镍催化羰基化合物碳氧及碳碳偶联机理的理论研究

The Ni catalyzed C-O & C-C coupling reactions of carbonyl compounds have shown great potential in synthesis of oxygen containing compounds, such as alcohols, esters and oxygenheterocycles. It's noteworthy that many of the couplings can show good chemo-, regio- or stereo- selectivities by alternating the substrates or ligands. However, the mechanism of most of these reactions, and especially the origin of the observed selectivity, is not clear yet. The ambiguity in mechanisms limits the development and application of the current, highly efficient synthetic strategies. .In this proposal, we planned to theoretically study the mechanism of the recently reported, highly selective Ni catalyzed coupling reactions, such as the C-O coupling of aldehydes (Tishchenko reaction) and the C-C coupling of aldehyde/ketones with alkenes. By comparing the energy demands of different mechanistic possibilities, we are able to gain the most favorable one for each of the concerned reaction, and distinguish the key structual parameters of the rate/selectivity determining species. Meanwhile, by anlyzing the electronic and steric effects of these species with frontier orbital theories, we can conclude the inherent structure-activity relationships of the subsrates and ligands involved in these reactions. We will then propose some novel coupling reactions according to the obtained conclusions, and validate the proposals with combined theoretical and experimental studies. We hope this proposal could be beneficial to the development of the current catalytic system and the design of highly efficient, selective novel couplings in the future.

近年来，镍催化羰基化合物的碳氧及碳碳偶联为合成多取代醇、酮、酯及氧杂环等含氧化合物提供了新思路。在这些反应中，通过调控底物或配体结构进而实现高化学、区域或立体选择性偶联的现象广泛存在。然而目前人们对这些反应的机理仍存在很多困惑，对反应机理细节、活性催化剂形式以及速率决定步骤等问题的理解仍存在分歧，而且缺少对选择性控制因素的认识。这一点阻碍了人们对现有反应的推广和应用。.本项目拟运用量子化学计算方法研究镍催化醛的Tishchenko型碳氧及醛/酮与烯烃的碳碳偶联反应机理，阐明不同偶联反应的优势机理路径，揭示速率/选择性决定步骤的中间体及过渡态的关键结构特征。同时结合前线轨道理论对其电子及立体效应进行分析，总结不同反应中结构-活性关系的规律性特征。在此基础上理论预测新反应，并结合实验研究证实其可行性，从而为改进现有催化体系和设计高效、高选择性的新型催化体系提供有价值的思路与启示。

近年来，镍催化羰基化合物的碳氧及碳碳偶联为合成多取代醇、酮、酯及氧杂环等含氧化合物提供了新思路。在这些反应中，通过调控底物或配体结构进而实现高化学、区域或立体选择性偶联的现象广泛存在。然而目前人们对这些反应的机理仍存在很多困惑，对反应机理细节、活性催化剂形式以及速率决定步骤等问题的理解仍存在分歧，而且缺少对选择性控制因素的认识。这一点阻碍了人们对现有反应的推广和应用。.本项目运用理论计算与实验相结合的方法，在原计划镍催化的羰基化合物的偶联反应机理研究的基础上，进一步对系列其他过渡金属（如铑等）催化的偶联等反应机理进行了系统研究，侧重阐明不同偶联反应的优势机理路径，揭示速率/选择性决定步骤的中间体及过渡态的关键结构特征，并结合前线轨道理论对其电子及立体效应进行分析，总结了不同反应中结构-活性关系的规律性特征。.在本项目资助下，本课题组迄今共计发表主要SCI论文18篇（IF>3.0，含已接收尚未正式发表2篇）。其中项目负责人作为主要参与人（第一作者/共同第一作者/通讯作者)发表论文16篇，包括J. Am. Chem. Soc. 1篇；ACS catalysis 3篇；Chem. Eur. J. 4篇；Chem. Commun. 1篇；Chem. Asia. J. 3篇；Dalton Trans. 2篇；Phys. Chem. Chem. Phys. 1篇等。以上研究为本课题组未来进一步开展过渡金属催化的新型碳碳及碳杂键构筑反应奠定了坚实基础。