A General Approach to the Synthesis of (β2-Amino Acid Derivatives via Highly Efficient Catalytic Asymmetric Hydrogenation of α-Aminomethylacrylates

A new strategy was developed for the synthesis of a valuable class of alpha-aminomethylacrylates via the Baylis-Hillman reaction of different aldehydes with methyl acrylate followed by acetylation of the resulting allylic alcohols and S(N)2 '-type amination of the allylic acetates. Asymmetric hydrogenation of these diverse olefinic precursors using rhodium(Et-Duphos) catalysts provided the corresponding beta(2)-amino acid derivatives with excellent enantioselectivities and exceedingly high reactivities (up to >99.5% ee and S/C=10,000). The first hydrogenation of (Z)-configurated substrates was studied for the synthesis of beta(2)-amino acid derivatives. The high influence of the substrate geometry and steric hindrance on the reactivity and enantioselectivity was also disclosed for this reaction. This protocol provides a highly practical, facile and scalable method for the preparation of optically pure beta(2)-amino acids and their derivatives under mild reaction conditions.