Diols Jacobsen asymmetric epoxidation

In the example of the asymmetric epoxidation of olefins, enzymes, synthetic catalysts, and catalytic antibodies have been compared side-by-side with respect to performance in chemical synthesis (Jacobsen, 1994). Epoxidation of olefins is a reaction of considerable industrial interest where, historically, enzymes have not performed extremely well. One reason is the dependence of the enantiomeric purity of the diol and epoxide products on the regiospecificity of the attack on the racemic epoxide by a water molecule (Figure 20.1). 

Asymmetric epoxidation (Jacobsen) and dihydroxylation (Sharpless) are other potentially viable approach to epoxides, diols, and aminodiols. 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

Jacobsen and Ready <0IJA2687> have reported on the development of a highly aetive cyclic oligosalen catalyst (66), which is remarkably effective in promoting the asymmetric ring opening of epoxides by water and alcohols. For example, exposure of the notoriously recalcitrant substrate cyclohexene oxide (67) to water in methylene chloride/acetonitrile and 1.5 mol% of catalyst 66 led to smooth conversion to the chiral diol 68 in 98% yield and 94% ee. This catalyst is also effective in the kinetic resolution of epoxides with alcohols (i.e., 69 71)<01JA2687>. 

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