Highly Efficient Synthesis of Heterocyclic and Alicyclic 2-Amino Acid Derivatives by Catalytic Asymmetric Hydrogenation

A valuable class of new heterocyclic and alicyclic prochiral -aminomethylacrylates has been conveniently synthesized through a three-step transformation involving a Baylis-Hillman reaction, O-acetylation, and a subsequent allylic amination. The corresponding novel 2-amino acid derivatives were prepared with excellent enantioselectivities and high yields by catalytic asymmetric hydrogenation using the catalyst rhodium(Et-Duphos) (Et-Duphos=2,5,2,5-tetraethyl-1,2-bis(phospholanyl)benzene)) under mild reaction conditions (up to 99% ee and S/C=1000). The influence of the substrate on the enantioselectivity and reactivity is investigated, and the most suitable substrate configuration for the highly efficient enantioselective hydrogenation of -substituted -aminomethylacrylates under the Rh-Duphos system is reported. The current protocol provides a very practical, facile, and scalable method for the preparation of heterocyclic and alicyclic 2-amino acids and their derivatives.