A New and Highly Efficient Asymmetric Route to Cyclic α-Amino Phosphonates:  The First Catalytic Enantioselective Hydrophosphonylation of Cyclic Imines Catalyzed by Chiral Heterobimetallic Lanthanoid Complexes

Abstract

The catalytic and enantioselective hydrophosphonylation of cyclic imines is described for the first time. In addition, we have uncovered a new and highly efficient asymmetric approach to cyclic α-amino phosphonates using thiazolines as the imine model component. The desired pharmaceutically interesting phosphonates 5a−e could be synthesized by a heterobimetallic (R)-LnPB-catalyzed (Ln = lanthanoid metal, P = potassium, B = (R)=binaphthol) hydrophosphonylation of the CN double bond with up to 98% enantiomeric excess and up to 98% chemical yield. Using other types of organometallic catalysts (titanium(IV) complexes), the reaction proceeds with modest enantioselectivity. A detailed investigation concerning the dependence of enantioselectivity and chemical yield, respectively, on a series of reaction parameters (e.g., lanthanoid and alkali metal, solvent, reaction temperature, pressure, and catalytic amount) is reported. An optimized catalytic lanthanoid system "(R)-YbPB (5 mol %)/50 °C/48 h/THF−toluene (1:7)" was found. The catalytically active complex was isolated and analyzed by spectroscopic methods. In addition, 31P and 1H NMR spectroscopic and LDI-TOF mass spectrometric investigations were carried out to support a postulated mechanistic course for this (R)-LnPB-complex-catalyzed hydrophosphonylation reaction.