Chemoenzymatic synthesis of enantiomerically enriched 2-oxobicyclo[m.1.0]alkan-3-yl acetate derivatives

Racemic α′-acetoxy α,β-unsaturated cyclopentanone and cyclohexanone have been resolved into the corresponding enantiomerically enriched α′-hydroxylated and acetoxylated compounds with 96–97% ee via PLE hydrolysis. Stereoselectivity in the palladium(II)-catalyzed reaction between the enantiomerically enriched α′-acetoxylated compounds and diazomethane has been investigated. In the α′-acetoxylated cyclopentenone, preferential cyclopropanation occurs in the anti-form, whereas α′-acetoxylated cyclohexenone affords both syn- and anti-products (syn:anti, 61:36%). The relative configuration of the products was determined by NOE experiments.

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(1S,3S,5S)-(−)-2-Oxobicyclo[3.1.0]hexan-3-yl acetateC8H10O3Ee = 96%[α]D20=-22.0 (c 0.2, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 1S,3S,5S

(1R,3S,6S)-(−)-2-Oxobicyclo[4.1.0]heptan-3-yl acetateC9H12O3Ee = 97%[α]D20=-22.05 (c 0.2, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 1R,3S,6S

(1S,3S,6R)-(+)-2-Oxobicyclo[4.1.0]heptan-3-yl acetateC9H12O3Ee = 97%[α]D20=+5.05 (c 0.2, CHCl3)Source of chirality: enzymatic resolutionAbsolute configuration: 1S,3S,6R