Room Temperature Allenation of Terminal Alkynes with Aldehydes

A gold‐catalyzed room temperature allenation of terminal alkynes (ATA) with aldehydes affording 1,3‐disubstituted allenes with diverse functional groups has been developed by identifying a gold(I) catalyst and an amine. The practicality of this reaction has been demonstrated by a ten gram‐scale synthesis and the synthetic potentials have been demonstrated via various transformations and formal total synthesis of (−)‐centrolobine. Mechanistic studies revealed that the gold catalyst, the aldehyde effect, the fluoroalkyl hydroxyl solvent (TFE or HFIP) and the structure of amine are vital in this room temperature ATA reaction. Au(SIPr)NTf2 has been identified for the room temperature ATA reaction to afford diverse 1,3‐disubstituted allenes with 1‐methyl‐1,2,3,4‐tetrahydroisoquinoline as amine and aldehyde and TFE or HFIP as the mediator. A formal synthesis of (−)‐centrolobine and synthetic transformations have been demonstrated.