Electrochemical Azo‐free Mitsunobu‐type Reaction

The classic chemical Mitsunobu reaction suffers from the need of excess alcohol activation reagents and the generation of significant by‐products. Efforts to overcome these limitations have resulted in numerous creative solutions, but the substrate scope of these catalytic processes remains limited. Here we report an electrochemical Mitsunobu‐type reaction, which features azo‐free alcohol activation and broad substrate scope. This user‐friendly technology allows a vast collection of heterocycles as the nucleophile, which can couple with a series of chiral cyclic and acyclic alcohols in moderate to high yields and excellent ee’s. This practical reaction is scalable, chemoselective, uses simple Electrasyn setup with inexpensive electrodes and requires no precaution to exclude air and moisture. The synthetic utility is further demonstrated on the structural modification of diverse bioactive natural products and pharmaceutical derivatives and its straightforward application in a multiple‐step synthesis of a drug candidate.