廉价金属催化的醇和不饱和烃的自身氢转移不对称碳碳成键反应研究

Construction of carbon–carbon (C-C) bond represents a fundamentally important transformations in organic synthesis. As energy crisis and environment protection becoming principal concerns, the development of reactions employing earth-abundant and eco-friendly base metal as catalysts is an important objective in modern sustainable chemistry. In particular, it’s of great significance to develop new strategies to convert abundant feedstocks from the chemical industry and renewable biomass to high value products. Metal-catalyzed asymmetric hydrogen-autotransfer (AHA) cross-coupling of alcohols and hydrocarbons constituted one of most efficient C-C bond forming reactions, since it’s free of byproducts and has 100% atom-economy, excellent step-economy and redox-economy. The AHA reactions developed to date, however, rely on the use of noble metals, which are of considerable economic and environment cost, and the use of which may be unsustainable in the long run or in the large scale reaction. The base-metal catalyzed AHA reaction has not been reported so far. Furthermore, the substrate scope of current AHA reactions is limited to activated alkenes and both the reactivity and selectivity are moderate. We aim to develop the first base-metal catalyzed AHA system for cross-coupling of alcohols and unsaturated hydrocarbons, such as alkynes and alkenes. Through the development of new chiral NHC ligands, this project is planning to expand the substrate scope and improve the regio- and stereoselectivity, and eventually to provide an efficient and practical strategy for C-C bond construction. Moreover, the project is aimed to provide methods to effectively transform abundant feedstocks, such as unsaturated hydrocarbon and alcohols, to value-added chiral alcohols which have found widespread application in pharmaceuticals, agrochemicals, and materials.

碳碳键的构建是有机合成化学中最重要的反应之一。由于能源、环境问题的日益严峻，发展地球储量丰富、便宜易得、对环境友好的第一周期过渡金属催化的反应，尤其是基于大宗化工产品或可再生生物质来源原料的转化，具有重要意义。金属催化的醇和不饱和烃的自身氢转移不对称偶联反应具备高度步骤、原子、和氧化还原经济性，无副产物，是最高效的不对称催化碳碳成键反应之一。但是，目前该类反应有赖于以地球储量稀少、昂贵、毒性大的贵金属为催化剂，而且底物范围有限、选择性不高，廉价金属催化的例子还未见报道。本项目将对廉价金属催化的醇与炔烃和烯烃等不饱和烃的自身氢转移不对称交叉偶联反应进行研究，希望基于新型手性氮杂环卡宾配体的发展，实现底物范围的拓展和区域、立体选择性的有效控制，为高级手性醇的合成和碳碳键的不对称构建提供高效、经济的新策略。同时为廉价易得的化工产品不饱和烃和醇的高附加值转化提供科学技术支持。

本项目针对手性分子的精准构筑这一核心科学问题，基于优势手性片段的配体设计新策略，发展了ANIPE和SIPE类新型优势氮杂环卡宾配体，实现了4类镍卡宾催化的醇和不饱和烃的氢转移(不对称)碳碳成键反应，5类镍卡宾催化的烯烃或炔烃的分子内和分子间氢转移不对称碳碳成键反应，和4类镍催化的羰基化合物和不饱和烃的芳基化、烯基化和烷基化反应，高效高选择性合成了手性醇、吡啶、多氟芳烃、吡啶酮、烷基芳烃、酮和胺等化合物；项目从配体设计新策略和新型手性卡宾配体的发展到多类廉价金属催化氢转移不对称碳碳成键反应和羰基加成反应中的应用，实现了多类手性物质的高效高选择性合成，取得了系列原创性成果，完成了研究目标。所发展的新策略、新配体和新方法，有望为手性科学的发展做出进一步贡献。项目共发表论文27篇（包括Science 1篇，Nat. Catal. 1篇，J. Am. Chem. Soc. 5篇，Angew. Chem. Int. Ed. 3篇，ACS Catal. 1篇，CCS Chem. 1篇，Chin. J. Chem. 2篇），申请中国发明专利2件，申请PCT专利 1件，授权中国发明专利和美国专利各1件，培养研究生12名，完成了预定研究任务。