Study On New Process Of Asymmetric Synthesis Of D-phenylalanine

D-phenylalanine is the non-natural amino acid, which is widely used in the fields of medical, pesticides, food, light industry and so on. Nowadays there have been no ferment methods for producing D-phenylanlanine. The widely used method is racemic resolution, which needs huge amount of resolving agent, is low yield, high cost and may cause serious environmental problems. Therefore, study on the new process of asymmetric synthesis of D-phenylalanine is meaningful.Transition metal-catalyzed asymmetric hydrogenation is one of the effective ways to construct chiral compounds, having such advantages as high selectivity, high conversion, atom economy and easy operation, which therefore proves high potentials in industrial application. In this paper, the new process of asymmetric synthesis of D-phenylalaine by asymmetric catalytic hydrogenation of(Z)-methyl-2-acetamidocinnamate with chiral unidentate phosphorus ligands and rhodium as catalysts, had been investigated.First, the intermediate(Z)-methyl-2-acetamidocinnamate, the starting material of asymmetric catalytic hydrogenation, was synthesized by a two-steps route that used benzaldehyde and N-acetylglycine as starting materials, and then the reaction conditions had been optimizated.We synthesized 2-methyl-4-(phenylmethylene)oxazol-5(4H)-one by Erlenmyer condensation reaction. Then we chose triethylamine as catalyst and the reaction solution is stirred under mild condition to synthesize the substrate(Z)-methyl-2-acetamidocinnamate. This laboratory preparation can be expanded to the scale of kilograms. We also expanded the scale of this reaction to synthesis 22 α-dehydroamino acid derivatives, such as(Z)-methyl-2-acetylamino-3-(4-bromophenyl)acrylate,(Z)-methyl-2-benzoylamino-3-(4-bromophenyl)acrylate,(Z)-methyl-2-acetyla mino-3-(3-bromophenyl)acrylate,(Z)-methyl-2-benzoylamino-3-(3-bromophenyl)acry late,(Z)-methyl-2-acetylamino-3-(4-nitrophenyl)acrylate,(Z)-methyl-2-benzoylamino-3-(4-nitrophenyl)acrylate and so on.We used(S)-BINOL as materials to synthesize(S)-Mono Phos and other 4 kinds of phosphorus ligands. In this paper, we used(Z)-methyl-2- acetamidocinnamate as substrate and focused study on the catalyst performances of the chiral phosphorus ligands-[Rh(COD)2]BF4 complexes. It showed that(S)- Mono Phos is the best ligand,which gains quantitative conversion and high enantioselectivity as 95.5% in the asymmetric hydrogenation of(Z)-methyl-2- acetamidocinnamate. When the material ratio of substare and catalyst is 3000(S/C=3000), the reaction is still quantitative and the ee value remains. If the N atom of the phosphorus ligand is linked with one H atom, the ee value is obviously low, which is less than 90%. Using(S)-Mono Phos as the potimal phosphorus ligands, we find the ee value between 86% and 100% in the reaction of asymmetric hydrogenation of other 21 α-dehydroamino acid derivatives.Especially we found that high quantitative conversion and high ee value as 100% in the asymmetric hydrogenation of(Z)-methyl-2-benzoylamino-3-(4-nitrophenyl)acrylate.It was the first time to realize the synthesis of D-phenylalanine in the scale of kilograms. In the amplification experiment, we used three different high pressure vessels(125 mL, 300 mL and 5000 mL) and the results showed the same with the results obtained in Lab. Hydrogenated products was hydrolyzed by hydrochloric acid,and then D-phenylalanine was obtained with total yield of 92% and optical purity of99%. The structure of the compounds was characterized by NMR.