金属铁催化的双烷基亲电试剂的选择性还原偶联反应研究

Reductive cross-electrophile coupling reactions have recently been developed to a versatile and sustainable synthetic tool for selective C-C bond formation. The employment of cheap and abundant electrophiles avoids the pre-formation and handling of organometallic reagents. Iron is an attractive catalyst in cross-coupling reactions due to its low toxicity, high abundance, and low price. However, the use of iron catalysts in C-C cross-couplings requires strongly reducing conditions for the formation of a reactive low-valent catalyst species. This resulted in magnesium being the widely used as reducing agent in the iron-catalyzed reductive cross-coupling reactions. The low functional group tolerance of this system is usually associated with the highly basic and nucleophilic organomagnesium halides formed in-situ. Therefore, the study of iron-catalyzed reductive cross-coupling reactions is still rare by now. The development of novel iron-catalyzed cross-coupling system with better functional group compatibility is of upmost importance and urgence at this stage. Another challenge of this research area is the selective cross-coupling of two alkyl electrophiles to construct the Csp3-Csp3 bonds. This proposal was aimed to solve the two challenges together by using milder reducing agents to change the catalytic cycles from the mechanistic manifold.

金属催化的亲电试剂的还原偶联反应已经发展成为选择性构建碳碳键的通用方法。有机亲电试剂的种类繁多、廉价易得，在催化合成中直接使用可以避免预制备和处理大量危险、不稳定的有机金属试剂。由于金属铁的低毒、丰富、廉价的特性使得其在金属催化中具有很大的吸引力，然而铁催化的还原偶联反应的研究并不多。这是由于金属铁催化的还原偶联反应中涉及到格氏试剂的生成，因此往往官能团兼容性比较差。发展兼容性好的铁催化的交叉还原偶联反应仍是目前的一个挑战。另外，金属催化的还原偶联反应可以选择性地构建sp2-sp2和sp2-sp3碳碳键，而在选择性地实现双烷基亲电试剂的交叉偶联构建sp3-sp3碳碳键上还存在着挑战。本研究计划就是从催化反应的基本机理出发，拟通过改变还原剂来调控催化循环的途径，从而实现双烷基亲电试剂的选择交叉偶联来构建sp3-sp3碳碳键的。

金属催化的亲电试剂的还原偶联反应已经发展成为选择性构建碳碳键的通用方法。有机亲电试剂的种类繁多、廉价易得，在催化合成中直接使用可以避免预制备和处理大量危险、不稳定的有机金属试剂。本研究从研究铁催化的的还原偶联反应的开始，逐渐过渡到金属镍催化，发展了金属镍催化的迁移交叉偶联反应。同时利用金属链迁移的策略，也实现了双烷基亲电试剂的交叉偶联反应。重要的是，这些反应可以通过配体控制反应的区域选择性。通过对反应的机理的研究以及理论计算也解释了不同配体对反应的影响。为解决还原偶联中底物匹配性的问题提供了理论指导，也为进一步探索金属迁移的有机合成应用提供了基础。