Self-reproduction of chirality on α-aminophosphonates: asymmetric synthesis of α-alkylated diethyl pyrrolidin-2-yl-phosphonate

A simple method for the asymmetric synthesis of α-substituted diethyl pyrrolidin-2-yl-phosphonate is described. The chiral oxazolopyrrolidine phosphonate was alkylated diastereospecifically with an alkyl halide. The key intermediate is an α-phosphonate-stabilized carbanion that can be alkylated without loss of optical activity and a single enantiomer of product was formed exclusively in 10–80% yield. The configurational assignment of the products relied on 1H–1H NOESY analysis of the alkylated oxazolopyrrolidine phosphonates. This represents an unprecedented case of self-regeneration of stereocenters (SRS) of cyclic aminophosphonates. The enantiomerically pure α-aminophosphonate diethyl-(2S)-(2-methylpyrrolidin-2-yl)-phosphonate, a surrogate of 2-methyl proline, was obtained upon hydrogenolysis of the chiral auxiliary in 83% yield.