Synthesis Of Chiral ?-functionalized Amino Acid Derivatives By Asymmetric Hydrogenation Of Enamides

Chiral amines are an important class of organic compounds, and often used as chiral selectors and chiral auxiliary. However, the common utility is as a kind of important intermediates in the synthesis of chiral pharmaceuticals. Therefore, their chiral motifs are widely present in many natural or artificial drugs, and this is the reason we devote our effort to the synthesis of chiral amine.Recently, chiral pharmaceutical synthesis is one of the hot issues concerning the development of drugs, and the requirement of optically pure chiral amines for the chiral transformation promotes the application and development of asymmetric hydrogenation in industry. As one of the mostly efficient and convenient method, the complexes of transition metal and chiral organic phosphine ligands are employed for the asymmetric hydrogenation of enamines and furnishes the chiral amines. From the industry's point of view, asymmetric hydrogenation used in synthetic drugs possesses several overriding advantages, such as high atom economy, simple process, extensive applicability and environmental friendliness.Highly active chiral catalysts have a major role in stereoselectivity and chemical selectivity control in the enantioselective hydrogenation of enamines. Up to date, sets of catalysts were devised by our group, and those catalysts were proved to be efficient and feasible for the asymmetric hydrogenation of imines and enamines.Herein, two challenging enamines were synthesized, and different catalytic systems were employed for their asymmetric hydrogenation. The optically active ?-functionalized amino acid derivatives were obtained by artificial synthesis. Thereby new asymmetric catalytic systems are established and expand asymmetric hydrogenation reaction. Thus it will mostly favor the synthesis of much more biologically active molecules1) Series of (3-olefinated-?-acetoxy enamido esters were synthesized, the reaction was catalyzed by Rh/Tangphos complexes under the gentle condition, furnishing sets of y,8-unsaturated amido esters with high stereoselectivity and chemoselectivity(> 99% con.,> 99% ee). This strategy provides a new efficient route for y,8-unsaturated amino acids and their derivatives synthesis, wherein over-reduction products were effectively avoided. Moreover, the methodology is successful for Ramipril synthesis.2) Several tetrasubstituted ?-acetoxy ?-enamido esters via 4-step transformation were synthesized, further asymmetric hydrogenation catalyzed by Rh/Tangphos was conducted and succeeded in the synthesis of (2R,3R)-?-acetoxyl-a-amino acid esters (up to 99% con. and 99% ee). Therefore, ?-functionalized amino acid derivatives with two chiral centers were realized via one step transformation.