THE CHEMISTRY OF PHOSPHAPEPTIDES - FORMATION OF FUNCTIONALIZED PHOSPHONACHLORIDATES UNDER MILD CONDITIONS AND THEIR REACTION WITH ALCOHOLS AND AMINES

A variety of methods have been explored for the convergent synthesis of phosphonamidates and phosphonates via phosphonochloridates. In the absence of complex functionality, phosphorus pentachloride is an effective reagent for the conversion of diethyl and diisopropyl phosphonates to phosphonochloridates. Subsequent reaction with amines and alcohols provides good yields of the phosphonamidates and mixed phosphonates, respectively. However, in the presence of more complex functionality, a milder method utilizing oxalyl chloride to generate the phosphonochloridate from a monomethyl phosphonic acid is required. Aminolysis of the dimethyl phosphonates generates the requisite monomethyl phosphonic acids which are cleanly converted to phosphonochloridates and reacted with amines and primary alcohols.