Enantioselective Copper-Catalyzed Synthesis of Axially Chiral Deuterated Biaryl Ethers and Phenols from Cyclic Iodonium Salts

Abstract

Axially chiral biaryl compounds hold significant value in medicinal chemistry and asymmetric catalysis, while the incorporation of a deuterated methoxy group can substantially improve the pharmacokinetic properties of these molecules. This study reports a method for the synthesis of axially chiral biaryl deuterated anisoles through the asymmetric ring-opening of cyclic iodonium salts. By employ-ing inexpensive commercially available deuterated methanol (CD₃OD) as both the nucleophile and deuterium source, the protocol enables the efficient, one-step introduction of deuterated methoxy, ethoxy, and hydroxy groups under mild, base-free conditions. The reaction exhibits excellent substrate scope and outstanding enantioselectivity.