Transient Boryl Assistance Enables Stereoselective Alkylation of Acyclic Tetrasubstituted Enolates

ABSTRACT The enantioselective construction of acyclic quaternary carbon stereocenters and vicinal quaternary/tertiary stereocenters represents two persistent challenges in organic synthesis. Herein, we report a unified transient boryl‐assisted, catalytic enantioselective strategy that enables the synthesis of both isolated quaternary carbon stereocenters and vicinal quaternary/tertiary stereocenters. Central to this strategy are the boryl‐organized stereodefined acyclic tetrasubstituted enolates and their subsequent stereoselective alkylation, achieved through highly enantioselective copper‐catalyzed conjugate borylation of α ‐substituted α,β ‐unsaturated esters. The resulting borylative alkylation products are obtained with high enantio‐ and diastereoselectivity (up to 98% ee and > 20:1 d.r.) and undergo diverse downstream transformations of the boryl unit, providing versatile access to acyclic quaternary/tertiary stereocenters. Following its stereodirecting role, the boron unit can be removed in a one‐pot protodeboronation to furnish esters bearing isolated α ‐quaternary stereocenters with high ee values (up to 94% ee). This catalytic strategy provides a general solution to the stereocontrolled alkylation of acyclic tetrasubstituted enolates and enables modular access to complex quaternary carbon architectures.