The mechanism of the first step of the Mitsunobu reaction

Abstract

Previous DFT calculations employing phosphine (PH3) and dimethyl azodicarboxylate showed that a cyclic O,N-phosphorane was energetically favored relative to betaine formation. In this study strong experimental support for the formation of the phosphorane is described. The question of whether betaine formation occurs via nucleophilic attack of the phosphine on the azodicarboxylate as has been previously assumed, or via a [4 cycloaddition (cheletropic) reaction to give the O,N-phosphorane, followed by ring-opening to give the betaine has not been resolved. An answer to this intriguing question is provided.