Theoretical Investigations On Several Cycloaddition Reactions Catalyzed By Lewis Base

During the past decades,the cycloaddition reactions,which are among the most important methods to construct complex cyclic molecules,have developed rapidly and have made significant achievements.With the aid of Lewis base catalysts,those cycloaddition reactions which are economical,environment-friendly,or those reacting under mild reaction conditions but presenting high yield and high stereoselectivities have attracted wide attention of researchers.Many functionalized cycloaddition products have been synthesized hitherto,and have potential applications in chemical industry,material and biomedicine science.Despite the extraordinary achievements in the experimental side for the cycloaddition reactions,our knowledge about the mechanistic details as well as the origin of enantioselectivity still remains elusive.The studies of the cycloaddition reactions catalyzed by Lewis bases,which are performed at the microcosmic level,will give us an indepth understanding of the essential laws of the catalytic cycles.This can provide the theoretical directions for the design and improvement of the catalysts,thereby,provide the important guidance for the experimental studies on the cycloaddition reactions.Therefore,in this paper,several cycloaddition reactions catalyzed by Lewis base,which were reported in experimental literatures,are investigated by using the density functional theory(DFT)method.Based on the experimental studies,the detailed reaction pathways were suggested and explored.All the geometry optimizations(including reactants,intermediates,transition states and products)in every pathway were carried out with Gaussian 09 program package,as well as the energy calculations.The aims of this paper are to provide detailed mechanistic information and useful insights into these kinds of cycloaddition reactions.The important and valuable results in this dissertation can be summarized as follows:The mechanisms and stereoselectivities of the tandem cross-Rauhut-Currier(RC)/cyclization reaction of methyl acrylate with(E)-2-benzoyl-3-phenyl-acrylonitrile catalyzed by 1,4-diazabicyclo[2.2.2]octane(DABCO)have been explored from the molecular level.The results indicate that the favorable mechanism includes three steps: the first step is the nucleophilic attack of DABCO on methyl acrylate to form zwitterionic intermediates Inta1,the second step is the reaction of intermediates Inta1 with(E)-2-benzoyl-3-phenylacrylonitrile to generate intermediate Inta2,and the last step is an intramolecular SN2 process to give the final product Pa and release the catalyst DABCO.The results show that the SN2 substitution is the rate-determining step(RDS)and the activation energy barrier for this step is computed to be 35.9 kcal/mol,whereas the second step is the stereoselectivity-determining step.The mechanisms of the DABCO-catalyzed annulations of allenoates with diethyl azodicarboxylate have been studied using DFT calculations.The calculated results indicate that the favorable mechanism of this reaction includes four stages: the first is the nucleophilic attack of DABCO on allenoates forms a zwitterionic intermediate Intb1,the second stage is the ?-addition of intermediate Intb1 to diethyl azodicarboxylate,followed by the intramolecular 4-exo-trig cyclization,and the last stage is the catalyst DABCO liberation gives the final product.The second step is the rate-determining and Z/E-selectivity determining step,the energy barriers via transition state TSb1/2 is 22.6 kcal/mol.By contrast,the mechanisms of PPh3-mediated cycloaddition reaction of diethyl azodicarboxylate and allenoates were investigated as too.The results indicate that the mechanism includes four steps: the first step is the formation of a zwitterionic intermediate via the addition of PPh3 to diethyl azodicarboxylate,the second step is the addition of the zwitterionic intermediate to the ?-carbon atom of allenoates,followed by the intramolecular cycloaddition,finally,the elimination of triphenylphosphine oxide(OPPh3)affords pyrazoline.The second is found to be the rate-determining step with a barrier of 26.6 kcal/mol.Our calculation results are in consistent with the experimental observations.In summary,these works provide detailed mechanisms and we expect that our results should be useful for understanding other analogous reactions.