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. 2023 Jun 16;13(12):8038-8048.
doi: 10.1021/acscatal.3c01174. Epub 2023 May 31.

Deep Electroreductive Chemistry: Harnessing Carbon- and Silicon-based Reactive Intermediates in Organic Synthesis

Wen Zhang  1 , Weiyang Guan  1 , Jesus I Martinez Alvarado  1 , Luiz F T Novaes  1 , Song Lin  1
Affiliations

Deep Electroreductive Chemistry: Harnessing Carbon- and Silicon-based Reactive Intermediates in Organic Synthesis

Wen Zhang et al. ACS Catal. .

Abstract

This Viewpoint outlines our recent contribution in electroreductive synthesis. Specifically, we leveraged deeply reducing potentials provided by electrochemistry to generate radical and anionic intermediates from readily available alkyl halides and chlorosilanes. Harnessing the distinct reactivities of radicals and anions, we have achieved several challenging transformations to construct C-C, C-Si, and Si-Si bonds. We highlight the mechanistic design principle that underpinned the development of each transformation and provide a view forward on future opportunities in growing area of reductive electrosynthesis.

Keywords: alkene difunctionalization; alkyl halide; chlorosilane; cross-electrophile coupling; electroreduction; electrosynthesis; radical-polar crossover.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Electroreductive synthesis: (A) Select early examples of electroreductive reactions. (B) Select fine chemicals produced by reductive electrolysis in industry.
Figure 2.
Figure 2.
Electroreductive chemistry of alkyl halides and chlorosilanes contributed by our group.
Figure 3.
Figure 3.
Strategies and select reagents used to generate alkyl radicals from alkyl halides.
Figure 4.
Figure 4.
Electroreductive carbofunctionalization of alkenes with alkyl bromides. (A) Reaction design princeple. (B) Reduction potentials of some relevant reagents and intermediates.
Figure 5.
Figure 5.
Electroreductive carbofunctionalization of alkenes: reaction development. (A) Optimal reaction condition. (B) Representative reaction scope. (C) Synthesis of precursor of bioactive molecules.
Figure 6.
Figure 6.
Electrochemically driven XEC reaction. (A) Reaction design principle. (B) Initial trial with unactivated alkyl bromides: alkyl radical reduction is in competition with radical side reactions. (C) The use of anion stabilizing substituents promotes the desired reactivity.
Figure 7.
Figure 7.
Electrochemical XEC of alkyl halides: reaction development. (A) Optimal reaction conditions. (B) Representative reaction scope. (C) Formal benzylic C-H bond methylation
Figure 8.
Figure 8.
(A) and (B) Control experiments to probe the mechanism of electrochemical XEC of alkyl halides, (C) synthesis scale-up, and (D) development of deuterohalogenation.
Figure 9.
Figure 9.
Electroreductive disilylation of alkenes. (A) Reaction design principle. (B) Optimal reaction conditions. (C) Representative reaction scope.
Figure 10.
Figure 10.
(A) Radical and anion probe substrates used to investigate the mechanism of reductive alkene disilylation. (B) Extension of this reactivity to other substrates.
Figure 11.
Figure 11.
Electroreductive silyl cross-electrophile coupling. (A) Reaction design of electroreductive disilylation of alkenes and DFT calculations support for the proposed mechanism. (B) Optimal reaction conditions. (C) Representative reaction scope.
Figure 12.
Figure 12.
Extension of electroreductive silyl cross-electrophile coupling to oligosilanes and cyclic silanes. (A) Reaction design principle. (B) Optimal reaction conditions. (C) Representative reaction scope.
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