A General Approach to the Synthesis of β²‐Amino Acid Derivatives <i>via</i> Highly Efficient Catalytic Asymmetric Hydrogenation of α‐Aminomethylacrylates

Abstract

Abstract A new strategy was developed for the synthesis of a valuable class of α‐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 β 2 ‐amino acid derivatives with excellent enantioselectivities and exceedingly high reactivities (up to &gt;99.5% ee and S/C=10,000). The first hydrogenation of ( Z )‐configurated substrates was studied for the synthesis of β 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 β 2 ‐amino acids and their derivatives under mild reaction conditions.