Synthesis of dipeptides via addition of N-(nitroacetyl)amino-acid derivatives to Michael acceptors: scope, stereoselectivity, and absolute configuration

Abstract

Michael addition of N-nitroacetyl derivatives 1 of proline esters using KF under phase-transfer catalysis resulted in the formation of adducts 3-9 with chemical yields ranging from 40-90% (Scheme). Stereoselectivity of up to 51% was obtained on addition of benzyl N-(nitroacetyl)-L-prolinate (1a). The absolute configuration at the newly created chiral centre was established in the case of 9 by carrying out a reductive acylation and comparing the product 10 with an authentic sample of ethyl N-(O⁵-ethyl N²-acetyl-L-glutam-1-yl)-L-prolinate (L, L-10).