Catalytic Enantioconvergent Allenylation of Aldehydes with Propargyl Halides

Abstract

Abstractα‐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.