Visible-Light-Mediated Cyclization of Intramolecular Electron Donor-Acceptor (EDA) Complexes and Its Application in the Total Synthesis of Corynanthe-Type Alkaloids.

Abstract

A visible-light-driven one-pot decarboxylative cyclization cascade via an intramolecular electron donor-acceptor (EDA) complex is reported. By covalently tethering an indole donor and an NHPI ester acceptor with an alkyl linker, this strategy enables efficient assembly of the signature 6/5/6/6 tetracyclic skeleton of corynanthe-type monoterpene indole alkaloids under mild, metal- and photocatalyst-free neutral conditions. The transformation features a broad substrate scope (22 examples), excellent yields (68-98%), and facile gram-scale scalability. Using this reaction as the key step, we achieved the enantioselective total synthesis of (+)-hirsutinol and (-)-dihydrocorynantheol in 8 linear steps, which represents, to the best of our knowledge, the first application of an intramolecular EDA strategy in the total synthesis of indole alkaloids.