Asymmetric synthesis of aziridine 2-phosphonates from enantiopure sulfinimines (N-sulfinyl imines). Synthesis of alpha-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.
Davis
Franklin A
FA
Department of Chemistry, Temple University, Philadelphia, Pennsylvania 19122, USA. fdavis@temple.edu
Wu
Yongzhong
Y
Yan
Hongxing
H
McCoull
William
W
Prasad
Kavirayani R
KR
D000588:Amines / Q000737:chemistry*; D001388:Aziridines / Q000138:chemical synthesis*; D002384:Catalysis; D002855:Chromatography, Thin Layer; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D063065:Organophosphonates / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000737:chemistry*
D000588:Amines; D001388:Aziridines; D007202:Indicators and Reagents; D063065:Organophosphonates; D013457:Sulfur Compounds; C033132:aziridine