| In recent years,organocatalysis has attracted more and more attention due to its low-cost,excellent stereoselectivity,environment-friendly,and so on.Morevoer,the explorations on the mechanism and stereoselectivity of organocatalytic reactions have also received considerable attention for theoretical chemists.According to the role of organocatalyst,the organocatalysis can be divided into four types,namely,Lewis acid,Lewis base,Br?nsted acid,and Br?nsted base.In this dissertation,we have investigated two types of organocatalytic reactions using the density functional theory(DFT),i.e.,Lewis acid catalysis and Lewis base catalysis(N-heterocyclic carbene catalysis),and we have theoretically disclosed the different role of Lewis acid/base catalysts in various kinds of reactions.These theoretical studies would provide valuable guidance for rational design organocatalyst in future.In the 2nd~5th chapters,we have investigated the mechanisms of five organocatalytic reactions in depth.1.The mechanism and diastereoselectivity of Lewis acid-catalyzed [2 + 2] cycloaddition reaction of ketene and alkene.In this chapter,four possible reaction channels,including two non-catalyzed diastereomeric reaction channels(Channels A and B)and two Lewis acid(LA)ethylaluminum dichloride(EtAlCl2)catalyzed diastereomeric reaction channels(Channels C and D),have been investigated.The calculated results indicate that Channel A(associated with R-configurational cycloputanone product)is more energy favorable than Channel B(associated with the S-configurational cyclobutanone product)under non-catalyzed condition,but Channel D leading to S-configurational cyclobutanone is more energy favorable than Channel C leading to R-configurational cycloputanone under LA-promoted condition,which is consistent with the experimental results.And Lewis acid can make the energy barrier of ketene-alkene [2+2] cycloaddition much lower.In order to explore the role of LA in ketene and C=X(X=O,CH2,and NH)[2+2] cycloadditions,we have tracked and compared the interaction modes of frontier molecular orbitals(FMOs)along the intrinsic reaction coordinate(IRC)under the two different conditions.Our computational results demonstrate that Lewis acid lowers the energy barrier of the ketene and C=X(X=O,CH2,and NH)[2+2] cycloadditions by changing the overlap modes of the FMOs.2.The mechanisms and stereoselectivity of NHC-catalyzed [3 + 2] annulation reaction of enals with ?-ketoamides.The calculated results reveal that the favorable pathway comprises of seven steps,i.e.,addition of the catalyst,formation of Breslow intermediate,formation of enolate intermediate,C–C bond formation step,proton transfer process,ring-closure process and the regeneration of the catalyst.For the proton transfer process,apart from the direct proton transfer mechanism,the base TMEDA and the in situ generated Br?nsted Acid TMEDA·H+ mediated proton transfer mechanisms are also investigated;the free energy for the curial proton transfer steps is found to be significantly lowered by explicit inclusion of the Br?nsted Acid TMEDA·H+.The computational results show that the C–C bond formation step is the stereoselectivity-determining step.Global reaction index(GRI)analysis has been performed to confirm that NHC mainly plays a role of Lewis base catalyst.In addition,the distortion/interaction,NCI,and NBO analyses show that the intermolecular weak interaction and electron delocalization of the reaction active site determine the stereoselectivity,with RR-configured product being generated preferentially.3.The mechanism and stereoselectivity of [4 + 2] annulation reaction between ?-oxidized enals and azodicarboxylates catalyzed by the N-heterocyclic carbene.The calculated results reveal that the catalytic cycle can be characterized by three stages(Stages 1,2,and 3).Stage 1 is the nucleophilic addition of NHC catalyst to enals upon the intramolecular proton transfer to generate the Breslow intermediate.In this stage,except the direct proton transfer mechanism,the H2 O and bicarbonate anion(HCO3-)mediated proton transfer mechanism are also investigated,the free energy barrier for the crucial proton transfer steps in Stage 1 is found to be significantly lower by explicit inclusion of bicarbonate anion(HCO3-).For Stage 2,the removal of the leaving group occurs,followed by C–C bond rotation for the formation of cis-dienolate.Stage 3 is the endo/exo [4 + 2] cycloaddition and dissociation of catalyst from the final products.The formal [4 + 2] cycloaddition step is calculated to be the enantioselectivity determining step,CH-? interaction is the main factor that determines the stereoselectivity and thus leading to the R-configured PR generate preferentially.4.The mechanisms and stereoselectivities of the C(sp2)–C(sp3)single bond activation of cyclobutenones and its [4 + 2] cycloaddition reaction with imines via N-heterocyclic carbene(NHC)organocatalysis.According to our calculated results,the fundamental reaction pathway contains four steps: nucleophilic addition of NHC to cyclobutenone,the C–C bond cleavage for the formation of enolate intermediate,[4 + 2] cycloaddition of enolate intermediate with isatin imine,and the elimination of NHC catalyst.In addition,the calculated results also reveal that the second reaction step is rate-determining step,whereas the third step is regio-and stereo-selectivity determining step.For the regio-and stereo-selectivity determining step,all the four possible attack modes were considered.The addition of C=N bond in isatin imine to the dienolate intermediate is more energy favorable than the addition of C=O bond to dienolate intermediate.Moreover,the Re face addition of C=N bond in isatin imine to the Re face of dienolate intermediate leading to the SS configuration N-containing product was demonstrated to be most energy favorable,which is mainly due to the stronger electron delocalization in the corresponding transition state.Furthermore,by tracking the frontier molecular orbital(FMO)changes of C–C bond cleavage process in the rate-determining step,we found that this process obeys the conservation principle of molecular orbital symmetry.5.The theoretical investigation on mechanism and stereoselectivities of aminomethylation reaction of ?,?-unsaturated aldehyde with N,O-acetal enabled by N-heterocyclic carbene and Br?nsted acid/base(BA/BB).The calculated results disclose that the reaction contains seven steps,i.e.,formation of the actual catalysts NHC and Br?nsted acid Et3N·H+ coupled with activation of C–O bond of N,O-acetal,nucleophilic attack of NHC on ?,?-unsaturated aldehyde,formation of Breslow intermediate,?-protonation for the formation of enolate intermediate,nucleophilic addition on Re/Si face of enolate by the activated iminium cation,esterification coupled with regeneration of Et3N·H+,and dissociation of NHC from product.The addition on prochiral face of enolate should be the stereocontrolling step,in which chiral ?-carbon is formed.Furthermore,NBO,GRI,and FMO analyses have been performed to explore the roles of catalysts and origin of stereoselectivity.Surprisingly,the added Br?nsted base(BB)Et3N plays an indispensable role in the esterification process,indicating the reaction proceeds under the NHC-BA/BB multi-catalysis rather than NHC-BA dual catalysis proposed in the experiment.In the 6th chapter,we have summaried the above studies and propected for the future work. |
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