Current‐Regulated Selective Nickel‐Catalyzed Electroreductive Cross‐Electrophile Carbonylation to β/γ‐Hydroxy Ketones

The nickel catalyzed multi‐component cross‐electrophile carbonylation which emerges as a powerful and efficient method for constructing diverse ketones has attracted increasing attention of organic chemists. However, the selectivity of this reaction poses a significant challenge. In this work, we have developed a current‐regulated selective nickel‐catalyzed electroreductive cross‐electrophile carbonylation, which offers a direct convergent synthesis of β/γ‐hydroxy ketones, which represent pivotal structural motifs found in numerous natural products, bioactive molecules, pharmaceutical compounds, and essential building blocks. A diverse range of multi‐substituted or stereospecific β/γ‐hydroxyketones can be accessed with high chemo‐ and regioselectivity from epoxides, aryl iodides, and a simple CO source (ClCO2Pr). This electroreductive carbonylation strategy exhibits high functional group tolerance and can be applied in late‐stage derivatization of drugs and natural products. Notably, chiral epoxides can be employed as reactants with chirality retention, enabling the synthesis of asymmetric β‐hydroxy ketones. Our approach demonstrates a novel electrochemical selectivity‐controlled strategy in multi‐component cross‐electrophile coupling.