Photochemical C-O Coupling of Chiral Alcohols with Aryl Halides by Nickel Catalysis

Although photochemically driven earth-abundant nickel catalysis is progressively becoming a major method in constructing carbon-oxygen bonds, there remains a lack of universal strategy that can be broadly applied to the coupling of various chiral alcohols with aryl halides without compromising enantiomeric excess. Herein, we report a light-driven nickel-catalyzed method that achieves stereochemistry-preserving C-O coupling between optically active alcohols with aryl halides, without the need for any external photosensitizer. The method is compatible with a wide range of coupling substrates, including compounds bearing bases and nucleophile-sensitive functional groups, providing a robust route to valuable chiral aryl alkyl ethers. The gram-scale synthesis of fragments of the antidiabetic drug empagliflozin further highlights its applicability and generality in drug discovery.