Substrates 2,3-disubstituted oxiranes

The patterns of regio- and stereoselectivities become more complex in disubstituted oxiranes. Beginning with 2,2-disubstituted oxiranes, attack is always at the accessible C-atom. In terms of substrate enantioselectivity, it was found that 2-butyl-2-methyloxirane (2-methyl-1,2-epoxyhexane, 10.43, R = Bu) was hydrolyzed with a preference for the (5)-enantiomer. This substrate enantioselectivity was lost for branched analogues, namely 2-(/er/-bu-tyl)-2-methyloxirane (10.43, R = /-Bu) and 2-(2,2-dimethylpropyl)-2-meth-yloxirane (10.43, R = (CH3)3CCH2) [124], Thus, it appears that the introduction of a geminal Me group suppresses the enantioselectivity seen with branched monoalkyloxiranes, and reverses it for straight-chain alkyloxiranes. 

Disubstituted oxiranes of general structure 10.44, namely 2-alkyl-3-methyloxiranes, are another case in point. Again, nucleophilic attack is exclusively or predominantly at the more accessible C(3), with substrate... 

Table 2. Selectivities from the resolution of 2,2-disubstituted oxiranes by bacterial cells (substrate structures are given in Chart 1)...

Among the sterically more demanding substrates, 2,2-disubstituted oxiranes were hydrolyzed in virtually complete enantioselectivities using enzymes from bacterial sources (E > 200), in particular Mycobacterium NCIMB 10420, Rhodococcus (NCIMB 1216, DSM 43338, IFO 3730) and closely related Nocardia spp. (Scheme 2.93) [608, 609]. All bacterial epoxide hydrolases exhibited a preference for the (S)-enantiomer. In those cases where the regioselectivity was determined, attack was found to exclusively occur at the unsubstituted oxirane carbon atom. 

Only limited data are available on the biohydrolysis of 2,2-disubstituted oxiranes (Fig. 3, Table 3) employing mammalian and yeast epoxide hydrolases. For instance, the presence of a geminal dimetbyl group in 2.1 resulted in complete enantioselectivity when mEH was used as a catalyst. Thus, epoxide 2.1 was resolved to yield the corresponding (/f)-diol and the remaining (5)-epoxide 2.1 both in more than 95% e.e. at 50% conversion. On the other hand, a simple 2-methyl-2-alkyl oxirane such as 2.2 could not be resolved with high efficiency employing mEH. For this substrate pattern, bacterial epoxide hydrolases proved to be extremely useful. 

Oxiranes of terminal monosubstituted and internal disubstituted olefins do not undergo the isomerization under standard conditions, but give aldehydes at elevated temperature. For the special substrates described in Sch. 35, different modes of reaction originated from intermediary carbocationic species, involve neighboring functional group participation, oxidation, etc. An improvement employing other silicon Lewis acids, for example Mc3SiI and McsSiBr, was developed by Kraus, Detty, and Sakurai [17,19f,62]. 

Gross et al. reported the first use of a chiral ruthenium porphyrin Ru"(L,)(CO) as a catalyst for styrene epoxidation . Chiral ruthenium porphyrin systems have also been reported by Che et a/. . The utilization of another chiral ruthenium porphyrin, Ru"(L2)(CO) as a catalyst for enantioselective epoxidation of olefins with 2,6-dichloropyridine A-oxide has been described by Berkessel and Frauenkron ". The highest enantiomeric excesses of the oxiranes were obtained in the epoxidation of tetrahydronaphthalene and styrene, 77% and 70% ee, respectively, with high jdelds (up to 88%). Terminal aliphatic olefins and tra 5-disubstituted olefins, represented by 1-octene and rraw-stilbene, were sluggish substrates and gave low ee s. The epoxidation of tetrahydronaphthalene with iodosylbenzene catalyzed by Ru(II)(L2)(CO) produced only 52% ee... 

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