BIFU CTIONAL COMPOUNDS

PRIORITY CLAIM

This application claims priority to US Application No. 61/610,083 filed 13 March 2012 which is incorporated herein by reference in its entirety.

FIELD OF THE INVENTION

The invention pertains to the field of chemical synthesis. More particularly, the invention pertains to novel molecules comprising lactones and anhydrides derived from glycidyl acrylates.

DESCRIPTION OF RELATED ART

US Patent No. 6,852,865 describes catalysts and methods for the carbonylation of epoxides, the methods therein can be used to make molecules of the present invention, however no examples of glycidyl acrylates as substrates are disclosed in the '865 patent. US 7,875,734 discloses the beta lactone derived from glycidyl methacrylate, but no uses for this compound are described.

The preparation and polymerization of glycidyl acrylates is well known in the literature. For instance, US Patent No. 2,556,075 describes the synthesis and

polymerization of glycidyl acrylate (CAS 106-92-1), glycidyl methacrylate (CAS 106-91- 2), and glycidyl crotonate (CAS 23584-01-2). US Patent No. 2,772,296 describes additional methods of making glycidyl acrylates. However, there are no literature examples of the uses of the lactone or anhydride analogs of these epoxides, nor of the substances that are hereinbelow described.

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, 75 ^th 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, 5 ^th 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, 3 ^rd 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 other 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 iraws-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, IN 1972).

The terms "halo" and "halogen" as used herein refer to an atom selected from fluorine (fluoro, -F), chlorine (chloro, -CI), 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 1^1 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. 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 or two 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 "heterocycle," "hetercyclyl," "heterocycloaliphatic," or "heterocyclic" groups.

The term "epoxide", as used herein, refers to a substituted or unsubstituted oxirane. 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 "glycidyl", as used herein, refers to an oxirane substituted with a hydroxyl methyl group or a derivative thereof. The term glycidyl as used herein is meant to include moieties having additional substitution on one or more of the carbon atoms of the oxirane ring or on the methylene group of the hydroxymethyl moiety, examples of such substitution may include, but are not limited to: alkyl groups, halogen atoms, aryl groups etc. The terms glycidyl ester, glycidyl acrylate, glydidyl ether etc. denote substitution at the oxygen atom of the above-mentioned hydroxymethyl group, i.e. that oxygen atom is bonded to an acyl group, an acrylate group, or an alkyl group respectively.

The term "acrylate" or "acrylates" as used herein refer to any acyl group having a vinyl group adjacent to the acyl carbonyl. The terms encompass mono-, di- and trisubstituted vinyl groups. Examples of acrylates include, but are not limited to: acrylate, methacrylate, ethacrylate, cinnamate (3-phenylacrylate), crotonate, tiglate, and senecioate. Because it is known that cylcopropane groups can in certain instances behave very much like double bonds, cyclopropane esters are specifically included within the definition of acrylate herein.

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 from an aliphatic moiety containing between one and six carbon atoms by removal of a single hydrogen atom. 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 from a straight- or branched-chain aliphatic moiety having at least one carbon-carbon double bond by the removal of a single hydrogen atom. 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-\ 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, butenyl, l-methyl-2- buten-l-yl, and the like.

The term "alkynyl," as used herein, refers to a monovalent group derived from a straight- or branched-chain aliphatic moiety having at least one carbon-carbon triple bond by the removal of a single hydrogen atom. 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-\ 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, refers 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 carbocyles include cyclopropane, cyclobutane, cyclopentane, cyclohexane, bicyclo[2,2, l]heptane, norbornene, phenyl, cyclohexene, naphthalene, spiro[4.5]decane,

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 five 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 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 π 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]-l,4-oxazin-3(4H)-one. A heteroaryl group may be mono- or bicyclic. The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring",

"heteroaryl group", or "heteroaromatic", any of which terms include rings that are optionally substituted. The term "heteroaralkyl" refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. As used herein, the terms "heterocycle", "heterocyclyl", "heterocyclic radical", and

"heterocyclic ring" are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7-14-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term "nitrogen" includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), ΝΗ (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.

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.

As described herein, compounds of the invention may contain "optionally substituted" moieties. In general, the term "substituted", whether preceded by the term "optionally" or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an "optionally substituted" group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable or chemically feasible compounds. The term "stable", as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein. In some chemical structures herein, substituents are shown attached to a bond which crosses a bond in a ring of the depicted molecule. This means 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. 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; -(CH ₂ )o_4R°; -(CH ₂ )o- ₄ 0R°;

-0-(CH ₂ )o- ₄ C(0)OR ⁰ ; -(CH ₂ )C CH(OR ⁰ ) ₂ ; -(CH ₂ ) ₀ ^SR°; -(CH^Ph, which may be substituted with R°; -(CH ₂ )o-40(CH ₂ )o-iPh which may be substituted with R°; - CH=CHPh, which may be substituted with R°; -N0 ₂ ; -CN; -N ₃ ; -(CH ₂ ) ₀ ^N(R°) ₂ ; - (CH ₂ )o- ₄ N(R°)C(0)R°; -N(R°)C(S)R°; -(CH ₂ ) ₀ - ₄ N(R°)C(O)NR° ₂ ; -N(R°)C(S)NR° ₂ ; - (CH ₂ )o- ₄ N(R°)C(0)OR°; -N(R°)N(R°)C(0)R°; -N(R°)N(R°)C(0)NR° ₂ ; -

N(R ⁰ )N(R°)C(0)OR°; -(CH ₂ ) ₀ _ ₄ C(O)R ^o ; -C(S)R°; -(CH ₂ ) ₀ _ ₄ C(O)OR ^o ; -(CH ₂ y

4C(0)N(R°) ₂ ; -(CH ₂ )o^C(0)SR°; -(CH ₂ )c C(0)OSiR ⁰ 3; -(CH ₂ ) ₀ _ ₄ OC(O)R ^o ; - OC(0)(CH ₂ )o^SR- SC(S)SR°; -(CH ₂ ) ₀ - ₄ SC(O)R°; -(CH ₂ ) ₀ ^C(O)NR° ₂ ; -C(S)NR° ₂ ; - C(S)SR°; -SC(S)SR°, -(CH ₂ ) ₀ ^OC(O)NR° ₂ ; -C(0)N(OR°)R°; -C(0)C(0)R°;

-C(0)CH ₂ C(0)R°; -C(NOR°)R°; -(CH ₂ ) ₀ ^SSR°; -(CH ₂ ) ₀ - ₄ S(O) ₂ R°; -(CH ₂ ) ₀ - ₄ S(O) ₂ OR°; -(CH ₂ )o^OS(0) ₂ R°; -S(0) ₂ NR° ₂ ; -(CH ₂ ) ₀ ^S(O)R°; -N(R°)S(0) ₂ NR° ₂ ; -N(R°)S(0) ₂ R°; -N(OR°)R°; -C(NH)NR° ₂ ; -P(0) ₂ R°; -P(0)R° ₂ ; -OP(0)R° ₂ ; -OP(0)(OR°) ₂ ; SiR° ₃ ; -(Ci_ 4 straight or branched alkylene)0-N(R°) ₂ ; or -(Ci^ straight or branched alkylene)C(0)0- N(R°) ₂ , wherein each R° may be substituted as defined below and is independently hydrogen, Ci-8 aliphatic, -CH ₂ Ph, -0(CH ₂ )o-iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0^1 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R°, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or polycyclic ring having 0^1 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

Suitable monovalent substituents on R° (or the ring formed by taking two independent occurrences of R° together with their intervening atoms), are independently halogen, -(CH ₂ y ₂ R ^e , -(haloR*), -(CH ₂ y ₂ OH, -(CH ₂ y ₂ OR ^e , -(CH ₂ y ₂ CH(OR') ₂ ; -O(haloR'), -CN, -N ₃ , -(CH ₂ y ₂ C(0)R ^e , -(CH ₂ y ₂ C(0)OH, -(CH ₂ y ₂ C(0)OR ^e , -(CH ₂ )o- ₄ C(0)N(R°) ₂ ; -(CH ₂ y ₂ SR ^e , -(CH ₂ y ₂ SH, -(CH ₂ y ₂ NH ₂ , -(CH ₂ y ₂ NHR ^e , -(CH ₂ )o- ₂ NR' ₂ , -N0 ₂ , -SiR's, -OSiR' ₃ , -C(0)SR ^e -(C1-4 straight or branched alkylene)C(0)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 Ci^ aliphatic, -CH ₂ Ph, -O(CH ₂ ) ₀ -iPh, or a 5-6-membered saturated, partially

unsaturated, or aryl ring having 0^1 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R° include =0 and =S.

Suitable divalent substituents on a saturated carbon atom of an "optionally substituted" group include the following: =0, =S, =NNR ^* ₂ , = NHC(0)R ^* ,

= NHC(0)OR ^* , = NHS(0) ₂ R ^* , =NR ^* , =NOR ^* , -0(C(R ^* ₂ )) ₂ _ ₃ 0-, or -S(C(R ^* ₂ )) ₂ _ ₃ S- wherein each independent occurrence of R ^* is selected from hydrogen, Ci_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: -0(CR ₂ ) ₂ _ ₃ 0- wherein each independent occurrence of R is selected from hydrogen, Ci_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(0)OH, -C(0)OR ^e , -NH ₂ , -NHR", -NR' ₂ , or -N0 ₂ , wherein each R* is unsubstituted or where preceded by "halo" is substituted only with one or more halogens, and is independently Ci_4 aliphatic, -CH ₂ Ph, -O(CH ₂ ) ₀ -iPh, or a 5-6- membered saturated, partially unsaturated, or aryl ring having 0^1 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

Suitable substituents on a substitutable nitrogen of an "optionally substituted" group include -R ^† , -NR ^† ₂ , -C(0)R ^† , -C(0)OR ^† , -C(0)C(0)R ^† , -C(0)CH ₂ C(0)R ^† , - S(0) ₂ R ^† , -S(0) ₂ NR ^† ₂ , -C(S)NR ^† ₂ , -C( H)NR ^† ₂ , or -N(R ^† )S(0) ₂ R ^† ; wherein each R ^† is independently hydrogen, Ci_6 aliphatic which may be substituted as defined below, unsubstituted -OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R ^† , taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms

independently selected from nitrogen, oxygen, or sulfur.

Suitable substituents on the aliphatic group of R ^† are independently halogen, -R", -(haloR*), -OH, -OR", -O(haloR'), -CN, -C(0)OH, -C(0)OR ^e , -NH ₂ , -NHR", -NR' ₂ , or -N0 ₂ , wherein each R* is unsubstituted or where preceded by "halo" is substituted only with one or more halogens, and is independently Ci_4 aliphatic, -CH ₂ Ph, -O(CH ₂ ) ₀ -iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0^1 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 of a chemical reaction, while not being consumed or undergoing a permanent chemical change itself. "Tetradentate" refers to ligands having four sites capable of coordinating to a single metal center.

DETAILED DESCRIPTION OF THE INVENTION

Among other things, the present invention encompasses the recognition that bifunctional compounds having the combination of an acrylate moiety and a beta lactone or succinic anhydride functional group have utility as bifunctional reagents and as monomers for the production of new polymeric materials. The invention encompasses novel compounds having this combination of functional groups as well as methods to make and use them, and new polymers incorporating them. (I) Compounds of the invention.

In one aspect, the present disclosure encompasses novel compounds conforming to formula I:

where, R ¹ , R ² , and R ³ are each independently selected from the group consisting of: -H, optionally substituted Ci-12 aliphatic, optionally substituted Ci-12 heteroaliphatic, optionally substituted C6-14 aryl, and optionally substituted 5- to 14-membered heteroaryl; wherein, [R ¹ and R ³ ] or [R ² and R ³ ] can be taken together with intervening atoms to form an optionally substituted cylcoaliphatic or heterocyclic ring; and wherein R ¹ and R ³ may be taken together to be a carbon-carbon bond (in which case R ² is bonded to an alkyne); or wherein R , R , and R are R , R , and R , wherein: R ¹ , R ² , and R ³ are each independently selected from the group consisting of -H, Ci-6 aliphatic, and optionally substituted aryl;

R ¹⁰ and R ¹¹ are each independently selected from an optionally substituted group consisting of: -H, -F, optionally substituted Ci-12 aliphatic, optionally substituted Ci-12 heteroaliphatic, optionally substituted C6-14 aryl, and optionally substituted 5- to 14-membered heteroaryl; where R ¹⁰ and R ¹¹ can can be taken together with the intervening carbon atom to form an optionally substituted spirocycle optionally containing one or more heteroatoms; or wherein R ¹⁰ and R ¹¹ are R ¹² and R ¹³ , wherein:

R ¹² and R ¹³ are each independently selected from the group consisting of -H, -F, optionally substituted Ci-6 aliphatic, and optionally substituted aryl; wherein R ¹² and R ¹³ can be taken together with the intervening carbon atom to form an optionally substituted spirocycle;

R ²⁰ is optionally present, and if present is selected from the group consisting of -F, optionally substituted Ci-12 aliphatic, optionally substituted Ci-12 heteroaliphatic, optionally substituted C6-14 aryl, and optionally substituted 5- to 14-membered heteroaryl; when two or more R ²⁰ groups are present, two or more of them can be taken together with intervening atoms to form one or more carbocycles or heterocycles.

In one aspect, the present disclosure encompasses novel compounds conforming to formula I:

where, R ¹ , R ² , and R ³ are each independently selected from the group consisting of: -H, optionally substituted C _1-12 aliphatic, optionally substituted C _1-12 heteroaliphatic, optionally substituted C6-i ₄ aryl, and optionally substituted 5- to 14-membered heteroaryl; wherein, [R ¹ and R ³ ] or [R ² and R ³ ] can be taken together with intervening atoms to form an optionally substituted cylcoaliphatic or heterocyclic ring; and wherein R ¹ and R ³ may be taken together to be a carbon-carbon bond (in which case R ² is bonded to an alkyne);

R ¹⁰ and R ¹¹ are each independently selected from an optionally substituted group consisting of: -H, -F, optionally substituted C _1-12 aliphatic, optionally substituted C _1-12 heteroaliphatic, optionally substituted C6-i ₄ aryl, and optionally substituted 5- to 14-membered heteroaryl; where R ¹⁰ and R ¹¹ can can be taken together with the intervening carbon atom to form an optionally substituted spirocylcle optionally containing one or more heteroatoms; and

R ²⁰ is optionally present, and if present is selected from the group consisting of -F, optionally substituted C _1-12 aliphatic, optionally substituted C _1-12 heteroaliphatic, optionally substituted C6-i ₄ aryl, and optionally substituted 5- to 14-membered heteroaryl; when two or more R ²⁰ groups are present, two or more of them can be taken together with intervening atoms to form one or more carbocycles or heterocycles.

In another aspect, the present disclosure encompasses novel compounds having formula II:

1 2 3 10 11 20

where, each occurrence of R , R R\ R , R , and R ^{^} is as defined above and in the classes and subclasses herein.

In some embodiments, a compound is of formula I or II, wherein R ¹⁰ and R ¹¹ are each independently selected from an optionally substituted group consisting of: -H, -F, optionally substituted Ci-12 aliphatic, optionally substituted Ci-12 heteroaliphatic, optionally substituted C6-14 aryl, and optionally substituted 5- to 14-membered heteroaryl; where R ¹⁰ and R ¹¹ can can be taken together with the intervening carbon atom to form an optionally substituted spirocycle optionally containing one or more heteroatoms.

In some embodiments, a compound is of formula I or II, wherein R ¹⁰ and R ¹¹ are R ¹² and R ¹³ .

In certain embodiments of compounds of formulae I or II, R ²⁰ is absent and the present disclosure encompasses compounds of formula la or Ila:

wherein each occurrence of R\ R , R R , and R is as defined above and in the classes and subclasses herein.

In certain embodiments, the present disclosure encompasses compounds of formula lb:

1 2 3 12 13

wherein each occurrence of R\ ir, R R , and R ^1J is as defined above and in the classes and subclasses herein.

In certain embodiments, the present disclosure encompasses compounds of formula lb:

wherein each occurrence of R ¹ , R ² , and R ³ is as defined above,

R ¹² and R ¹³ are each independently selected from the group consisting of -H, -F, optionally substituted Ci-6 aliphatic, and optionally substituted C6-10 aryl, wherein R ¹² and R ¹³ can be taken together with the intervening carbon atom to form an optionally substituted spirocycle.

In certain embodiments, the present disclosure encompasses compounds of formula lib:

1 2 3 12 13

wherein each occurrence of R ¹ , R , R , R ^lz and R ^1J is as defined above.

In certain embodiments, the present disclosure encompasses compounds of formula Ic:

wherein each occurrence of R ¹ , R ² , R ³ and R ^12' is as defined above. In certain embodiments, the present disclosure encompasses compounds of formula Ic:

where R is as defined above, and

R ^{1 '} , R ^2' , and R ^3' are each independently selected from the group consisting of -H, Ci-6 aliphatic, and optionally substituted Ce-w aryl.

In certain embodiments, the present disclosure encompasses compounds of formula lie:

where R ¹ , R ² , R ³ and R ¹² are as defined above.

Representative compounds of formula I are presented in Tables la and lb:

In certain embodiments, the present disclosure encompasses a composition comprising any one or more of the compounds from Tables la and lb. In certain embodiments, the present disclosure encompasses a composition comprising any single compound from Table la or lb. embodiment, the present disclosure encompasses a composition comprising

the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In another embodiment the present disclosure encompasses a composition

comprising the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

Representative compounds of formula II are presented in Tables Ila and lib: 22

In one embodiment, the present disclosure encompasses a composition comprising any one or more of the compounds from Tables Ila or lib. In certain embodiments, the present disclosure encompasses a composition comprising any single compound from Table Ila or lib.

In one embodiment, the present disclosure encompasses a composition comprising

the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In another embodiment, the present disclosure encompasses a composition

comprising the compound In another embodiment, the present disclosure encompasses a composition

comprising the co

In another embodiment, the present disclosure encompasses a composition

comprising the compound

In the foregoing examples of compounds of the present invention, the compounds have not been drawn with stereochemistry indicated. It is to be understood that the racemic compounds as well as their enantioenriched counterparts are encompassed by the present disclosure. In particular, the glycidyl moiety in molecules of the invention may be racemic, enantioenriched, or enantiopure. The present disclosure therefore encompasses compounds (R)-I, and (S)-l and mixtures thereof as well as compounds (R)-II, and (S)-1I and mixtures thereof:

wherein each occurrence of R , R , R R , R , and R ^u is as defined above and in the classes and subclasses herein.

In certain embodiments, compounds of the invention are provided as racemic mixtures. In other embodiments, compounds of the invention are provided as enantiomerically- or diastereotopically-enriched form. In certain embodiments, the compounds are provided in greater than 70% enantiopurity. In other embodiments, the compounds are provided in greater than 80% enantiopurity. In other embodiments, the compounds are provided in greater than 90% enantiopurity. In other embodiments, the compounds are provided in greater than 95% enantiopurity. In other embodiments, the compounds are provided in greater than 99% enantiopurity. In other embodiments, the compounds are provided in essentially enantiopure form.In certain embodiments, the compounds of the present invention also contain minor amounts regioisomeric compounds. For example, in certain embodiments, compounds of the present invention comprise a compound of formula I in combination with a compound of formula I-r:

where, each occurrence of R , R , R ^J , R , R , and R ^u is as defined above and in the classes and subclasses herein.

Similarly, in certain embodiments, the present invention encompasses compounds of formula la, lb, Ic, or any compound of Tables la or lb, characterized in that they contain the corresponding regioisomer conforming to formula I-r. In certain

embodiments, the regioisomer conforming to formula I-r is present in an amount from about 0.001% to about 10% based on the major isomer corresponding to formula I. In certain embodiments, the regioisomer I-r is present in an amount between 0.001% and 0.5%, or between about 0.1% and 1%, or between about 0.2% and 2%, or between about 0.5% and 5%, or between about 5% and 10%. In certain embodiments the present invention encompasses compounds of any of formulae I, la, lb, Ic, or a compound of Tables la or lb with the proviso that the compound not have the structure . In certain embodiments the present invention encompasses compounds of formula I, or a compound of Tables la or lb with the proviso that the compound not have the structure . In certain embodiments the present invention encompasses compounds of formula I, with the proviso that the compound not have the structure . in certain embodiments the present invention encompasses a compounds from Table la, with the proviso that the compound not have the structure or .

In certain embodiments the present invention encompasses a compounds from proviso that the compound not have the structure or

In certain embodiments the present invention encompasses compounds of any of formulae II, Ila, or lib, with the proviso that the compound not have the structure . In certain embodiments the present invention encompasses compounds compounds of any Ila, or lib, with the proviso that the compound not

have the structure In certain embodiments the present invention encompasses compounds compounds of any of formulae II, Ila, or lib, with the proviso

that the compound not have the structure

(II) Methods of preparing compounds of the present invention. In another embodiment, the present invention encompasses methods to synthesize the above-described compounds.

In one embodiment, methods of the present invention include the step of carbonylating a glycidyl acrylate of formula III to yield a ring-expanded product comprising a β-lactone of structure I as shown in Scheme 1 :

Scheme 1

1 2 3 10 11 20

wherein each occurrence of R , R R R , R , and is as defined above.

In one embodiment, the method of Scheme 1 includes the step of contacting a compound of formula III with a catalyst comprising a transition metal carbonyl complex under an atmosphere comprising carbon monoxide gas. Catalyst compositions and reaction conditions suitable for performing the carbonylation step of Scheme 1 are disclosed in US Patent Nos. 5,310,948; 5,359,081; 6,852,865; 7, 145,022; 7,420,064, and US 7,569,709 and in pending application PCT/US12/52857. The entirety of each of the above-referenced documents is hereby incorporated herein by reference.

In certain embodiments, the method of the Scheme 1 comprises the step contacting a compound III with an atmosphere containing a partial pressure of CO between about 1 atm and about 130 atm. In certain embodiments, the carbon monoxide pressure is in the range of from about 50 psi to about 2000 psi. In certain embodiments, the carbon monoxide pressure is in the range of from about 300 psi to about 1000 psi. In certain embodiments, the carbon monoxide pressure is in the range of from about 400 psi to about 700 psi.

In certain embodiments, the method of Scheme 1 includes the step of contacting compound III with a catalyst containing a metal carbonyl complex having the formula (M) _y L„(CO) _x where M is a transition metal, L is a coordinating ligand and need not be present, y denotes the number of metal atoms in the complex and is an integer from 1 to 6, n denotes the number of coordinating ligands present in the complex and is an integer from 0 to 6, and x represents the number of carbon monoxide ligands in the complex is an integer from 1 to 16. In some cases, the metal carbonyl complex is neutral. In other cases the metal carbonyl complex is charged. In certain embodiments, the metal carbonyl complex is anionic. In certain embodiments, the metal carbonyl complex comprises a transition metal from Groups 8, 9, or 10. In some embodiments, the metal carbonyl complex comprises a cobalt carbonyl complex. In certain embodiments, the metal carbonyl complex comprises a carbonyl cobaltate anion.

In certain embodiments, the method of Scheme 1 includes the step of contacting compound III with a catalyst comprising a metal carbonyl complex in combination with a Lewis acidic co-catalyst. In some embodiments, the Lewis acidic co-catalyst comprises a neutral Lewis acid while in other embodiments, the Lewis acidic co-catalyst is cationic. In certain embodiments, the Lewis acid co-catalyst comprises a metal-ligand complex. In specific embodiments, the Lewis acid co-catalyst comprises a cationic metal-ligand complex comprising a metal atom coordinated with a multidentate ligand. In certain embodiments, the Lewis acidic co-catalyst comprises a chromium or aluminum atom coordinated with a tetradentate ligand comprising a porphyrin or salen moiety. In certain embodiments these aluminum or chromium complexes are cationic.

In certain embodiments, the method of Scheme 1 comprises contacting compound III with a catalyst comprising a cationic aluminum or chromium complex in combination with an anionic metal carbonyl complex. In certain embodiments, the catalyst comprises a cationic aluminum-centered Lewis acid in combination with a carbonyl cobaltate anion. In other embodiments, the catalyst comprises a cationic chromium-centered Lewis acid in combination with a carbonyl cobaltate anion. In certain embodiments, the catalyst is chosen from among those disclosed in US Patent No. 6,852,865 and in US Patent Application Serial No. 12/204,411.

In certain embodiments, the method of Scheme 1 includes the step of dissolving or suspending compound III and the carbonylation catalyst in a solvent and contacting the resulting solution or suspension with the carbon monoxide atmosphere. The solvent of this step should be able to dissolve the starting glycidyl acrylate to some extent and should also dissolve and be unreactive toward the catalyst(s) employed. The optimal choice of solvent may vary depending on the substrate to be carbonylated and the catalyst system employed, but in general aprotic solvents of medium to high polarity are suitable as a reaction medium. In some embodiments, the solvent comprises an ether such as DME, THF, TBME, diethyl ether, or dioxane. In other embodiments, the solvent comprises a non-protic polar solvent such as ethyl acetate, propyl acetate, acetonitrile, acetone, nitromethane, or DMF. In other embodiments, the solvent comprises a halogenated solvent such as dichloromethane, chloroform, or trichloroethane. In other embodiments, the solvent may comprise an aromatic compound such as benzene, toluene, or xylene. In certain embodiments, the solvent is chosen from the group consisting of toluene, xylene, mesitylene, and 1,4-dioxane.

In certain embodiments, the step of carbonylating compound III is conducted at a temperature of from about -20 to about 100 °C. In certain embodiments, the reaction is conducted at a temperature in the range of about 30 to about 90 °C. In certain

embodiments, the reaction is conducted at a temperature in the range of about 60 to about 80 °C. In certain embodiments, the method of Scheme 1 includes the steps of initiating the reaction at a temperature below ambient, then allowing the reaction to warm. In certain embodiments, the method includes the steps of initiating the reaction at a low temperature and then heating the mixture to a temperature in the range of about 30 to about 90 °C.

In certain embodiments, methods of Scheme 1 , include one or more steps to monitor the progress of the reaction. This can be done by well known means such as in situ measurement of the IR absorbance spectrum of the reaction mixture or by analyzing aliquots of the reaction mixture for the disappearance of starting the materials III and/or the accumulation of products I. Suitable methods for the latter include, but are not limited to chromatographic methods such as GC, HPLC, TLC, and spectroscopic methods such as NMR, IR, UV-vis and mass spectroscopy.

The methods of Scheme 1 may optionally include the further step of stopping the reaction when the conversion has proceeded to a desired degree. Stopping the reaction may comprise one or more steps including cooling the reaction mixture, venting the reaction mixture, adding one or more quenching reagents, diluting the reaction mixture, and stripping solvents or volatiles from the reaction mixture. A further step of purifying the products of the reaction may also be included.

In certain embodiments, the method of Scheme 1 includes the step of contacting compound III with carbon monoxide in a continuous flow process. In certain embodiments, the method of Scheme 1 includes the step of contacting compound III with carbon monoxide in a batch process.

In another embodiment, methods of the present invention include the step of carbonylating a substituted β-lactone of formula I to provide a ring expanded product comprising a substituted succinic anhydride derivative of formula II as shown in Scheme 2:

Scheme 2

1 2 3 10 11 20

wherein each occurrence of R , R R R , R , and is as defined above.

In one embodiment, the method of Scheme 2 comprises the step of contacting a compound of formula I with a catalyst comprising a transition metal carbonyl complex under an atmosphere comprising carbon monoxide gas. Catalyst compositions and reaction conditions suitable for performing the carbonylation step of Scheme 2 are disclosed in US Patent Nos. 6,852,865; 7,145,022; and 7,420,064, in US Patent

Application Serial Nos. 1 1/705,528; 10/820,958; and 12/204,41 1 and in Japanese Patent Application No. 07332867 filed Dec. 21, 1995. The entirety of each of the above- referenced documents is hereby incorporated herein by reference.

In certain embodiments, the method of the Scheme 2 comprises the step of contacting a compound I with an atmosphere containing a partial pressure of CO between about 1 atm and about 130 atm. In certain embodiments, the carbon monoxide pressure is in the range of from about 50 psi to about 2000 psi. In certain embodiments, the carbon monoxide pressure is in the range of from about 300 psi to about 1000 psi. In certain embodiments, the carbon monoxide pressure is in the range of from about 400 psi to about 700 psi.

In certain embodiments, the method of Scheme 2 includes the step of contacting compound I with a catalyst comprising a metal carbonyl complex having the formula (M)yL„(CO) _x where M is a transition metal, L is a coordinating ligand and need not be present, y denotes the number of metal atoms in the complex and is an integer from 1 to 6, n denotes the number of coordinating ligands present in the complex and is an integer from 0 to 6, and x represents the number of carbon monoxide ligands in the complex is an integer from 1 to 16. In some cases, the metal carbonyl complex is neutral. In other cases the metal carbonyl complex is charged. In certain embodiments, the metal carbonyl complex is anionic. In certain embodiments, the metal carbonyl complex comprises a transition metal from Groups 8, 9, or 10. In some embodiments, the metal carbonyl complex comprises a cobalt carbonyl complex. In certain embodiments, the metal carbonyl complex comprises a carbonyl cobaltate anion. In certain embodiments, the method of Scheme 2 includes the step of contacting compound I with a catalyst comprising a metal carbonyl complex in combination with a Lewis acidic co-catalyst. In some embodiments, the Lewis acidic co-catalyst comprises a neutral Lewis acid, while in other embodiments, the Lewis acidic co-catalyst is cationic. In certain embodiments, the Lewis acid co-catalyst comprises a metal-ligand complex. In specific embodiments, the Lewis acid co-catalyst comprises a cationic metal-ligand complex comprising a metal atom coordinated with a multidentate ligand. In certain embodiments, the Lewis acidic co-catalyst comprises a chromium or aluminum atom coordinated with a tetradentate ligand comprising a porphyrin or salen moiety. In certain embodiments these aluminum or chromium complexes are cationic. In certain embodiments, the method of Scheme 2 includes the step of contacting compound I with a catalyst system comprising a cationic aluminum or chromium complex in combination with an anionic metal carbonyl complex. In certain embodiments, the catalyst system comprises a cationic aluminum-centered Lewis acid in combination with a carbonyl cobaltate anion. In other embodiments, the catalyst system comprises a cationic chromium-centered Lewis acid in combination with a carbonyl cobaltate anion. In certain embodiments, the catalyst is chosen from among those disclosed in US Patent No.

6,852,865 and in US Patent Application Serial No. 12/204,41 1.

In certain embodiments, the method of Scheme 2 is comprises dissolving compound I and the carbonylation catalyst in a solvent that is in contact with the carbon monoxide atmosphere. The solvent of this step should be able to dissolve the starting glycidylacrylate to an appreciable extent, and should also dissolve and be unreactive toward the catalyst(s) employed. The optimal choice of solvent may vary depending on the substrate to be carbonylated and the catalyst system employed, but in general aprotic solvents of medium to high polarity are suitable as a reaction medium. In some embodiments, the solvent comprises an ether such as DME, THF, TBME, diethyl ether, or dioxane. In other embodiments, the solvent comprises a non-protic polar solvent such as ethyl acetate, propyl acetate, acetonitrile, acetone, nitromethane, or DMF. In other embodiments, the solvent comprises a halogenated solvent such as dichloromethane, chloroform, or trichloroethane. In other embodiments, the solvent may comprise an aromatic compound such as benzene, toluene, or xylene.

In certain embodiments, the step of carbonylating compound I is conducted at a temperature of from about -20 to about 100 °C. In certain embodiments, the reaction is conducted at a temperature in the range of about 30 to about 90 °C. In certain

embodiments, the reaction is conducted at a temperature in the range of about 60 to about 80 °C. In certain embodiments, the method of Scheme 2 includes the steps of initiating the reaction at a temperature below ambient, then allowing the reaction to warm. In certain embodiments, the method includes the steps of initiating the reaction at a low temperature and then heating the mixture to a temperature in the range of about 30 to about 90 °C.

In certain embodiments, methods of Scheme 1 , include one or more steps to monitor the progress of the reaction. This can be done by well known means such as in situ monitoring the IR absorbance spectrum of the reaction mixture, or by analyzing aliquots of the reaction for the disappearance of starting materials I and/or the

accumulation of products II. Suitable methods for the latter include, but are not limited to GC, HPLC, TLC, NMR, and mass spectroscopy. The method of Scheme 2 may optionally comprise the further step of stopping the reaction when the conversion has proceeded to a desired degree. Stopping the reaction may comprise one or more steps including but not limited to: cooling the reaction mixture, venting the reaction mixture, adding one or more quenching reagents, diluting the reaction mixture, and stripping solvents or volatiles from the reaction mixture. A further step of isolating the products of formula II from the reaction may also be included.

In certain embodiments, the method of Scheme 2 includes the step of contacting compound I with carbon monoxide in a continuous flow process. In certain embodiments, the method of Scheme 2 includes the step of contacting compound I with carbon monoxide in a batch process.

In another embodiment, methods of the present invention include the step of doubly carbonylating a glycidyl acrylate of formula III to provide a ring expanded product comprising a substituted succinic anhydride derivative of formula II as shown in Scheme 3:

Scheme 3

1 2 3 10 11 20

wherein each occurrence of R , R R R , R , and is as defined above.

In one embodiment, the method of Scheme 3 comprises the step of contacting a compound of formula III with a catalyst comprising a transition metal carbonyl complex under an atmosphere comprising carbon monoxide gas. Catalyst compositions and reaction conditions suitable for performing the carbonylation step of Scheme 3 are disclosed in US Patent Application Serial Nos. 12/204,41 1 and 61/040,944 the entirety of each of which is hereby incorporated herein by reference.

In certain embodiments, the method of the Scheme 3 comprises the step of contacting a compound III with an atmosphere containing a partial pressure of CO between about 1 atm and about 130 atm. In certain embodiments, the carbon monoxide pressure is in the range of from about 50 psi to about 2000 psi. In certain embodiments, the carbon monoxide pressure is in the range of from about 300 psi to about 1000 psi. In certain embodiments, the carbon monoxide pressure is in the range of from about 400 psi to about 700 psi.

In certain embodiments, the method of Scheme 3 includes the step of contacting compound III with a catalyst comprising a metal carbonyl complex having the formula (M)yL„(CO) _x where M is a transition metal, L is a coordinating ligand and need not be present, y denotes the number of metal atoms in the complex and is an integer from 1 to 6, n denotes the number of coordinating ligands present in the complex and is an integer from 0 to 6, and x represents the number of carbon monoxide ligands in the complex is an integer from 1 to 16. In some cases, the metal carbonyl complex is neutral. In other cases the metal carbonyl complex is charged. In certain embodiments, the metal carbonyl complex is anionic. In certain embodiments, the metal carbonyl complex comprises a transition metal from Groups 8, 9, or 10. In some embodiments, the metal carbonyl complex comprises a cobalt carbonyl complex. In certain embodiments, the metal carbonyl complex comprises a carbonyl cobaltate anion.

In certain embodiments, the method of Scheme 3 includes the step of contacting compound III with a catalyst comprising a metal carbonyl complex in combination with a Lewis acidic co-catalyst. In some embodiments, the Lewis acidic co-catalyst comprises a neutral Lewis acid, while in other embodiments, the Lewis acidic co-catalyst is cationic. In certain embodiments, the Lewis acid co-catalyst comprises a metal-ligand complex. In specific embodiments, the Lewis acid co-catalyst comprises a cationic metal-ligand complex comprising a metal atom coordinated with a multidentate ligand. In certain embodiments, the Lewis acidic co-catalyst comprises a chromium or aluminum atom coordinated with a tetradentate ligand comprising a porphyrin or salen moiety. In certain embodiments these aluminum or chromium complexes are cationic.

In certain embodiments, the method of Scheme 3 includes the step of contacting compound III with a catalyst system comprising a cationic aluminum or chromium complex in combination with an anionic metal carbonyl complex. In certain

embodiments, the catalyst system comprises a cationic aluminum-centered Lewis acid in combination with a carbonyl cobaltate anion. In other embodiments, the catalyst system comprises a cationic chromium-centered Lewis acid in combination with a carbonyl cobaltate anion. In certain embodiments, the catalyst is chosen from among those disclosed in US Patent No. 6,852,865 and in pending US Patent Application Serial No. 12/204,41 1.

In certain embodiments, the method of Scheme 3 includes the step of dissolving compound III and the carbonylation catalyst in a solvent that is in contact with the carbon monoxide atmosphere. The solvent of this step should be able to dissolve the starting glycidylacrylate to an appreciable extent, and should also dissolve and be unreactive toward the catalyst(s) employed. With respect to solvents, methods of the invention are improved by the presence of a solvent that includes a Lewis base. The term Lewis base as used herein refers to any nucleophilic species that is capable of donating an electron pair.

In certain embodiments, the Lewis base is distinct from the epoxide. In other embodiments, the Lewis base is the epoxide (i.e., the reaction is performed in neat epoxide).

In certain embodiments of the methods of Scheme 3, the solvent used will fully dissolve the substrate III and provide a reaction mixture in which the catalyst employed is at least partially soluble. Suitable solvents may include ethers, ketones, aromatic hydrocarbons, halocarbons, esters, nitriles, and some alcohols. For example, without limitation, a suitable solvent may include: 1,4-dioxane; tetrahydrofuran; tetrahydropyran; dimethoxyethane; glyme; diethyl ether; t-butyl methyl ether; 2,5-dimethyl tetrahydrofuran; ethyl acetate; propyl acetate; butyl acetate; acetone; 2-butanone; cyclohexanone; toluene; acetonitrile; and difluorobenzene. In some embodiments, the solvent includes 1,4- dioxane, toluene, and/or dimethoxyethane. In one embodiment, solvent includes 1,4- dioxane. Mixtures of two or more of the above solvents are also useful, and in some cases may be preferred to a single solvent. For example, mixtures of toluene and 1,4-dioxane are useful.

In certain embodiments of the methods of Scheme 3, Lewis bases of low to moderate polarity improve the performance of the reaction over polar solvents. Thus, in certain embodiments, the solvent may include a Lewis base which is less polar than 1,3- dioxane (ε = dielectric constant at 20 C = 13.6). In certain embodiments, the solvent includes a Lewis base which is less polar than ortho-difluorobenzene (ε = 13). In certain embodiments, the solvent includes a Lewis base which is less polar than meta- difluorobenzene (ε = 5). In certain embodiments, the solvent includes a Lewis base with substantially the same polarity as 1,4-dioxane (ε = 2.2). In certain embodiments, Lewis bases of low to moderate electron donicity improve the performance of the reaction over strongly donating Lewis bases. Thus, in certain embodiments, the solvent may include a Lewis base with lower electron donicity than tetrahydrofuran. In certain embodiments, the solvent may include a Lewis base with lower electron donicity than 2-methyltetrahydrofuran. In certain embodiments, the solvent may include a Lewis base with lower electron donicity than 2,5-dimethyltetrahydrofuran. In certain embodiments, the solvent may include a Lewis base with higher electron donicity than difluorobenzene. In certain embodiments, the solvent may include a Lewis base with higher electron donicity than toluene. In certain embodiments, the solvent may include a Lewis base with substantially the same electron donicity as 1,4-dioxane. In certain embodiments, the step of doubly carbonylating compound III is conducted at a temperature of from about -20 to about 100 °C. In certain embodiments, the reaction is conducted at a temperature in the range of about 30 to about 90 °C. In certain embodiments, the reaction is conducted at a temperature in the range of about 60 to about 80 °C. In certain embodiments, the method of Scheme 3 includes the steps of initiating the reaction at a temperature below ambient, then allowing the reaction to warm. In certain embodiments, the method includes the steps of initiating the reaction at a low temperature and then heating the mixture to a temperature in the range of about 30 to about 90 °C.

In certain embodiments, methods of Scheme 3, include one or more steps to monitor the progress of the reaction. This can be done by well known means such as in situ monitoring the IR absorbance spectrum of the reaction mixture, or by analyzing aliquots of the reaction for the disappearance of starting materials III and/or the accumulation of products II. Suitable methods for the latter include, but are not limited to GC, HPLC, TLC, NMR, and mass spectroscopy.

The method of Scheme 3 may optionally comprise the further step of stopping the reaction when the conversion has proceeded to a desired degree. Stopping the reaction may comprise one or more steps including but not limited to: cooling the reaction mixture, venting the reaction mixture, adding one or more quenching reagents, diluting the reaction mixture, and stripping solvents or volatiles from the reaction mixture. A further step of isolating the products of formula II from the reaction may also be included.

In certain embodiments, the method of Scheme 3 includes the step of contacting compound III with carbon monoxide in a continuous flow process. In certain

embodiments, the method of Scheme 3 includes the step of contacting compound III with carbon monoxide in a batch process.

In certain embodiments, methods of the present invention encompass

carbonylation of an epoxide of Formula III with the proviso that the epoxide not have the

In certain embodiments, methods of the present invention encompass

carbonylation of a beta lactone of Formula I with the proviso that the epoxide not have the structure

(III) Uses of compounds of the present invention as bifunctional monomers.

In another embodiment, the present invention encompasses the use of lactones of formulae I or II as bifunctional monomers.

In one example of this embodiment, the acrylate functional group of I or II is polymerized using methods well known in the art to provide an acrylate polymer with lactone or anhydride side-chains— the latter are denoted by Z in Scheme 4 as shown below:

Scheme 4

1 2 3 10 11 20

where R , R R R , R , and are as defined above and described in the classes and subclasses herein and n is an integer from 1 to about 100,000.

It will be understood that the reactive Z groups in polymers PI in Scheme 4 can be further manipulated to introduce other functionality via ring-opening reactions with nucleophilic groups such as alcohols, water, amines, and thiols. Similarly, the Z groups can be used to cross-link the polymers by addition of polyols, polyamines, amino alcohols and the like.

In another method provided by the present invention: when the Z group is a beta lactone, the lactone can be pyrolized to form an alkene:

It will be further understood that the compounds I and II can be used alone as monomers to afford heavily functionalized polymers. For example, monomers I and II can be co-polymerized with one or more additional alkenes such as ethylene, propylene, higher alpha olefins, styrene, divinyl benzene, vinyl toluene, acrylonitrile, butadiene, isobutylene and the like to provide functionalized polyolefins. Similarly, they can be co- polymerized with one or more additional acrylates such as acrylic acid, methacrylic acid, crotonic acid, or their esters or amides to provide functionalized co-polymers. In a complementary example of this embodiment, the lactone functional group of compounds of formula I can be polymerized using methods well known in the art to provide polyhydroxypropionate polymers with acrylate side-chains (denoted P2 in Scheme

5):

Scheme 5

1 2 3 10 11 20

where R , R R R , R , and are as defined above and described in the classes and subclasses herein and n is an integer from 1 to about 100,000.

The acrylate side-chains can now serve as reactive groups for further reaction by radical chemistry, Michael addition, etc., to further functionalize or to cross-link the polymer.

In another embodiment, the present invention provides copolymers arising from the copolymerization of monomer I with other monomers. Suitable other monomers include but are not limited to lactide, beta propiolactone, beta butyrolactone, gamma caprolactone, glycolide and the like. Additional monomer units in the polymer chain P2 can be derived from compounds such as diols, diacids, hydroxy acids, carbon dioxide, epoxides, phosgene, dialkyl carbonates, isocyanates, and combinations of any two or more of these.

In certain embodiments, the present invention encompasses random-, block-, or tapered-copolymers of I with any one or more of these comonomers. It will be recognized that many variations of the inventive copolymers can be formed by manipulation of the polymerization conditions including but not limited to the ratio of monomers provided, the catalyst(s) employed, and the timing of addition of the monomers and/or catalysts. Similarly, compounds of formula II, can be polymerized via their anhydride functionality. This can be achieved by reaction with polyols, polyamines, or polysulfides, or, as shown in Scheme 6, by alternating co-polymerization with epoxides in the presence of a suitable catalyst to provide polyesters of formula P3 (methods and catalysts suitable to achieve the latter are disclosed in PCT Application WO 2009/025850 the entirety of which is hereby incorporated herein by reference). Scheme 6 depicts yet another embodiment of the present invention.

P3

Scheme 6

where each of R , R , R R , R , and R ^u is as defined above and described in the classes and subclasses herein; R ³⁰ is optionally present, and if present is defined as R ²⁰ described hereinabove; and n is an integer from 1 to about 100,000.

The above-described examples show only a few of the numerous uses to which these new bifunctional monomers may be applied in the art of polymer synthesis. Many further applications will be apparent to those skilled in the art of polymer synthesis and are encompassed by the present invention.

In addition to the above described uses in polymer synthesis, the bifunctional molecules I and II are useful as reagents for surface modifications of items such as wood, textiles, papers, and polymers. For example, the free hydroxyl groups of the cellulose in wood or paper can be made to react with the anhydride moiety of II or the beta lactone of I to covalently link the compound to the cellulosic material. The acrylate sidechain can then act as a site for further chemical modification using other chemistries such as radical, cationic,or anionic polymerization, Michael additions etc. to modify the properties of the surface. EQUIVALENTS

All material cited in this application, including, but not limited to, patents and patent applications, regardless of the format of such literature and similar materials, are expressly incorporated herein by reference in their entirety. In the event that one or more of the incorporated literature and similar materials differs from or contradicts this application, including but not limited to defined terms, term usage, described techniques, or the like, this application controls.

The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described in any way. While the present disclosure has been particularly shown and described with reference to specific illustrative embodiments, it should be understood that various changes in form and detail may be made without departing from the spirit and scope of the present disclosure. Therefore, all embodiments that come within the scope and spirit of the present disclosure, and equivalents thereto, are intended to be claimed. The claims and descriptions of the present disclosure should not be read as limited to the described order of elements unless otherwise stated.