基于加成-偶联策略的铁催化烯（炔）碳硼化反应研究

In recent years, iron-catalyzed cross-coupling reaction has received extensive attention as a green and sustainable C-C bond construction method. In addition to its advantages of abundance, cheapness and low toxicity, iron exhibits superior abilities in activating electrophilic reagents, especially in breaking inert C-O bonds and catalyzing decarboxylation of redox-active esters. However, due to the low ability of transmetalization, iron-catalyzed cross-coupling reaction is focused on high-activity nucleophiles such as Grignard reagents and zinc reagents, which limits the development of iron catalysis. This project intends to carry out iron-catalyzed carboboration of alkenes and alkynes, which can avoid the disadvantage of low ability of transmetalization of iron by addition-coupling strategy, and can also extend the concept of carboboration with the abilities of iron in breaking inert C-O bonds and catalyzing decarboxylation of redox-active esters. This project intends to establish an applicable iron-catalysis system to realize C-O activated carboboration and decarboxylative carbocarbation of alkenes and alkynes. In this project, we will adjust factors, such as ligand, solvent etc., to control the regioselectivities and stereoselectivities of carboboration. The modification of bioactive molecules containing alkenyl, alkynyl, carbonyl, phenolic hydroxyl and carboxyl groups will be proformed. By conducting physical organic chemistry experiments and density functional calculations, reaction mechanism and related selectivities will be explained.This project can expand the concept of iron-catalyzed cross-coupling, providing a green and efficient method for constructing carbon-carbon bonds.

铁催化偶联反应作为一种绿色可持续的碳碳键构建方法，近年来得到广泛关注和研究。除了储量丰富、廉价易得和低毒环保等优势，铁催化剂展现了优越的亲电试剂活化能力，尤其是催化惰性C-O键断裂和活性羧酸酯脱羧的能力；但其较弱的转金属化能力使铁催化偶联反应局限于格氏试剂、锌试剂等高活性亲核试剂，限制了铁催化的应用发展。申请人拟开展铁催化烯（炔）碳硼化反应研究，通过加成-偶联策略避免铁催化转金属化能力较弱的缺点，并结合铁催化惰性C-O键断裂和活性羧酸酯脱羧的能力拓展碳硼化反应的应用范围。本项目拟建立合适的铁催化体系，实现烯（炔）的C-O键活化碳硼化反应和羧酸酯脱羧碳硼化反应；通过配体、溶剂等因素调控反应的区域选择性、立体选择性；对含烯基、炔基、羰基、酚羟基和羧基的生物活性分子进行转化修饰；通过机理实验和密度泛函计算对反应历程进行解释。本研究的开展可拓展铁催化偶联反应的概念，为碳碳键构建提供绿色高效的方法。

由于铁具有地球储量丰富、廉价易得、生物低毒、环境友好等优点，铁催化有机合成反应重新得到了化学家的关注。有机硼化物作为重要的合成中间体，其合成研究具有重要价值。本项目对铁催化烯烃、炔烃的硼化反应体系进行了探索，实现了不同于前人工作的反应效果，并对铁催化硼化反应体系进行了机理研究。具体工作包括：①在无需配体调节的情况下，实现了铁催化脂肪族烯烃区域选择性控制的硼氢化反应，机理实验说明不同溶剂环境中铁盐与联硼试剂生成的不同类型的铁硼中间体是决定区域选择性的关键因素；②实现了铁催化烯丙醇的直接硼化脱羟反应，且能够立体选择性控制的得到E式选择性的产物，机理研究说明铁盐具有通过路易斯酸性活化C-OH键断裂和催化硼转移的双重作用，铁硼中间体与烯丙醇形成的六元环过渡态是立体选择性控制的关键；③实现了铁催化炔丙醇和炔丙胺γ-区域选择性的顺式硼氢化反应，多种结构和官能团的底物能够被该反应兼容。该项目的实施为不同类型有机硼化物的合成提供了高效实用的策略，有望应用于实际生产中；此外，该项目加深了对于铁催化硼化反应体系的机理，为该领域的进一步深入研究提供了理论支持。