A DFT Study of N-Heterocyclic Carbene Catalyzed [4+2] Annulation between Saturated Carboxylate with ortho-Quinone Methide: Possible Mechanisms and Origin of Enantioselectivity

作者：Wang, Wei; Wei, Donghui^*

来源：ChemistrySelect, 2017, 2(28): 8856-8864.

DOI：10.1002/slct.201701679

• Annulation
• Deprotonation
• DFT
• NHC
• Stereoselectivity

The possible mechanisms of N-heterocyclic carbene (NHC) catalyzed [4+2] annulation between saturated carboxylate and ortho-quinone methide have been investigated for the first time using density functional theory. The calculated results indicate that the entire catalytic cycle contains four reaction steps: (1) the nucleophilic attack on carbonyl carbon of saturated carboxylate by NHC, which is coupled with the dissociation of triazole-oxide anion, (2) the alpha-C(sp(3))-H deprotonation by BrOnsted base, (3) the [4+2] cycloaddition affording the SR/RS/SS/RR-configurational intermediates, and (4) the dissociation of NHC and products. The [4+2] cycloaddition step is stereoselectivity-determining, and the RS-configurational pathway is the most energy favorable path, which is consistent with the experimental observations. Frontier molecular orbital (FMO) analysis indicates that NHC can lower the energy barrier of [4+2] cycloaddition by reducing the energy gap of two reactant parters, which is further confirmed by the additional calculations of the uncatalyzed [4+2] cycloaddition pathway. In addition, non-covalent interaction and distortion energy analyses were performed for exploring the origin of the stereoselectivity. Moreover, the natural bond orbital (NBO) charge population and global reactivity index (GRI) analyses were also carried out to disclose the role of NHC.

• 出版日期2017-9-29
• 单位郑州大学