手性“受阻路易斯酸碱对”催化剂的设计、合成及应用

“Frustrated Lewis Pairs (FLPs)” are a class of compounds that consist of a sterically hindered pair of a Lewis acid and a Lewis base. The steric hindrance prevents the pair from forming the acid-base adduct, thereby inducing new chemical reactivities. Since Professor Douglas Stephan discovered that a B/P frustrated Lewis pair was capable of cleaving the H-H bond of the hydrogen gas in 2006, FLPs have been used in the activation of various small molecules, such as carbon dioxide, NO, cyclopropanes. At the same time, catalysis using FLPs has been successfully applied in hydrogenation, hydrosilylation and hydroboration reactions. Recently, asymmetric catalysis enabled by chiral FLPs has become a hot research topic. Despite continual development, the area faces several challenges. Firstly, the number of available chiral catalysts is limited. Secondly, the compatible reaction types are currently confined to mainly hydrogenations, and the substrate scope is usually narrow. Finally, the turnover numbers and the selectivities are relatively low compared to those of transition metal catalysis. To overcome these limitations, we propose to develop new chiral FLPs catalysts with higher reactivities to explore different reaction types and expand the substrate scope. In the end, we hope to identify several catalysts that are able to catalyze different reactions in a highly efficient and selective fashion.

"受阻路易斯酸碱对"是由大位阻路易斯酸和路易斯碱共同组成，它们由于位阻因素，难以生成酸碱加合物，进而表现出了特殊的化学性质。自Stephan教授于2006年报道发现硼磷组成的"受阻路易斯酸碱对"具有裂解氢气的活性以来，该类化合物陆续实现了二氧化碳、一氧化氮、环丙烷等多种化合物的活化。同时，该类化合物作为催化剂，在氢化、硅氢化和硼氢化等反应中得到了广泛地应用。近期，使用手性"受阻路易斯酸碱对"研究不对称催化已成为该领域的研究热点。然而，该研究面临着几个挑战。首先，由于发展的时间较短，已报道的手性催化剂还很少；其次，已实现不对称催化的反应类型较少，主要是氢化反应，且底物局限性大；最后，反应的转化数和选择性尚无法达到过渡金属催化的水平。针对这些问题，本项目拟开展新型手性"受阻路易斯酸碱对"催化剂的合成研究，再使用这些新催化剂拓展反应类型，解决底物局限，期望实现高效高选择性的不对称反应。

本项目主要针对手性"受阻路易斯酸碱对(FLPs)"不对称催化研究领域中缺乏高效催化剂、反应类型和底物适用范围受限等问题，设计合成具有新型结构的手性硼催化剂，研究新催化剂的反应活性和选择性以及构效关系，同时，拓展硼催化反应类型，解决底物适用性限制。在项目资助期内，本课题组设计并合成了多种新型结构手性硼催化剂，通过烯烃硼氢化反应现场生成系列并环双硼和螺环双硼催化剂，该类催化剂在亚胺氢化和喹啉氢化反应中的活性和选择性已达到世界领先水平，突破了转化数的世界纪录；而且，该类催化剂与其他已知催化剂相比，具有较大结构差异，已成为本课题组的标志。我们还发展出了多个硼催化新反应，包括硼催化惰性环丙烷开环反应、硼催化吡啶的串联还原反应和硼催化负氢迁移诱导的成环反应等，大大丰富了硼催化化学，为该领域的进一步发展做出了重要贡献。在该项目资助下，共发表高水平论文7篇（其中5篇Angew. Chem. Int. Ed.，1篇ACS Catal.和1篇Org. Lett.）。项目负责人王晓晨于2018年获得ACP Lectureship Award，2019年获得首届“科学探索奖”。综上所述，我们很好地实现了研究目标。