Tuning Effect of Additive in Tandem Asymmetric Michael–MPV Reaction and its Applications

Abstract

We have found that pentafluorobenzoic acid (PFBA) was the most effective additive in the tandem Michael addition – Meerwein–Ponndrof–Verley (MPV) reduction of α,β-disubstituted α,β-unsaturated ketones 3 (R₂ = alkyl) with mercapto alcohol 1 as a chiral auxiliary to improve both yield and diastereoselectivity of the products 4. The tuning effect of additives depended on the pH value. In addition, we have done asymmetric synthesis of 1,3-mercapto alcohols bearing contiguous three stereogenic centers and total synthesis of Whisky lactone and Cognac lactone, utilizing the above tandem reaction as a key reaction.