A DFT study on N-heterocyclic carbene catalyzed [4+2] annulation reaction with in situ generated heterocyclic ortho-quinodimethane: Mechanism, origin of enantioselectivity and role of catalyst

作者：Xu, Hao; Zhu, Zhenhua; Guo, Yuen; Liu, Chunmei; Zhang, Wenjing; Zhu, Yanyan^*; Wang, Yulong; Tang, Mingsheng

来源：Tetrahedron, 2018, 74(9): 1009-1015.

DOI：10.1016/j.tet.2018.01.030

• Reaction mechanism
• NHC catalyst
• Cycloaddition
• DFT

Activation of inert sp(3) C-H bonds has attracted widespread attention and been developed with significant progress in recent years, but understanding the mechanism of this kind of reaction continues to be one of the most challenging topics in organic chemistry. In this paper, detailed mechanism of N-heterocyclic carbine (NHC) catalyzed [4+2] annulation reaction with in Situ generated heterocyclic orthoquinodimethane have been investigated using density functional theory (DFT). The computational results show that the additive DBU plays an important role in NHC-catalyzed C-H activation. The title reaction proceeds the processes of the introduction of the NHC catalyst to the carboxylic ester, DBU-assisted sp(3) C-H deprotonation, Michael addition, [4+2] cycloaddition, the dissociation of the catalyst and the product generation. The calculated results indicate that Michael addition is rate-determining and stereoselectivity-determining. With the use of NHC as the chiral catalyst, optically active products were obtained in good yields with excellent enantioselectivities. Furthermore, the theoretically predicted the main product is S configuration, which is in good agreement with the experimental result. The special role of NHC and origin of stereoselectivity were also identified by natural bond orbital (NBO), global reaction index (GRI) and frontier molecular orbital (FMO) analyses. This work might be helpful for understanding the significant roles of NHC catalyst and thus provide insights on the rational design of potential new catalysts for this kind of reactions and suggest enlightening clues on rational design of efficient organocatalysts for the C (sp(3))-H activation.

• 出版日期2018-3-1
• 单位郑州大学