Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14850, United States.
J Am Chem Soc. 2020 Dec 9;142(49):20661-20670. doi: 10.1021/jacs.0c08532. Epub 2020 Nov 24.
Electrochemistry grants direct access to reactive intermediates (radicals and ions) in a controlled fashion toward selective organic transformations. This feature has been demonstrated in a variety of alkene functionalization reactions, most of which proceed via an anodic oxidation pathway. In this report, we further expand the scope of electrochemistry to the reductive functionalization of alkenes. In particular, the strategic choice of reagents and reaction conditions enabled a radical-polar crossover pathway wherein two distinct electrophiles can be added across an alkene in a highly chemo- and regioselective fashion. Specifically, we used this strategy in the intermolecular carboformylation, -Markovnikov hydroalkylation, and carbocarboxylation of alkenes-reactions with rare precedents in the literature-by means of the electroreductive generation of alkyl radical and carbanion intermediates. These reactions employ readily available starting materials (alkyl halides, alkenes, etc.) and simple, transition-metal-free conditions and display broad substrate scope and good tolerance of functional groups. A uniform protocol can be used to achieve all three transformations by simply altering the reaction medium. This development provides a new avenue for constructing Csp-Csp bonds.
电化学以可控的方式直接获得反应性中间体（自由基和离子），从而实现选择性的有机转化。这一特性已在各种烯烃官能化反应中得到证明，其中大多数反应都是通过阳极氧化途径进行的。在本报告中，我们进一步扩展了电化学的范围，将其应用于烯烃的还原官能化。特别是，通过试剂和反应条件的战略性选择，实现了自由基-极性交叉途径，其中可以以高度化学和区域选择性的方式在烯烃上添加两个不同的亲电试剂。具体而言，我们通过电还原生成烷基自由基和碳负离子中间体，在文献中罕见的分子间甲酰化、Markovnikov 氢烷基化和碳羧化反应中使用了这种策略——这些反应采用了易得的起始原料（卤代烷烃、烯烃等）和简单的、无过渡金属的条件，并显示出广泛的底物范围和对官能团的良好耐受性。通过简单改变反应介质，可以使用统一的方案实现这三种转化。这一发展为构建 Csp-Csp 键提供了新途径。
