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