The Research Of Double Axially Chiral Bisphosphorylimide Catalyzed Vinylogous Mannich-type Reaction

Amino carbonyl compounds are valuble synthons in the preparation of many natural products with useful biological properties, and the vinylogous Mannich reaction is a main kind of reaction for the synthesis of chiral molecules containing nitrogen. Constructing nitrogenous chiral molecules with the asymmetric Mannich reactions has always been a hotspot in research of organic chemistry. In this paper, we investigated the asymmetric vinylogous Mannich-type reactions using the new double axially chiral bisphosphorylimide Br?nsted acid catalyst, and good catalytic results have been achieved, specific experimental contents and results are as follows:In this paper, our group designed and synthesized eight new double axially chiral bisphosphorylimide catalysts and they were applied to catalyze(E)-2(benzylidenneamino) phenol and(furan-2-yloxy) trimethylsilane asymmetric Mannich reactions. We screened a series of reaction conditions, which may influence the yield and stereoselectivity. Such as catalysts and their dosage, reaction solvents and their dosage, reaction temperature, reaction time, molecular sieve and so on. Under the best condition :-10℃, N2 protected, the o-xylene as solvent, 1 equivalent imine, 3 equivalent(furan-2-yloxy)trimethylsilane, 5mol% 3,3’ position of 2 naphthyl-(R)-BINOL bisphosphorylimide derivatives as catalyst. We investigated 14 kinds of phenolic imines and obtained excellent results. The Mannich reaction products of high stereoselectivities(up to 98% ee, 98:2dr) and high yields(up to 78%). The 1H NMR, 13 C NMR and HPLC of thereaction products were all characterized.The eight new double axially chiral bisphosphorylimide catalysts were applied to catalyze asymmetric Mannich reaction with(E)-N-benzylideneaniline and(furan-2-yloxy) trimethylsilane, we screened a series of reaction conditions, which may influence the yield and stereoselectivities of this reaction. Such as catalysts and their dosage, reaction solvents and their dosage, reaction temperature, reaction time and so on.Under the best condition, we obtained medium yield and stereoselectivity. Through the result we can infer that the hydroxyl may influence the activity of the catalyst, we need further research.Overall, the eleven new double axially chiral bisphosphorylimide catalysts were applied to catalyze asymmetric vinylogous Mannich-type reaction. Good catalytic results have been achieved. The results prove the new chiral catalyst fits for the asymmetric Mannich reaction and expends the scope of application of the catalyst.