Enantioselective construction of cycloalkyl amines via nickel-catalysed alkene desymmetrization

Abstract

Three-dimensional chiral cyclic frameworks containing multiple stereocenters are prevalent skeletons in natural products and bioactive molecules. Nevertheless, the synthetic methods for these architectures are limited to date. In this study, an efficient synthetic route for cyclic chiral amines with two adjacent stereocenters was developed by employing symmetric cyclopentenylamine derivatives as starting materials. This reaction demonstrates a broad substrate scope with various functional groups, resulting in excellent yields and stereoselectivities. The proposed mechanism involves a sophisticated sequence of NiH species-mediated transformations, including NiH insertion, β-hydride elimination, reversed NiH insertion and alkylation steps, which collectively enable the precise construction of these complex chiral architectures.