Chiral Phosphoric Acid Catalyzed Asymmetric 1,6-Conjugated Addition Of 3-Indole Methanols

3-Indolemethanol compounds can form carbocation or imine intermediates under the catalysis of Br(?)nsted acid,and optically pure indole derivatives can be obtained with high enantioselectivity through various chiral transformations.Asymmetric 1,6-conjugated addition reaction as a long-conjugated reaction mode which has been difficult to control the enantioselectivity of products and has been studied very limitedly.The realization of asymmetric 1,6-conjugated addition reaction was very challenging.In this thesis,the asymmetric 1,6-conjugated addition reaction of 3-indolemethanols with thiocarboxylic acid or 2-substituted indole was realized to construct axial chiral tetrasubstituted allenes.This paper divides the subject into two parts according to the different types of 3-indolylcarbinol.In the first part,3-indole methanols containing CF3 and thiocarboxylic acid were used chiral phosphoric acid catalyzed to realized the asymmetric 1,6-conjugate addition reaction.We optimized a series of reaction environments such as the type of chiral phosphoric acid catalyst,the type of dissolution system,reaction temperature,catalyst charge number and reaction time,and finally selected the best reaction conditions.After that,we investigated the expansibility of the substrates.Among the 23 expanded substrates,the yield reached 75%-95% and the enantiomeric excess reached 70%-92%.This strategy realizes the asymmetric 1,6-conjugate addition reaction of 3-indole methanols and thiocarboxylic acids for the first time,and generates axial chiral tetrasubstituted allenes with high yield and high regional selectivity.In the second part,3-indole methanols containing ester and 2-substituted indoles were used chiral phosphoric acid catalyzed to realized the asymmetric 1,6-conjugate addition reaction.We optimized a series of reaction environments such as the mold of chiral phosphoric acid catalyst,the type of dissolution system,reaction temperature,catalyst charge number and reaction time,and finally selected the best reaction conditions.After that,we investigated the expansibility of the substrates.Among the expanded 25 substrates,the yield reached 65%-96% and the enantiomeric excess reached 49%-97%.This strategy realizes the asymmetric 1,6-conjugate addition reaction of 3-indole methanol and 2-indolyl derivatives with organic catalysis for the first time,and generates axial chiral tetrasubstituted allenes with high yield and high regional selectivity.