铁钴催化的有机钛试剂协同型偶联反应的研究

The facile cooperative cross-coupling by virtue of the bridge action between transition-metal catalyst and organometallic is currently one of most challenging topics in the area of catalytic coupling reactions. Organotitanium proves to be cheap, low toxic and relatively stable and can be presented in a variety of forms. Actually this organometallic species usually shows high chemo-, regio- and stereoselectivity. Importantly, the cooperativity in the coupling reactions using organotitanium can be achieved more easily than those using main group organometallics such as RLi,RMgX, etc. This is due to the fact that the central titanium atom can coordinate with a large number of diverse types of ligands, and thus the bridge action occurs easily either through its coordination with the ligands of catalyst or with the leaving group or through the coordination of catalyst metal with titanium's ligands. This project will focus on the cooperative cross-couplings of various organotitaniums using low-price, low- toxicity iron and cobalt metal as a catalyst by taking advantage of the above-mentioned merits of organotitanium. Towards this goal, the planned cooperative cross-couplings can be achieved via the cooperative bridge action of organotitanium, catalyst and leaving group by altering the types of ligands of organotitanium or catalyst, the species of organotitanium and leaving groups. This project will investigate the scope of iron or cobalt-catalyzed couplings of various organotitanium and enhance the reaction rate and selectivity through the cooperative participation of two metal ions. Thus, the couplings which are previously difficult to be achieved, such as the couplings through the cleavage of C-F or C-O bonds, and highly regio- and stereoselective couplings will be achieved. Obviously, this project will significantly expand the scope and types of the couplings of organotitanium, the couplings catalyzed by iron or cobalt and the cooperative couplings. It will enrich the couplings of organotitanium as well as the couplings catalyzed by iron or cobalt and illustrate the efficacy of cooperative reactivity in organometallic catalysis.

在催化偶联中，利用催化金属与被催化金属试剂之间的"桥联"等作用进行协同型偶联反应，是当前该领域中颇具挑战的课题之一。有机钛试剂廉价，低毒，化学性质相对稳定，形态多样，具有较高的化学、区域和立体选择性。同时，钛原子配位能力强，配位数目大，配体种类多样，在被其他金属催化时，很容易通过与配体或离去基等的络合作用而产生"桥联"作用，进而发生协同型偶联反应。本课题将利用钛试剂的这些突出特点，采用价格低，毒性小的铁和钴作为催化金属，通过对钛试剂及形态、催化剂与配体和离去基团的调整等；建立三组分间的"桥联"机制，实施协同型反应，提高反应性能和选择性，拓展反应范围。如实施碳氟键，氧醚键等低活性键的偶联反应，同时探索区域选择性和不对称偶联反应等。显然，本课题将较大程度上拓展钛试剂参与的偶联反应、铁钴催化的偶联反应以及协同型偶联反应的类型和范围,对丰富与发展钛试剂、铁钴催化的偶联反应及协同效应有重要的意义。

在催化偶联中利用催化金属与被催化金属试剂之间的"桥联"等作用进行协同型偶联反应，是当前该领域中颇具挑战的课题之一。有机钛试剂廉价、低毒、形态多样；而且钛原子配位能力强，配位数目大，配体种类多样，所以在被其他金属催化时，很容易通过与配体或离去基等的络合作用而产生"桥联"作用，进而发生协同型偶联反应。在以往的过渡金属催化中，过渡金属多集中使用价格昂贵的钯等或毒性较大的镍。尽管价格低、毒性小的铁和钴催化的偶联反应取得了一些的进展，但多集中在 C(sp2) — C(sp3) 之间的偶联；在文献中有限的 C(sp2) — C(sp2) 型偶联实例中，常常需要在偶联位点附近有特殊的活化基团（如 2-吡啶基或 C=NR 等）或采用特殊的催化体系（如FeF3/NHC等）。本课题是利用有机钛试剂的上述优点，采用价格低，毒性小的铁和钴作为催化金属，通过钛与钴或铁的协同作用，突破以往的局限，实施双低毒金属的协同偶联，并拓展反应范围，发现新型偶联反应。.本专项课题很好地实现了项目的前期目标，通过钛试剂、铁催化体系与反应条件的筛选与优化，建立一种新的钴钛协同催化偶联反应。与以往的反应相比，具有明显的优势：（1）反应只需要亚化学计量的钛酸酯；（2）催化体系非常简单，仅由 FeCl3 和 PBu3 组成；（3）反应操作简便，并在室温和单一溶剂中进行；（4）反应适用范围广，且具有很高化学选择性和区域选择性；（5）含活泼氢基团如OH, COOH，OCNHR等可不经保护。.本项目部分成果已在国际重要期刊 Org. Lett. 上发表，且该文已被 Synfact 期刊作为亮点文章报道。