Asymmetric Synthesis of Aziridine 2-Phosphonates from Enantiopure Sulfinimines (N-Sulfinyl Imines). Synthesis of α-Amino Phosphonates

An aza-Darzens reaction, involving the addition of chloromethylphosphonate anions to enantiopure sulfinimines, has been developed for the asymmetric synthesis of aziridine 2-phosphonates. Best results involve cyclization of the syn and anti diastereomerically pure alpha-chloro-beta-amino phosphonates to cis- and trans-N-sulfinyl aziridine 2-phosphonates, respectively, with n-BuLi. A transition-state hypothesis is proposed wherein the chloromethylphosphonate anion adds to the C-N bond on the side that is opposite the bulky p-tolyl sulfinyl group. The N-sulfinyl group is easily removed by treatment with MeMgBr or TFA/MeOH, which affords the NH-aziridines in good yield. Using transfer hydrogenation conditions, the NH-aziridines were regioselectively opened to the corresponding enantiopure alpha-amino phosphonates without N-activation and in excellent yield.