铜催化C-H键活化与自由基介导构筑C-C键的反应研究

In recent years, considerable advances have been made in C-C bond construction via transition-catalyzed C-H bond activation or radical reactions. However, the systematic studies on C-C bond formation via combination of transition-catalyzed C-H bond activation with radical reactions are still in its infancy, and the reactions are limited to palladium-catalyzed C-H activation with intramolecular directing group. Copper is a kind of metal with cheap, low toxicity and rich valence state, which can be used in C-H activation without directing group and radical mediated processes. Therefore, based on the strategy of combining copper-catalyzed C(sp2, sp)-H bond activation with radical mediated processes, this project intends to prepare highly valuable organic synthesis intermediates diarylmethanes and substituted alkynes by C-C bond construction, specific as follows: (1) Developing new approaches for preparing diarylmethanes from toluene derivatives, aryl acetonitrile derivatives and phenyl sulfonea derivatives; (2) Developing new approaches for preparing substituted alkynes from alcohols, acetonitrile derivatives and phenyl sulfonea derivatives; (3) Study the application and mechanism of related reactions. Compared with the traditional methods, methods in this research synthesize target molecules without using organic halogen compounds, organoboron, and equivalent organometallic reagents. This project can not only establish the highly efficient catalysis system of combining Cu catalyzed C-H activation with radical mediated processes but also provide some new ideas in the C-C bond formation.

近年来，通过过渡金属催化C-H键活化或自由基介导构筑C-C键分别取得了巨大的成就。但将二者有机结合起来对C-C键构筑反应进行研究还非常有限，且反应类型主要局限于贵金属钯催化分子内导向C-H键活化。铜廉价低毒，价态丰富，既可催化非导向C-H键活化，也能参与自由基反应。本项目拟将铜催化C(sp2, sp)-H键活化与自由基介导优势互补结合，通过C-C键构筑制备重要的有机合成中间体双芳基甲烷和取代炔烃化合物，内容如下：（1）从甲苯、芳基乙腈及苯甲醇衍生物出发，一锅法高效制备含氟、氮杂原子双芳基甲烷化合物；（2）以醇类、乙腈及苯甲砜衍生物为底物，与末端炔烃偶联高效制备取代炔烃化合物；（3）相关反应的应用拓展及机理研究。本项目的实施有望建立铜催化C-H键活化与自由基介导相结合的高效催化体系，避免传统方法制备以上目标化合物需使用有机卤化物、有机硼及当量有机金属试剂的局限，也为C-C键构建提供新思路。

通过自由基介导或无金属参与构筑C-C键及有机合成中间体具有重要的研究意义。本项目围绕廉价易得的有机小分子，如腈类化合物、醛类化合物、苄基卤化物以及酯类化合物等，在铜催化或者无金属条件下，发展了一系列制备高价值有机合成中间体化合物的新方法。内容如下：（1）发展了铜催化甲苯衍生物对芳基乙腈类化合物的直接sp3C-H键官能团化，绿色高效制备了取代腈类衍生物。(2) 研究了以廉价易得亚磷酸为还原剂和促进剂，实现了苄卤化合物的绿色还原及芳烃的苄基化反应。(3) 制备了一种新型磷盐l两性离子，再氘代乙腈存在下，可制备氘代内磷盐，并以此催化含活泼氢物质的氢氘交换反应，亦可高效制备出各种末端氢被氘代的烯烃化合物。(4) 采三氯化磷为氯化试剂实现了叔丁基酯类化合物的高效酰氯化反应，制备了一系列酰氯。(5) 报道了在无金属条件下，从酯类化合物出发，高选择性制备酮和腈类化合物的反应研究。(6) 在亚磷酸和碘存在条件下，实现了醛类化合物高选择性制备苄基碘和二芳基甲烷类化合物的研究。以上研究为上述相关化合物的合成提供了廉价、简洁、高效的新方法。