合成功能化的环状胺基芳基卡宾应用于铁催化C-H键的胺基化反应

Stable carbenes have attracted much attention owing to their powerful abilities as ligands and organocatalysts. In comparison with cyclic(diamino)carbenes (NHCs), another important of carbene species, cyclic(monoamino)carbenes (CMCs) exhibit favorable reactivities such as activation of small molecules. However, up to date, this type of carbene only limits to cyclic(alkyl)(amino)carbenes. The construction of cyclic(amino)(aryl)carbenes (CAArCs) by the replacement of alkyl group with aryl moiety has never been achieved. Given the totally difference in their electronic properties and more easily modification of aryl substitute, synthesis of stable CAArCs and studies their reactivity toward small molecule activation and application in transition metal-mediated catalysis as ligands is desirable. Our proposed project involves the synthesis of bulky phosphino- or pyridyl-substituted functionalized CAArCs and the corresponding iron complexes, investigation of their reactivity in the small molecules activation (including hydrogen, carbon dioxide and ammonia), as well as their applications as catalysts in the direct iron-catalyzed amination through C-H bond activation. Incorporation of bulky and nucleophilic phosphino- or pyridyl substitutes into aryl skeleton dramatically increases the kinetically stability of the free carbenes. It should be note that the resulting two-donor species could act as a bidentate ligand and coordinate with transition metals such as iron leading to the corresponding complexes with a five- or six-membered ring structure. Taking account of their attractive merits of iron catalysis, this project also focuses on investigating the catalytic activity of the resulting iron complexes in the C-H bond amination for the direct formation of C-N bond. The significancy of this study includes expanding the research scope of carbene chemistry by the synthesis of novel functionalized CAArCs, acceleration of the development of carbene-based ligands, and affording the experiences for the development of novel iron catalysis.Therefore, the proposed project on the synthesis of phosphino- or pyridyl-substituted CAArCs and investigation of their catalytic activity in iron-catalyzed C-H amination is of interest having significant scientific research value.

环状单胺基卡宾因具有与过渡金属类似的反应活性如能活化小分子等，引起了研究者的广泛关注。但目前对它的研究仅局限于环状烷基胺基卡宾,而这类卡宾存在烷基结构难以修饰的研究缺陷。考虑到芳香取代基与烷基截然不同的电学特性，结构更易修饰，本项目拟以芳基为支撑骨架,将富电性的膦或吡啶基团融入卡宾分子，构建较大的位阻结构来有效地保护卡宾中心，制备基于膦或吡啶取代的功能化环状胺基芳基卡宾。同时，考虑到铁催化具有廉价、绿色与环境友好等特点，结合当前C-H键胺基化反应研究的发展趋势，拟将卡宾－膦或吡啶作为双齿配体制备五元或六元环状铁络合物，发展基于Ｃ-Ｈ键活化的铁催化胺基化反应。本项目的研究可以有效地拓展卡宾化学的研究领域，为设计与合成高效的卡宾配体提供研究经验，发展具有重要应用价值的铁催化反应体系。因此，对合成功能化的环状胺基芳基卡宾应用于铁催化C-H键的胺基化反应的研究具有丰富科学内涵和重要的研究价值。

在该项目中，我们成功发展了一类新型的卡宾配体–环状胺基芳基卡宾。它通过简单地将环状烷基胺基卡宾邻近的烷基替换为芳基基团，从而使得卡宾中心更具亲电特性，同时也保留了环状烷基胺基卡宾强的亲核特性。因而这类卡宾具有更窄的HOMO–LUMO轨道能级差。其相应的异吲哚鎓盐已通过三步操作“一锅法”成功制备，并在低温条件下发生去质子合成环状胺基芳基卡宾负载的铑及金络合物。进一步的研究揭示出这些络合物能作为优异催化剂应用于催化[3+2]环加成、惰性碳-氢键的烷基化与芳基胺的三成份环化反应。这些研究证明环状胺基芳基卡宾具有作为优秀配体的潜力。另一方面，我们发现强富电性的环状烷基胺基卡宾负载的铑络合物能作为高效催化剂前体，实现芳基酮与苯酚的高选择性氢化反应。值得注意的是，该氢化反应能够把化惰性芳基骨架同时保留活泼的羰基基团。该催化体系对多种不饱和官能团如酯基、羧基、酰胺及氨基酸表现出良好兼容性。特别是，这一反应能够以十克级的规模进行，并不影响氢化反应的化学选择性。除此之外，我们课题组也首次揭示出廉价的第一过渡系金属铬盐能高效地催化惰性碳-氧键与格式试剂的区域与化学选择性交叉偶联反应。在自然科学基金青年项目的资助下，目前我们课题组已发表两篇JACS、一篇ACIE及四篇OL研究论文，并有一篇综述性论文发表在《化学综述》上。这些初步结果激励着我们继续在单胺基卡宾及铬催化化学领域开展探索性研究，希望在不久的将来能有更为突出的原创性研究成果出现，以此来回报国家自然科学基金委的基金资助。