Practical Large-Scale Synthesis of 3,4-Isopropylidenedioxypyrrolidine Hydrotosylate: Atom Economical Self-Hydrogenolysis of a Crystalline Borane−Benzylamine Adduct

Abstract

An efficient four-step sequence has been developed for the synthesis of 3,4-isopropylidenedioxypyrrolidine hydrotosylate starting from inexpensive N-benzylmaleimide. This approach features a novel N-debenzylation procedure that utilizes the corresponding borane−benzylamine complex as an internal hydrogen-transfer source. This palladium-catalyzed tandem protonolysis/hydrogenolysis allows cleavage of the borane−amine adduct and debenzylation in a single operation.