A Mild and General Larock Indolization Protocol for the Preparation of Unnatural Tryptophans

A niild and general protocol for the Pd(0)catalyzed heteroannulation of o-bromoanilines and alkynes is described. Application of a Pd(0)/p(Bu-t)(3), catalyst system enables the efficient coupling of o-bromoanilines at 60 degrees C, mitigating deleterious side reactions and enabling access to a broad range of useful unnatural tryptophans. The utility of this new protocol is demonstrated in the highly convergent total synthesis of the bisindole natural product (-)-aspergilazine A.