Organocatalysis Asymmetric Michael Addition Reaction Of Azadienes

Azadiene is an important reaction intermediate which was used as high active substrate in asymmetric reactions,and representative one of this compounds is 2-arylene-N-toluenesulfonylbenzofuran-3(2H)-imine(hereinafter referred to as azadiene).Because aromatization can give a driving force during Michael addition reaction,azadiene is often used as a highly reactive reaction substrate for asymmetric reactions to synthesize a number of important compounds with pharmacological and biological activities that are not easily available.Although azadienes have been widely used in asymmetric synthetic reactions in the recent years,the development of the reaction about azadienes are still insufficient.Our group summarized previous reports on azadiene and inspired by those works,then we tried to apply the excellent substrate and selected three nucleophiles named rhodanine,ɑ-butenolide and 1-naphthol to carry out some Michael reactions,under the mediation of organic small molecule catalysts,sulfur-containing chiral center compounds,α,β-unsaturated butenolide derivatives and chiral triarylmethane skeleton compounds with potential pharmacological effects were synthesized in high efficiency and stereoselectivity.Part Ⅰ: In this part,we designed and implemented a squaramide catalyzed asymmetric Michael addition reaction of azadienes and rhodanines.Firstly,we confirmed the feasibility of the rection by the template substrates,then we optimized the reaction conditions,and selected the chiral catalysts,solvents,amount of solvent,temperature and amount of catalysts,we obtained the optimized conditions that can maximize the stereoselectivity and yield of the product in the end.The method has good applicability for different substituted azadienes and rhodanines.The yields of the obtained products were 66-99%,drs were ranged from 10:1 to >20: 1 and the ee values were 60->99%.By this method,we successfully synthesized a series of sulfur-containing tetra-substituted stereocenter compounds with high enantioselectivity and diastereoselectivity.At the same time,the method of asymmetric Michael addition successfully solved the problem of constructing a sulfur-containing tetra-substituted carbon stereocenter.In addition,the reaction extended the catalytic route of asymmetric nucleophilic addition of rhodanine.Part Ⅱ: In this work,we designed a squaramide-mediated vinylogous Michael addition reaction of azadienes and ɑ-butenolides.After applying the template substrates and racemic catalyst to determine the feasibility of the reaction,we optimized the reaction conditions,including catalyst type,solvent type,solvent amount,temperature,and catalyst amount.Finally,we got the optimized reaction conditions with highest enantioselectivity and yield of this reaction,and then the versatility of the substrate was explored.The vinylogous Michael addition products were generated in high yield(56->99%)and excellent enantioselectivity(ee value was up to 98%).This synthetic strategy not only directly constructed γ,γ-disubstituted ɑ,β-unsaturated butyrolactone with a benzofuran skeleton in optical purity,but also realized adjacent quaternary and ternary stereocenters coexisted in one compound.In addition,this strategy also extended the catalytic route of asymmetric nucleophilic addition of α-butenolide.Part Ⅲ: In this part,we designed the asymmetric Michael addition reaction between azadienes and 1-naphthols mediated by squaramide catalysts.First of all,we chosed the template substrate for the evaluation of reaction feasibility.After confirmed that the reaction proceeded smoothly and the product structure met the expectation,we optimized the reaction conditions.The conditions such as catalyst type,solvent type,and temperature were screened in turn.After control experiments,we obtained the optimal reaction conditions which could synthesize products with the best enantioselectivity and yield,and the universalities of the different substrates of azadienes and 1-naphthols were then carried out smoothly.It could produce a series of Michael addition products with high yield(66-99%)and excellent asymmetric selectivity(71-98% ee).The chiral triarylmethane skeleton compounds were generated by the Friedel-Crafts alkylation of 1-naphthols with mild synthesis strategy,short reaction time and high efficiency.