Diastereoselective Phosphonylation of Chiral Cyclic Imines for the Synthesis of Phosphoproline Derivatives

Abstract We report here the first diastereoselective synthesis of (2 S ,5 R )‐5‐methyl‐5‐(phosphono)‐proline, a phosphoproline derivative from L‐pyroglutamic acid. The main feature of this methodology is the transformation of L‐pyroglutamic acid into chiral cyclic imines as a versatile intermediate followed by diastereoselective nucleophilic addition of trialkyl phosphites or diethyl phosphite in the presence of PhB(OH) 2 , Ph 2 P(O)OH, (PhO) 2 P(O)OH, Ph(H)P(O)OH and TiCl 4 . N ‐Cbz Cleavage with simultaneous hydrolysis of phosphonate and carboxylate esters in the quaternary cyclic α‐aminophosphonate, gave the target compound.