Synthesis Of Biscarboline Chiral Catalysts And Their Applications In Enantioselective Reactions

In recent years,a large number of chiral drugs have been developed and put on the market.A chiral drug consists of one or more stereogenic center?s?.Chiral amines and allyl alcohols are important pharmaceutical intermediates and precursors from which a large number of chiral drugs are synthesized.This paper mainly focuses on the study of asymmetric allylation of aldehydes and the hydrogenation of ketimines to afford propyl alcohols and chiral amines using chiral catalysts.It is divided into three chapters.The first chapter involves the research progresses of enantioselective allylation of aldehydes,including the study of chiral auxiliary groups and Lewis acid-base catalyzed aldehyde allylation.In the second chapter,the biscarboline skeleton was continuously synthesized for various derivatives synthesis based on the early reports,and they were used as chiral catlysts in order to apply for ally asymmetric addition of aldehydes.First,reduction of C=O at C-3,C-3?is carried out to form a alcohols,which can react with acid chloride to form a biscarboline esters.After they oxidized to form N,N'-dioxides compounds under the UHP-TFA system,they could be used as chiral catalysts in asymmetric addition of aldehydes with HSiCl₃.The experimental results showed that such catalysts have high enantioselective activity,especially when the catalyst had tert-butyl substituent,the%ee values could reach to 87%at-80?for24 h,.When large size of aldehydes were used,the highest ee%value of 92%was obtained at-25?for 24 h.In the third chapter,chiral?-amino alcohols,which have good catalytic activity,contain an nitrogen atom and an oxygen atom,which may coordinate with various metallic elements.Therefore,a chiral catalyst containing proline moiety as a chiral source was designed and synthesized.In the experiments,the biscarboline skeleton combining different kinds of prolinol was synthesized pout.The enantioselective activity of the hydrosilation of ketimine was investigated.Experiments showed that the catalysts have moderate enantioselective activity?70%ee?at 10?.