Enzyme and Palladium Catalysis as a Powerful Combination in Asymmetric Transformations of meso-2-Alkene-1,4-diol Derivatives. Application to Enantiodivergent Synthesis of (R)- and (S)-(2,4-Cycloalkadienyl)acetic Acids

Enzymatic hydrolysis of meso-diacetates cis-1,4-diacetoxy-2-cyclohexene (4a) and cis-1,4-diacetoxy-2-cycloheptene (4b) was used to prepare enantiomerically pure (> 98 % ee) 4-acetoxy-2-cyclohexenol (5a) and 4-acetoxy-2-cycloheptenol (5b), respectively. The latter compounds 5 are useful synthons for further functionalization via Pd(0)-catalyzed nucleophilic substitution. Using palladium chemistry it was possible to direct the nucleophilic substitution of either of the allylic oxygen groups to selectively obtain both enantiomers of the product. This methodology was applied to the enantiodivergent synthesis of diene acids (S)- 10 and (R)- 10, which were transformed to enantiomeric lactones via a palladium-catalyzed oxidation.