Asymmetric Reduction Of Ketoimines With Trichlorosilane Catalyzed By Chiral Biscarboline N,N'-Dioxide Derivatives

Chiral amines are key intermediates for many compounds whose chiral carbons are attached to nitrogen atoms and have been widely used in medicines,pesticides,foods and so on.Thus,it is important to obtain such compounds in asymmetric synthesis of imines catalyzed by chiral catalysts.This paper which gives a preliminary study on asymmetric synthesis of chiral amines is mainly divided into two chapters.Chapter one is the research review of asymmetric reductions of imines mainly catalyzed by Br?nsted acid and Lewis basic organocatalysts.In chapter two,we continued to explore asymmetric reductions of ketoimines with trichlorosilane catalyzed by axially chiral biscarboline-N,N?-dioxide catalysts on the basis of our previous works.First,we synthesized eight novel amides which had different chiral amino acid methyl ester substituents in position C-3,C-3?.It was found that two sets of 1H and 13 C NMR spectra were recorded for all the amides except one substituted with proline methyl ester.It showed that they were single chiral amides not mixtures by further study.Then,their catalytic enantioselectivities in ketoimines with trichlorosilane were investigated.The amide owing proline methyl ester substituent gave the highest value of 67%ee.Next,three axially chiral biscarboline-N,N?-dioxide catalysts were synthesized from amides mentioned above as enantiomerical purity which were applied in the asymmetric reductions of ketoimines with trichlorosilane.As the results showed,the reduction at 0 ? was successfully accomplished in 16-24 h,leading to the corresponding products in a high yield(> 90%).And the substrates with electron donating substituents on the aromatic ring afforded a better performance(> 70%ee).Wherein the biscarboline-N,N?-dioxide catalyst containing phenylalanine methyl ester moiety provided the highest enantioselectivity such as 80%.In summary,we developed structurally novel and efficient axially chiral biscarboline-N,N?-dioxide catalysts.Not only were the optimal catalyst and reaction conditions screened out,but also the substrates were expanded.On this basis,the mechanism of the reaction was also studied,which provided theoretical and experimental basis for the subsequent development and application of the catalysts.