Ring-opening metathesis polymerization of bridged bicyclic and polycyclic olefins containing two or more heteroatoms

A method is provided for synthesizing a polymer in a controlled fashion using a ring-opening metathesis polymerization (ROMP) reaction, wherein polymerization is carried out using a catalytically effective amount of an olefin metathesis catalyst and a bridged bicyclic or polycyclic olefin monomer that contains at least two heteroatoms directly or indirectly linked to each other. Preferred catalysts are Group 8 transition metal complexes, particularly complexes of Ru and Os. Such complexes include the ruthenium bisphosphine complex (PCy3)2(Cl)2Ru═CHPh (1) and the ruthenium carbene complex (IMesH2)(PCy3)(Cl)2Ru═CHPh (2). The invention also provides novel regioregular polymers synthesized using the aforementioned methodology, wherein the polymers may be saturated, unsaturated, protected, and/or telechelic. An exemplary polymer is poly((vinyl alcohol)2-alt-methylene)(MVOH).

TECHNICAL FIELD

This invention relates generally to synthesis of polymers, including regioregular and telechelic polymers, via ring-opening metathesis polymerization (ROMP). More particularly, the invention pertains to synthesis of regioregular polymers via a ROMP reaction using bridged bicyclic and polycyclic olefin monomers and a Group 8 transition metal complex as the metathesis catalyst. The polymers provided herein have utility in a variety of fields, including not only polymer chemistry per se, but also in the pharmaceutical, biomedical, and packaging industries.

BACKGROUND OF THE INVENTION

Interest in making well-defined linear polymers substituted with polar and/or functional groups has been spurred, in part, by the commercial utility of ethylene-vinyl alcohol (EVOH) copolymers. EVOH copolymers, as a class, exhibit excellent barrier properties toward gases and hydrocarbons and have found use in the food packaging, biomedical, and pharmaceutical industries. See Lagaron et al. (2001)Polym. Testing20:569-577, and Ramakrishnan (1991)Macromolecules24:3753-3759. Furthermore, the lack of understanding of the property-structure relationships in these materials has fueled academic interest in the microstructure of EVOH copolymers. See Ramakrishnan (1991), supra; Ramakrishnan (1990)Macromolecules23:4519-4524; Valenti et al. (1998)Macromolecules31:2764-2773; and Bruzaud et al. (2000)Macromol. Chem. Phys. 201:1758-1764. The most widely employed synthetic route to EVOH copolymers is the free radical polymerization of ethylene and vinyl acetate, followed by saponification (Ramakrishnan (1990)). These EVOH copolymers contain a degree of branching, much like low-density polyethylene (LDPE), and have a random distribution of alcohol functionality along the polymer backbone ((Ramakrishnan (1991); Valenti et al., supra), both of which limit the elucidation of the structure-property relationships in these materials.

The direct incorporation of polar functional groups along the backbone of linear polymers made via ring-opening metathesis polymerization (“ROMP”) is now possible due to the development of functional group-tolerant late transition metal olefin metathesis catalysts. Recently, Hillmyer et al. reported the ROMP of alcohol-, ketone-, halogen-, and acetate-substituted cyclooctenes with a ruthenium olefin metathesis catalyst (Hillmyer et al. (1995)Macromolecules28: 6311-6316). However, the asymmetry of the substituted cyclooctene allowed for head-to-head (HH), head-to-tail (HT), and tail-to-tail (TT) coupling, yielding polymer with regiorandom placement of the functional groups. A similar problem was encountered by Chung et al., who reported the ROMP of a borane-substituted cyclooctene with an early transition metal catalyst followed by oxidation to yield an alcohol functionalized linear polymer (Ramakrishnan et al. (1990), supra). A solution to this regiorandom distribution of functional groups was reported by Valenti et al., who used the acyclic diene metathesis (ADMET) polymerization of an alcohol-containing symmetric diene (Valenti et al., supra; Schellekens et al. (2000)J. Mol. Sci. Rev. Macromol. Chem. Phys. C40:167-192)) However, the molecular weights of these polymers were restricted to <3×104g/mol by ADMET, and their rich hydrocarbon content limits the barrier properties of the final EVOH copolymers (Lagaron et al., supra).

Transition metal carbene complexes, particularly ruthenium and osmium carbene complexes, have been described as metathesis catalysts in U.S. Pat. Nos. 5,312,940, 5,342,909, 5,831,108, 5,969,170, 6,111,121, and 6,211,391 to Grubbs et al., assigned to the California Institute of Technology. The ruthenium and osmium carbene complexes disclosed in these patents all possess metal centers that are formally in the +2 oxidation state, have an electron count of 16, and are penta-coordinated. Such complexes have been disclosed as useful in catalyzing a variety of olefin metathesis reactions, including ROMP, ring closing metathesis (“RCM”), acyclic diene metathesis polymerization (“ADMET”), ring-opening metathesis (“ROM”), and cross-metathesis (“CM” or “XMET”) reactions. Examples of such catalysts are (PCy3)2(Cl)2Ru═CHPh (1) and (IMesH2)(PCy3)(Cl)2Ru═CHPh (2):
In the above molecular structures, “Mes” represents mesityl(2,4,6-trimethylphenyl), “Ph” is phenyl, and “Cy” is cyclohexyl.

Catalysts (1) and (2) have been shown to afford the ROMP of many substituted cyclic olefins. See, for example, Bielawski et al. (2000)Angew. Chem., Int. Ed. 39:2903-2906; Sanford et al. (2001)J. Am. Chem. Soc. 123:6543-6554; Amir-Ebrahimi et al. (2000)Macromolecules33:717-724; and Hamilton et al. (2000)J. Organomet. Chem606:8-12. Recent development of ruthenium catalysts, such as (2), coordinated with an N-heterocyclic carbene has allowed for the ROMP of low-strain cyclopentene and substituted cyclopentene. Bielawski et al., supra. The ROMP of a symmetric cyclopentene yields a regioregular polyalkene, as no difference exists between HH, HT, and TT couplings. Hence, the ROMP of alcohol- or acetate-disubstituted cyclopentene monomers was attempted (Scheme 1).

Unfortunately, neither catalyst (1) nor the more active (2) could afford the ROMP of these cyclopentene monomers.

Accordingly, there is a need in the art for a method of synthesizing polymers using catalysts that are tolerant of functional groups and a process that enables precise control over molecular weight, molecular weight distribution, and polydispersity. Ideally, such a method would also be useful in the synthesis of regioregular and/or telechelic polymers. The invention is directed to such a method, and now provides a highly effective polymerization process in which a ROMP reaction is carried out using substituted bridged bicyclic or polycyclic olefin monomers and a transition metal carbene complex such as (1) or (2). The process can be used to synthesize regioregular and/or telechelic polymers, in a manner that enables careful control over polymer properties such as molecular weight and polydispersity.

SUMMARY OF THE INVENTION

The invention is directed, in part, to a method for synthesizing a polymer using a ring-opening metathesis polymerization (ROMP) reaction, wherein the reaction is carried out by contacting a bridged bicyclic or polycyclic olefin monomer with a catalytically effective amount of an olefin metathesis catalyst under reaction conditions effective to allow the ROMP reaction to occur. The bridged bicyclic or polycyclic olefin monomer contains a plurality of heteroatoms, i.e., two or more heteroatoms, with two (or possibly more, if present) heteroatoms directly or indirectly linked to each other. By a “bridged” bicyclic or polycyclic olefin is meant that three carbon atoms in the molecule are ring atoms in two different cyclic structures.

The olefin metathesis catalyst for carrying out the aforementioned polymerization reaction is preferably a Group 8 transition metal complex having the structure of formula (I)
in which:M is a Group 8 transition metal;L1and L2are neutral electron donor ligands;X1and X2are anionic ligands; andR1and R2are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups,wherein any two or more of X1, X2, L1, L2, R1, and R2can be taken together to form a cyclic group, and further wherein any one or more of X1, X2, L1, L2, R1, and R2may be attached to a support.

Preferred catalysts contain Ru or Os as the Group 8 transition metal, with Ru particularly preferred.

The catalysts of the second group are transition metal carbene complexes, preferably ruthenium carbene complexes, wherein L2is as defined above and L1is a carbene having the structure of formula (II)
such that the complex has the structure of formula (IIA)
wherein:X1, X2, L1, L2, R1, and R2are as defined above;X and Y are heteroatoms selected from N, O, S, and P;p is zero when X is O or S, and p is 1 when X is N or P;q is zero when Y is O or S, and q is 1 when Y is N or P;Q1, Q2, Q3, and Q4are independently selected from hydrocarbylene, substituted hydrocarbylene, heteroatom-containing hydrocarbylene, substituted heteroatom-containing hydrocarbylene, and —(CO)—, and further wherein two or more substituents on adjacent atoms within Q may be linked to form an additional cyclic group;w, x, y, and z are independently zero or 1; andR3, R3A, R4, and R4Aare independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, and substituted heteroatom-containing hydrocarbyl,wherein any two or more of X1, X2, L2, R1, R2, R3, R3A, R4, and R4Acan be taken together to form a cyclic group, and further wherein any one or more of X1, X2, L2, R1, R2, R3, R3A, R4, and R4Amay be attached to a support.

The second group of catalysts, accordingly, is exemplified by the ruthenium carbene complex (IMeSH2)(PCY3)(Cl)2Ru═CHPh (2):

Additional transition metal carbene complexes useful as catalysts in conjunction with the present invention include, but are not limited to, neutral ruthenium or osmium metal carbene complexes containing metal centers that are formally in the +2 oxidation state, have an electron count of 16, are penta-coordinated, and are of the general formula (IIIA). Other preferred metathesis catalysts include, but are not limited to, cationic ruthenium or osmium metal carbene complexes containing metal centers that are formally in the +2 oxidation state, have an electron count of 14, are tetra-coordinated, and are of the general formula (IIIB). Still other preferred metathesis catalysts include, but are not limited to, neutral ruthenium or osmium metal carbene complexes containing metal centers that are formally in the +2 oxidation state, have an electron count of 18, are hexa-coordinated, and are of the general formula III(C).
In the foregoing structures, X1, X2, L1, L2, R1, and R2are as defined previously, r and s are independently zero or 1, t is an integer in the range of zero to 5, Y is any noncoordinating anion, Z1and Z2are independently selected from —O—, —S—, —NR2—, —PR2—, —P(═O)R2—, —P(OR2)—, —P(═O)(OR2)—, —C(═O)—, —C(═O)O—, —OC(═O)13, —OC(═O)O—, —S(═O)—, or —S(═O)2—, and any two or more of X1, X2, L1, L2, Z1, Z2, R1, and R2may be taken together to form a cyclic group, e.g., a multidentate ligand, and wherein any one or more of X1, X2, L1, L2, Z1, Z2, R1, and R2may be attached to a support.

The bridged bicyclic or polycyclic olefin monomer has the structure of formula (VII)
wherein:X3and X3Aare heteroatoms selected from O, N, and S;X4is a one-atom or two-atom linkage (with a “one-atom” linkage referring to a linkage that provides a single, optionally substituted spacer atom between the two adjacent carbon atoms, and a “two-carbon” linkage, similarly, referring to a linkage that provides two optionally substituted spacer atoms between the two adjacent carbon atoms);k is zero when one or both of X3or X3Aare N, and k is 1 when neither X3or X3Ais N;m is zero when X3is O or S, and m is 1 when X3is N;n is zero when X3Ais O or S, and n is 1 when X3Ais N;one of R15and R16is hydrogen and the other is selected from hydrogen, hydrocarbyl (e.g., C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, C5-C20aryl, C6-C24alkaryl and C6-C24aralkyl), substituted hydrocarbyl (e.g., substituted C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, C5-C20aryl, C6-C24alkaryl, and C6-C24aralkyl), heteroatom-containing hydrocarbyl (e.g., heteroatom-containing C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, C5-C20aryl, C6-C24alkaryl, and C6-C24aralkyl), substituted heteroatom-containing hydrocarbyl (e.g., substituted heteroatom-containing C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, C5-C20aryl, C6-C24alkaryl, and C6-C24aralkyl), and —(L)v—Fn wherein v is zero or 1, L is hydrocarbylene, substituted hydrocarbylene and/or heteroatom-containing hydrocarbylene, and Fn is a functional group;P* is a protecting group that is inert under polymerization conditions but removable from the synthesized polymer; andR17and R18are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and amino protecting groups, wherein R17and R18may be taken together to form a cyclic group.

The ROMP reaction results in protected, unsaturated regioregular polymers when X4is a single atom linkage, e.g., a methylene group, and when —X3(R17)mis identical to —X3A(R18)n. These unsaturated regioregular polymers can be hydrogenated to give the corresponding saturated polymers, which are then deprotected to yield the final polymeric product. As an example, starting with monomers wherein X3and X3Aare O, X4is methylene, and R15and R16are hydrogen, the polymer synthesized via ROMP is an unsaturated, protected analog of poly((vinyl alcohol)2-alt-methylene)(MVOH), which can then be hydrogenated and deprotected to give MVOH per se (see Examples 1, 3 and 4).

In another embodiment, the reaction is carried out in the presence of a chain transfer agent, i.e., an α,ω-difunctional olefin, so as to provide a telechelic polymer. If the initial bicyclic or polycyclic olefin monomer contains a single atom linkage at X4, and —X3(R17)mis identical to —X3A(R18)n, as above, the telechelic polymer is regioregular.

The invention also provides, as novel compositions of matter, regioregular polymers that are synthesized using the methodology of the invention. The polymers are saturated or unsaturated, and, in a first embodiment, are comprised of recurring units having the structure of formula (XV)
wherein:m, k, X3, R17, and P* are as defined with respect to the cyclic olefin monomers of formula (VII);α is an optional double bond; andX4is a single-atom linkage having the structure CR19R20wherein R19and R20are independently selected from hydrogen, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups;

The polymer may be telechelic, in which case the polymer terminates in two functional groups that enable further reaction.

In another embodiment, the polymers are comprised of recurring units having the structure of formula (X)
wherein X3, X4, R17, and m are defined as for formula (XV), and further wherein the polymer may be telechelic and terminate in two functional groups, as described above with respect to polymers of formula (XV).

The invention represents a substantial improvement relative to prior synthetic methods that have been used to prepare ethylene-(vinyl alcohol) (EVOH) and analogous polymers and copolymers having pendant heteroatom-containing functional groups. That is, prior methods for synthesizing such polymers resulted in random distribution of hydroxyl groups or other functionalities along the polymer backbone, limiting the utility of the polymers prepared. Earlier routes to polymers within the aforementioned class also resulted in branched and/or relatively low molecular weight polymers (less than about 30,000). See, e.g., Ramakrishnan (1990), Ramakrishnan (1991), Valenti et al. (1998), Lagaron et al. (2001), and Schellekens et al. (2000)J. Mol. Sci. Rev. Macromol. Chem. Phys. C40:167-192. By contrast, the present methodology allows for polymer synthesis to take place in a controlled fashion over a large molecular weight range, such that the molecular weight, molecular weight distribution, polydispersity index (PDI), and linearity of the resulting polymer product can be controlled. In addition, completely regioregular polymers can be prepared by using a symmetric bicyclic or polycyclic olefin as the monomeric substrate for the ROMP reaction.

DETAILED DESCRIPTION OF THE INVENTION

I. Definitions and Nomenclature

It is to be understood that unless otherwise indicated this invention is not limited to specific reactants, reaction conditions, ligands, metal complexes, or the like, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

As used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a compound” encompasses a combination or mixture of different compounds as well as a single compound, reference to “a substituent” includes a single substituent as well as two or more substituent groups that may or may not be the same, and the like.

As used herein, the phrase “having the formula” or “having the structure” is not intended to be limiting and is used in the same way that the term “comprising” is commonly used.

The term “alkyl” as used herein refers to a linear, branched, or cyclic saturated hydrocarbon group typically although not necessarily containing 1 to about 20 carbon atoms, preferably 1 to about 12 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, octyl, decyl, and the like, as well as cycloalkyl groups such as cyclopentyl, cyclohexyl and the like. Generally, although again not necessarily, alkyl groups herein contain 1 to about 12 carbon atoms. The term “lower alkyl” intends an alkyl group of 1 to 6 carbon atoms, and the specific term “cycloalkyl” intends a cyclic alkyl group, typically having 4 to 8, preferably 5 to 7, carbon atoms. The term “substituted alkyl” refers to alkyl substituted with one or more substituent groups, and the terms “heteroatom-containing alkyl” and “heteroalkyl” refer to alkyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms “alkyl” and “lower alkyl” include linear, branched, cyclic, unsubstituted, substituted, and/or heteroatom-containing alkyl and lower alkyl, respectively.

The term “alkylene” as used herein refers to a difunctional linear, branched, or cyclic alkyl group, where “alkyl” is as defined above.

The term “alkenyl” as used herein refers to a linear, branched, or cyclic hydrocarbon group of 2 to about 20 carbon atoms containing at least one double bond, such as ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl, eicosenyl, tetracosenyl, and the like. Preferred alkenyl groups herein contain 2 to about 12 carbon atoms. The term “lower alkenyl” intends an alkenyl group of 2 to 6 carbon atoms, and the specific term “cycloalkenyl” intends a cyclic alkenyl group, preferably having 5 to 8 carbon atoms. The term “substituted alkenyl” refers to alkenyl substituted with one or more substituent groups, and the terms “heteroatom-containing alkenyl” and “heteroalkenyl” refer to alkenyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms “alkenyl” and “lower alkenyl” include linear, branched, cyclic, unsubstituted, substituted, and/or heteroatom-containing alkenyl and lower alkenyl, respectively.

The term “alkenylene” as used herein refers to a difunctional linear, branched, or cyclic alkenyl group, where “alkenyl” is as defined above.

The term “alkynyl” as used herein refers to a linear or branched hydrocarbon group of 2 to about 20 carbon atoms containing at least one triple bond, such as ethynyl, n-propynyl, and the like. Preferred alkynyl groups herein contain 2 to about 12 carbon atoms. The term “lower alkynyl” intends an alkynyl group of 2 to 6 carbon atoms. The term “substituted alkynyl” refers to alkynyl substituted with one or more substituent groups, and the terms “heteroatom-containing alkynyl” and “heteroalkynyl” refer to alkynyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms “alkynyl” and “lower alkynyl” include linear, branched, unsubstituted, substituted, and/or heteroatom-containing alkynyl and lower alkynyl, respectively.

The term “alkoxy” as used herein intends an alkyl group bound through a single, terminal ether linkage; that is, an “alkoxy” group may be represented as —O-alkyl where alkyl is as defined above. A “lower alkoxy” group intends an alkoxy group containing 1 to 6 carbon atoms, and includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, t-butyloxy, etc. Analogously, “alkenyloxy” and “lower alkenyloxy” respectively refer to an alkenyl and lower alkenyl group bound through a single, terminal ether linkage, and “alkynyloxy” and “lower alkynyloxy” respectively refer to an alkynyl and lower alkynyl group bound through a single, terminal ether linkage.

The term “aryl” as used herein, and unless otherwise specified, refers to an aromatic substituent containing a single aromatic ring or multiple aromatic rings that are fused together, directly linked, or indirectly linked (such that the different aromatic rings are bound to a common group such as a methylene or ethylene moiety). Preferred aryl groups contain 5 to 20 carbon atoms and either one aromatic ring or 2 to 4 fused or linked aromatic rings, e.g., phenyl, naphthyl, biphenyl, and the like, with more preferred aryl groups containing 1 to 3 aromatic rings, and particularly preferred aryl groups containing 1 or 2 aromatic rings and 5 to 14 carbon atoms. “Substituted aryl” refers to an aryl moiety substituted with one or more substituent groups, and the terms “heteroatom-containing aryl” and “heteroaryl” refer to aryl in which at least one carbon atom is replaced with a heteroatom. Unless otherwise indicated, the terms “aromatic,” “aryl,” and “arylene” include heteroaromatic, substituted aromatic, and substituted heteroaromatic species.

The term “aryloxy” as used herein refers to an aryl group bound through a single, terminal ether linkage, wherein “aryl” is as defined above. An “aryloxy” group may be represented as —O-aryl where aryl is as defined above. Preferred aryloxy groups contain 5 to 20 carbon atoms, and particularly preferred aryloxy groups contain 5 to 14 carbon atoms. Examples of aryloxy groups include, without limitation, phenoxy, o-halo-phenoxy, m-halo-phenoxy, p-halo-phenoxy, o-methoxy-phenoxy, m-methoxy-phenoxy, p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy, 3,4,5-trimethoxy-phenoxy, and the like.

The term “alkaryl” refers to an aryl group with an alkyl substituent, and the term “aralkyl” refers to an alkyl group with an aryl substituent, wherein “aryl” and “alkyl” are as defined above. Preferred aralkyl groups contain 6 to 24 carbon atoms, and particularly preferred aralkyl groups contain 6 to 16 carbon atoms. Examples of aralkyl groups include, without limitation, benzyl, 2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl, 4-phenylcyclohexyl, 4-benzylcyclohexyl, 4-phenylcyclohexylmethyl, 4-benzylcyclohexylmethyl, and the like. Alkaryl groups include, for example, p-methylphenyl, 2,4-dimethylphenyl, p-cyclohexylphenyl, 2,7-dimethylnaphthyl, 7-cyclooctylnaphthyl, 3-ethyl-cyclopenta-1,4-dienyl, and the like.

The terms “halo,” “halide,” and “halogen” are used in the conventional sense to refer to a chloro, bromo, fluoro, or iodo substituent. The terms “haloalkyl,” “haloalkenyl,” and “haloalkynyl” (or “halogenated alkyl,” “halogenated alkenyl,” and “halogenated alkynyl”) refer to an alkyl, alkenyl, or alkynyl group, respectively, in which at least one of the hydrogen atoms in the group has been replaced with a halogen atom.

“Hydrocarbyl” refers to univalent hydrocarbyl radicals containing 1 to about 30 carbon atoms, preferably 1 to about 20 carbon atoms, more preferably 1 to about 12 carbon atoms, including linear, branched, cyclic, saturated, and unsaturated species, such as alkyl groups, alkenyl groups, aryl groups, and the like. The term “lower hydrocarbyl” intends a hydrocarbyl group of 1 to 6 carbon atoms, and the term “hydrocarbylene” intends a divalent hydrocarbyl moiety containing 1 to about 30 carbon atoms, preferably 1 to about 20 carbon atoms, most preferably 1 to about 12 carbon atoms, including linear, branched, cyclic, saturated and unsaturated species. The term “lower hydrocarbylene” intends a hydrocarbylene group of 1 to 6 carbon atoms. Unless otherwise indicated, the terms “hydrocarbyl” and “hydrocarbylene” are to be interpreted as including substituted and/or heteroatom-containing hydrocarbyl and hydrocarbylene moieties, respectively.

The term “heteroatom-containing” as in a “heteroatom-containing alkyl group” (also termed a “heteroalkyl” group) or a “heteroatom-containing aryl group” (also termed a “heteroaryl” group) refers to a molecule, linkage, or substituent in which one or more carbon atoms are replaced with an atom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus or silicon, typically nitrogen, oxygen or sulfur. Similarly, the term “heteroalkyl” refers to an alkyl substituent that is heteroatom-containing, the term “heterocyclic” refers to a cyclic substituent that is heteroatom-containing, the terms “heteroaryl” and heteroaromatic” respectively refer to “aryl” and “aromatic” substituents that are heteroatom-containing, and the like. Examples of heteroalkyl groups include alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylated amino alkyl, and the like. Examples of heteroaryl substituents include pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, etc., and examples of heteroatom-containing alicyclic groups are pyrrolidino, morpholino, piperazino, piperidino, etc. It should be noted that a “heterocyclic” group or compound may or may not be aromatic, and further that “heterocycles” may be monocyclic, bicyclic, or polycyclic as described above with respect to the term “aryl.”

In addition, the aforementioned functional groups may, if a particular group permits, be further substituted with one or more additional functional groups or with one or more hydrocarbyl moieties such as those specifically enumerated above. Analogously, the above-mentioned hydrocarbyl moieties may be further substituted with one or more functional groups or additional hydrocarbyl moieties such as those specifically enumerated.

When the term “substituted” appears prior to a list of possible substituted groups, it is intended that the term apply to every member of that group. That is, the phrase “substituted alkyl, alkenyl and alkynyl” is to be interpreted as “substituted alkyl, substituted alkenyl and substituted alkynyl.” Analogously, the term “optionally substituted alkyl, alkenyl and alkynyl” is to be interpreted as “optionally substituted alkyl, optionally substituted alkenyl and optionally substituted alkynyl,” and a “bridged bicyclic or polycyclic olefin monomer” is to be interpreted as a “bridged bicyclic olefin monomer” or a “bridged polycyclic olefin monomer.”

The term “regioregular polymer” is used to refer to a polymer with a regular arrangement of the “connectivity” between the monomer units.

The term “telechelic” is used in the conventional sense to refer to a macromolecule, e.g., a polymer, that is capped by at least one reactive end group. Preferred telechelic compounds herein are regioregular polymers having two terminal functional groups each capable of undergoing further reaction.

“Optional” or “optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. For example, the phrase “optionally substituted” means that a non-hydrogen substituent may or may not be present on a given atom, and, thus, the description includes structures wherein a non-hydrogen substituent is present and structures wherein a non-hydrogen substituent is not present.

In the molecular structures herein, the use of bold and dashed lines to denote particular conformation of groups follows the IUPAC convention. A bond indicated by a broken line indicates that the group in question is below the general plane of the molecule as drawn (the “α” configuration), and a bond indicated by a bold line indicates that the group at the position in question is above the general plane of the molecule as drawn (the “β” configuration).

The ring-opening metathesis polymerization reactions of the invention are carried out catalytically, using a Group 8 transition metal complex as the catalyst. These transition metal carbene complexes include a metal center in a +2 oxidation state, have an electron count of 16, and are penta-coordinated. The complexes are represented by the structure of formula (I)
wherein the various substituents are as follows:

M, which serves as the transition metal center in the +2 oxidation state, is a Group 8 transition metal, particularly ruthenium or osmium. In a particularly preferred embodiment, M is ruthenium.

In preferred catalysts, the R1substituent is hydrogen and the R2substituent is selected from C1-C20alkyl, C2-C20alkenyl, and C5-C20aryl. More preferably, R2is phenyl, vinyl, methyl, isopropyl, or t-butyl, optionally substituted with one or more moieties selected from C1-C6alkyl, C1-C6alkoxy, phenyl, and a functional group Fn as defined in part (I) of this section. Still more preferably, R2is phenyl or vinyl substituted with one or more moieties selected from methyl, ethyl, chloro, bromo, iodo, fluoro, nitro, dimethylamino, methyl, methoxy, and phenyl. In the most preferred embodiments, the R2substituent is phenyl or —C═C(CH3)2.

It should be emphasized that any two or more (typically two, three, or four) of X1, X2, L1, L2, R1, and R2can be taken together to form a cyclic group, as disclosed, for example, in U.S. Pat. No. 5,312,940 to Grubbs et al. When any of X1, X2, L1, L2, R1, and R2are linked to form cyclic groups, those cyclic groups may be five- or six-membered rings, or may comprise two or three five- or six-membered rings, which may be either fused or linked. The cyclic groups may be aliphatic or aromatic, and may be heteroatom-containing and/or substituted, as explained in part (I) of this section.

The cyclic group may, in some cases, form a bidentate ligand or a tridentate ligand. Examples of bidentate ligands include, but are not limited to, bisphosphines, dialkoxides, alkyldiketonates, and aryldiketonates. Specific examples include —P(Ph)2CH2CH2P(Ph)2—, —As(Ph)2CH2CH2As(Ph2)—, —P(Ph)2CH2CH2C(CF3)2O—, binaphtholate dianions, pinacolate dianions, —P(CH3)2(CH2)2P(CH3)2—, and —OC(CH3)2(CH3)2CO—. Preferred bidentate ligands are —P(Ph)2CH2CH2P(Ph)2— and —P(CH3)2(CH2)2P(CH3)2—. Tridentate ligands include, but are not limited to, (CH3)2NCH2CH2P(Ph)CH2CH2N(CH3)2. Other preferred tridentate ligands are those in which any three of X1, X2, L1, L2, R1, and R2(e.g., X1, L1, and L2) are taken together to be cyclopentadienyl, indenyl, or fluorenyl, each optionally substituted with C2-C20alkenyl, C2-C20alkynyl, C1-C20alkyl, C5-C20aryl, C1-C20alkoxy, C2-C20alkenyloxy, C2-C20alkynyloxy, C5-C20aryloxy, C2-C20alkoxycarbonyl, C1-C20alkylthio, C1-C20alkylsulfonyl, or C1-C20alkylsulfinyl, each of which may be further substituted with C1-C6alkyl, halide, C1-C6alkoxy or with a phenyl group optionally substituted with halide, C1-C6alkyl, or C1-C6alkoxy. More preferably, in compounds of this type, X, L1, and L2are taken together to be cyclopentadienyl or indenyl, each optionally substituted with vinyl, C1-C10alkyl, C5-C20aryl, C1-C10carboxylate, C2-C10alkoxycarbonyl, C1-C10alkoxy, or C5-C20aryloxy, each optionally substituted with C1-C6alkyl, halide, C1-C6alkoxy or with a phenyl group optionally substituted with halide, C1-C6alkyl or C1-C6alkoxy. Most preferably, X, L1and L2may be taken together to be cyclopentadienyl, optionally substituted with vinyl, hydrogen, methyl, or phenyl. Tetradentate ligands include, but are not limited to O2C(CH2)2P(Ph)(CH2)2P(Ph)(CH2)2CO2, phthalocyanines, and porphyrins.

In a first group of catalysts, L1is as defined for L2, and, in this embodiment, L1and L2will generally, although not necessarily, be the same. In these catalysts, L1and L2are typically phosphines of the formula PR5R6R7, where R5, R6, and R7are as defined earlier herein. As above, the most preferred L1and L2ligands, in this first catalyst group, are selected from tricyclohexylphosphine, tricyclopentylphosphine, triisopropylphosphine, triphenylphosphine, diphenylmethylphosphine, and phenyldimethylphosphine, with tricyclohexylphosphine and tricyclopentylphosphine particularly preferred. These catalysts are, accordingly, exemplified by ruthenium bisphosphine complexes such as (PCy3)2(Cl)2Ru═CHPh (1).

In a second group of catalysts, the complexes are ruthenium carbene complexes, wherein L1has the structure of formula (II)
such that the complexes have the structure of formula (IIA)
wherein the substituents are as follows:

X and Y are heteroatoms typically selected from N, O, S, and P. Since O and S are divalent, p is necessarily zero when X is O or S, and q is necessarily zero when Y is O or S. However, when X is N or P, then p is 1, and when Y is N or P, then q is 1. In a preferred embodiment, both X and Y are N.Q1, Q2, Q3, and Q4are linkers, e.g., hydrocarbylene (including substituted hydrocarbylene, heteroatom-containing hydrocarbylene, and substituted heteroatom-containing hydrocarbylene, such as substituted and/or heteroatom-containing alkylene) or —(CO)—, and w, x, y, and z are independently zero or 1, meaning that each linker is optional. Preferably, w, x, y, and z are all zero. Further, two or more substituents on adjacent atoms within Q may be linked to form an additional cyclic group.

In addition, any two or more of X1, X2, L2, R1, R2, R3, R3A, R4, and R4Acan be taken together to form a cyclic group, and any one or more of X1, X2, L2, R1, R2, R3, R3A, R4, and R4Amay be attached to a support, as explained above with respect to complexes of formula (I).

Preferably, R3Aand R4Aare linked to form a cyclic group, such that the complexes of this embodiment have the structure of formula (IV)
wherein R3and R4are defined above, with preferably at least one of R3and R4, and more preferably both R3and R4, being alicyclic or aromatic of one to about five rings, and optionally containing one or more heteroatoms and/or substituents. Q is a linker, typically a hydrocarbylene linker, including substituted hydrocarbylene, heteroatom-containing hydrocarbylene, and substituted heteroatom-containing hydrocarbylene linkers, wherein two or more substituents on adjacent atoms within Q may also be linked to form an additional cyclic structure, which may be similarly substituted to provide a fused polycyclic structure of two to five cyclic groups. Q is often, although again not necessarily, a two-atom linkage or a three-atom linkage, e.g., —CH2—CH2—, —CH(Ph)—CH(Ph)— where Ph is phenyl; ═CR—N═, giving rise to an unsubstituted (when R═H) or substituted (R=other than H) triazolyl group; and —CH2—SiR2—CH2— (where R is H, alkyl, alkoxy, etc.).

In a more preferred embodiment, Q is a two-atom linkage having the structure —CR8R9—CR10R11— or —CR8═CR10—, preferably —CR8R9—CR10R11—, in which case the complex has the structure of formula (V)
wherein R8, R9, R10, and R11are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups as defined in part (I) of this section. Examples of functional groups here include carboxyl, C1-C20alkoxy, C5-C20aryloxy, C2-C20alkoxycarbonyl, C2-C20alkoxycarbonyl, C2-C20acyloxy, C1-C20alkylthio, C5-C20arylthio, C1-C20alkylsulfonyl, and C1-C20alkylsulfinyl, optionally substituted with one or more moieties selected from C1-C10alkyl, C1-C10alkoxy, C5-C20aryl, hydroxyl, sulfhydryl, formyl, and halide. Alternatively, any two of R8, R9, R10, and R11may be linked together to form a substituted or unsubstituted, saturated or unsaturated ring structure, e.g., a C4-C12alicyclic group or a C5or C6aryl group, which may itself be substituted, e.g., with linked or fused alicyclic or aromatic groups, or with other substituents.

Examples of such catalysts include, but are not limited to, the following:

Additional transition metal carbene complexes include, but are not limited to:neutral ruthenium or osmium metal carbene complexes containing metal centers that are formally in the +2 oxidation state, have an electron count of 16, are penta-coordinated, and are of the general formula (IIIA);cationic ruthenium or osmium metal carbene complexes containing metal centers that are formally in the +2 oxidation state, have an electron count of 14, are tetra-coordinated, and are of the general formula (IIIB); andneutral ruthenium or osmium metal carbene complexes containing metal centers that are formally in the +2 oxidation state, have an electron count of 18, are hexa-coordinated, and are of the general formula III(C)
wherein X1, X2, L1, L2, R1, and R2are as defined previously, r and s are independently zero or 1, t is an integer in the range of zero to 5, Y is any noncoordinating anion (e.g., a halide ion), Z1and Z2are independently selected from —O—, —S—, —NR2—, —PR2—, —P(═O)R2—, —P(OR2)—, —P(═O)(OR2)—, —C(═O)—, —C(═O)O—, —OC(═O)—, —OC(═O)O—, —S(═O)—, or —S(═O)2—, and any two or more of X1, X2, L1, L2, Z1, Z2, R1, and R2may be taken together to form a cyclic group, e.g., a multidentate ligand, and wherein any one or more of X1, X2, L1, L2, Z1, Z2, R1, and R2may be attached to a support. As understood in the field of catalysis, suitable solid supports may be of synthetic, semi-synthetic, or naturally occurring materials, which may be organic or inorganic, e.g., polymeric, ceramic, or metallic. Attachment to the support will generally, although not necessarily, be covalent, and the covalent linkage may be direct or indirect, if indirect, typically through a functional group on a support surface.

The transition metal complexes used as catalysts herein can be prepared by several different methods, such as those described by Schwab et al. (1996)J. Am. Chem. Soc. 118:100-110, Scholl et al. (1999)Org. Lett. 6:953-956, Sanford et al. (2001)J. Am. Chem. Soc. 123:749-750, U.S. Pat. Nos. 5,312,940 and 5,342,909. Also see U.S. patent application Ser. No. 10/115,581 to Grubbs, Morgan, Benitez, and Louie, filed Apr. 2, 2002, for “One-Pot Synthesis of Group 8 Transition Metal Carbene Complexes Useful as Olefin Metathesis Catalysts,” commonly assigned herewith to the California Institute of Technology.

The transition metal complexes used as catalysts herein, particularly the ruthenium carbene complexes, have a well-defined ligand environment that enables flexibility in modifing and fine-tuning the activity level, stability, solubility and ease of recovery of these catalysts. See, e.g., U.S. Pat. No. 5,849,851 to Grubbs et al. In addition, the solubility of the carbene complexes may be controlled by proper selection of either hydrophobic or hydrophilic ligands, as is well known in the art. The desired solubility of the catalyst will largely be determined by the solubility of the reaction substrates and reaction products. It is well known in the art to design catalysts whose solubility is distinguishable from that of the reaction substrates and products, thereby facilitating recovery of the catalyst from the reaction mixture.

III. Synthesis of Polymers via Romp

In one embodiment, the invention is directed to a method for synthesizing a polymer using a ring-opening metathesis polymerization (ROMP) reaction, comprising contacting a bridged bicyclic or polycyclic olefin monomer with a catalytically effective amount of an olefin metathesis catalyst under reaction conditions effective to allow the ROMP reaction to occur, wherein the olefin monomer contains a plurality of heteroatoms, at least two of which are directly or indirectly linked to each other. By “directly” linked is meant that the two heteroatoms are linked to each other through a direct, covalent bond. By “indirectly” linked is meant that one or more spacer atoms are present between the heteroatoms; generally, the “indirect” linkage herein refers to the presence of a single atom (that may or may not be substituted) to which each heteroatom is linked through a direct covalent bond. Preferably, the bicyclic or polycyclic olefin monomer contains one double bond, and the two heteroatoms are symmetrically positioned with respect to any axis that is perpendicular to the double bond.

As an example, the bicyclic or polycyclic olefin monomer may be represented by the structure of formula (VII)
wherein the various substituents are as follows:X3and X3Aare heteroatoms selected from O, N and S, and P* is a protecting group. The definitions of k, m, and n derive from the identity of the X3and X3Aheteroatoms. That is, k is zero when one or both of X3or X3Aare N, and is 1 when neither X3nor X3Ais N. Therefore, if one of X3and X3Ais N and the other is N or O, the monomer contains a direct covalent bond between two nitrogen atoms or between a nitrogen atom and an oxygen atom, whereas when X3and X3Aare O or S, the monomer contains a linkage P* between X3and X3A, where P* serves as a protecting group for both heteroatoms. In addition, m is necessarily zero when X3is O or S, and is 1 when X3is N. Similarly, n is necessarily zero when X3Ais O or S, and n is 1 when X3Ais N.X4is a one-atom or two-atom linkage, i.e., a linkage that introduces one or two optionally substituted spacer atoms between the two carbon atoms to which X4is bound. Generally, although not necessarily, X4will be of the formula —CR19R20—(X5)h— wherein h is zero or 1, X5is CR21R22, O, S, or NR23, and R19, R20, R21, R22, and R23are independently selected from hydrogen, hydrocarbyl (e.g., C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, C5-C20aryl, C6-C24alkaryl, C6-C24aralkyl, C1-C20alkyl, C5-C20aryl, C5-C30aralkyl, or C5-C30alkaryl), substituted hydrocarbyl (e.g., substituted C1-C20alkyl, C2-C20alkenyl, C2-C20alkynyl, C5-C20aryl, C6-C24alkaryl, C6-C24aralkyl, C1-C20alkyl, C5-C20aryl, C5-C30aralkyl, or C5-C30alkaryl), heteroatom-containing hydrocarbyl (e.g., C1-C20heteroalkyl, C5-C20heteroaryl, heteroatom-containing C5-C30aralkyl, or heteroatom-containing C5-C30alkaryl), substituted heteroatom-containing hydrocarbyl (e.g., substituted C1-C20heteroalkyl, C5-C20heteroaryl, heteroatom-containing C5-C30aralkyl, or heteroatom-containing C5-C30alkaryl) and functional groups such as those enumerated in part (I) of this section.

When h is 1, preferred linkages are wherein X5is CR21R22, giving rise to a substituted or unsubstituted ethylene moiety. That is, when R19, R20, R21, and R22are hydrogen, then X4is ethylene. When h is zero, the linkage is substituted or unsubstituted methylene, and a particularly preferred linkage within this group is methylene per se (i.e., when R19and R20are both hydrogen.)

P*, as indicated above, is a protecting group. P* is inert with respect to the reagents and reaction conditions used for polymerization, as well as the reagents and conditions used for any subsequent reactions (e.g., hydrogenation, as described infra), but must be removable following completion of ROMP and any subsequent polymer modification reactions. As may be deduced from the structure of formula (VII) and the above definitions, P* is a protecting group for functional groups having the structure —X3H (or —X3AH), wherein X3(or X3A) is O or S. Accordingly, when X3and X3Aare O or S, P* will be a protecting group “linkage” used to protect 1,3-diols and 1,3-dithiols, respectively. A number of such bifunctional protecting groups are known in the art and described, for example, in Greene et al.,Protective Groups in Organic Synthesis, 3rdEd. (New York: Wiley, 1999). In the present method, a preferred protecting group for 1,3-diols (i.e., cyclic olefins of formula (VII) wherein X3and X3Ais OH) is —Si(R24)2— wherein R24is tertiary alkyl, preferably tertiary lower alkyl, e.g., t-butyl, and the deprotecting agent normally used is tetrabutylammonium fluoride. Other preferred protecting groups for 1,3-diols are cyclic acetals and ketals, such as methylene acetal, ethylidene acetal, t-butylmethylidene ketal, 1-t-butylethylidene ketal, 1-phenylethylidene ketal, cyclopentylidene ketal, cyclohexylidene ketal, benzylidene acetal, and acetonide (isopropylidene ketal), with acetonide particularly preferred. Such groups are typically removed via acid hydrolysis, preferably, although not necessarily, at an elevated temperature. With acetonide-protected 1,3-diols, deprotection may be achieved not only via acid hydrolysis, but also using other means, e.g., with boron trichloride or bromine. Preferred protecting groups for 1,3-dithiols (i.e., cyclic olefins of formula (VII) wherein X3is SH) are methylene, benzylidene (both removable with sodium/ammonia), and isopropylidene (removable with mercury (II) chloride).

R17and R18are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and amino protecting groups. R17and R18may also be linked to form a protecting group linking the nitrogen atoms to which they are attached. Removal of such protecting groups and regeneration of the unprotected amino moieties can be carried out using the method of Bøgevig et al. (2002)Angew. Chem. Int. Ed. 41:1790-1793.

Representative olefin monomers in which X3and X3Aare different are those wherein k and m are zero, n is 1, X3is O, X3Ais N, and R18is an amino protecting group, e.g., a carboxylic acid ester such as —(CO)—O-t-Bu. When X4is methylene, and R15and R16are hydrogen, the monomer is 2-oxa-3-aza-bicyclo[2.2.1]hept-5-ene-3-carboxylic acid t-butyl ester, having the structure (VIIA)
The monomer can be readily synthesized using a hetero-Diels Alder reaction. See Mulvihill et al. (1998),J. Org. Chem. 63:3357. Following polymerization, deprotection can be achieved using the method of Vogt et al. (1998)Tetrahedron54:1317-1348.

Representative olefin monomers in which X3and X3Aare the same are those wherein X3and X3Aare O, k is 1, m, and n are zero, and P* is a protecting group for 1,3-diols. When X4is methylene, and R15and R16are hydrogen, an exemplary monomer is 3,3-di-tert-butyl-2,4-dioxa-3-sila-bicyclo[3.2.1]oct-6-ene (compound (3) in the examples):

Regioregular polymers can be readily synthesized using monomers of formula (VII) in which X3Ais identical to X3, X4is methylene or substituted methylene (i.e., CR19R20wherein R19and R20are as defined earlier herein), R18is identical to R17, and n is identical to m, such that the synthesized polymer is an unsaturated regioregular polymer comprised of recurring units having the structure of formula (VIII)

It will be appreciated that when X3is O or S, such that m is zero and k is 1, the unsaturated regioregular polymer is comprised of recurring units having the structure of formula (VIIIA)

The polymerization reaction is generally carried out in an inert atmosphere by dissolving a catalytically effective amount of an olefin metathesis catalyst (preferably a Group 8 transition metal complex of formula (I)) in a solvent, and adding the bicyclic or polycyclic olefin monomer (preferably a monomer of formula (VII)), optionally dissolved in a solvent, to the catalyst solution. Preferably, the reaction is agitated (e.g., stirred). The progress of the reaction can be monitored by standard techniques, e.g., nuclear magnetic resonance spectroscopy. Examples of solvents that may be used in the polymerization reaction include organic, protic, or aqueous solvents that are inert under the polymerization conditions, such as aromatic hydrocarbons, chlorinated hydrocarbons, ethers, aliphatic hydrocarbons, alcohols, water, or mixtures thereof. Preferred solvents include benzene, toluene, p-xylene, methylene chloride, 1,2-dichloroethane, dichlorobenzene, chlorobenzene, tetrahydrofuran, diethylether, pentane, methanol, ethanol, water, or mixtures thereof. More preferably, the solvent is benzene, toluene, p-xylene, methylene chloride, 1,2-dichloroethane, dichlorobenzene, chlorobenzene, tetrahydrofuran, diethylether, pentane, methanol, or ethanol. Most preferably, the solvent is toluene or 1,2-dichloroethane. The solubility of the polymer formed in the polymerization reaction will depend on the choice of solvent and the molecular weight of the polymer obtained. Under certain circumstances, no solvent is needed.

Reaction temperatures can range from about 0° C. to 100° C., and are preferably in the range of about 25° C. to 75° C., and the reaction time will generally be in the range of about 12 to 48 hours. The molar ratio of cyclic olefin monomer to the catalyst is selected based on the desired molecular weight of the polymer, the desired polydispersity index (PDI, defined as Mw:Mn), and the activity of the particular catalyst. As the present method is a controlled polymerization, there is a substantially linear relationship between molecular weight and the monomer/catalyst ratio (see Example 1 and FIGS.2A and2B). With more active catalysts, the polymerization reaction can proceed with far less catalyst, so that the [monomer]/[catalyst] ratio can be extraordinarily high (see Example 2), reducing overall cost significantly. However, to achieve a lower PDI, i.e., a PDI of at most about 1.4, a less active catalyst is desirable, in which case the [monomer]/[catalyst] ratio will be lower (see Example 1). In general, the transition metal carbene complexes of formula (IIA) are more active than the bisphosphine catalysts of formula (I) (i.e., complexes wherein L1and L2are tri-substituted phosphines or analogous ligands, as explained in part (II)). Accordingly, the former catalysts are preferred for minimizing catalyst loading and achieving a broader molecular weight distribution, i.e., a PDI of 2 or more, while the latter catalysts are preferred when higher catalyst loadings are acceptable and a narrower molecular weight distribution, i.e., a PDI of 1.4 or less, is desired. Achieving an Mnof over 200,000 will generally require a molar ratio of monomer to catalyst of 500:1 or more (see Example 2).

In order to provide a saturated regioregular polymer, the unsaturated polymer of formula (VIII) is hydrogenated using conventional reagents and conditions, e.g., using tosyl hydrazide as described in Example 3. The resulting hydrogenated polymer is comprised of recurring units having the structure of formula (IX)
When the unsaturated polymer is comprised of recurring units having the structure of formula (VIIIA), the hydrogenated polymer, correspondingly, is comprised of recurring units having the structure of formula (IXA)

Deprotection of (IX) is then effected as described above, using a reagent effective to provide a deprotected regioregular polymer comprised of recurring units having the formula (X)
which, when X3is O or S, such that m is zero and k is 1, have the structure of formula (XA)

The methodology of the invention also extends to the synthesis of telechelic polymers via a ROMP reaction. Telechelic polymers, as is well known, are macromolecules with one or more reactive end groups. Telechelic polymers are useful materials for chain extension processes, block copolymer synthesis, reaction injection molding, and network formation. Uses for telechelic polymers and syntheses thereof are described in Goethals,Telechelic Polymers: Synthesis and Applications(CRC Press: Boca Raton, Fla., 1989).

For most applications, highly functionalized telechelic polymers are preferred. Thus, it is desirable that the catalyst used to form the telechelic polymer be stable in the presence of functional groups. The Group 8 transition metal complexes described in part (II) are, in fact, stable with respect to a wide variety of functional groups, as described, for example, in U.S. Pat. Nos. 5,312,940, 5,342,909, 5,917,071 5,969,170, 6,111,121, and 6,313,332 to Grubbs et al., and in U.S. patent application Ser. No. 10/114,418 to Grubbs et al., filed Apr. 1, 2002, for “Cross-Metathesis Reaction of Functionalized and Substituted Olefins Using Group 8 Transition Metal Carbene Complexes as Metathesis Catalysts,” all of which are commonly assigned herewith to the California Institute of Technology.

In implementing the present methodology to synthesize telechelic polymers, the ROMP reaction is carried out in the presence of acyclic olefins act that as chain transfer agents to regulate the molecular weight of polymers produced. When α,ω-difunctional olefins are employed as chain transfer agents, difunctional telechelic polymers can be synthesized, and such difunctional olefins are the preferred chain transfer agents herein. When carrying out a ROMP reaction using a symmetric, α,ω-difunctional olefin as a chain transfer agent, the propagating alkylidene generated during the ring-opening metathesis process is terminated with a functional group, and the new functionally substituted alkylidene reacts with a monomer to initiate a new chain. This process preserves the number of active catalyst centers and leads to symmetric telechelic polymers with a functionality that approaches 2.0. The only polymer end groups that do not contain residues from the chain transfer agent are those from the initiating alkylidene and the end-capping reagent. In principle, these end groups could be chosen to match the end group from the chain transfer agent. See U.S. Pat. No. 5,880,231 to Grubbs et al.

Regioregular telechelic polymers can be synthesized with a cyclic olefin monomer of formula (VII) in which X3Ais identical to X3, X4is methylene or substituted methylene (i.e., CR19R20wherein R19and R20are as defined earlier herein), R18is identical to R17, and n is identical to m, such that the telechelic polymer resulting from the ROMP reaction is an unsaturated, regioregular polymer having the structure of formula (XII)
wherein j is the number of recurring monomer units in the polymer, and X3, X4R17, k, and m are as defined with respect to formula (VIII). As above, when X3is O or S, such that k is 1 and m is zero, the telechelic polymer of formula (XII) has the structure of formula (XIIA)

Polymer (XII) may then be hydrogenated, as described previously, to give a saturated telechelic polymer having the structure (XIII)
which, when X3is O or S, such that k is 1 and m is zero, has the structure of formula (XIIIA)

Deprotection of (XIII) provides a saturated, deprotected telechelic polymer having the structure of formula (XIV)
while deprotection of (XIIIA) results in a saturated, deprotected telechelic polymer having the structure of formula (XIVA)

The regioregular polymers provided using the present methodology, including unsaturated, saturated, deprotected, and/or telechelic polymers, are novel polymers and are claimed as such herein. Accordingly, it will be appreciated in light of the above description that novel polymers of the invention include, but are not limited to, polymers of formulae (VIII), (VIIIA), (IX), (IXA), (X), (XA), (XII), (XIIA), (XIII), (XIIIA), (XIV), and (XIVA). Accordingly, the novel polymers can be generally represented as those comprised of recurring units having the structure of formula (XV)
wherein:α is an optional double bond;X3is O, N or S;X4is CR19R20wherein R19and R20are independently selected from hydrogen, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups;k is zero when X3is N, and k is 1 when X3is O or S;m is zero when X3is O or S, and m is 1 when X3is N;R17is selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and amino-protecting groups, or the two R17substituents may be taken together to form a cyclic group; andP* is a protecting group.

The polymer may be telechelic, in which case there are two terminal Z groups as indicated in formulae (XII) through (XIV), such that the polymer has the structure of formula (XVA)
wherein j is the number of recurring monomer units in the polymer X3, X4R17, k, and m are as defined with respect to formula (VIII), and β is an optional double bond, wherein either both α and β are present as double bonds, or neither α nor β is present.

In another embodiment, the polymers are comprised of recurring units having the structure of formula (X)
wherein X3, X4, R17, and m are defined as for formula (XV), wherein, as above, the polymer may be telechelic and terminate in two Z groups, as described above with respect to polymers of formula (XVA).

Such polymers have the structure of formula (XB)

The novel polymers have a number average molecular weight in the range of approximately 1,000 to approximately 1,000,000. In the preferred novel polymers, X3is O or S, and R19and R20are hydrogen, such that the polymers are comprised of dyads having the structure of formula (XVI)
dyads having the structure of formula (XVII)
or combinations thereof, wherein X3is O or S. When X3is O and T1and T2are methyl, the polymer is regioregular MVOH, i.e., poly((vinyl alcohol)2-alt-methylene).

Experimental

General Procedures. NMR spectra were recorded on a Varian Mercury 300 (300 MHz for1H and 74.5 MHz for13C). All NMR spectra were recorded in CDCl3or DMSO-d6and referenced to residual proteo species. Gel permeation chromatography (GPC) was carried out on two PLgel 5 mm mixed-C columns (Polymer Labs) connected in series with a DAWN EOS multiangle laser light scattering (MALLS) detector and an Optilab DSP differential refractometer (both from Wyatt Technology). No calibration standards were used, and dn/dc values were obtained for each injection assuming 100% mass elution from the columns. Differential scanning calorimetry (DSC) and thermogravimetric analysis were carried out simultaneously on a Netzsch STA 449C under a flow of N2at a heating rate of 10° C./min.

Materials. Toluene was dried by passage through solvent purification columns. cis-4-Cyclopentene-1,3-diol (>99%) was obtained from Fluka and used as received. cis-1,4-Diacetoxy-2-butene (95+%) (6) was obtained from TCI America and degassed by an argon purge prior to use. N,N-Dimethylformamide (anhydrous) (DMF), 1,2-dichloroethane (anhydrous), 2,6-lutidine (99+%, redistilled), and di-tert-butylsilylbis(trifluoromethanesulfonate) (97%) were obtained from Aldrich and used as received. (PCy3)2(Cl)2Ru═CHPh (1) was synthesized according to Schwab et al. (1996)J. Am. Chem. Soc. 118:100-110, (ImesH2)-(PCY3)(Cl)2Ru═CHPh (2) was synthesized as described in Sanford et al. (2001)J. Am. Chem. Soc. 123:749-750, and 3,3-di-tert-butyl-2,4-dioxa-3-sila-bicyclo[3.2.1]oct-6-ene (3) was synthesized according to Lang et al. (1994)Helv. Chim. Acta77:1527-1540.

Polymerization of 3,3-di-tert-butyl-2,4-dioxa-3-silabicyclo[3.2.1]oct-6-ene (3) via ROMP with Catalyst (1)

The process was repeated using varying amounts of (1) at 55° C. (Table 1). All polymerizations reached high conversion (≧80%) in approximately 1 day and were fully characterized by1H/13C NMR (FIGS. 1A and 1C) and MALLS/SEC. Over the molecular weight range 2×104to 2.2×105g/mol, PDI values were relatively low and constant for polymers produced in both chlorinated and aromatic solvents. Also, it is evident that the [3]/[1] ratio is reflected in the Mnof each polymer in a linear fashion. The graphs inFIGS. 2A and 2Bdisplay the molecular weight versus [monomer]/[catalyst] ratios for the series P1-4, carried out in toluene, and P5-7, carried out in 1,2-dichloroethane (1,2-DCE). The slopes of the graphs inFIGS. 2A and 2Bdiffer by a factor of approximately 2, which indicates a difference in the initiation rates of catalyst (1) in toluene and 1,2-DCE. Catalyst (1) appears to be initiating more readily in 1,2-DCE (P5-7), as the slope of roughly 1 is obtained when plotting DP vs. [monomer]/[catalyst]. A difference in initiation rates for (1) was previously observed (Sanford et al. (2001)J. Am. Chem. Soc. 123:6543-6554), and these data are consistent with faster initiation in chlorinated vs. aromatic solvents. Low PDI's and the linear relationship between molecular weight vs. [monomer]/[catalyst] are characteristic of a controlled polymerization.

TABLE 1monomer/timeMn(×10−3)Mw(×10−3)polymercatalystd(h)% yieldGPCaGPCaPDIP1b63219021.828.41.3P2b130179739.351.71.3P3b2502495103.4139.21.3P4b5101895222.3309.11.4P5c120218424.233.71.4P6c25027.57755.373.91.3P7c51027.580105.8131.61.2aSamples run in THF; molecular weight values obtained using MALLS with an average dn/dc value of 0.108 mL/g.bPolymerizations run in toluene.cPolymerizations run in 1,2-DCE.dCatalyst (1) used for polymerization.

Polymerization of 3,3-di-tert-butyl-2,4-dioxa-3-silabicyclo[3.2.1]oct-6-ene (3) via ROMP with Catalyst (2) and CTA (5)

Representative procedure for synthesis of an unsaturated, protected, telechelic polymer (Scheme 3): A small vial was charged with 0.25 g (1.0 mmol) of monomer (3) and a stirbar. The monomer was degassed by three freeze-pump-thaw cycles. Under an argon atmosphere, 0.25 mL (1.0×10−2) mmol) of a 6.90 mg/mL solution of (5) (as a charge transfer agent, or “CTA”) in toluene solution was added via a syringe. Then 0.75 mL (5.3×10−5mmol) of a 0.0595 mg/mL solution of (2) in toluene was added via a syringe. The vial was placed in a 55° C. heating apparatus and left stirring under argon for 23-113 h. The reaction mixture was dissolved in 2 mL of dichloromethane and precipitated into 50 mL of stirring methanol. The white polymer precipitate was washed several times with methanol and dried in vacuo overnight; yield of polymer (6) 82-90%.1H NMR (300 MHz, CDCl3): 5.73 trans (m, 2H), 5.35 cis (m, 2H), 5.06 cis (m, 2H), 4.62 trans (d, J=10.2 Hz, 2H), 1.4-1.8 (m, 2H), 1.0 (18H).13C NMR (75 MHz, CDCl3): 131.6, 131.3, 73.5, 43.2, 27.7, 27.6, 23.0, 20.2, 20.1.

The aforementioned process was repeated using different ratios of (3) to (2), different ratios of (3) to (5), and different reaction times, as indicated in Table 2. The molecular weight data is given in Table 2 as well. As may be seen in the table, when complex (2) was used as the ROMP catalyst, the molecular weight of the resulting telechelic polymer was controlled solely by the [monomer]/[CTA] ratio at thermodynamic equilibrium; furthermore, much lower catalyst loadings could be employed, thereby reducing costs considerably. When the ROMP of (3) with CTA (5) was carried out in toluene, the Mnwas controlled by the ratio of [3]/[5], and high conversions were obtained with a catalyst loading up to 4×104.

Entries P8-10 in Table 2 indicate that thermodynamic equilibrium was reached within 24 h, after which the molecular weight and conversion remained constant. As expected, as the monomer]/[CTA] ratio is doubled, the Mnincreases by a factor of 2 (P8 and P11).

TABLE 2monomer/monomer/Mn(×10−3)Mw(×10−3)polymercatalystcCTAtime (h)% yieldGPCaGPCaPDIP820,000100238457.4145.02.5P920,000100708258.3134.32.3P1020,0001001138057.1151.12.6P1140,0002002287120.2278.72.3aSamples run in THF, molecular weight values obtained using MALLS with an average dn/dc value of 0.110 mL/g.bAll polymerizations run in toluene.cCatalyst (2) used for polymerization.

Hydrogenation of Polymers after ROMP

Representative procedure for hydrogenation of protected unsaturated polymers (Scheme 4): A dry flask was charged with 0.35 g of polymer (4), prepared in Example 1 (Mn=80,360, PDI=1.3), 1.80 g of tosyl hydrazide (9.4 mmol, 6.5 equiv per double bond), 15 mL of xylenes, and a trace of BHT. The mixture was degassed by three freeze-pump-thaw cycles, and a reflux condenser was attached to the flask under argon. The reaction was heated to reflux for 4 h. The solution was cooled to room temperature and then precipitated into 125 mL of stirring methanol. The white polymer precipitate was washed several times with methanol and then dried in vacuo overnight; yield of polymer (7) was 0.34 g (99%). Mn=75,140 g/mol, PDI=1.2, dn/dc=0.076.1H NMR (300 MHz, CDCl3): 3.9-4.1 (2H), 1.4-1.7 (6H), 1.0 (18H).13C NMR (75 MHz, CDCl3): 74.1, 73.5, 73.4, 42.4, 42.3, 34.8, 34.3, 27.8, 27.7, 27.3, 22.8, 19.7.

FIG. 1Adisplays the13C NMR spectrum of the unsaturated polymer (4) made with catalyst (1). Upon hydrogenation, the loss of olefinic carbons is clearly evident inFIG. 1Bas the carbon, 1, in the sp2region at 131-132 ppm has disappeared and a new carbon, 1′, appears in the sp3region at 34 ppm.FIG. 1Cdisplays the1H NMR spectrum prior to saturation of the backbone. The four peaks between 4 and 6 ppm inFIG. 1Crepresent the two sets of cis and trans olefin protons, Ha, and methine protons, Hb. For polymers made with catalyst (1) (P1-7), integration is consistent between the two sets with a 1.4/0.6 trans/cis ratio or 70% trans olefins along the polymer backbone, while polymers made with catalyst (2) (P8-11) consisted of 50% trans olefins. These sets of peaks disappear (FIG. 1D) upon hydrogenation as the cis and trans methine protons collapse to a singe peak, Hf, at 4 ppm and new methylene protons, He+Hg/h, appear between 1.4 and 1.6 ppm.

Desilation of Saturated Polymers

Representative procedure for deprotection of protected saturated polymers: A dry flask was charged with 0.1952 g of polymer (7), prepared in Example 3, and a stirbar. A reflux condenser was attached, and the system was purged with argon. 20 mL of dry THF was added followed by 10 mL of dry DMF, at which point the solution became cloudy white. 8 mL of tetrabutylammonium fluoride (TBAF) 1.0 M in THF was added via a syringe. The reaction was brought to reflux (75° C.) for 40 h. It was then cooled to room temperature and precipitated into 400 mL of 1:1 methanol:CH2Cl2stirring at room temperature. A stringy precipitate was observed; it was vacuum-filtered and washed with copious amounts of both methanol and CH2Cl2and dried under dynamic high vacuum overnight to provide polymer (8), poly((vinyl alcohol)2-alt-methylene) (“MVOH”); yield of polymer (8), 0.0713 g (87%).1H NMR (300 MHz, DMSOd6): 4.53 (s, 2H), 3.56 (bs, 2H), 1.2-1.6 (6H).13C NMR (75 MHz, DMSO-d6): 69.3, 69.0, 44.4, 33.6, 33.3.

Once dried, the copolymers prepared using the aforementioned procedure were readily soluble in DMSO (at room temperature), but not in DMF, water, THF, or methanol. Only three sets of carbon resonances were observed in the13C NMR spectrum of poly((vinyl alcohol)2-alt-methylene originating from the ROMP polymer produced with catalyst (1) in DMSO-d6, as shown in FIG.3A. The peaks labeled 1 and 3 inFIG. 3Aeach consists of two peaks as shown in the insets. The13C NMR spectrum of MVOH originating from catalyst (2) differs from the spectrum shown inFIG. 3Aonly in that the peaks labeled 1 and 3 consist of two peaks of equal intensities. Recent research has elucidated the tacticity of poly(vinyl alcohol) (PVA) homopolymer with high-field NMR spectrometers. Nagara et al. report that the chemical shift data for the methine carbon (carbon 3 inFIG. 3A) follows the trend for triads: δmm>δmr/rm>δrr(Nagara et al. (2001) 42:9679-9686). By analogy, the methine region inFIG. 1Ais suggestive of a higher m dyad tacticity for MVOH produced with catalyst 1. In contrast, the equal intensities of these peaks in the material produced with catalyst (2) suggest equal m and r dyad distributions; the m and r dyads are shown below:

The carbon assigned as 2 can only exist in one local environment, as the two alcohol functionalities that surround it must always be in a cis relationship. The1H NMR spectra inFIG. 3Bshows complete removal of the silane protecting group, as no signals are present around 1.0 ppm. The peak at 4.5 ppm, Hd, was assigned to the alcohol protons as it disappeared upon addition of D2O, leaving the peak at 3.6 ppm, Ha, to be assigned to the methine protons. The remaining peaks between 1.2 and 1.6 ppm, Hb/b′+Hc/c′, are assigned as the six methylene protons. All of these assignments are in good agreement with the similar EVOH copolymers previously prepared, and the1H NMR spectra for MVOH made with catalysts (1) and (2) are the same.

Thermal Analysis:FIG. 4Ashows the DSC thermogram of the MVOH copolymer, originating from catalyst 1, with a clear melting transition at 193° C. (peak, 180° C. onset, a Tmof 180° C. was observed for the MVOH originating from catalyst (2)). This high Tmis consistent with a higher vinyl alcohol content in the copolymer as Mori et al. have shown that the Tmof EVOH copolymers varies over the range of ca. 120-200° C. with increasing vinyl alcohol content (Mori et al. (1994)Macromolecules27:1051-1056). The TGA curve displayed inFIG. 4Bshows an onset to decomposition at 360° C. The thermal stability of the MVOH copolymer is substantially better than PVA homopolymer, which displays thermal weight loss slightly below 300° C. A small decrease in weight is observed in the TGA curve around 60° C. and coincides with a large peak in the DSC thermogram. This is consistent with elimination of methanol, likely trapped in the MVOH copolymer upon precipitation. The melting temperature and increased thermal stability relative to PVA are comparable with structurally similar EVOH materials.