Enantioselective catalysts, MIPs

MIP catalyst 76 also performs enantioselective hydrolysis of non-activated d-and L-phenylalanine ethyl ester 78 at pH 7.4, with characteristic saturation kinetics (Scheme 13.19). While this catalyst does not have the precise shape complementarity to ester 78, a threefold enhancement compared to the blank reaction was observed. Furthermore, enantiodiscrimination was obtained, as compound 78 was hydrolyzed 1.44-fold faster than ent-78. Although the reported rate enhancement was modest compared to the standards in asymmetric synthesis, it can be considered as a first step in the development of imprinted polymers for enantioselective catalysts. 

The MIP-mediated hydrolysis of ester 70 in HEPES buffer (0.15 M, pH 7.3) and MeCN at 20 °C showed Michaelis-Menten kinetics and a 325-fold rate enhancement compared to the reaction performed in solution. By comparison, the hydrolysis of ent-70 showed a 234-fold enhancement under the same conditions, resulting in a pronounced enantioselectivity. Interestingly, the apparently slight difference between 70 and 71 resulted in a significant decrease in catalyst activity, as the rate enhancement compared to the reaction performed in solution was only 103-fold. 

Enantioselective hydrolysis of p-nitrophenyl-N-(benzylocycarbonyl)-L-leucinate compared to its D-isomer could also be performed with a MIP catalyst built up with a racemic template [55]. In that case, the enantiodiscrimination is insured by the presence of r-His monomer during the polymerization process, performed under finely tuned conditions. The random distribution of quaternary trimethyl-ammonium groups through the polymer framework makes this MIP very soluble in water. The MIP-catalyzed ester hydrolysis was performed in a mixture of... 

Figure 23 The preparation of enantioselective MIPs, imprinted with L-menthol 40 by ringopening metathesis pol mierization (ROMP). A copolymer of dicyclopentadiene 39 and the template monomer 41 was prepared by treatment with Grubb s catalyst. Template removal by treatment with an amine resulted in polymers capable of enantioselective recognition of 40 (adapted from Ref. 33).

In extension of this work, a platinum complex with a chiral phosphine ligand and a BINOL template was employed as a metallomonomer [28]. After removal of the template and activation of the complex with silver salts (generation of Lewis acidic platinum centers) the MIP was used as a catalyst for an asymmetric ene reaction. Enantioselectivities of 72% ee were observed (Fig. 15). This compares well to... 

Polbom and Severin studies have been reported that describe the use of MlPs in the reduction of ketones." This research was related closely to the work of Lemaire et al. on enantioselective hydride-transfer reactions using a catalytic Rh(l) complex" (see below), but, beneficially, an achiral catalyst and the catalytically more active Ru(ll) center was used. The MIP was prepared from a six-membered TSA for the reduction of benzophenone (Figure 2) and exhibited a sevenfold increase in hydrogenation rate relative to the control polymer. Impressive substrate selectivity was also observed with this imprinted catalyst because benzophenone was reduced preferentially with respect to acetophenone and in stark contrast use of the control polymer afforded the opposite selectivity. The 2-point connection of the catalyst to the polymer (Figure 2) was shown to improve the activity and selectivity over the analogous MIP with a single recognition site. 

Sellergren et al have developed enantioselective MIP-catalysts using a phosphonate as template. For the determination of the catalytic properties they compared the MIP and a control polymer. Rate constant ratios (IcMip/kcp) of up to 2.54 were observed. ... 

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