Styrene oxide-type substrates

Fungal cells (e.g., Aspergillus and Beauveria sp.) are best suited for styrene-oxide-type substrates. 

Styrene oxide-type substrates (Fig. 2) have been hydrolyzed with good enantioselectivity especially by fungal epoxide hydrolases and a recombinant epoxide hydrolase from Agrobacterium radiobacter. However, bacterial epoxide hydrolases, e.g., from No-cardia spp. and related Rhodococcus strains, were not useful for tins substrate pattern. Similarly, enzymes from yeasts and mammals showed only low to moderate selectivity (Table 2). 

Styrene oxide-type epoxides have to be regarded as a special group of substrates, as they possess a benzylic carbon atom, which facilitates the formation of a carbenium ion through resonance stabilization by the adjacent aromatic moiety... 

Recently, the first asymmetric cell-free application of styrene monooxygenase (StyAB) from Pseudomonas sp. VLB 120 was reported [294]. StyAB catalyses the enantiospecific epoxidation of styrene-type substrates and requires the presence of flavin and NADH as cofactor. This two-component system enzyme consists of the actual oxygenase subunit (StyA) and a reductase (StyB). In this case, the reaction could be made catalytic with respect to NADH when formate together with oxygen were used as the actual oxidant and sacrificial reductant respectively. The whole sequence is shown in Fig. 4.106. The total turnover number on StyA enzyme was around 2000, whereas the turnover number relative to NADH ranged from 66 to 87. Results for individual substrates are also given in Fig. 4.106. Excellent enantioselectivities are obtained for a- and -styrene derivatives. 

Also, the scope of suitable substrates has been explored. Thus, it was shown that substituted styrene derivatives such as various para-substituted styrene oxides [204] as well as )3-disubstituted derivatives [176] could be accommodated by one or both of these fungi. In the latter case, an interesting enantioconvergent hydrolysis of cz5-methyl substituted styrene oxide was observed, affording an 85% preparative yield of enantiopure (lP,2A)-diol. Further screening conducted on various other fungal strains indicated that this type of enzyme does indeed seem to be widespread within the fungal world [149,205]. 

Metal mediated epoxidahon is remarkably diverse, with many types of ligand systems being represented. For example, a cytochrome P450 BM-3 mutant (139-3) has been developed using directed evolution, which exhibits high activity towards epoxidation of several non-natural substrates. Thus, exposure of styrene 4 to BM-3 variant 139-3 in phosphate buffer containing methanol and NADPH resulted in the quantitative conversion to styrene oxide 5. For terminal aliphatic alkenes, however, allyhc hydroxylation is the predominant process <04T525>. 

PdCOTfj CIPr) generated in situ from [Pd(p,-Cl)(Cl)(IPr)]j and AgOTf was reported to catalyse the copper-free Wacker-type oxidation of styrene derivatives using ferf-butyl hydroperoxide (TBHP) as the oxidant (Table 10.7) [41]. Reaction conditions minimised oxidative cleavage of styrene, which is a common side-reaction in Wacker-type oxidations. However, when franx-stilbene was used as a substrate, a significant amount of oxidative cleavage occurred. 

Oxidative addition of the silyl species to nickel is followed by insertion of unsaturated substrates. Zero-valent nickel complexes, and complexes prepared by reducing nickel acetylacetonate with aluminum trialkyls or ethoxydialkyls, and in general Ziegler-Natta-type systems, are effective as catalysts (244, 260-262). Ni(CO)4 is specific for terminal attack of SiHCl3 on styrene (261). 

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