Enantioselective Hydrophosphonylation of in Situ Generated N-Acyl Ketimines Catalyzed by BINOL-Derived Phosphoric Acid

An efficient route to pharmacologically interesting isoindolinone-based a alpha-amino phosphonates is described via asymmetric hydrophosphonylation of in situ generated ketimines catalyzed by BINOL-derived phosphoric acid. The reaction proceeds smoothly at ambient temperature affording a variety of a alpha-amino phosphonates with a quaternary stereogenic center embedded in isoindolinone motif in high yields with excellent enantiomeric ratios (up to 98.5:1.5 er). Several interesting transformations of the products into valuable synthetic intermediates are also depicted.