Diastereoselective synthesis of β-amino acid derivatives from dihydropyridones

Abstract

A new method for the diastereoselective preparation of stereoisomeric 2,3-disubstituted β-amino acids is presented. It is based on trans- and cis-2,3-disubstituted dihydropyridones, which were derived from 2-monosubstituted N-acyl dihydropyridone derivatives. Alkylation of the enolates of 2-substituted dihydropyridones gave trans-2,3-disubstituted dihydropyridones with high diastereoselectivities. Inversion of the stereocenter at C-3 of the dihydropyridone nucleus by a deprotonation/reprotonation sequence yielded the stereoisomeric cis-2,3-disubstituted dihydropyridones in high yields and diastereoselectivities. Following removal of the N-acyl protective group, oxidative degradation of the resulting cis- or trans-2,3-disusbtituted dihydropyridones, respectively, by sodium periodate led to the corresponding diastereomeric β-amino acids.