Palladium-catalyzed C-H Activation Cyclization Reaction For Constructing Quaternary Carbon Stereocenters

Quaternary carbon structural units are widely found in natural products,pharmaceuticals,and biologically active molecules.In the field of metal catalyzed synthesis,the efficient construction of quaternary carbon has always been a recognized research hotspot and difficulty for chemists,especially for the synthesis of quaternary carbon stereocenters,which is more challenging.In recent years,metal catalyzed C-H activation reactions have developed rapidly due to their high atomic and step economy.Compared to traditional coupling reactions,metal catalyzed C-H activation reactions do not require pre functionalization of the substrate,reducing waste generation while shortening the synthesis route,making them an important synthesis method for preparing bioactive molecules and functional materials.This thesis mainly utilizes Heck reaction strategy to construct indene and indoline compounds containing quaternary carbon center through palladium catalyzed asymmetric C-H activation and directed cyclization reactions.The results are as follows:(1)In the presence of N-monoprotected chiral amino acids(MPAA),palladium-catalyzed oxime ether directed C-H activation and tandem cyclization of alkenyl aromatic hydrocarbon were used to prepare spiro or non spiro indene compounds containing all carbon quaternary carbon stereocenter with up to 98% yield and 99% enantioselectivity(>30 examples).This method has the advantages of convenient operation,simple catalytic system,mild reaction conditions,high yield,and good stereoselectivity.In terms of the reaction mechanism,this strategy involves processes such as Pd(II)-catalytically selective C-H activation,sequential transfer and insertion of tertiary and double bond,and reduction and elimination of palladium species,accompanied by transient axial center chiral transfer.It is worth noting that this is the first successful example involving in situ chiral transfer of axially chiral styrene intermediates,laying the foundation for the synthesis of various spirocyclic and non spirocyclic chiral indene compounds,and broadening the construction methods of quaternary carbon stereocenter.(2)Heck reaction strategy was extended from olefin double bond to heteroaromatic π bonds,which combines palladium catalyzed C-H activation and de aromatization strategies to study the construction of C2-quaternary carbon centered spirocyclic indoline compounds.It has been found that using pyrimidine as a guiding group can achieve palladium catalyzed C-H activation of indole and [3+2]cycloaddition reactions with alkynes,laying the foundation for the efficient synthesis of various biologically active spirocycloindoline compounds.In summary,this thesis has studied palladium catalyzed aryl C-H activation and intermolecular [3+2] cycloaddition reactions involving different guiding groups,achieving the construction of quaternary carbon center,providing a simple synthesis method for complex cyclic compounds containing quaternary carbon center with potential application value,and demonstrating the effectiveness of transient axial center chiral transfer strategies in the construction of quaternary carbon stereocenter.