Rapid access to the heterocyclic core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids via tandem cyclization of a neutral aminyl radical

Abstract

A streamlined approach to the tertiary amine-containing core of the calyciphylline A and daphnicyclidin A-type Daphniphyllum alkaloids is presented. A known carvone derivative is converted into the core structure in only four synthetic operations, and it is well poised for further elaboration. The key enabling methodology is a radical cyclization cascade beginning with addition of a secondary, neutral aminyl radical to the β-position of an enone, followed by trapping with a pendant alkyne.