Cobalt-Catalyzed Enantioselective Electroreductive Coupling for Chiral 4-Chromanols

Chiral 4-chromanols are privileged scaffolds with broad application in biological and pharmaceutical sciences. However, the sustainable and highly enantioselective synthesis of these structures remains a significant challenge. Herein, we report an enantioselective cobalt-catalyzed electroreductive coupling of salicylaldehyde derivatives, enabling the efficient synthesis of chiral 4-chromanol motifs in good yields and with excellent enantioselectivities (up to 99% ee). This approach has notable advantages, utilizing electricity as a green reductant and H 2 O as an ideal proton source. Moreover, both experimental and computational mechanistic studies revealed that the key oxacobaltacycle intermediate is formed via oxidative cycloaddition between the alkyne and carbonyl groups in the salicylaldehyde substrates.