ASYMMETRIC-SYNTHESIS OF SYN-ALPHA-ALKYL-BETA-AMINO ACIDS

An investigation into the reactivity of the highly stereoselective conjugate nucleophile lithium N-benzyl-N-alpha-methylbenzylamide 1 with alpha-alkyl-alpha,beta-unsaturated esters has led to the development of a versatile asymmetric synthesis of syn-alpha-alkyl-beta-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-alpha-alkyl-beta-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-alpha-alkyl-beta-amino acids.