Progress of Catalytic Mitsunobu Reaction in the Two Decades

Abstract An important goal of modern synthetic chemistry is the development of highly efficient and selective processes that minimize the formation of waste, which are desirable for economy and environmental requirements. The classic Mitsunobu reaction has been adopted widely for converting alcohols into numerous functional groups and undergoes an inversion of stereochemistry in S N 2 reaction when secondary alcohols are employed. However, the reaction is far from ideal in terms of its environmental impact, requiring stoichiometric amounts of a phosphine (III) and an azodicarboxylate, and producing stoichiometric amounts of hydrazine and phosphine oxide wastes. The first attempt to access the catalytic Mitsunobu reaction dates back to 2006 by Toy's group and since then, several groups including Taniguchi, O'Brien, Aldrich, Denton and their co‐workers have opted for this promising alternative. Generally, the substantial progress has been made in the development of catalytic Mitsunobu reaction involving redox‐driven and redox‐neutral processes. The elegant redox‐driven catalytic system applies either external reductants or oxidants to recycle azo or phosphine reagents, while the preeminent redox‐neutral catalytic system is undergoing the activation step to proceed. This review summarizes the related developments in the recent two decades and presents the future research direction.