电化学自由基/自由基氧化交叉偶联进展

Recent advances in electrooxidative radical/radical cross-coupling

自由基/自由基交叉偶联是近年来兴起的直接构建化学键的交叉偶联策略之一,能够有效地构建C-C键、C-X键、X-Y键.稳态自由基效应(persistent radical effect,PRE)概念的提出为自由基/自由基交叉偶联策略提供了理论基础.但由于自由基特性,其化学选择性的调控是目前该策略所面对的主要挑战.传统的自由基/自由基交叉偶联策略利用金属调控自由基活性,从而调控反应的化学选择性,但避免不了化学计量的氧化剂使用.有机电化学合成目前被认为是环境友好且高效的合成策略,利用电极上的电子转移策略可以避免当量氧化剂的使用,通过精确控制电压与电流可调控瞬态自由基和稳态自由基的生成速率,从而调控自由基/自由基交叉偶联反应,且电氧化策略将反应空间范围控制于阳极周围,保证瞬态自由基的存活和与其他自由基的高效偶联.本文以C-C键、C-X键、X-Y键等成键类型作为分类依据,综述了目前电化学自由基/自由基交叉偶联的最新进展,并对未来自由基/自由基交叉偶联的发展前景进行了展望.

Radical/radical cross-coupling is one of the recently emerged direct strategies for constructing chemical bonds,effectively constructing C-C,C-X,and X-Y bonds.The scientific significance of radical/radical cross-coupling reactions lies in the fact that their reaction barriers can be considered as zero,implying that the intermediate stage of the reaction does not require additional energy input for activation.Furthermore,theoretically,the coupling process is not rate-determining,indicating a faster reaction rate and shortened reaction time.However,the major challenge in these reactions is the issue of selectivity.This is primarily due to the transient and highly reactive nature of most radicals involved in synthesis reactions,as well as the rapid consumption of radicals by side reactions,leading to low radical concentrations in the reaction system.The concept of persistent radical effect(PRE)provides a theoretical basis for selective radical/radical cross-coupling strategy,which requires the presence of both persistent radicals and transient radicals to react.However,the main type of radicals currently is transient radicals.Persistent radicals,such as triphenylmethyl radicals,are relatively rare,requiring substrates containing largeπ-bonds or other stabilizing groups to stabilize radicals to form persistent radicals.Consequently,the limited types of persistent radicals restrict the application scope of radical/radical cross-coupling strategies.Our research group has developed strategies to regulate the activity of radicals by converting transient radicals into persistent ones.One methods involves reversible binding of Ni(II)with nitrogen radicals to form Ni(III)-N species,which forms persistent radicals.These strategies have successfully regulated radical activity,expanding the scope of radical/radical cross-coupling strategies.However,traditional radical/radical cross-coupling strategies utilize metal regulation of radical reactivity to regulate the chemoselectivity of the reaction,while the use of chemical oxidants in stoichiometric quantities cannot be avoided.Organic electrosynthesis is currently considered to be an environmentally friendly and efficient synthesis strategy,which can avoid the use of stoichiometric amounts of chemical oxidants by utilizing electron transfer strategies on electrodes.By contrast,the advantages of electrochemical methods for radical/radical cross-coupling reactions include the precise control of voltage or current,enabling efficient control of the generation rate of both transient and stable radicals,leading to the stable production of radical/radical cross-coupling products.Furthermore,compared to other species,radicals are highly reactive and easily lost,resulting in decreased yields.However,electrochemical oxidation of the substrates at the anode ensures that all substrates produce radicals,restricting the spatial range of the cross-coupling reaction to the vicinity of the anode and enabling the survival of transient free radicals and efficient coupling with other free radicals.Nevertheless,the lack of chemical selectivity remains a challenge for electrochemical strategies,limiting their application in radical/radical cross-coupling reactions compared to photoredox catalysis.This review article,categorized by bond types,provides a comprehensive overview of the recent advancements in electrochemical radical/radical cross-coupling reactions for the formation of C-C,C-N,C-S,C-O,S-S,and N-S bonds,and offers insights into the future development of radical/radical cross-coupling strategies.In the case of C-C bond formation,xanthene compounds serve as typical examples of C(sp^(3))radical precursors,capable of constructing C(sp^(2))-C(sp^(3))bonds with heteroaryl carbons.For C-N bond formation,nitrogen-centered radicals often require adjacent largeπbonds to stabilize them in radical/radical coupling strategies.Typical examples,such as diamines and phenothiazine compounds,are widely reported.In nitrogen-containing heterocycles,the nitrogen lone pair electron cloud can be stabilized by the aromatic ring,enabling these compounds to act as nitrogen radical precursors for radical/radical crosscoupling with carbon radical precursors.In C-S bonding reactions,although sulfide radicals can be easily generated under electrochemical conditions,controlling their chemoselectivity is challenging,as they are prone to self-coupling.Sulfonyl hydrazides and sodium sulfinates can effectively generate sulfonyl radicals under electrochemical conditions,while sulfides or sulfols can generate thiol radicals under similar oxidative conditions.These radical sources can effectively achieve radical/radical cross-coupling with carbon-centered or nitrogen-centered radicals.Moreover,sulfur-centered radicals can efficiently undergo cross-coupling with other heteroatom-centered radicals,forming N-S and S-S bonds.