Theoretical Study On Group IB Metals Catalyzed Aryl C-H Bond Activation Of Aniline

In the area of C-H bond activation,aromatic meta-C-H bond activation is one of the most challenging research directions at present.The development of Friedel-Crafts type substitution reactions due to the activation of C-H bonds at the aromatic meta-site can be divided into three main periods:（i）the early strategy is controlled by spatial effect（factors:number of substituents,ligands）,（ii）the mid-term strategy uses"templates"to precisely target（factors:covalent and non-covalent bonded substrates）,（iii）and the latter strategy changes the aromatic polarity to occur umpolung process via electronic effects.Despite the rapid development of the experimental aspects,the theoretical aspects of them have not been studied in a timely and thorough manner,which limits the progress of future experimental and theoretical studies.Therefore,this thesis will reveal the reaction mechanism of aromatic C-H bond activation by the reversal of aromatic polarity caused by electronic effects through density flooding theory.In this way,the theoretical study of aromatic C-H bond activation will be strengthened to provide important guidance for the development of the area of C-H bond activation of aromatic compounds.The research for this thesis is as follows.（1）Based on the experimental and theoretical results of the intramolecular"domino"rearrangement of 2-methyl-N-methoxyaniline（aniline）catalyzed by NHC-Cu to achieve the activation of meta-C-H bond,we theoretically predict the catalytic activity and substrate reactivity of aniline catalyzed by NHC-metal（Ag and Au）.The predicted results indicate that the methoxy 1,3’-transfer as well as the copper-catalyzed stepwise proton transfer process are the rate-determining steps for both the silver-and gold-catalyzed systems.The silver-and gold-catalyzed aniline obtain the major product2-methyl-6-methoxyaniline and the minor product 2-methoxy-3-methylaniline.This result is opposed to the products obtained by copper catalyst.Mechanistic studies have shown that the reaction undergoes four main processes:（i）cleavage of the N-O bond by oxidative addition of monovalent metals（silver,gold）.（ii）First rearrangement of methoxy group:nucleophilic substitution of aniline with methyl-substituted ortho-site.（iii）Second rearrangement of methoxy or methyl groups:migration of methoxy 1,3-M（?）bius aromatic transition state,methyl 1,2-Wagner-Meerwein rearrangement.（iv）Metal-catalyzed proton transfer to restore the aromaticity of the aryl group and to obtain the final major and minor products.（2）Theoretical study of NHC-Cu catalyzed intermolecular activation of aryl meta-C-H bond and nucleophilic substitution of aniline with nucleophile（1,3,5-trimethoxybenzene）.The calculations indicate that the reaction is an intermolecular nucleophilic substitution induced by electronic effects,where the cation is the main driving force.The highly reactive i Pr Cu-OCH₃,obtained after the cleavage of the N-O bond of aniline,is a key component of the concerted metalation-deprotonation,and the methanol produced from reaction is a key species for the"proton shuttling mechanism".2-methyl-5-（1,3,5-trimethoxyphenyl）aniline serves as major product,and 2-methyl-3-（1,3,5-trimethoxyphenyl）aniline and 2-methyl-4-（1,3,5-trimethoxyphenyl）aniline serve as minor products in the intermolecular nucleophilic substitution.And 2-methyl-6-methoxyaniline and 2-methoxy-3-methylaniline serve as minor products via the intramolecular domino rearrangement.Mechanistic studies suggest that the reaction undergoes four main processes:（i）oxidative addition of monovalent copper to cleave the N-O bond;（ii）generating methanol in a metal-coordinated deprotonation;（iii）rearrangement of the nucleophilic Nu group 1,2-Wagner-Meerwein;（iv）methanol-assisted"proton shuttling"to restore the aromaticity of the aryl group and to obtain the final major product.Among them,the concerted metalation-deprotonation is the rate-determining step for the major product.