Catalytic C2 prenylation of unprotected indoles: Late-stage diversification of peptides and two-step total synthesis of tryprostatin B

C2 prenylated indoles are widespread in a variety of bioactive natural alkaloids. Therefore, the selective installation of prenyl group at C2 position of NH indoles is of great significance. However, the known protocols generally require a multi-step procedure and stoichiometric promoters. Herein we develop a one-step C2 prenylation of NH indole with cheap tert- prenyl alcohol enabled by acid catalysis. Salient features include good regioselectivity, step- and atom-economy, broad substrate scope, and simple catalytic system. The mechanistic investigations demonstrate that both C2 prenylation and C3 prenylation/migration pathways are engaged in the reaction. Notably, this practical strategy can be applied to the late-stage diversification of tryptophan-based peptides and concise synthesis of tryprostatin B.