Density Functional Investigation On The Mechanism Of Small-molecule Organocatalyst Catalyzed The Synthesis Of The 2-substituted-3-(1H-indol-3-yl)-isoindolin-1-one Derivatives And 4-methoxy-1,1'-biphenyl

The design and development of green catalyst have attracted increasing interest in synthetic chemistry.Computational chemistry is an important tool that uses computer simulation to investigate roles and forms of catalysts as well as to obtain the structures and activation parameters.In this work,we employed Gaussian09 software and quantum chemistry methods to study the mechanisms of organocatalyst catalyzed the carbon-carbon formation reactions,especially deeper understanding for the effect of reaction conditions on the mechanism and the catalytic origin of the different catalysts to achieve the development of novel catalyst.The research contains two parts,shown as following.The mechanisms on the synthesis of 2-substituted-3-(1H-indol-3-yl)-isoindolin-1-one derivatives have been investigated with the PBEO/6-311+G**//PBEO/6-31G**method under unassisted,self-assisted,and water-assisted conditions.Two different mechanisms,M1 and M2 have been studied by DFT calculations,differing in the reaction sequence of substrates 1 with 2 or 3,and M1 is the more favored one.Our calculations also suggest that water-assisted pathway P1W is the most favorable one,which undergoes concerted nucleophilic addition and H-shift,nucleophilic addition and water elimination,and intramolecular cyclization and water elimination.The rate-determining step is the nucleophilic attack and water elimination.Moreover,we also explored the effect of nucleophilic attack of the nitrogen of(4-methoxyphenyl)methanamine on hydroxyl or carbonyl group carbon of phthalaldehydic acid on the activation energy of the rate-determining step.The difference between these two attacking sites is ascribed to the non-covalent interactions,which is further confirmed by the frontier molecular orbital and NBO analyses.We found that water molecules play a critical role in the whole reaction,not only act as solvent but also as an efficient catalyst,proton shuttle,and stabilizer to stabilize the structures of transition states and intermediates via?…H-O,O…H-N,O…H-C,and O…H-O interactions.This investigation contributes significantly to our understanding the effect of aqueous catalysis and substrates with-NH2 group on the mechanism and the synthetic routes,which provides a theoretical basis for further designing reactions.The B3LYP/6-311+G**(Br:Lanl2dz)//B3LYP/6-31G*(Br:Lanl2dz)method was carried out to investigate the mechanism of the cross coupling reaction of aryl halides and benzene.Radical mechanism and double decomposition mechanism was proposed,and the former is the most favorable one.The radical mechanism contains three steps,bromine benzyl ether radical generated firstly by t-BuOK,which combines with benzene to form cyclohexadienyl radical,then followed by a single electron oxidation and deprotonation by t-BuO-to get target product and t-BuOH.In addition,we found that t-BuOK acts as radical initiator and stabilizer in the radical reaction processes,which provides a guidance of theoretical research in the t-BuOH-catalyzed cross coupling reaction of C-C bond formation.