One-Step Asymmetric Construction of 1,4-Stereocenters via Tandem Mannich-Isomerization Reactions Mediated by a Dual-Functional Betaine Catalyst.

Abstract

The construction of chiral motifs containing nonadjacent stereocenters stands out as a major challenge as they are usually constructed in separate steps utilizing different chiral catalysts. Therefore, the development of new strategies to streamline the construction of such complex motifs has become a major focus of asymmetric synthesis. We report here an unprecedented asymmetric tandem Mannich-isomerization reaction that allows the direct construction of 1,4-stereocenters in a highly stereoselective manner. This asymmetric transformation demonstrated the potential of a tandem nucleophilic addition-isomerization reaction as a broadly useful strategy for the efficient construction of 1,4-stereocenters. Notably, this tandem reaction was mediated by a single chiral betaine as a dual-functional catalyst, promoting first an enantioselective intermolecular C-C bond forming reaction and next a stereoselective intramolecular 1,3-proton transfer reaction.