Theoretical Insights into Enantioselective [3+2] Cycloaddition between Cinnamaldehyde and Cyclic N-Sulfonyl Trifluoromethylated Ketimine Catalyzed by N-Heterocyclic Carbene
Theoretical Insights into Enantioselective [3+2] Cycloaddition between Cinnamaldehyde and Cyclic N-Sulfonyl Trifluoromethylated Ketimine Catalyzed by N-Heterocyclic Carbene
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DOI：
10.1021/acs.jpca.2c00900
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发表时间：
2022-05-26
影响因子：
2.9
通讯作者：
Xue，Ying
中科院分区：
文献类型：
--
作者：
Shen，Jingyi;Zhang，Yan;Xue，Ying
采用密度泛函理论（DFT）方法在M06-2X/SMD/6-311+G（d，p）//M06- 2X/SMD/6- 31 G（d，p）水平上研究了N-杂环卡宾（NHC）催化烯醛与环亚胺N-磺酰三氟甲基酮亚胺[3 + 2]环加成反应的立体选择性机理和起源.结果表明，该反应的有利路径包括亲核进攻、质子转移、C-C键的形成、烯醇中间体的互变异构、五元环的形成和催化剂的再生5个步骤。对于质子转移过程，碱辅助反应比直接质子转移过程降低了活化自由能，使反应更容易发生。C-C键的形成是立体选择性的关键步骤，在此过程中产生了两个手性中心和四种构型的中间体（RR/RS/SR/SS）。自由能垒和非共价相互作用分析证实，占主导地位的配置是SS，成为最终的反式在实验中观察到的产品。通过概念密度泛函理论和自然电荷分析，揭示了NHC作为一种双催化剂，既能通过刘易斯碱增加反应物的亲核性，又能活化C-H键，促进质子转移过程.对反应机理的理解对其它高立体选择性有机催化反应也有一定的帮助。
The density functional theory (DFT) method was used to investigate the mechanism and the origin of stereoselectivity ofN-heterocyclic carbene (NHC)-catalyzed [3 + 2] cycloaddition between enals and cyclic imineN-sulfonyl trifluoromethyl ketimines at the M06-2X/SMD/6-311+G(d,p)//M06-2X/SMD/6-31G (d,p) level. The results show that the favorable reaction path consists of five steps: nucleophilic attack, proton transfer, the formation of the C–C bond, the tautomerism of the enol intermediate, the formation of the five-membered ring, and the regeneration of the catalyst. For the process of proton transfer, the base-assisted reaction can reduce the activation free energy and make the reaction easier to occur compared with the direct proton transfer process. The formation of the C–C bond is the crucial step of stereoselectivity, in which two chiral centers and four configurations of intermediates (RR/RS/SR/SS) were generated. The free energy barriers obtained and the noncovalent interaction analysis confirm that the dominant configuration is SS, becoming the final trans-type product observed in experiment. Furthermore, through the analyses of the conceptual DFT and natural atomic charges, it is revealed that NHC acts as a double catalyst, which can not only increase the nucleophilicity of reactants by Lewis base but also activate the C–H bond and promote the proton transfer process. The understanding of the mechanism obtained in this study should be helpful to the other organic catalytic reactions with high stereoselectivity.