Asymmetric synthesis of syn-α-alkyl-β-amino acids

Abstract

An investigation into the reactivity of the highly stereoselective conjugate nucleophile lithium N-benzyl-N-α-methylbenzylamide 1 with α-alkyl-α,β-unsaturated esters has led to the development of a versatile asymmetric synthesis of syn-α-alkyl-β-amino acids. By performing the conjugate additions in toluene and diluting the reaction mixtures with THF prior to quenching of the reactions with the hindered acid, 2,6-di-tert-butylphenol 13, the product syn-α-alkyl-β-amino esters may be generated in good yield and with excellent stereocontrol. Several examples illustrate the ease with which these products may be debenzylated and hydrolysed to afford homochiral syn-α-alkyl-β-amino acids.