Cation-directed enantioselective synthesis of quaternary-substituted indolenines

Abstract

An asymmetric method for the synthesis of quaternary-substituted indolenines via a 5-endo-dig cyclization of an α-cyanocarbanion onto an isonitrile has been developed. This transformation relies on Brønsted acid activation of the isonitrile functional group under asymmetric phase transfer conditions in the presence of a Brønsted base. Good to excellent levels of enantioselectivity were obtained (85 : 15 to 96 : 4 e.r., 18 examples) using a bespoke bifunctional catalyst. Enantioenriched indolenines produced in this process can be intercepted by nucleophilic species with high levels of diastereoselectivity to generate complex indoline frameworks. This process offers a general asymmetric approach to reactions involving the isonitrile functional group.