A DFT Study on the N-Heterocyclic(NHC)-Catalyzed [3+2] Annulation Reaction of α-Aroyloxyaldehydes with Oxaziridines: Mechanism,Stereoselectivity,and Role of NHC

【作者】 张翘楚； 李雪； 魏东辉；

【Author】 Zhang,Qiaochu;Li,Xue;Wei,Donghui;The College of Chemistry and Molecular Engineering,Zhengzhou University;

【机构】 郑州大学；

【摘要】 N-heterocyclic(NHC)-catalyzed stereoselective [3 + 2] annulation reaction of α-aroyloxyaldehyde and oxaziridine has been theoretically studied by density functional theory(DFT).[1] The calculated results indicate that the overall catalytic cycle includes six steps, i.e.,(1) the complexation of NHC and α-aroyloxyaldehyde,(2) [1, 2]-proton transfer,(3) the dissociation of p-nitrobenzoic acid for the formation of azolium enolate intermediate,(4) C-O bond formation between the enolate intermediate and oxaziridine,(5) C-N bond formation to complete [3 + 2] cycloaddition, and(6) the regeneration of NHC catalyst. In the second step, the bicarbonate-assisted proton transfer process is more energetically favorable than the bimolecular/direct proton transfer process, whose outcome is in line with the previous theoretical works that the protonic media can promote proton transfer by lowering its energy barrier.[2-4] The fourth step(i.e. C-O bond formation) was found to be the stereoselectivity-determining step, and the generated R-isomer is more energy favorable than the S-isomer, which is in agreement with the experimental observations. The C-H…π interactions are the limiting factors for the stereoselectivity-determining step through the analysis of non-covalent interaction. The global reactivity index analysis shows that the catalyst NHC works as a Lewis base to strength the nucleophilicity of aldehydes as well as those in other mechanistic studies.[5-7] In addition, the electrophilic and nucleophilic Parr function analysis was employed to explain the chemoselectivity of oxaziridines.更多还原

【Abstract】 N-heterocyclic(NHC)-catalyzed stereoselective [3 + 2] annulation reaction of α-aroyloxyaldehyde and oxaziridine has been theoretically studied by density functional theory(DFT).[1] The calculated results indicate that the overall catalytic cycle includes six steps, i.e.,(1) the complexation of NHC and α-aroyloxyaldehyde,(2) [1, 2]-proton transfer,(3) the dissociation of p-nitrobenzoic acid for the formation of azolium enolate intermediate,(4) C-O bond formation between the enolate intermediate and oxaziridine,(5) C-N bond formation to complete [3 + 2] cycloaddition, and(6) the regeneration of NHC catalyst. In the second step, the bicarbonate-assisted proton transfer process is more energetically favorable than the bimolecular/direct proton transfer process, whose outcome is in line with the previous theoretical works that the protonic media can promote proton transfer by lowering its energy barrier.[2-4] The fourth step(i.e. C-O bond formation) was found to be the stereoselectivity-determining step, and the generated R-isomer is more energy favorable than the S-isomer, which is in agreement with the experimental observations. The C-H…π interactions are the limiting factors for the stereoselectivity-determining step through the analysis of non-covalent interaction. The global reactivity index analysis shows that the catalyst NHC works as a Lewis base to strength the nucleophilicity of aldehydes as well as those in other mechanistic studies.[5-7] In addition, the electrophilic and nucleophilic Parr function analysis was employed to explain the chemoselectivity of oxaziridines.更多还原