Li Yan, Zhang Mingchao, Zhang Zhiqiang
School of Chemical Engineering, University of Science and Technology Liaoning, Anshan 114051, P. R. China.
J Org Chem. 2023 Sep 15;88(18):12997-13008. doi: 10.1021/acs.joc.3c01015. Epub 2023 Aug 29.
To disclose the reaction mechanism and selectivity in the NHC-catalyzed reaction of 2-bromoenal and 6-methyluracil-5-carbaldehyde, a systematic computational study has been performed. According to DFT computations, the catalytic cycle is divided into eight elementary steps: nucleophilic attack of the NHC on 2-bromoenal, 1,2-proton transfer, C-Br bond dissociation, 1,3-proton transfer, addition to 6-methyluracil-5-carbaldehyde, [2 + 2] cycloaddition, NHC dissociation, and decarboxylation. The Bronsted acid DABCO·H plays a crucial role in proton transfer and decarboxylation steps. The addition to 6-methyluracil-5-carbaldehyde determines both chemoselectivity and stereoselectivity, leading to -configured carbocycle-fused uracil, in agreement with experimental results. NCI analysis indicates that the CH···N, CH···π, and LP···π interactions should be the key factor for determining the stereoselectivity. ELF analysis shows the main role of the NHC in promoting C-Br bond dissociation. The mechanistic insights obtained in the present work may guide the rational design of potential NHC catalysts.
为了揭示氮杂环卡宾（NHC）催化2-溴烯醛与6-甲基尿嘧啶-5-甲醛反应的机理和选择性，我们进行了系统的计算研究。根据密度泛函理论（DFT）计算，催化循环分为八个基本步骤：NHC对2-溴烯醛的亲核进攻、1,2-质子转移、C-Br键解离、1,3-质子转移、加成到6-甲基尿嘧啶-5-甲醛、[2 + 2]环加成、NHC解离和脱羧。布朗斯特酸DABCO·H在质子转移和脱羧步骤中起着关键作用。加成到6-甲基尿嘧啶-5-甲醛决定了化学选择性和立体选择性，生成构型为 - 的碳环稠合尿嘧啶，与实验结果一致。非共价相互作用（NCI）分析表明，CH···N、CH···π和孤对电子···π相互作用应该是决定立体选择性的关键因素。电子定域函数（ELF）分析表明NHC在促进C-Br键解离中起主要作用。本工作中获得的机理见解可能指导潜在NHC催化剂的合理设计。
