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Electrochemical Oxidation of Organic Molecules at Lower Overpotential: Accessing Broader Functional Group Compatibility with Electron-Proton Transfer Mediators.
Accounts of Chemical Research ( IF 18.3 ) Pub Date : 2020-02-12 , DOI: 10.1021/acs.accounts.9b00544
Fei Wang 1 , Shannon S Stahl 1
Affiliation  

Electrochemical organic oxidation reactions are highly appealing because protons are often effective terminal electron acceptors, thereby avoiding undesirable stoichiometric oxidants. These reactions are often plagued by high overpotentials, however, that greatly limit their utility. Single-electron transfer (SET) from organic molecules generates high-energy radical-cations. Formation of such intermediates often requires electrode potentials far above the thermodynamic potentials of the reaction and frequently causes decomposition and/or side reactions of ancillary functional groups. In this Account, we show how electrocatalytic electron-proton transfer mediators (EPTMs) address this challenge. EPTMs bypass the formation of radical-cation intermediates by supporting mechanisms that operate at electrode potentials much lower (≥1 V) than those of analogous direct electrolysis reactions.The stable aminoxyl radical TEMPO (2,2,6,6-tetramethylpiperidine N-oxyl) is an effective mediator for electrochemical alcohol oxidation, and we have employed such processes for applications ranging from pharmaceutical synthesis to biomass conversion. A complementary electrochemical alcohol oxidation method employs a cooperative Cu/TEMPO mediator system that operates at 0.5 V lower electrode potential than the TEMPO-only mediated process. This difference, which arises from a different catalytic mechanism, rationalizes the broad functional group tolerance of Cu/TEMPO-based aerobic alcohol oxidation catalysts.Aminoxyl mediators address long-standing challenges in the "Shono oxidation," an important method for α-C-H oxidation of tertiary amides and carbamates. Shono oxidations are initiated by a high-potential SET step that limits their utility. Aminoxyl-mediated Shono-type oxidations have been developed that operate at much lower potentials and tolerate diverse functional groups. Analogous reactivity underlies α-C-H cyanation of secondary cyclic amines, a new method that enables efficient diversification of piperidine-based pharmaceutical building blocks and preparation of non-natural amino acids.Electrochemical oxidations of benzylic C-H bonds are commonly initiated by SET to generate arene radical cations, but such methods are again plagued by large overpotentials. Mediated electrolysis methods that promote hydrogen-atom-transfer (HAT) from benzylic C-H bonds to Fe-oxo species and phthalimide N-oxyl (PINO) support C-H oxygenation, iodination, and oxidative-coupling reactions. A complementary method merges photochemistry with electrochemistry to achieve amidation of C(sp3)-H bonds. This unique process operates at much lower overpotentials compatible with diverse functional groups.These results have broad implications for organic electrochemistry, highlighting the importance of "overpotential" considerations and the prospects for expanding synthetic utility by using mediators to bypass high-energy outer-sphere electron-transfer mechanisms. Principles demonstrated here for oxidation are equally relevant to electrochemical reductions.

中文翻译:

有机分子在较低的超电势下的电化学氧化:与电子-质子转移介体的功能基团相容性更高。

电化学有机氧化反应非常吸引人,因为质子通常是有效的末端电子受体,从而避免了不希望的化学计量氧化剂。这些反应常常被高电势所困扰,然而,这极大地限制了其效用。来自有机分子的单电子转移(SET)产生高能自由基阳离子。这种中间体的形成通常需要电极电位远高于反应的热力学电位,并且经常引起辅助官能团的分解和/或副反应。在此帐户中,我们将展示电催化电子质子转移介体(EPTM)如何应对这一挑战。EPTM通过支持机制绕过自由基阳离子中间体的形成,该机制在比类似直接电解反应的电极电势低得多的电极电势(≥1 V)下运行。稳定的氨氧基TEMPO(2,2,6,6-四甲基哌啶N-氧基)是电化学乙醇氧化的有效介体,我们已将此类方法用于从药物合成到生物质转化的各种应用中。互补的电化学醇氧化方法采用协作的Cu / TEMPO介体系统,该系统的电极电势比仅TEMPO介导的过程低0.5V。这种差异是由不同的催化机理引起的,从而使基于Cu / TEMPO的好氧醇氧化催化剂的宽泛的官能团耐受性合理化。氨氧基介质解决了“ Shono氧化”中的长期挑战,“ Shono氧化”是叔酰胺和氨基甲酸酯进行α-CH氧化的重要方法。Shono氧化反应是通过限制其实用性的高电位SET步骤引发的。已开发出氨氧基介导的Shono型氧化,其电势低得多,并能耐受各种官能团。类似的反应性是仲环胺的α-CH氰化的基础,这是一种新方法,可以使哌啶类药物的组成部分有效多样化,并可以制备非天然氨基酸.SET通常会引发苄基CH键的电化学氧化以生成芳烃自由基阳离子,但是这种方法又被大的过电位所困扰。介导的电解方法可促进氢苄基CH键与Fe-oxo物种之间的氢原子转移(HAT)和邻苯二甲酰亚胺N-氧基(PINO)支持CH的氧化,碘化和氧化偶联反应。一种补充方法是将光化学与电化学结合以实现C(sp3)-H键的酰胺化。这种独特的工艺在与各种官能团兼容的低电势下运行。这些结果对有机电化学具有广泛的意义,突出了“电势过高”考虑的重要性以及通过使用介体绕过高能外层电子来扩展合成效用的前景。 -转移机制。这里证明的氧化原理与电化学还原同样重要。
更新日期:2020-02-13
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