Theoretical Studies On The Mechanism Of Squaramide And Transition-metal Copper Catalyzed Friedel-Crafts Alkylation Reactions

The Friedel-Crafts reaction is a synthetic method for the construction of carbon-carbon bonds in organic synthesis,including Friede-Crafts acylation and Friedel-Crafts alkylation.Wherein,the Friedel-Crafts alkylation can be regarded as a C-H insertion by an alkylation reagent to form final alkylation products.In this thesis,the mechanisms of squaramide and transition-metal copper catalyzed Friedel-Crafts alkylation reaction were studied by Density Functional Theory(DFT),respectively.Main content includes the following two parts:1.At the M06-2x/6-311G(d,p)//B3LYP/6-31G(d)level of theory,the mechanism of squrarmide-catalyzed the Friedel-Crafts reaction between trifluoromethyl ketimine and naphthol was studied by Density Functional Theory(DFT).Through calculations,the squaramide firstly coordinate with the naphthol through intermolecular hydrogen bonding.Then,four possible pathways from trifluoromethyl ketimine electrophile could be located,respectively.Comparing the relative energy barriers of the four located transition states,the favorable transition state model is,the two N-H groups of squaramide catalyst simultaneously form effective hydrogen bonds with the nucleophile compound.Also,the protonated amine would form one hydrogen bond with the electrophile complex.Moreover,the barrier of the Re-face transition state of the nucleophile attacks electrophile is lower than that of the Si-face transition state.In addition,noncovalent interaction(NCI)analyses showed that there are strong noncovalent interactions and weak steric hindrance in the transition state of Re-face,so the R-configuration adduct is dominant,which is consistent with the experiment.2.We systematically studied the mechanism of the transition-metal copper catalyzed Friedel-Crafts reaction of Indoles and aziridine at the level of?B97XD/6-311G(d,p)//?B97XD/6-31G(d).The calculation results showed that the whole catalytic cycle included the cleavage of C-N bond,the formation of C-C bond,oxidative addition and reduction elimination.It was found that the formation process of C-C bond was the rate-determining step in the whole reaction.Through energy decomposition analysis(EDA),we found that in TS3R,the deformation energy of the whole structure is smaller,and the interaction is relatively larger.Through the noncovalent interaction analysis(NCI),the strongest C-H…? hydrogen bond interactions and the weakest steric hindrance are found in TS3R.In addition,comparing with the frontier orbital theoretical analysis(FMO)of TS3S,TS4R,and TS4S,the calculated Egap of TS3R was the smallest,which is in good agreement with the experimental observations.