稀土金属催化的胺的碳-碳单键活化和连续加成/环化反应

The activation of C–C single bonds represents a challenging but attractive subject in organic synthesis. The rare earth catalyzed cleavage of C–C single bonds under mild conditions remains little explored due to their highly electrophilic and single, thermodynamically stable oxidation state (Ln3+), which gives rise to the absence of conventional oxidative-addition/reductive-elimination processes and the difficulty of -C elimination. Furthermore, rare earth-catalyzed tandem addition of a N-H bond to unsaturated carbon-carbon and unsaturated carbon-heteroatom functionalities is also a challenging subject, and has received relatively limited attention. The project will pioneer the use of rare earth metal complexes in catalytic -alkynyl and aryl elemination of amines and explore the novel two-component cyclization of allylamines (or propargylic amines) with polar unsaturated functionalities. The investigation contents mainly include the design and synthesis of highly active rare earth complex catalysts, revealing new reactivity patterns of C–C single bonds, establishing the alkynyl-exchange reaction of propargylic amines with terminal alkynes and the replacement of aryl of benzylamines by the alkynyl catalyzed by rare earth complexes, development of atom-economical, high bond forming efficient, and operationally simple methods for synthesis of 1,3-diheteroatom five-membered heterocycles from allylamines (propargylic amines) and another readily available and inexpensive starting material containing polar unsaturated functionalities. In this case it may be expected that the present rare earth catalyzed alkynyl-exchange reaction will be an important complementary to both the classical alkyne metathesis and the Cu-catalyzed alkynyl-exchange reaction. Furthermore, several new strategies for controlling sequential activation of multiple functionalities will be established, by which a series of new organic compounds may be efficiently synthesized. In addition, some similarity and difference between transition metals and rare earth metals in activation of unstrained C–C single bonds as well as catalytic tandem addition of a N-H bond to unsaturated carbon-carbon and unsaturated carbon-heteroatom functionalities will be revealed.

碳-碳单键活化是合成化学中最具挑战性而又有吸引力的研究领域之一。因具有强亲电性和缺乏常规氧化还原活性，致使温和条件下稀土催化的C-C单键活化非常罕见；同时，也严重制约了稀土金属对不饱和极性和非极性官能团的串联活化。本项目将开拓性研究稀土催化胺的-炔基和芳基的消除反应和烯（炔）丙胺与简单极性不饱和官能团的直接环化反应，主要内容包括设计合成高活性稀土催化剂；建立C-C单键活化的新模式，分别实现炔丙胺和苄胺分子中的炔基和芳基的选择性取代；发展基于烯丙胺和炔丙胺的原子经济性和步骤经济性的合成双杂原子五员杂环化合物的新方法。项目的实施，将弥补现有炔烃复分解反应和炔基交换反应的不足；建立多个化学键定向有序活化的新策略，高效合成结构新颖有机分子；揭示稀土金属和过渡金属在活化非张力碳-碳单键和串联活化极性与非极性不饱和官能团方面的异同点。

项目主要针对C-C键活化和多官能团串联活化/环化反应中存在的一些挑战性科学问题及新的相关稀土金属有机基元反应展开研究。取得了突破性进展，主要成果包括：发展了多种调控稀土有机配合物反应活性和选择性的新策略，实现了一些稀土有机配合物常规反应性的反转，如发现通过三核稀土配合物结构的刚性和立体屏蔽效应，可以激活高度惰性的稀土-氧键，使之优先于稀土-烷基键发生复分解和加成反应，拓展了稀土配合物的应用范围；发展了一系列新的稀土配合物与小分子的复分解/环化反应，如与CO的脱氧偶联/环化反应、与CO2的脱氧胺羰化/环化反应、与CS2的脱硫/硫代酰胺化/环化/硫代羧基化反应、联磷配体与CS2的降解重组/环化反应、白磷的直接多官能团化/环化反应等，为设计新的稀土催化反应提供了参考；发现炔丙胺能与端炔进行炔基交换反应；实现了氨基取代烯烃与腈的连续分子间和分子内加成/环化反应；发展了首例烯烃氢脒基化反应；提出了双金属协同活化远程非极性、非张力碳-碳键策略，成功地解决金属烯醇基和共轭烯醇基配合物难发生δ-或更远碳消除反应问题，实现了酮和酯的碳碳单键活化选择性从传统的碳羰基键向远程非张力非极性C(sp3)-C(sp3)键转变；建立了一种新的中继非张力碳碳键连续断裂的方法，首次实现了环己醇去[2+2+2]-环加成反应。上述大部分反应是其它金属迄今不能或难以促进的转化，具有重要互补性和潜在应用价值。发表相关研究论文17篇，其中Angew. Chem. Int. Ed. 3篇。获得授权中国发明专利3件。接待3人次国外专家来课题组进行短期课题合作研究。培养博士7人，硕士1人，博士后1人。