Enantioselective polymerization

The enantioselective Upase CA-catalyzed copolymerization of racemic substituted lactones (P-butyrolactone) and achiral lactones (DDL) yielded S-enriched optically active copolymers with an enantiomeric excess (ee) of BL. The highest ee-value was achieved in the copolymerization of DDL with 8-caprolactone in isopropyl ether [77]. 

Kawakami and coworkers synthesized stereoregular and optically active polysiloxanes by polycondensation with deamination or dehydrogenation. Optically active disiloxane disilanol [173] and achiral bis(dimethylamino)si- 

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Lipase catalysis is often used for enantioselective production of chiral compounds. Lipase induced the enantioselective ring-opening polymerization of racemic lactones. In the lipase-catalyzed polymerization of racemic (3-BL, the enantioselec-tivity was low an enantioselective polymerization of (3-BL occurred by using thermophilic lipase to give (/ )-enriched PHB with 20-37% enantiomeric excess (ee). ... 

Optically active polyesters were synthesized by lipase CA-catalyzed ring-opening polymerization of racemic 4-methyl or ethyl-e-caprolactone. The (5 )-isomer was enantioselectively polymerized to produce the polyester with >95% ee. Quantitative reactivity of 4-substituted e-caprolactone using lipase CA as catalyst was analyzed. The polymerization rate decreased by a factor of 2 upon the introduction of a methyl substitutent at the 4-position. Furthermore, 4-ethyl-8-caprolactone polymerized five times slower than the 4-methyl-8-caprolactone. This reactivity difference is strongly related to the enantioselectivity. Interestingly, lipase CA displayed 5 -selectivity for 4-methyl or ethyl-8-caprolactone, and the enantioselectivity was changed to the (f )-enantiomer in the case of 4-propyl-8-caprolactone. 

Lipase BC induced the enantioselective polymerization of 3-methyl-4-oxa-6-hexanolide (MOHEL). The initial reaction rate of the 5 -isomer was seven times... 

PPF catalyzed an enantioselective polymerization of bis(2,2,2-trichloroethyl) tra 5-3,4-epoxyadipate with 1,4-butanediol in diethyl ether to give a highly optically active polyester (Scheme 9). °° The molar ratio of the diester to the diol was adjusted to 2 1 to produce the (-) polymer with enantiomeric purity of >96%. The polymerization of racemic bis(2-chloroethyl) 2,5-dibromoadipate with excess of 1,6-hexanediol using lipase A catalyst produced optically active trimer and pentamer. The polycondensation of 1,4-cyclohexanedimethanol with fumarate esters using PPL catalyst afforded moderate diastereoselectivity for the cis/trans monocondensate and markedly increased diastereoselectivity for the dicondensate product. 

In vitro synthesis of polyesters using isolated enzymes as catalyst via non-biosynthetic pathways is reviewed. In most cases, lipase was used as catalyst and various monomer combinations, typically oxyacids or their esters, dicarboxylic acids or their derivatives/glycols, and lactones, afforded the polyesters. The enzymatic polymerization often proceeded under mild reaction conditions in comparison with chemical processes. By utilizing characteristic properties of lipases, regio- and enantioselective polymerizations proceeded to give functional polymers, most of which are difficult to synthesize by conventional methodologies. 

Enzymatic enantioselective oligomerization of a symmetrical hydroxy diester, dimethyl /Lhydroxyglutarate, produced a chiral oligomer (dimer or trimer) with 30-37% ee [24]. PPL catalyzed the enantioselective polymerization of e-substituted-e-hydroxy esters to produce optically active oligomers (DP < 6) [25]. The enantioselectivity increased with increasing bulkiness of the monomer substituent. Optically active polyesters with molecular weight of more than 1000 were obtained by the copolymerization of the racemic oxyacid esters with methyl 6-hydroxyhexanoate. 

Lipase catalysis induced the enantioselective polymerization, yielding optically active oligoesters and polyesters. The polymerization of racemic bis(2-chloroethyl) 2,5-dibromoadipate with excess of 1,6-hexanediol using lipase A catalyst produced optically active trimer and pentamer [46]. 

Fig. 4. Enantioselective polymerization of epoxy-containing diester with 1,4-butanediol...

Ring-opening polymerization of a-methyl-substituted medium-size lactones, a-methyl-y-valerolactone and a-methyl-c-caprolactone, proceeded by using lipase CA catalyst in bulk [82]. As to (R)- and (S)-3-methyl-4-oxa-6-hexa-nolides (MOHELs), lipase PC induced the polymerization of both isomers. The apparent initial rate of the S-isomer was seven times larger than that of the R-isomer, indicating that the enantioselective polymerization of MOHEL took place through lipase catalysis [83]. 

Note Enantioselective polymerization of cz5 -(i ,5)-2,3-dimethylthiirane can produce poly[sulfanediyl-(i ,i )-l,2-dimethylethane-l,2-diyl] or its enantiomer. 

By enantioselective polymerization polymer chains, each containing only one configurational kind of monomeric unit, are produced from a mixture of stereoisomeric monomer molecules. The number of kinds of polymer chain generated therefore equals the number of various stereoisomers in the monomer mixture. In the course of propagation, the enantiomeric composition of the polymer and unreacted monomer remains identical to the intial composition. When optically active monosubstituted cyclic monomers are polymerized, stereoregular polymers are formed with both isotactic polyR and polyS chains... 

Several optically active polymers of acrylates and methacrylates have been obtained by enantioselective polymerization of a racemic monomer initiated by a Grignard compound complexed with chiral reagent. Complexing agents for the polymerization of (K,S)-a-methylbenzyl methacrylate include chiral alcohols, such as quinine and cinchonine [63], (— )-sparteine and its derivatives [64-67], and other axially disymmetric biphenyl compounds [68,69]. Other racemic monomers used include (/ ,S)-a-methylbenzyl acrylate [70], (K,S)-l-phenylethyl acrylate, methacrylate and a-ethylacrylate [71], and 1,2-diphenylethylmethacrylate [72]. 

Miller, S. A. Waymouth, R. M. Stereo- and Enantioselective Polymerization of Olefins with Homogeneous Ziegler-Natta Catalysts. In Ziegler Catalysts-, Fink, G., Miilhaupt, R., Brintzinger, H.-H., Eds. Springer Berlin, 1995 p 441. 

An enantioselective polymerization of four-mem-bered lactones was demonstrated. Racemic a-methyl-/3-propiolactone was stereoselectively polymerized by Pseudomonas cepacia lipase (lipase PC) to give an optically active (S)-enriched polyester with enantiomeric excess (ee) of 50%.154 From racemic /3-BL, (P)-enriched PHB with 20—37% ee was formed by using thermophilic lipase as catalyst.155... 

Lipase-catalyzed ring-opening polymerization of nine-membered lactone, 8-octanolide (OL), has been reported.165 Lipases CA and PC showed the high catalytic activity for the polymerization. Racemic fluorinated lactones with a ring size from 10 to 14 were enantioselectively polymerized by lipase CA catalyst to give optically active polyesters.166... 

Chiral C2-symmetric bridged metallocenes are the most successful highly enantioselective polymerization catalysts. The catalysts produce PPs with microstructures ranging from almost atactic to almost perfectly isotactic, and often contain a small amount of isolated regio-irregularities. The basic structures of these catalysts are shown in Scheme 1. 

Ligand design in the enantioselective polymerization of racemic lactide... 

During the two decades after this important discovery, a tremendous amount of research has been directed toward the polymerization of sterically demanding achiral monomers with chiral initiators to create enantiomerically pure helical polymers (also known as helix-sense selective or screw-sense-selective polymerization ). These polymers, known as atropisomers, are stable conformational isomers that arise from restricted rotation about the single bonds of their main chains. Key aspects of these reactions are enantiopure initiators that begin the polymerization with a one-handed helical twist, and monomers with bulky side-chains that can maintain the helical conformation due to steric repulsion. Notable examples of this fascinating class of polymers that are configurationally achiral but conformationally chiral include [8, 38, 39] poly(trityl methacrylate), polychloral, polyisocyanates, and polyisocyanides. Important advances in anionic and metal-based enantioselective polymerization methods have been reported in recent years. 

One of the most studied polymerization systems employs alkyllithium initiators that are modified by chiral amine ligands for the polymerization of sterically bulky methacrylates [8,38,39,40,41], acrylates [42],crotonates [43], and acrylamides [44]. A primary example is the reaction of triphenylmethyl methacrylate with an initiator derived from 9-fluorenyllithium and (-)-sparteine (3) at -78 °C (Scheme 4). The resultant isotactic polymer is optically active, and is postulated to adopt a right-handed helix as it departs from the polymerization site. This polymer has been particularly successful as a chiral stationary phase for the chromatographic resolution of atropisomers [8]. Many modifications of the or-ganolithium initiator/chiral ligand system have been explored. Recently, Okamo-to has applied enantiopure radical initiators for the enantioselective polymerization of bulky methacrylate monomers [45]. 

The discovery that group IV metallocenes can be activated by methylaluminox-ane (MAO) for olefin polymerization has stimulated a renaissance in Ziegler-Natta catalysis [63]. The subsequent synthesis of well-defined metallocene catalysts has provided the opportunity to study the mechanism of the initiation, propagation, and termination steps of Ziegler-Natta polymerization reactions. Along with the advent of cationic palladium catalysts for the copolymerization of olefins and carbon monoxide [64, 65], these well-defined systems have provided extraordinary opportunities in the field of enantioselective polymerization. 

A final example involves the enantioselective polymerization of racemic 10-hydroxyundecanoic acid by CRL (Scheme 11.8) [31], The polymerization reaction was stopped when 50% monomer conversion was reached and polymers with a molecular weight of lkgmoT (PDI = 1.3) were isolated. Subsequent H-NMR analysis using the Mosher s acid derivatization procedure on the residual monomer and hydrolyzed monomer revealed an ee of 33 and 60%, respectively. Comparison with Mosher s esters of R-2-octanol and rao2-octanol showed that the S-monomer was preferentially incorporated in the polymer. 

Lipase catalysis is often used for the enantioselective production of chiral compounds indeed, lipase has been known to induce an enantioselective ROP of racemic lactones. In the lipase-catalyzed polymerization of racemic j8-butyrolactone (/3-BL), the enantioselectivity was low rather, an enantioselective polymerization of /3-BL occurred by employing a thermophilic lipase to yield the (R)-enriched polymer with 20-37% enantiomeric excess (e.e.) [101]. The enantioselectivity was greatly improved by copolymerization with seven- or 13-membered nonsubstituted lactones, using the lipase CA catalyst, whereby the e.e.-value reached almost 70% for the copolymerization of /3-BL with DDL [102]. It should be noted that, in the case of the lipase CA catalyst, the (S)-isomer was reacted preferentially to produce the (S)-enriched, optically active copolymer. The lipase CA-catalyzed copolymerization of i5-CL (six-membered) with DDL proceeded enantioselectively, to yield the (R)-enriched optically active polyester with an e.e.-value of 76%. 

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