One-Pot Synthesis of alpha-Amino Bisphosphonates from Nitriles via Tf2O/HC(OR)(3)-Mediated Interrupted Ritter-Type Reaction

A versatile synthesis of alpha-amino bisphosphonates has been achieved through one-pot interrupted Ritter-type reaction under mild conditions. The reactive Ritter intermediate nitrilium is in situ generated by treatment of nitrile with readily accessible Tf2O/HC(OR1)(3), which is trapped by phosphite ester to deliver the desired product. This protocol is efficient, scalable, and well compatible with a broad scope of substrates. In addition, plentiful characteristic J(P-C) couplings including unusual five-bond long-range 5J(P-C) and 3J(P-C) across quaternary carbon and hetero (N) atoms were observed in C-13 NMR spectra.