Practical asymmetric access to carboxy-differentiated aspartate derivatives via 1,3-dipolar cycloaddition of a nitrone with (R)-4-ethyl-N-vinyloxazolidin-2-one

Access to α-Substituted Amino Acid Derivatives via 1,3-Dipolar Cycloaddition of α-Amino Ester Derived Nitrones

“…In the case of 5-heterosubstituted isoxazolidines, the direct reductive cleavage is commonly known as not convenient since this ring-opening process affords unstable β-amino aldehydes. As a valuable alternative, the N -quaternization-mediated ring-opening of 3-monosubstituted 5-heterosubstituted isoxazolidines (X = OR, NR 2 , Scheme ) has been described as an effective method to cleave the N−O bond via β-elimination (disproportionation pathway) . The thermal procedures using alkylating agents (BnBr, MeI, Me 2 SO 4 , ...) with or without external base added in the reaction medium (DABCO, Et 3 N, NaH, ...) were previously applied to 5-oxa- − and 5-aza-isoxazolidines , to afford β-amino acid esters or β-amino imides respectively in high yields.…”

Isoxazolidine: A Privileged Scaffold for Organic and Medicinal Chemistry

“…Such strategies were also fruitfully applied to 5-oxazolidinyl isoxazolidines, leading to 1,3-amino imides. , In the case of 5-alkoxy-isoxazolidines, the ring opening can also lead to N -protected 1,3-aminoesters without prior quaternarization of the nitrogen atom but thanks to the influence of a strong electron-withdrawing N -acyl substituent, as demonstrated by the group of Dujardin. ,, Indeed, by a typical SmI 2 treatment that led to amidoaldehydes from N -acetyl isoxazolidines, the authors synthesized 1,3-aminoesters 185 (60–75% yields) from N -trifluoroacetyl isoxazolidines 150 , while use of the Mo­(CO) 6 protocol was unsuccessful to open the isoxazolidine ring (Scheme ).…”