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.
Abstract
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.