Gold‐Catalyzed Cyclization of Yndiamides with Isoxazoles via α‐Imino Gold Fischer Carbenes

Abstract

AbstractGold catalysis is an important method for alkyne functionalization. Here we report the gold‐catalyzed formal [3+2] aminative cyclization of yndiamides and isoxazoles in a direct synthesis of polysubstituted diaminopyrroles, which are important motifs in drug discovery. Key to this process is the formation, and subsequent cyclization, of an α‐imino gold Fischer carbene, which represents a new type of gold carbene intermediate. The reaction proceeds rapidly under mild conditions, with high regioselectivity being achieved by introducing a subtle steric bias between the nitrogen substituents on the yndiamide. DFT calculations revealed that the key to this regioselectivity was the interconversion of isomeric gold keteniminiun ions via a low‐barrier π‐complex transition state, which establishes a Curtin‐Hammett scenario for isoxazole addition. By using benzisoxazoles as substrates, the reaction outcome could be switched to a formal [5+2] cyclization, leading to 1,4‐oxazepines.