| Indole ring is one of the most common heterocycles in nature,and has extremely important research value in many fields such as medicine and chemical engineering.Due to the enormous structural diversity of biologically active indole,many important structural components of drugs contain indole.In the field of organocatalysis,indole alcohols can be converted into optically active indole derivatives through various conversion methods.In recent years,asymmetric catalytic reactions of 2-indole alcohol and 3-indole alcohol have been reported,but reports on 6-indole alcohol are rare.On the other hand,asymmetric 1,10-conjugated addition reactions,as an ultra-long conjugated system,are difficult to control the enantiomeric excess of the product in the reaction,and have been rarely reported.Therefore,achieving asymmetric 1,10-conjugated addition reactions is still a major problem to be solved.This study successfully achieved the asymmetric 1,10-conjugated addition reaction of 6-indole alcohol with thiazolone catalyzed by chiral phosphoric acid,and also opened a new way for the asymmetric synthesis of axially chiral tetrasubstituted allenes.In addition,in order to expand the chemical reaction potential of 6-indole alcohol,we further achieved the [3+3]cycloaddition reaction of 6-indole alcohol with 4-hydroxycoumarin and 1,3-cyclohexanedione.The specific work is as follows:This paper is divided into two parts.In the first part,we used chiral phosphoric acid as a catalyst to achieve the asymmetric 1,10-conjugate addition reaction of 6-indole alcohol with thiazolidone.After determining the feasibility of this reaction,we conducted a lot of screening work in order to improve the yield,enantiomeric excess,and diastereomeric excess of the product to a more ideal result.During this period,we screened conditions such as the type and amount of catalyst,solvent type and amount.After this series of screening work,we have obtained the optimal condition that are most suitable for this reaction.Then,in order to investigate the applicability of this reaction,we conducted a substrate expansion test.Under optimal conditions,asymmetric 1,10-conjugated addition reactions of 6-indolyl alcohol and thiazolidone containing various substituents can smoothly occur,and axial chiral tetrasubstituted dienes(60-91% yield,86-96% ee,6:1-15:1 dr)can be obtained with good results.In this study,we used a strategy of stereoremote control to complete the asymmetric 1,10-conjugate addition reaction of 6-indole alcohol with thiazolidone.More noteworthy is that this is the first time that a series of axially chiral tetrasubstituted allenes with quaternary carbon chiral centers and sulfur-containing have been synthesized through asymmetric 1,10-conjugated addition reactions.In the second part,we have achieved the [3+3] cycloaddition reaction of 6-indole alcohol with 4-hydroxycoumarin and 1,3-cyclohexanedione by using acetic acid as a catalyst.After determining the feasibility of this reaction,we conducted a lot of screening work in order to improve the yield of the cycloaddition product to a more ideal result.During this period,we screened conditions such as the type and amount of catalyst,solvent type and amount.After this series of screening work,we have obtained the optimal conditions that are most suitable for this reaction.Then,in order to investigate the applicability of this reaction,we conducted a substrate expansion test.Under optimal conditions,the [3+3] cycloaddition reaction of 6-indole alcohol containing various substituent groups with 4-hydroxycoumarin and 1,3-cyclohexanedione can smoothly occur,and the pyranocoumarin(70-96%)and pyranoderivative(52-94%)containing indole skeleton can be obtained respectively with good yields.In this study,we successfully achieved the [3+3] cycloaddition reaction of 6-indole alcohol with 4-hydroxycoumarin and 1,3-cyclohexanedione.What is more noteworthy is that the reaction obtained pyranocoumarin and pyran derivatives containing indole skeleton under mild conditions with high yield,and the applicability of this reaction is also extremely broad,providing a novel method for constructing coumarin compounds containing indole skeleton. |
