Dynamic Kinetic Reductive Conjugate Addition for Construction of Axial Chirality Enabled by Synergistic Photoredox/Cobalt Catalysis

Conjugate addition is among the most important synthetic protocols for constructing carbon skeletons and is widely used to synthesize natural products and drugs. However, asymmetric catalysis studies have mainly focused on constructing stereogenic centers arising from conjugate alkenes. Here, we report the first photoinduced cobalt-catalyzed dynamic kinetic reductive conjugate addition reaction that enables the formation of heterobiaryls with axial chirality (45 examples, up to 91% yield and 97% ee). This method features mild reaction conditions, good functional-group tolerance, and excellent enantiomeric control. Significantly, large amounts of metal waste and precious metal catalysts can be avoided under these conditions. Migration of the chiral arylcobalt species into the alkene might be the rate-determining step based on kinetic studies.

Automated summary

Conjugate addition is a crucial method for synthesizing carbon skeletons and has been widely used in the synthesis of natural products and drugs. However, asymmetric catalysis studies have primarily focused on the construction of stereogenic centers from conjugate alkenes. In this study, we describe the first photoinduced cobalt-catalyzed dynamic kinetic reductive conjugate addition reaction that allows for the formation of heterobiaryls with axial chirality (45 examples, with yields up to 91% and enantiomeric excess of 97%). This method offers mild reaction conditions, good tolerance to various functional groups, and excellent control over enantiomeric outcomes. Importantly, it eliminates the generation of large amounts of metal waste and the need for precious metal catalysts. Kinetic studies suggest that the migration of the chiral arylcobalt species into the alkene may be the rate-determining step.