa. The reaction was carried out at 25° C. for 6 hours to afford 23 grams of polycarbonate as a white solid. The average molecular weight of the polymer was determined by gel permeation chromatography to be 81,000 g/mol with a molecular weight distribution of 1.34. The polymer formed contained more than 99% carbonate linkages.




Example 24
The following materials are added sequentially into a stainless steel high pressure reactor of volume of 200 mL at ambient temperature: 0.1 mmole of cobalt complex I-b (R1 is ethylene diamine, X is dinitrophenyl anion; R2=H; R3 and R4 are tertiary butyl; there are organic base groups at position 5 of the two benzene rings in the ligand, n is 0) and 1 mole of propylene oxide. The reactor was then filled with carbon dioxide and the pressure was maintained constant at 2.0 MPa. The reaction was carried out at 25° C. for 6 hours to afford 26 grams of polycarbonate as a white solid. The average molecular weight of the polymer was determined by gel permeation chromatography to be 83,000 g/mol with a molecular weight distribution of 1.19. The polymer formed contained more than 99% carbonate linkages. The polymer formed contained more than 99% carbonate linkages.
Example 25
The following materials are added sequentially onto a stainless steel high pressure reactor of volume of 200 mL at ambient temperature: 0.1 mmole of cobalt complex I-a (R1 is 2,3-butylene diamine, X is nitrate anion; R2=H; R3 and R4 are methoxyl group; R1 is tertiary butyl; there is an organic base group at position 3 of one of the benzene rings in the ligand, n is 2) and 1 mole of propylene oxide. The reactor was then filled with carbon dioxide and the pressure is maintained constant at 2.0 MPa. The reaction was carried out at 25° C. for 6 hours to afford 22 grams of polycarbonate as a white solid. The average molecular weight of the polymer was determined by gel permeation chromatography to be 73,000 g/mol with a molecular weight distribution of 1.14. The polymer formed contained more than 99% carbonate linkages.
Example 26
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the pressure was changed from 2.0 MPa to 0.1 MPa. The reaction was carried out at 25° C. for 10 hours to afford 25 grams of poly(propylene carbonate) with a molecular weight of 100,400 g/mol and a molecular weight distribution of 1.17. The polymer formed contained more than 99% carbonate linkages.
Example 27
The same equipment and reaction conditions were employed as in Example 10 with the same catalyst and the same conditions except that the pressure was changed from 2.0 MPa to 6.0 MPa. The reaction was carried out at 25° C. for 6 hours to afford 29 grams of poly(propylene carbonate) with a molecular weight of 125,000 g/mol and a molecular weight distribution of 1.25. The polymer formed contained more than 99% carbonate linkages.







TABLE E10





Summary of Examples 10-27.

















Reaction Conditions













Catalyst

Cat.
Epoxide
P
T
t























Ex
Cat
R1
R2
R3
R4
R5
X
n

(mmol)
(mg)
(mmol)
MPa
psi
(deg C.)
(h)





10
I-a
Cy
H
tBu
tBu
tBu
NO3
2
PO
0.1
70.5
1000
2
290
25
6


11









0.02
14.1
1000
2
290
25
24


12









0.008
5.64
1600
2
290
50
10


13









0.5
353
1000
2
290
25
3


14









0.1
70.5
1000
2
290
100
0.5


15









0.1
70.5
1000
2
290
10
10


26









0.1
70.5
1000
0.1
15
25
10


27









0.1
70.5
1000
6
870
25
6


16








BO
0.1
70.5
1000
2
290
25
6


17








OO
0.1
70.5
1000
2
290
25
10


18








PO/CHO
0.1
70.5
1000
2
290
50
6


19

Cy
H
tBu
tBu
tBu
OAc
2
PO
0.1
70.2
1000
2
290
25
6


20

En
H
tBu
tBu
tBu
NO3
2
PO
0.1
65.1
1000
2
290
25
6


21

Ph
H
tBu
tBu
tBu
NO3
2
PO
0.1
69.9
1000
2
290
25
6


25

Bu
H
OMe
OMe
tBu
NO3
2
PO
0.1
62.7
1000
2
290
25
6


22
I-b
Pr

tBu


DNP
0
PO
0.1
89
1000
2
290
25
6


24
I-b
En
H
tBu


DNP
0
PO
0.1
87.7
1000
2
290
25
6


23
I-c
En
H
tBu
tBu

DNP
0
PO
0.1
88.2
1000
2
290
25
6












Results















PPC

TOF
MW

g PC/
kg PC/

















Ex
yield (g)
conv. (%)
TON
(h−1)
(kDa)
PDI
g Cat
mol Cat.







10
27
26.4
2644
441
101
1.2
383
270



11
21
20.6
10284
429
233
1.3
1489
1050



12
19
11.6
23262
2326
318
1.4
3369
2375



13
48
47.0
940
313
53
1.3
136
96



14
34
33
3330
6660
112
1.4
482
340



15
18
17.6
1763
176
914
1.4
255
180



26
25
24.5
2449
244.9
100
1.2
355
250



27
29
28.4
2840
473.4
125
1.3
411
290



16
31
26.7
2669
444.9
127
1.2
440
310



17
34
19.7
1974
197.4
109
1.4
482
340



18
59





837
590



19
34
33.3
3330
555
95
1.3
484
340



20
29
28.4
2840
473
112
1.2
446
290



21
25
24.5
2449
408
92
1.2
358
250



25
22
21.5
2155
359.1
73
1.1
351
220



22
23
22.5
2253
375
81
1.3
258
230



24
26
25.5
2547
424.4
83
1.2
296
260



23
23
22.5
2253
375.4
81
1.3
261
230










While we have described a number of embodiments of this invention, it is apparent that our basic examples may be altered to provide other embodiments that utilize the compounds and methods of this invention. Therefore, it will be appreciated that the scope of this invention is to be defined by the appended claims rather than by the specific embodiments that have been presented by way of example.

## Claims

1. A metal complex of the formula:



wherein:
M is cobalt;






comprises a salen ligand; and
(Z)m represents one or more activating moieties tethered to the salen ligand, where  represents a linker moiety;
m is an integer between 1 and 4 inclusive and represents the number of Z groups present on a linker moiety; and
each (Z) represents an activating moiety comprising a guanidinium group.

2. The metal complex of claim 1, wherein the guanidinium group has a formula:



wherein
X− is an anion;
each occurrence of R1 and R2 is independently an optionally substituted radical selected from the group consisting of C1-20 aliphatic, C1-20 heteroaliphatic; phenyl, a 3- to 8-membered saturated or partially unsaturated monocylic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle, a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein two or more R1 and R2, groups can be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more additional heteroatoms.

3. The metal complex of claim 1, wherein the guanidinium group has a formula:



wherein
X− is an anion; and
each of R4, R5, R6, R7, and R8 is independently hydrogen or C1-20 aliphatic, where any of (R4 and R5), (R5 and R6), (R6 and R7), (R7 and R8), and (R4 and R7) can be taken together with intervening atoms to form rings.

4. The metal complex of claim 3, wherein one or more of R4, R5, R6, and R7, is optionally substituted C1-12 aliphatic.

5. The metal complex of claim 3, wherein (R4 and R5) and (R6 and R7) are taken together to form rings.

6. The metal complex of claim 5, wherein



comprises:




where
R1a and R1a′ are independently a  (Z)m group, hydrogen, or an optionally substituted radical selected from the group consisting of: C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle; a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen and sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 atoms independently selected from nitrogen, oxygen and sulfur; and a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms selected from nitrogen, oxygen and sulfur;
Rd at each occurrence is independently a (Z)m group, hydrogen, halogen, —OR, —NR2, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2; —CNO, —NRSO2R, —NCO, —N3, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; where two or more Rd groups may be taken together with intervening atoms to form one or more optionally substituted rings optionally containing one or more heteroatoms,
R4b is selected from the group consisting of:




where
Rc at each occurrence is independently a (Z)m group, hydrogen, halogen, —OR, —NR2, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2; —CNO, —NRSO2R, —NCO, —N3, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; where two or more Rc groups may be taken together with the carbon atoms to which they are attached and any intervening atoms to form one or more optionally substituted rings; when two Rc groups are attached to the same carbon atom, they may optionally be taken together along with the carbon atom to which they are attached to form an optionally substituted moiety selected from the group consisting of: a 3- to 8-membered spirocyclic ring, a carbonyl, an oxime, a hydrazone, and an imine;
Y is a divalent linker selected from the group consisting of: —NR—, —N(R)C(O)—, —C(O)NR—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO2—, —SiR2—, —C(═S)—, —C(═NR)—, or —N═N—; a polyether; a C3 to C8 substituted or unsubstituted carbocycle; and a C1 to C8 substituted or unsubstituted heterocycle;
R at each occurrence is independently hydrogen, an optionally substituted radical selected the group consisting of acyl; C1-6 aliphatic; C1-6 heteroaliphatic; carbamoyl; arylalkyl; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; an oxygen protecting group; and a nitrogen protecting group, where two R groups on the same nitrogen atom can optionally be taken together to form an optionally substituted 3- to 7-membered ring,
X′ is a nucleophile capable of ring opening an epoxide;
m′ is 0 or an integer from 1 to 4, inclusive;
m′′ is 0 or an integer from 1 to 6, inclusive;
q is 0 or an integer from 1 to 4, inclusive; and
x is 0, 1, or 2.

7. The metal complex of claim 5, wherein



is selected from the group consisting of:




where




represents an optionally substituted moiety linking the two nitrogen atoms, and is selected from the group consisting of: phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or an optionally substituted C2-20 aliphatic group, wherein one or more methylene units are optionally and independently replaced by —NRy—, —N(Ry)C(O)—, —C(O)N(Ry)—, —OC(O)N(Ry)—, —N(Ry)C(O)O—, —OC(O)O—, —O—, —C(O)—, —OC(O)—, —C(O)O—, —S—, —SO—, —SO2—, —C(═S)—, —C(═NRy)—, —C(═NORy)— or —N═N;
R4a, R4a′, R5a, R5a′, R6a, and R6a′ are each independently a (Z)m group, hydrogen, halogen, —OR, —NR2, —SR, —CN, —NO2, —SO2R, —SOR, —SO2NR2; —CNO, —NRSO2R, —NCO, —N3, —SiR3; or an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; wherein any two adjacent R4a, R4a′, R5a, R5a′, R6a, and R6a′ groups can be taken together with intervening atoms to form one or more optionally substituted rings,
R′ represents one or more substituents optionally present on the phenyl ring and each R′ is independently selected from the group consisting of: halogen, —NO2, —CN, —SRy, —S(O)Ry, —S(O)2Ry, —NRyC(O)Ry, —OC(O)Ry, —CO2Ry, —NCO, —N3, —OR7, —OC(O)N(Ry)2, —N(Ry)2, —NRyC(O)Ry, —NRyC(O)ORy; and an optionally substituted radical selected from the group consisting of C1-20 aliphatic; C1-20 heteroaliphatic; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, where two or more adjacent R′ groups can be taken together to form an optionally substituted saturated, partially unsaturated, or aromatic 5- to 12-membered ring containing 0 to 4 heteroatoms;
R at each occurrence is independently hydrogen, an optionally substituted radical selected the group consisting of acyl; C1-6 aliphatic; C1-6 heteroaliphatic; carbamoyl; arylalkyl; phenyl; a 3- to 8-membered saturated or partially unsaturated monocyclic carbocycle, a 7-14 carbon saturated, partially unsaturated or aromatic polycyclic carbocycle; a 5- to 6-membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 3- to 8-membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; a 6- to 12-membered polycyclic saturated or partially unsaturated heterocycle having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and an 8- to 10-membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur; an oxygen protecting group; and a nitrogen protecting group, where two R groups on the same nitrogen atom can optionally be taken together to form an optionally substituted 3- to 7-membered ring,
Ry is —H, or an optionally substituted radical selected from the group consisting of C1-6 aliphatic, 3- to 7-membered heterocyclic, phenyl, and 8- to 10-membered aryl;
X′ is a nucleophile capable of ring opening an epoxide; and
k is 1.

8. The metal complex of claim 7, wherein the metal complex comprises a substructure conforming to a formula selected from the group consisting of:

9. The metal complex of claim 8, wherein  comprises a C3-30 aliphatic group.

10. The metal complex of claim 9, wherein  comprises a C4-8 aliphatic group.

11. The metal complex of claim 9, wherein  comprises a C3 aliphatic group.

12. The metal complex of claim 8, wherein  is selected from the group consisting of:






where s=0-6 and t=1-4
where * represents the site of attachment to the ligand, and each # represents a site of attachment the guanidinium activating moiety.

13. The metal complex of claim 6, wherein X′ is selected from the group consisting of: chlorine, bromine, an optionally substituted C1-12 carboxylate, azide, an optionally substituted phenoxide, and sulfonate.

14. The metal complex of claim 13, wherein X′ is selected from the group consisting of: chloride, acetate, trifluoroacetate, azide, pentafluorobenzoate, and a nitrophenolate.

15. A method for the synthesis of aliphatic polycarbonate polymers comprising the step of contacting one or more epoxides with carbon dioxide in the presence of a metal complex of claim 1.

16. The method of claim 15, wherein the epoxide is selected from the group consisting of: ethylene oxide, propylene oxide, butylene oxide, cyclohexene oxide, 1,2 octene oxide, 3-vinyl cyclohexene oxide, epichlorohydrin and mixtures of any two or more of these.

17. The method of claim 16, wherein the epoxide is ethylene oxide, propylene oxide, or cyclohexene oxide.

18. The method of claim 15, wherein the epoxide is ethylene oxide.

19. The method of claim 15, wherein the epoxide is propylene oxide.

20. The method of claim 15, wherein a pressure of carbon dioxide is between about 50 and 800 psi.