Organocatalytic Esterification of P(O)-OH Functionalities with Alcohols

By introducing the catalytic variant of the Mitsunobu reaction to the field of organophosphorus chemistry, we present an organocatalytic strategy for the direct esterification of P(O)-OH compounds with alcohols, providing a sustainable and scalable route to phosphinate esters. This metal-free protocol is characterized by the integration of a carbonyl group-containing catalyst P═O with Dean-Stark water removal, which obviates the need for strong oxidants, halides, or bases, thereby rendering it environmentally benign. It demonstrates remarkable functional group tolerance and 39 organophosphinates were synthesized with moderate to excellent yield. From a mechanistic perspective, this approach involved the dehydration, ligand exchange and proton transfer with ring-opening, which was supported by the results of the DFT calculations.