Electrochemical α-C(sp3)-H/O-H cross-coupling of isochromans and alcohols assisted by benzoic acid

Isochroman moieties are present in a wide variety of biologically active molecules, but converting isochromans to alpha-substituted derivatives under mild conditions is challenging. Herein, we report a mild, convenient protocol for synthesis of alpha-alkoxy isochroman derivatives by means of electrochemical alpha-C(sp(3))-H/O-H cross-coupling reactions of isochromans and alcohols in the presence of benzoic acid, which facilitated the electro-oxidation process and increased the product yield. Various alcohols and isochromans, as well as other structurally similar substrates, gave moderate to high yields of the desired coupling products, and the reaction could be carried out on a gram scale.

Automated summary

A mild and convenient protocol for the synthesis of alpha-alkoxy isochroman derivatives has been reported in this study. The electrochemical alpha-C(sp(3))-H/O-H cross-coupling reactions of isochromans and alcohols in the presence of benzoic acid were used, which facilitated the electro-oxidation process and increased the product yield. The desired coupling products were obtained in moderate to high yields.