双齿环状芳基胺基卡宾–铬(0)催化环内化学键的功能化研究

The use of earth-abundant first-row transition metal of chromium to replace expensive transition metal catalysts in developing efficient chromium catalysis is highly interesting, which exhibits important scientific significance and extensively application prospects. However, current chromium catalysis typically focused on the Nozaki-Hiyama-Kishi reactions and polymerization of olefins. As a result, it's necessary to the synthesis of efficient chromium catalysts and exploration of novel chromium-catalyzed transformations. This proposal aims to design and synthesis of bis[cyclic(amino)(aryl)carbenes] to construct stable, structurally well-defined zero-valent chromium catalysts by serving as stronger σ-donor, and overcomes the obstacle that current low-valent chromium catalysis heavily rely on the use of Grignard reagents as substrates and reductants. To tackle the issue that current reactions are mainly limited to the substrates of three- and four-membered rings, this proposal emphasizes on the exploration of the unique catalytic capacity of low-valent chromium in the activation of unactivated cyclo-C–O, C–N and C–C bonds that still remains a great challenge in organic synthesis, and focuses on the developing novel ring-opening and ring-expanision reactions by the cleavage of these cyclo-chemical bonds for the preparation of structurally diversity linear and benzoxacycle products. In summary, the studies of this project not only allows for developing novel carbene species in the synthesis of unknown zero-valent chromium complexes by the expansion of carbene chemistry, but also enables to explore the unique catalytic capacity of chromium and application in the organic synthesis, thus rendering it having rich scientific meaning and important research significance.

以地球含量较丰富的前过渡金属铬替代贵金属催化剂，发展经济实用的铬催化合成策略具有重要的科学研究意义。然而目前铬催化主要局限于Nozaki-Hiyama-Kishi及烯烃聚合反应，因此有必要开发新型的铬催化有机合成反应。本项目拟通过设计与合成双齿环状芳基胺基卡宾，利用它较强的σ供电性能来稳定低价金属铬，构建结构明晰的零价铬催化剂，克服当前低价铬催化依赖于格式试剂的研究缺陷。重点研究低价铬在导向基团的协助作用下活化惰性的环内碳–氧、碳–氮及碳–碳键的催化性能，发展环内化学键的开环与扩环反应。解决当前开环及扩环反应受限于环张力极大的三元及四元环底物的研究难题，合成结构多样性的链状及苯并大环衍生物。该项目的研究不仅可以开发新型的卡宾物种，制备未知的零价铬催化剂，拓展卡宾化学的研究领域；而且可以探索金属铬独特的催化性能及在有机合成化学中的应用，具有较丰富的科学内涵与重要的研究意义。

金属铬作为地壳含量丰富的前过渡金属元素，其在惰性化学键活化及交叉偶联方面的反应性质与催化活性未被探索与开发出来。该项目的研究内容侧重于发展双齿环状单胺基卡宾配体，利用它们较强的σ供电性能来稳定低价金属铬，探索低价铬在活化惰性环内碳–氧、碳–氮及碳–碳键方面的催化性能，发展环内化学键的开环与扩环反应。通过项目的实施，我们发展了环状单胺基卡宾-亚胺和环状单胺基卡宾-膦双齿配体负载的铬络合物，揭示出这些络合物能化学选择性地催化硝基还原制备胺类化合物；利用这两类单胺基卡宾配体性质差异，对铬催化炔烃加氢的立体选择性进行了有效调控。研究发现低价铬能催化环内碳-氧的断裂与芳基化，发展了环内碳-氧键的Kumada偶联及与芳基酯碳-氧键的化学选择性还原交叉偶联反应；并以低价铬为活性物种，实现了铬催化芳基碳-氮键和酰胺碳-氮键的Kumada偶联反应，开发出苯甲酰胺的对位烷基化及单胺基卡宾-铬络合物催化碳-氧键的多组分偶联等合成反应。这些研究表明金属铬拥有一些独特的反应性能与催化活性，发展了多种有机铬催化的新型合成反应，极大地拓展了铬催化的研究范围，为后续开展进一步研究奠定了坚实的基础。在项目的资助下，课题组发表学术研究论文24篇，包括低价铬催化研究论文3篇JACS和1篇Nat. Commun.，及3篇ACIE研究论文，申请中国发明专利两项。在项目执行期，课题组共培养了7名博士研究生和2名硕士研究生；研究成果被X-MOL科普网报道5次，被专业学术摘要网站Organic Chemistry Portal介绍。基于这些研究成果，项目负责人获得了“ACP Lectureship Award”和“Thieme Chemistry Journal Award”等奖励。