Meyrelles Ricardo, Brutiu Bogdan R, Maryasin Boris
Institute of Organic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 38, 1090, Vienna, Austria.
Institute of Theoretical Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 17, 1090, Vienna, Austria.
Chempluschem. 2025 Apr;90(4):e202400751. doi: 10.1002/cplu.202400751. Epub 2025 Feb 11.
The Lewis acid-catalyzed coupling of alkenes and aldehydes presents a modern, versatile synthetic alternative to classical carbonyl addition chemistry, offering exceptional regio- and stereoselectivity. In this work, we present a comprehensive computational investigation into the reaction mechanism of this transformation. Our findings confirm the occurrence of an enantioselective transannular [1,5]-hydride shift step and demonstrate that the enantioselectivity of the reaction arises predominantly from steric clashes between functional groups in the cyclization step. Combining computational and experimental results, we establish that the Lewis acid catalyst facilitates the initial C-O coupling step between the alkene and the activated aldehyde. Investigations into systems with longer alkyl chains reveal that while they follow a similar mechanistic pathway, cyclization becomes kinetically hindered, preventing the reaction from proceeding. These insights illuminate the factors governing reaction outcomes and limitations, paving the way for future developments in this area.
路易斯酸催化的烯烃与醛的偶联反应为经典的羰基加成化学提供了一种现代、通用的合成方法，具有出色的区域选择性和立体选择性。在这项工作中，我们对这种转化反应的机理进行了全面的计算研究。我们的研究结果证实了对映选择性跨环[1,5]-氢迁移步骤的存在，并表明反应的对映选择性主要源于环化步骤中官能团之间的空间冲突。结合计算和实验结果，我们确定路易斯酸催化剂促进了烯烃与活化醛之间的初始C-O偶联步骤。对具有更长烷基链的体系的研究表明，虽然它们遵循相似的机理途径，但环化在动力学上受到阻碍，阻止了反应的进行。这些见解阐明了控制反应结果和局限性的因素，为该领域的未来发展铺平了道路。
