Conversion of Alcohols to Phosphorothiolates Using a Thioiminium Salt as Coupling Agent

Abstract

We report a method for the direct and rapid conversion of primary and secondary alcohols to the corresponding phosphorothiolates in yields ranging from 64% to 97%, using as a coupling agent the iminium salt prepared from N,N-dimethylthioformamide and Meerwein's salt. Selective reaction of primary alcohols in the presence of secondary alcohols is possible. The reaction of secondary alcohols proceeds stereospecifically with inversion of configuration.

Progress in the Chemistry of Phosphorothioates

“…Porter and coworkers used the thioiminium salt prepared from N,Ndimethylthioformamide and Meerwein's salt as the coupling agent for the direct conversion of primary and secondary alcohols to the corresponding phosphorothioic esters by reaction with sodium phosphorothioate (Scheme 28). [38] Alternatively, the reaction can be performed with phosphorothioic acid in the presence of imidazole, under vigorous stirring. The mechanism proposed by the authors consists in the nucleophilic addition of the alcohol to the thioiminium salt with loss of ethanethiolate, then nucleophilic displacement of dimethylformamide (DMF) by the phosphorothioate salt to…”