Catalytic Enantioconvergent Allenylation of Aldehydes with Propargyl Halides.

Abstract

α-Allenol is a versatile synthon in organic synthesis. The catalytic asymmetric synthesis of α-allenols from readily available starting materials remains a prominent challenge, especially when simultaneous control over axial and central chirality is required. Herein, we describe the Cr-catalyzed enantioconvergent allenylation of aldehydes with racemic propargyl halides to rapidly access a wide range of chiral α-allenols with adjacent axial and central chiralities. This method features excellent regio-, diastereo- and enantioselectivity control with broad substrate scope, and provides facile access to all four stereoisomers when allied with a Mitsunobu reaction. Preliminary mechanistic studies support radical-based reaction pathways. The synthetic utility is demonstrated by the application in late-stage functionalization and the formal total synthesis of (+)-varitriol.