The Application And Mechanism Of Reductive Amination Catalyzed By The Transition Metals Or Organocatalysts

The reductive amination is the classical reaction of C-N bond formation. Amine is prepared by direct or indirect reductive amination. The chiral amine could be synthesized by asymmetric reductive amination, in which chiral catalyst is the key. We reviewed systematically the progress on the reductive amination catalyzed by transition metal and Lewis-basic organocatalyst. In this dissertation, the application and mechanism of reductive amination catalyzed by the transition metal were studied. Then, the carbohydrate-derived Lewis baic organocatalysts were designed and synthesized. The magnetic Nano-Fe3O4-supported organocatalysts were prepared. These catalysts were used to catalyze the asymmetric reduction aminationRaney Ni-catalyzed reductive amination of paraformaldehyde has been investigated. The reaction was proceed in methanol solvent at 100 ℃. The high yield (up to 97%) was obtained. In the reductive amination, the raw materials, intermediates and target products were tracked and monitored. Thus, the mechanism was speculated and discussed in detail by the density functional theory (DFT). The reaction pathway undergoes the dissociation of paraformaldehyde, the addition of amine with formaldehyde, dehydration to form the imine and hydrogenation. It can guide the effects of substrates on the yields.Amination of resorcinol catalyzed by Raney Ni has been examined with good yield (up to 93%) in water solvent and 200 ℃. Using the first principles density functional theory, some detailed mechanism of the amination is explored. The resorcinol is adsorbed on the Ni surface at the hollow site to form ketone by isomerization. Ketone can couple with secondary amine mediated by resorcinol to afford hemiaminal. Hemiaminal undergoes dehydration to get final product. For formation of hemiaminal, the steric effect of the alkyl group of secondary amine is obvious. It was speculated that resorcinol could not react with dibutylamine, which was verified by experiment.The backbone of D-glucosamine hydrochloride was fine-tuned and modified. The amino group in the position C-2 was first protected by acetylation. The hydroxyl group in the position C-1 was modified by glycoside and benzyl glycoside. Then the hydroxyl groups in the position C-4 and C-6 were protected by benzylidene acetal. Finally, the acetyl group in the position C-2 was removed by alkaline alcohol solution. The total yield of five step reaction was 59%. The pyridinecarboxylic was introduced into carbohydrate backbone and the five carbohydrate-derived pyridinecarboxylic organocatalysts were prepared for the enantioselective reduction of imines with trichlorosilane. The reduction was proceeded in high yield (up to 93%) and moderate enantioselectivity (up to 75%). A possible catalytic mechanism was discussed that the chiral center of carbohydrate affected the enantiomeric selectivity of the reaction.The azide group was transferred to the D-glucosamine hydrochloride, employing the imidazole-1-sulfonyl azide as the diazo-transfer reagent catalyzed by copper sulfate and potassium carbonate. Then, the azidoglucopyranosylacetate was obtained by acetylation. Under modified Meldal’s condition, the N-Formyl-L-valine derived alkynes was linked with azidoglucopyranosylacetate with good yield. It proved that the diazo-transfer reaction and CuAAC reaction did not change the configuration. The carbohydrate-based valine-derived formamide organocatalyst had high catalytic activity for asymmetric reduction of imines with trichlorosilane. The reduction can proceed at room temperature in toluene with high yield (up to 98%) and excellent enantioselectivity (up to 94%).Magnetic nano-Fe3O4-supported organocatalysts were synthesized by anchoring valine-derived formamide onto the surface of Fe3O4 magnetic nanoparticle, which applied in the asymmetric reduction of imines with trichlorosilane at room temperature in toluene. The highest level of yield (up to 97%) and enantioselectivity (up to 92%) catalyzed by magnetic nano-Fe3O4-supported organocatalysts were obtained. The catalyst was characterized by XRD、TEM、FT-IR and TG. This methodology can simplify the recovery of the organocatalyst and its separation from reaction system. By an external magnet, the catalyst can be recycled and reused five times without a remarkable activity decline.