Nucleophilic Additions to N‐Glycosylnitrones. Asymmetric Synthesis of α‐Aminophosphonic Acids

The hypothesis which explains the diastereoselectivity of the 1,3‐dipolar cycloaddition of the N‐glycosylnitrones 1–3 leading to the 5,5‐disubstituted isoxazolidines 4–6 on the basis of a kinetic anomeric effect predicts that nucleophiles should add to N‐glycosylnitrones with a high degree of diastereoselectivity. To test this prediction, the nucleophilic addition of lithium and potassium dialkylphosphites to the crystalline (Z)‐nitrone 11, prepared from oxime 9 and (benzyloxy)acetaldehyde has been examined. The addition of lithium phosphites gave the N‐glycosyl‐N‐hydroxyaminophosphonates 12–16 (d. e. 78–92%) in high yields (Scheme 4). The addition of potassium phosphites showed a much lower diastereoselectivity. Glycoside cleavage, hydrogenolysis, and dealkylation of 12–16 gave (+)‐(S)‐phosphoserine (+)‐19 (34–45% from 9). Its absolute configuration was confirmed by an X‐ray analysis of the N‐(3,3,3‐trifluoro‐2‐methoxy‐2‐phenylpropionyl) derivative 24. Similarly, the crystalline nitrone 25 gave the N‐glycosyl‐N‐hydroxyaminophosphonate 26, which was transformed into (+)‐(S)‐phosphovaline (+)‐31 (42% from 9). The diastereoselectivity of the nucleophilic addition and the enantiomeric purity of (+)‐31 were determined by the analysis of the derivative 30 (d.e. 92%) and 32 (d.e. 93%), respectively. The addition of lithium diethyl phosphite to the nitrone 33, prepared in situ, gave the N‐glycosyl‐N‐hydroxyaminophosphonate 34, (41%; d.e. 91%), which was transformed in (+)‐(S)‐phosphoalanine (+)‐37 (21% from 9).