Metal-free catalytic nucleophilic substitution of primary alcohols with secondary phosphine oxides†

Abstract

Due to their inert nature and low reactivities, the dehydrative version of the MA reaction has not been achieved under metal-free conditions. Here, we develop a direct and efficient metal-free nucleophilic substitution reaction of primary alcohols with secondary phosphine oxides using trimethyliodosilane (TMSI) as the catalyst, providing a simple and green method for synthesis of useful tertiary phosphine oxides. This method is very effective as it can be extended to various primary alcohols, including benzylic and allylic, and even the more inert primary aliphatic alcohols. Many products can be obtained with high purity by simple washing and/or recrystallization under column chromatography-free conditions. This method can also be scaled up easily and applied in one-pot step-wise transformations to synthesize useful chemicals. Mechanism studies suggested that the reaction can be considered as a dehydrative version of the Michaelis–Arbuzov reaction and that both alcohol dehydroxylation and dehydrogenation processes may be involved in the reaction.