Chiral from racemic monomers

Polymers derived from natural sources such as proteins, DNA, and polyhy-droxyalkanoates are optically pure, making the biocatalysts responsible for their synthesis highly appealing for the preparation of chiral synthetic polymers. In recent years, enzymes have been explored successfully as catalysts for the preparation of polymers from natural or synthetic monomers. Moreover, the extraordinary enantioselectivity of lipases is exploited on an industrial scale for kinetic resolutions of secondary alcohols and amines, affording chiral intermediates for the pharmaceutical and agrochemical industry. It is therefore not surprising that more recent research has focused on the use of lipases for synthesis of chiral polymers from racemic monomers. 

Hilker et al (44) combined dynamic kinetic resolution with enzymatic polycondensation reactions to synthesize chiral polyesters from dimethyl adipate and racemic secondary diols. The concept offered an efficient route for the one-pot synthesis of chiral polymers from racemic monomers. Palmans at al (18,43) generalized the approach to Iterative Tandem Catalysis (ITC), in which chain growth during polymerization was effected by two or more intrinsically different catalytic processes that were compatible and complementary. 

TTie extension of tandem catalysis to polymer chemistry is, however, not trivial. In order to reach high molecular weight polymers, each reaction has to proceed with almost perfect selectivity and conversion. Obviously, combining different catalytic reactions limits the choice of suitable reactions since they must also be compatible with each other. We recently introduced Iterative Tandem Catalysis (ITC), a novel polymerisation method in which chain growth during polymerisation is effectuated by two or more intrinsically different catalytic processes that are both compatible and complementary. If the catalysts and monomers are carefully selected, ITC is able to produce chiral polymers from racemic monomers, as was shown by us for the ITC of 6-MeCL and the DKR polymerisation of sec-diols and diesters. ... 

In polymer chemistry, one of the most challenging tasks is to efficiently synthesize optically active synthetic polymers. The extraordinary enantioselectivity of lipases offers new perspectives towards these materials, and it is therefore not surprising that some research efforts have focused on the use of lipases to synthesize chiral polymers from racemic monomers. Methodologies like kinetic resolution and even chemoenzymatic dynamic kinetic resolution (DKR) have already been exploited on the industrial scale to afford chiral intermediates for the pharmaceutical and agrochemical industry. Recently, these methodologies have been successfully applied in the synthesis of chiral polymers. 

Carbon-13 spectroscopy has been used very effectively by Corno and coworkers [115-117] to characterize the distributions of monomer sequences in copolymers derived from episulfides using anionic catalysts. Although chiral monomers were not employed in these studies, it is worth noting that tacticity effects had a relatively small effect on the resonance patterns observed, but that the chemical shifts of in-chain carbon atoms in different sequences were s ibstantially different. On the basis of assignments and empirical shift parameters developed by Corno, et al., the spectra of stereoregular ethylene sulfide-propylene sulfide copolymers and propylene sulfide-isobutylene sulfide copolymers should be readily analyzed. Studies on copolymers derived from racemic monomers indicate them to have random structures a similar result can be e3q>ected for copolymers derived from optically active monomers. 

A special case of asymmetric enantiomer-differentiating polymerization is the isoselective copolymerization of optically active 3-methyl-1-pentene with racemic 3,7-dimethyl-1-octene by TiCl4 and diisobutylzinc [Ciardelli et al., 1969]. The copolymer is optically active with respect to both comonomer units as the incorporated optically active 3-methyl-l-pentene directs the preferential entry of only one enantiomer of the racemic monomer. The directing effect of a chiral center in one monomer unit on the second monomer, referred to as asymmetric induction, is also observed in radical and ionic copolymerizations. The radical copolymerization of optically active a-methylbenzyl methacrylate with maleic anhydride yields a copolymer that is optically active even after hydrolytic cleavage of the optically active a-methylbenzyl group from the polymer [Kurokawa and Minoura, 1979]. Similar results were obtained in the copolymerizations of mono- and di-/-menthyl fumarate and (—)-3-(P-styryloxy)menthane with styrene [Kurokawa et al., 1982],... 

Extension of DKR to polymer chemistry would readily result in chiral polyesters, polycarbonates, or polyamides from an optically inactive monomer mixture. Scheme 10 describes three variants of chemoenzymatic catalysis applied in polymer chemistry that recently appeared in the literature. Route A uses AA and BB monomers to prepare chiral polymers from racemic/diasteromeric diols. Route B converts an enantiomer mixture of AB monomers to homochiral polymers. Route C is the enzymatic ring-opening polymerization of co-methylated lactones to homochiral polyesters. Details will be given in Sect. 3.4.2. 

The extension of DKR to polymer chemistry is not trivial in practice since side reactions that are relatively unimportant in DKR (dehydrogenation, hydrolysis) have a major impact on the rate of polymerization and attainable chain lengths because the stoichiometry of the reactants is an important issue. As a result, the reaction conditions and catalyst combinations used in a typical DKR process will not a priori lead to chiral polymers from racemic or achiral monomers with good molecular weight (>10kDa) and high ee (>95%). 

There are two ways of obtaining chiral substances using a chiral crystal environment. One is to produce the chiral compounds from the prochiral ones, and the other is to obtain the chiral compounds from racemic ones. The former method is called absolute asymmetric synthesis, since the asymmetry is introduced from the physical conditions such as the chiral crystal environment. Several examples [ 1 -7] have been reported since the first example of the chiral polymer produced in the photopolymerization of the chiral monomer crystal [8]. We also observed that chiral 3-lactam compounds were produced from the prochiral oxoamide crystals [9,10]. 

There are several alternative methods for the synthesis of optically active polymers from achiral or racemic monomers that do not involve polymerization catalysts. Optically active polymers have been formed from achiral dienes immobilized in a chiral host lattices [ 106]. In these reactions, the chiral matrix serves as a catalyst and can be recovered following the reaction. For example, 1,3-penta-dienes have been polymerized in perhydrotriphenylene and apochoUc acid hosts, where asymmetric induction occurs via through-space interactions between the chiral host and the monomer [107,108]. The resultant polymers are optically active, and the optical purities of the ozonolysis products are as high as 36%. In addition, achiral monomers have been found to pack in chiral crystals with the orientations necessary for topochemical soHd-state polymerization [109]. In these reactions, the scientist is the enantioselective catalyst who separates the enantiomeric crystals. The oligomers, formed by a [27H-27i] asymmetric photopolymerization, can be obtained in the enantiomeric pure form [110]. 

Figure 8.4 MALDI-TOF MS analysis of the oligopeptides obtained from racemic and chiral nonracemic mixtures of Cig-Glu-NCA monomer, (a) Racemic and (b) 4 6 S R mixtures. For clarity, the distribution of oniy...

Circularly polarised emission is possible from polymers containing chiral groups. Scherf and coworkers have prepared a cyclophane-substituted PPP by the Suzuki route using the dibromocyclophane 35 and the corresponding bis-boronic acid 36 (Scheme 15) [98,99]. If racemic monomers were used the resulting polymer 37 was not chiral with the cyclophanes randomly distributed on either face of the polymer (atactic). If resolved enantio-pure monomers were used, then the stereoregular isotactic 38 or syndiotactic 39 polymers could be obtained depending upon which enantiomer of each monomer was used. The isotactic polymer is chiral and both enantiomers have been prepared. 

There is, however, another aspect of the chirality of isotactic polymers, which is associated with the helical form of isotactic polypropylene first observed in the X-ray diffraction experiments conducted in Milan by the Natta group. In this manner, Natta discovered the reason for the crystalline properties of this polymer synthesized from the catalyst developed by Karl Ziegler. But, in a sample of isotactic polypropylene, or other isotactic polymers arising from vinyl monomers, both left- and right-handed helical conformations are present so that no chiral optical property is observed. Each crystalline state in a sample of isotactic polypropylene is a racemic mixture of helical forms. 

Second, monomers of high optical purity could be Isolated In limited amounts starting from racemic mixtures. In such a case the stereoelective polymerization can be considered as an original resolution method of special interest for monomers which are not easily prepared by conventional synthetic ways under their optically active form. Increase in stereoelectivity is observed when using chiral media, i.e. enantiomerically enriched monomers or external chiral additives. 

It is clear that stereoselectivity implies stereoelectivity, and that a relationship must exist between the actual stereoselectivity and stereoelectivity observed when a racemic monomer is polymerized using a given chiral catalyst. If the relative overall rate constants of polymerization of the two enantiomers on a single chiral catalytic center are known (e.g, from a stereoelective polymerization experiment), the average relative cunounts of the two enantiomeric monomeric units in a polymer chain formed in the stereoselective polymerization can, with certain assumptions, be evaluated. 

In most cases these monomers have chiral centers, so both the monomers and the repeating units in the polymers will contain asymmetric carbon atoms and will be capable of existing as different optical isomers. Also in most cases investigated to date, racemic mixtures of the monomers were polymerized to give optically inactive polymers, so tacticlty could not be determined by, or correlated with, optical activity. Nevertheless, stereoregularity in either the o- or 3-substituted polyesters and polyamides prepared from these monomers can be discussed in terms of tacticlty in the normal sense as illustrated in Figure 2 for the polymers with either isotactic or syndiotactic dyads in which the substituents are either on the o- or 3-carbon position (or both). 

Part 1(2) OA Polymers from Racemic Chiral Monomers or Polymers... 

From racemic mixtures of monomers containing one chiral center in the heterocycle and an achiral lateral chain an OA polymer is obtained with the asymmetric carbon atom in the main chain by a stereoelective process using asymmetric initiators (see Section... 

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