Stereoselective Synthesis of Chiral Homoallylic Alcohols with Functionalized Alkenes via Radical-Involved Triple Catalysis

The stereoselective synthesis of chiral homoallylic alcohols bearing functionalized internal alkenes is crucial for accessing diverse bioactive compounds and complex molecular architectures. However, current methods often rely on polar pathways with preformed allylic metal reagents, facing limitations in scope and reaction conditions. Herein, we report a radical-involved strategy for the asymmetric reductive coupling of readily accessible Z/E-mixed, functionalized internal 1,3-dienes (bearing boronate ester or sulfone moieties) with a broad range of aldehydes. This transformation is achieved under mild conditions using a synergistic photoredox/Cr/Co triple catalytic system, affording valuable chiral homoallylic alcohols with vicinal stereocenters and a stereodefined E-alkenyl C═C bond in high yields and with good regio-, diastereo-, and enantioselectivities (up to 99% ee). The synthetic utility is demonstrated through versatile product derivatizations. Comprehensive mechanistic investigations, including deuterium labeling and DFT calculations, elucidate a pathway involving regioselective Co-mediated hydrogen atom transfer to the diene, followed by stereoselective capture of the resulting allylic radical by a chiral chromium complex and subsequent C–C bond formation with the aldehyde, rationalizing the observed selectivity.