Catalytic 1,4-Reduction of alpha,beta-Unsaturated Ketones and Application to Asymmetric Synthesis of Warfarin

摘要

We recently found that alpha,beta-unsaturated ketone la was reduced in ethanol in the presence of {Pd(dppb)(H_2O)_2}(OTf)_2 (5 mol%) (dppb = diphenylphosphinobutane)(Scheme 1). Pd-H species have been proposed to be key intermediates in the Pd-catalyzed oxidation of alcohols, where they are usually decomposed to Pd(0) and re-oxidized to complete the catalytic cycle. We speculated that the Pd-H species generated by oxidation of ethanol under our conditions might act as a reducing agent. While Pd-H species are known to be important intermediates in several reactions, their use in the asymmetric conjugate reduction has not previously been reported, to our knowledge. In terms of atom economy and environmental concerns, a conjugate reduction using ethanol as a hydride source would be extremely beneficial. Therefore, we planned to examine the asymmetric conjugate reduction using beta,beta-disubstituted enones as the substrates.