Enantioselective β-Protonation of Enals via a Shuttling Strategy

Remote asymmetric protonation is a long-standing challenge due to the small size of protons. Reactions involving electron-deficient olefins pose a further difficulty due to the electrophilic nature of these substrates. We report a shuttling system that delivers a proton in a highly enantioselective manner to the beta-carbon of enals using a chiral N-heterocyclic carbene (NHC) catalyst. Choices of a Bronsted base shuttle and a Bronsted acid cocatalyst are critical for highly stereoselective beta-protonation of the homoenolate intermediate and regeneration of the NHC catalyst results in functionalization of the carbonyl group. Thioesters with a beta-chiral center were prepared in a redox-neutral transformation with an excellent yield and ee.