Asymmetric Amination,Oxidation,Alkylation And Sulfenylation Of 3-CF3-Oxindoles With Quinidine Or Quinine Derivatives

Fluorine organic compounds are very rare in natural,but the strong electron-withdrawing nature and large hydrophobic domain of the trifluoromethyl group makes trifluoromethyl substitution attractive for pharmaceuticals and agrochemicals.Recently,approaches to quaternary carbon center with a trifluoromethyl group have become one of interesting topics for synthetic chemists.Oxindoles have important position in the field of pharmaceutical chemistry,due to its wide application of pharmacology.In this dissertation,an asymmetric amination,oxidation,alkylation and sulfenylation of 3-CF3-oxindoles catalyzed by a quinidine derivative was described,for filling up the blank of research area of quaternary carbon center with a trifluoromethyl group.We initiated our study toward organocatalytic asymmetric amination of 3-CF3-oxindoles.Screening of the protecting groups on nitrogen of 3-CF3-oxindoles,solvent and catalyst,using 3-CF3-oxindole with N-COOMe as substrate,and in the presence of catalytic amount of quinidine(Q8)are the best in terms of both chemical yield and enantioselectivity(84%yield and 96 ee%).We have completed 8 examples of asymmetric amination of 3-CF3-oxindoles(32?93%yield,80?96 ee%),The stereoselectivity of the reaction 3-CF3-oxindoles with electro-donating groups led to corresponding products in good yield and with good enantioselectivity(83?93%yield,90?96 ee%),while 3-CF3-oxindoles bearing electro-withdrawing groups were not competent substrates at the optimal reaction conditions,only 3-CF3-oxindoles with chlorine can be tolerated,but with only 32%yield.An asymmetric oxidation of 3-CF3-oxindoles catalyzed by a quinine was described.Screening of the protecting groups on nitrogen of 3-CF3-oxindoles,solvent,catalyst and oxidizing reagent,using 3-CF3-oxindole with N-COOCH(iPr)2 as substrate,and in the presence of catalytic amount of quinine are the best in terms of both chemical yield and enantioselectivity(85%yield,87 ee%).An asymmetric alkylation of 3-CF3-oxindoles catalyzed by a quinidine derivative was described.Screening of the protecting groups on nitrogen of 3-CF3-oxindoles,solvent and catalyst,We found that by increasing the steric hindrance of 9-NH2 in quinidine and the protecting groups on nitrogen of 3-CF3-oxindoles,the enantioselectivity of the product increased(96%ee).An asymmetric sulfenylation of 3-CF3-oxindoles catalyzed by a quinidine derivative was described.Screening of the protecting groups on nitrogen of 3-CF3-oxindoles,solvent and catalyst,using 3-CF3-oxindole with N-COOMe as substrate,and in the presence of catalytic amount of quinidine(Qd-OiPr)are the best in terms of both chemical yield and enantioselectivity(84%yield and 94 ee%).We have completed 14 examples of asymmetric amination of 3-CF3-oxindoles(71?92%yield,70?94 ee%),3-CF3-oxindoles with electro-donating groups led to corresponding products in good yield and with good enantioselectivity(71?87%yield,72?94 ee%),while 3-CF3-oxindoles bearing electro-withdrawing groups were not competent substrates due to its significant decomposition at the optimal reaction conditions.As for the sulfenylation reagents based on thiophenol,both electro-donating groups and electro-withdrawing groups were well tolerated(77?92%yield,70?94 ee%).In this dissertation,an asymmetric amination,oxidation,alkylation and sulfenylation of 3-CF3-oxindoles catalyzed by a organic small molecular(Quinidine derivatives)was described,to build quaternary carbon center with a trifluoromethyl group.The stereoselectivity of the reaction was better and the substrate was tolerant.