Beyond Conventional Organic Electrosynthesis: The Role of Fluorinated Solvents

Abstract

Organic electrosynthesis has emerged as a unique platform for chemical manufacturing owing to not only the use of electricity as a green reagent but also, especially, to its distinct reactivity. While conventional solvents are sought to remain inert and solely provide a liquid environment for the electrochemical process to occur, fluorinated alcohol solvents have been shown to redefine this concept. In fact, the singular properties of these solvents allow them to actively interact with the substrates and reaction intermediates driving dramatic changes in the chemo- and regioselectivity as well as on the reaction yields. Given the rapid permeation of these solvents in the burgeoning field of electro-organic synthesis, this mini-review strives to provide a concise but up-to-date critical revision for the growing community of scientists working at the interface of synthetic chemistry and electrochemistry. Here, the main electrosynthetic transformations where they have been exploited besides their key role in activating certain reaction pathways will be highlighted. Finally, a forward-looking perspective on the more practical evolution and implementation of these systems will be discussed.

Keywords: electrosynthesis; fluorinated solvent; organic chemistry; solvent effect; sustainability.

1

Schematic representation of a single-compartment 2-electrode electrochemical cell. The oxidation (of Red₁ species) and reduction (of Ox₂ species) occurring at the anode and cathode gives rise to Ox₁ and Red₂ species, respectively. In this scenario, one of them could be the targeted product, while the other reaction will take place as a sacrificial process to sustain the current, or both could be desired products. Likewise, one or both of these species could be precursor(s) that yield the product via homogeneous reaction in the reaction medium.

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The many roles of fluorinated alcohols in organic electrosynthesis.

1. Electro-oxidative Alkene Oxygenation Adapted by Lei et al.

2. Proposed Mechanism of Alkene Oxygenation by Lei et al.

3. Indole/Aniline Functionalization by HFIP by Pan et al.

4. Cobaltaelectro-catalyzed C–H/N–H Activation by Ackermann et al.

5. Reaction Mechanism of Cobaltaelectro-catalyzed C–H/N–H Activation by Ackermann et al.

6. Rhodaelectro-catalyzed C–H Annulation by Ackermann et al.

7. Undirected C–H Alkenylation of Arenes by Ackermann et al.

8. Heteroarene Electro-oxidative C–H Amination by Feng et al.

9. Trifluoromethoxylation of Heteroaromatic Compounds by Qing et al.

10. C­(sp³)-H fluorination by Ackermann et al.

11. Cross Dehydrogenative Coupling of Phenols and Naphthols by Waldvogel et al.

12. Electrocatalyzed Benzothiophene Functionalization by Waldvogel et al.

13. Electro-oxidative Cross Dehydrogenative-Coupling Of phenols by Vercammen et al.

14. Proposed Reaction Pathway for the Electro-oxidative Cross Dehydrogenative Coupling by Feng et al.

15. Electro-oxidative Cross Dehydrogenative Coupling by Feng et al.

16. Dehydrogenative C–S Cross-Coupling by Xu et al.

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Cyclic voltammograms of N-isopropyl-2-phenoxypropanethioamide (1) and (Z)-N-isopropyl-2-methylbenzo­[b]­[1,4]­oxathiin-3­(2H)-imine (2). (0.1 M Et₄NPF₆). (a) 1 (3 mm), MeCN, E_p/2 = 1.26 V; (b) 1 (3 mM), Sc­(OTf)₃ (1 mM), MeCN, E _p/2 = 1.18 V; (c) 1 (3 mM), MeCN/TFA (9:1), E _p/2 = 1.18 V; (d) 1 (3 mM), Sc­(OTf)₃ (1 mM), MeCN/TFA (9:1), E _p/2 = 1.15 V; (e) 2 (3 mM), MeCN; (f) 2 (3 mM), Sc­(OTf)₃ (1 mM), MeCN; g) 2 (3 mM), Sc­(OTf)₃ (1 mM), MeCN/TFA (9:1). Reprinted (in part) with permission from ref . Copyright 2019 Wiley–VCH–Verlag GmbH & Co. KGaA.

17. Dehydrogenative P–N Coupling Reaction by Waldvogel et al.

18. [3+2] Annulation of Styrenes and Dicarbonyl Compounds and Proposed Mechanism by Lei et al.

19. Electrosynthesis of Benzofurans by Kowey et al.

20. [3+2] Cycloaddition Indole Synthesis by Sun et al.

21. Electrocatalyzed 4-Imidazolidinones Synthesis by Sharma et al.

22. C_(sp3)–H Lactonization by Park et al.

23. Proposed Mechanism for the Electrocatalyzed C_(sp3)–H Lactonization by Park et al.

24. Manganese-Catalyzed Electrochemical Azidation-Annulation by Sarkar et al.

25. Electro-oxidative Synthesis of Sulfur Ylides by Guo et al.

26. Acyl Nitroso Diels-Alder Reaction by Hilt et al.

27. Selective Isoeugenol Dimerization by Einaga et al.

28. Desulfurative Electrooxidation C–N Coupling by Zheng et al.

29. λ³-bromanes synthesis by Suna et al.

30. λ³-Iodane Synthesis by Moran et al.

31. Electron Shuttle for Dehalogenation of Persistent Compounds by Morandi et al.