Synthesis Of Chiral Biscarboline N,N'-dioxide Derivatives And Their Application In Asymmetric Hydrosilylation

Chiral amines have been widely used as intermediates in pharmaceutical industry.A vast majority of drugs are amines or contain functional groups derived from amines.An increasing number of these molecules are non-racemic.Therefore,many researchers made the enantioselective synthesis of amines.In this study,chiral axial N,N'-dioxide primary amines and biscarboline N,N'-oxide derivatives containing P elements were designed and synthesized.We continued to explore the enantioselectivity of the two kinds of catalysts in catalytic enantioselective reductions of ketimines with trichlorosilane.Five chiral axial N,N'-dioxide primary amines were synthesized from L-tryptophan via several steps.They were employed in catalytic enantioselective reductions of ketimines with trichlorosilane for the first time.As the results showed,the reduction of ketimines with the catalyst at 0 ? was successfully accomplished in 24 h,leading to conversion yields up to80%-98% and the enantioselectivity up to 68%.We found that it has good stereoselectivity which is a cyclic amide in C-3,C-3?.Based on the analysis of the structure and catalytic effect,the stereoselectivity would be higher when ketimines have an electron donating substituent rather than an electron withdrawing group.The experimental results showed that the catalyst contained a cyclohexyl amine moiety(5 mol %)presented the best stereoselectivity up to 68%.In view of the excellent properties of phosphorus ligands in asymmetric catalytic reactions,biscarboline N,N'-oxide derivatives containing P elements were designed,synthesized and employed in catalytic asymmetric allylic alkylation of aldehydes,enantioselective reduction of ketimines and asymmetric Morita-Baylis-Hillman reactions(MBH).Unluckily,we found the reactions could not take place.In conclusion,we synthesized a series of chiral axial N,N'-dioxide primary amines and biscarboline N,N'-oxide derivatives containing P elements catalysts which were employed in catalytic enantioselective reductions of ketimines with trichlorosilane for the first time.It was found that 16 b was an effective catalyst with excellent conversion yields up to 98% and the enantioselectivity up to 68%.The scope of the catalyst for the reduction of imines wassuccessfully expanded.