Chiral intermediates monomers

Another recent example by Peukert and Jacobsen (199) took advantage of the first polymer supported Jacobsen s catalyst 8.53 (Fig. 8.31) comparable with the soluble catalyst in asymmetric epoxidation and its full characterization (200, 201). The supported catalyst, prepared from the activated carbonate of hydroxymethyl PS and from a soluble phenolic catalyst (201), was used to catalyze the opening of racemic alkyl epoxides (Mi, Fig. 8.31) with substituted phenols and yielded the 50-member aryloxy alcohol library L15 with good enantiomeric purity (average >90%, never below 80% e.e.). 8.53 was also used to produce the chiral intermediate monomer set M3 (Fig. 8.31) which was used to make two 50-member chiral libraries L16 (1,4-diary-loxy 2-propanols) and L17 (3-aryloxy-2-hydroxy propanamines) with excellent enantiomeric excess following the straightforward synthetic schemes reported in Fig. 8.31. 

Molecular modeling studies relative to both preinsertion intermediates and insertion states indicate that for all the metallocenes from 1 to 39 of Scheme 1.2 (independent of their structure and symmetry), when a substantial stereoselectivity is calculated for primary monomer insertion, this is mainly due to nonbonded energy interactions of the methyl group of the chirally coordinated monomer with the chirally oriented growing chain. 

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. 

Polyhydroxyalkanoates (PHA) is a family of structurally diverse biopolyesters accumulated by many bacteria as carbon and energy source (Figure 16.1)d PHA have been exploited with a series of applications including environmentally friendly biodegradable plastics for packaging purposes, biofuels, medical implants, and recently, smart materials. PHA monomers are also produced as chiral intermediates for medical or fine chemical applications. ... 

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. 

For instance, Figure 1.9a plots as a function of Go the optimized energies for the model complex 5, that is, a ir-ligand with C2 symmetry with (R, R) chirality of coordination of the bridged ir-ligand. Let us recall that, in our framework, energy minima with 0O 0° or 0O 180° can correspond to preinsertion intermediates suitable for primary and secondary monomer insertions, respectively. 

Figure 1.10 Preinsertion intermediates for secondary propene insertion into primary polypropylene chain for (a) isospecific model complex based on (R, R)-coordinatedisopropyl-bis(l-indenyl) ligand and (b) syndiospecific model complex based on isopropyl(cyclopentadienyl-9-fluorenyl) ligand for R chirality at metal atom. Stereoselectivity of isospecific model site is in favor of opposite monomer prochiral faces for primary and secondary insertions (cf. Figures 1.4 and 1.10a). Stereoselectivity of syndiospecific model site is in favor of same monomer prochiral face for primary and secondary insertions (cf. Figures 1.6a and 1.1 Ob).

Figure 1.25 Minimum-energy diastereoisomeric monomer free intermediates for butadiene polymerization catalyzed by titanium complexes presenting Cp group as ancillary ligand. Chiralities of coordination of allyl groups (assumed to be si) and back-biting double bonds (si or re) are indicated, in order to easily visualize possible stereoregularity (iso or syndio) of model chains. In fact, like and unlike chiralities would possibly lead to isotactic and syndiotactic enchainments, respectively.

An intermediate case between the polymerization of enantiomerically pure and racemic monomers is the polymerization of a partially resolved mixture of enantiomers with variable optical purity. Two processes are distinguishable, depending on whether polymerization occurs in the presence of an achiral (or racemic) or of a chiral (optically active) catalyst. 

Preparation of addition polymers having the oxolene (dihydrofuran) functionality can be envisioned to occur in two possible ways (Scheme 13). Both, in fact, have been observed (77MI11102). Whereas furan (53) or its derivatives do not homopolymerize under free radical conditions, 1 1 alternating copolymers possessing the 1,4-structure are produced with maleic anhydride (50). Intermediate formation of a CT complex between monomers (50) and (53) is believed to be necessary before polymerization can occur. On the other hand, cationic polymerization is quite facile. The outcome is straightforward with benzo[f>]furan derivatives, producing 1,2-polymers. Optically active poly(benzofurans) are formed when the cationic polymerizations are conducted in the presence of a chiral anion. 

Olefin polymerization using heterogeneous catalysts is a very important reaction and stereochemical aspects have been studied extensively. For a review on this topic see Pino et al. [9], Briefly, the origin of stereoregularity in polyolefins (47) is explained by the chiral nature of the acdve site during polymerization. If the absolute configuration of the first intermediate can be controlled by chiral premodification then we should obtain a non-racemic mixture of R - and "S"-chains. This has indeed been observed e.g. with catalyst M4 for the polymerization (partial kinetic resolution) of racemic 3,7-dimethyl-l-octene (ee 37%) and also for the racemic monomer 46 using Cd-tartate M5. 

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