A Carbodiimide-Mediated P-C Bond-Forming Reaction: Mild Amidoalkylation of P-Nucleophiles by Boc-Aminals.

Abstract

The first example of a carbodiimide-mediated P-C bond-forming reaction is described. The reaction involves activation of β-carboxyethylphospinic acids and subsequent reaction with Boc-aminals using acid-catalysis. Mechanistic experiments using 31P NMR spectroscopy and DFT calculations support the contribution of unusually reactive cyclic phosphinic/carboxylic mixed anhydrides in a reaction pathway involving ion-pair swapping . The utility of this protocol is highlighted by the direct synthesis of Boc-protected phosphinic dipeptides, as precursors to potent Zn-aminopeptidase inhibitors.