College of Chemistry, and Institute of Green Catalysis, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, Henan, P. R. China.
Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou 450001, Henan, P. R. China.
Org Biomol Chem. 2022 Feb 23;20(8):1662-1670. doi: 10.1039/d1ob02429a.
By performing density functional theory (DFT) calculations, we investigated and identified the fundamental pathway for N-heterocyclic carbene (NHC)-catalyzed synthesis of axially chiral benzothiophene-fused biaryls using enal and 2-benzyl-benzothiophene-3-carbaldehyde, which includes (1) nucleophilic attack on enal by the organocatalyst NHC, (2) [1,2]-proton transfer, (3) oxidation, (4) stereoselective formation of the C-C σ bond, (5) intramolecular [2 + 2] cycloaddition, (6) dissociation of NHC, (7) release of CO, and (8) transformation to axial chirality. Moreover, the calculated results can reasonably explain the observed chemo- and stereoselectivities for the formation of both benzothiophene/benzofuran-fused biaryls in these kinds of reactions. Further non-covalent interaction (NCI) and atoms-in-molecules (AIM) analyses demonstrate that the hydrogen bond interactions are responsible for the stability of key stereoselective transition states. This work would be useful for understanding the origin of stereoselectivity of NHC-catalyzed intermolecular cyclization reactions for the synthesis of axially benzothiophene/benzofuran-fused biaryl compounds.
通过进行密度泛函理论（DFT）计算，我们研究并确定了 N-杂环卡宾（NHC）催化的利用烯醛和 2-苄基苯并噻吩-3-甲醛合成轴手性苯并噻吩并联芳烃的基本途径，其中包括（1）有机催化剂 NHC 对烯醛的亲核攻击，（2）[1,2]-质子转移，（3）氧化，（4）C-C σ 键的立体选择性形成，（5）分子内[2 + 2]环加成，（6）NHC 的解离，（7）CO 的释放，以及（8）轴向手性的转变。此外，计算结果可以合理地解释在这些反应中观察到的苯并噻吩/苯并呋喃并联芳烃形成的化学和立体选择性。进一步的非共价相互作用（NCI）和原子在分子（AIM）分析表明，氢键相互作用是关键立体选择性过渡态稳定性的原因。这项工作对于理解 NHC 催化的用于合成轴手性苯并噻吩/苯并呋喃并联芳烃的分子间环化反应的立体选择性起源非常有用。
