Nucleophilic Substitution Reactions of (Alkoxymethylene)dimethylammonium Chloride

The use of imidate esters as potential replacements for diethyl azodicarboxylate and triphenylphosphine in the Mitsunobu reaction is described. A series of secondary alcohols were allowed to react with (chloromethylene)dimethylammonium chloride, generated from dimethylformamide (DMF) and oxalyl chloride, to give imidate esters. Reaction of these salts with potassium benzoate or potassium phthalimide gave the products of S(N)2 substitution in excellent yields with clean inversion of stereochemistry. Optimization of reaction conditions is discussed as a means to increase the atom economy of the process by minimizing the quantity of nucleophile required.