New Staudinger Strategy Enabled N-Acyl Phosphinamidites Synthesis

A new Staudinger strategy entails a unique C-P bond cleavage, instead of N-P bond cleavage, during the construction of N-acyl phosphinamidites by using acyl-phosphine substrates. The reaction is performed under very mild conditions, with no need for additional catalysts or additives, and thus preserves stereogenic centers that are sensitive to epimerization. A range of novel N-acyl phosphinamidites, including those bearing a chiral amino acid skeleton and axial chirality as well as complex natural product scaffolds, were produced with N-2 gas as the only byproduct. These N-acyl phosphinamidites are potential novel P-O ligands, and preliminary screening results have demonstrated their application as chiral organic catalysts.