Enantioselective reduction Baeyer-Villiger oxidation

Scheme 13.17 depicts a synthesis based on enantioselective reduction of bicyclo[2.2.2]octane-2,6-dione by Baker s yeast.21 This is an example of desym-metrization (see Part A, Topic 2.2). The unreduced carbonyl group was converted to an alkene by the Shapiro reaction. The alcohol was then reoxidized to a ketone. The enantiomerically pure intermediate was converted to the lactone by Baeyer-Villiger oxidation and an allylic rearrangement. The methyl group was introduced stereoselec-tively from the exo face of the bicyclic lactone by an enolate alkylation in Step C-l. 

In 1985, we reported that reduction of a prochiral 1,3-diketone A (Figure 3.6) with fermenting baker s yeast (Saccharomyces cerevisiae) was enantioselective to give (5)-hydroxy ketone B of 98-99% ee.26 I noticed that the Baeyer-Villiger oxidation of B would furnish (S)-hydroxylactone, a building block synthetically equivalent to the terminal epoxide moiety of (+)-JH III. This idea was used for the synthesis of (+)- and (-)-JH III in 1987.27... 

Baeyer-Villiger oxidation (p. 853) catalytic hydrogenation (p. 844) chemoselective reaction (p. 848) dissolving-metal reduction (p. 846) enantioselective reaction (p. 857) epoxidation (p. 855) functional group interconversion (p. glycol (p. 858)... 

Together with enantioselective hydrolysis/acylation reactions, enantioselective ketone reductions dominate biocatalytic reactions in the pharma industry [10], In addition, oxidases [11] have found synthetic applications, such as in enantioselective Baeyer-Villiger reactions [12] catalyzed by, for example, cyclohexanone monooxygenase (EC 1.14.13) or in the TEMPO-mediated oxidation of primary alcohols to aldehydes, catalyzed by laccases [13]. Hence, the class of oxidoreductases is receiving increased attention in the field of biocatalysis. Traditionally they have been perceived as difficult due to cofactor requirements etc, but recent examples with immobilization and cofactor regeneration seem to prove the opposite. 

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