New isosteres of ( R)-2-methylhomoserine and ( R)-2-methylaspartic acid by alkylation of a chiral imine leading stereoselectively to a quaternary stereogenic center

Abstract

Imines obtained from either chiral 3-amino-4-silyloxymethylpyrrolidin-2-one 5a or 5b underwent alkylation to give, in good yield and total stereoselection, the corresponding 3,3,4-trisubstituted pyrrolidin-2-ones 8a– d where both the amino and the silyloxymethyl groups lie cis to each other, as shown by 1H NMR spectroscopic data and NOE experiments. By removal of both the imino group and the chiral inducer from 8b, the pyrrolidin-2-one 12, an isostere of ( R)-2-methylhomoserine 2 and the pyrrolidin-2-one 14, an isostere of ( R)-2-methylaspartic acid 4 were obtained straightforwardly.