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.