A density functional theory study on mechanisms of [4 + 2] annulation of enal with α‐methylene cycloalkanone catalyzed by N‐heterocyclic carbene

• Published in: International journal of quantum chemistry 2019-12, Vol.119 (24), p.n/a
• Main Authors: He, Nan, Zhu, Yanyan, Zhu, Zhenhua, Yang, Yankai, Zhang, Wenjing, Wei, Donghui, Qu, Lingbo, Tang, Mingsheng, Chen, Hongsheng
• Format: Article
• Language: English
• Subjects: [4 + 2] cycloaddition; Catalysts; Chemical reactions; Chemistry; Cycloaddition; Density functional theory; Energy gap; Lewis base; Methylene; Molecular orbitals; N‐heterocyclic carbene; Organic chemistry; Physical chemistry; Protons; Quantum physics; reaction mechanism; Reaction mechanisms; Regeneration
• ISSN: 0020-7608; 1097-461X
• DOI: 10.1002/qua.26039

Density functional theory was used to study the reaction mechanisms of the N‐heterocyclic carbene (NHC)‐catalyzed [4 + 2] annulation reaction between enal and α‐methylene cycloalkanone for the formation of tricyclic benzopyran‐2‐one. The simulations suggest that the energy‐favorable catalytic cycle includes five steps: (a) the nucleophilic addition of enal by NHC catalyst; (b) [1, 2]‐proton transfer for the formation of Breslow intermediate; (c) [1, 4]‐proton transfer for the formation of enolate intermediate; (d) the [4 + 2] cycloaddition process, product formation; and (e) catalyst regeneration. The proton transfer process was particularly designed in two independent ways, the direct proton transfer and the Brønsted acid DBU∙H+‐mediated proton transfer. Our study reveals that [1, 2]‐proton transfer process is the rate‐determining step with the accessible energy barrier, which agrees with the experimental observation. Further analysis of the global reaction index confirmed that NHC was primary used as a Lewis base during the reaction processes. The frontier molecular orbital (FMO) analysis indicates that the introduction of the NHC catalyst facilitates the reaction to occur due to the narrower energy gap of FMO. Density functional theory calculations provide mechanistic insights into the N‐heterocyclic carbene (NHC)‐catalyzed [4 + 2] annulation reaction between enal and α‐methylene cycloalkanone, to form tricyclic benzopyran‐2‐one. The obtained results demonstrated the energy‐favorable pathway of the title reaction. NHC is found to be primarily used as a Lewis base during the reaction processes. These results can inform the rational design of new NHC‐based catalysts for other reactions of this class.