Researches on Direct Asymmetric Nucleophilic Addition/Substitution of 3-Vinylindoles

Author:Li Xiao Yun

Supervisor:guo qi xiang huang yan min


Degree Year:2019





3-Vinylindole is one of the most important 3-functional indoles.Because of its unique structure,3-vinylindole and its derivatives are sophisticated building blocks in asymmetric transformations.Among these reactions,3-vinyl indoles have already been successfully used as dienes,dienophiles,and electrophiles in asymmetric catalysis.In this dissertation,we discovered 3-vinylindoles as nuclephiles reacting with different prochiral electrophiles,building a new platform for synthesis of chiral 3-substituted indoles bearing multiple functional groups.Occupying certain proportion in therapeutic drugs,chiral 3-substituted indole is one of the most important part of indole compounds.We described a highly efficient nucleophilic addition of arylglyoxals with 3-vinylindoles catalyzed by chiral calcium phosphate.Structurally diverse chiral 3-substituted indoles bearing allyl alcohol and α-hydroxy ketone units are prepared in excellent yields,good diastereoselectivities,and high to excellent enantioselectivities.These products are good building blocks for the synthesis of polysubstituted chiral tetrahydrocarbozol-2-ones.The mechanism study indicates that the most likely role of the catalyst is to activate the hydrate of arylglyoxal and control the stereoselectivity via desymmetric coordination.Bisindole compounds are important heterocycles possessinging good biological activities.We developed the chiral Br?nsted acid-catalyzed asymmetric nucleophilic sustitution of 3-vinylindoles and 3-indolylmethanols.Various structurally diverse 3-substituted bisindole compounds were prepared in good to excellent yields,with good to excellent stereoselectivities.Otherwise,water is the only byproduct,complying with the conception of green chemistry.Seen the targeting chiral 3-substituted indoles as building blocks,the synthesis of(+)-Gliocladin C and polycyclic indoles were initially explored.Axially chiral indole compounds are difficult to build for their poor conformational stabilities.By elaborate designing the structure of 3-vinylindole,adjusting appropriate steric hindrance and choosing the right electrophiles,we discovered the nucleophilic addition of quinone imide ketones with the well-designed 3-vinylindoles catalyzed by chiral phosphoric acid,and successfully built a new class of chiral 3-substituted indole compounds.