Electroselective C(sp3)–H deuteration of isoindolinones

Abstract

Development of precise deuteration reactions is highly desirable for organic synthesis, analytical chemistry and pharmaceutical chemistry. The electrochemical C(sp³)–H deuteration of isoindolinones via a H/D exchange reaction is presented for the first time. This paired electrochemical protocol provides an efficient way to synthesize deuterated isoindolinones under mild neutral conditions (39 examples, up to 97% D-incorporation). This precise deuteration method can be used for site-selective D-labeling of a number of pharmaceutical molecules. Furthermore, valuable bisdeuterated isoindolines are generally accessible via a reduction of isoindolinones. This protocol provides an efficient route for the construction of C–D bonds with high regioselectivity.