Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

Abstract

Electrochemistry represents one of the most intimate ways of interacting with molecules. This review discusses advances in synthetic organic electrochemistry since 2000. Enabling methods and synthetic applications are analyzed alongside innate advantages as well as future challenges of electroorganic chemistry.

Figure 1

(A) Two hundred years of electroorganic chemistry: an “organocentric” view of selected milestones; basic principles of the undivided cell (B) and divided cell (C) explained through amide oxidations; color code (D) and cell notations (E) used in the review. Image credits: the image of “Volta Pile”, Copyright Wellcome Images, adapted under CC BY 4.0; the image of “Heyrovsky’s Polarograph”, Copyright Lukáš Mižoch, adapted under CC BY-SA 3.0; the image of Janke & Kunkel “Electrolytical Work Table”, Copyright IKA, adapted with permission.

Figure 2

Oxidation of carboxylates: the Kolbe reaction and related processes.

Figure 3

Oxidation of sulfinic acid salts.

Figure 4

Generation of N-centered radicals through direct electrolysis.

Figure 5

Generation of N-centered radicals through indirect electrolysis.

Figure 6

Electrochemical generation of nitrene and nitrenium species.

Figure 7

Shono oxidation: variation of nitrogen substituents.

Figure 8

Shono oxidation: variation of trapping nucleophiles. Figure 8A inset: cyclic voltammogram adapted with permission from J. Am. Chem. Soc. 2008, 130, 10496–10497. Copyright (2008) American Chemical Society.

Figure 9

Use of electroauxiliary in the Shono oxidation.

Figure 10

Electrochemical generation of acyl iminium cation pools.

Figure 11

Synthetic applications of Shono-type anodic oxidations.

Figure 12

Electrochemical oxidation of alcohols. Reprinted from J. Am. Chem. Soc. 2015, 137, 16179–16186. Copyright (2015) American Chemical Society.

Figure 13

Generation of oxocarbenium cation pool and applications in glycosylation.

Figure 14

Generation of oxocarbenium, thionium, and other carbocations with electroauxiliaries.

Figure 15

Electrochemical oxidation of aldehydes.

Figure 16

Indirect electrochemical α-functionalization of carbonyls.

Figure 17

Electrochemical benzylic oxidation.

Figure 18

Arene functionalization through electrochemical oxidation.

Figure 19

Arene oxidation with the cation pool strategy.

Figure 20

Diversity-oriented synthesis of polycyclic scaffolds through the modification of an anodic product derived from 2,4-dimethylphenol.

Figure 21

Biaryl synthesis through electrochemical phenol oxidation.

Figure 22

Aryl ether formation through anodic phenol dimerization.

Figure 23

Electrochemical generation of phenonium cations.

Figure 24

Electrochemical oxidation of catechol and aminophenols.

Figure 25

Electrochemically promoted nucleophilic aromatic substitution (GC/NMR yields listed in this figure).

Figure 26

Arene functionalization with electrogenerated electrophiles and radicals.

Figure 27

Electrochemical fluorodesulfurization and Pummerer-type fluorination.

Figure 28

Electrochemical fluorination of miscellaneous functional groups.

Figure 29

Anodic olefin coupling reactions of enol ethers and ketene acetal equivalents.

Figure 29

Anodic olefin coupling reactions of enol ethers and ketene acetal equivalents.

Figure 30

Anodic olefin coupling with heteronucleophiles.

Figure 31

Electrocatalytic cycloadditions.

Figure 32

Anodic oxidation of other electron-rich olefins.

Figure 33

Olefin functionalization with electrogenerated electrophiles. Inset photo in Figure 33B reprinted from Angew. Chem. Int. Ed. 2011, 50, 5153–5156. Copyright (2011) John Wiley & Sons.

Figure 34

Electrochemical dehydrogenation and heteroarene synthesis.

Figure 35

Electrochemical oxidation of allylic and unactivated C–H bonds.

Figure 36

Oxidation of miscellaneous functional groups.

Figure 37

Anodic oxidation in palladium catalysis.

Figure 38

Reduction of aldehydes and ketones.

Figure 39

Reduction of esters and amides.

Figure 40

Reduction of activated olefins.

Figure 41

Reduction of allylic systems and aromatics.

Figure 42

Reduction of alkyl halides.

Figure 43

Direct and indirect reduction of aryl halides.

Figure 44

Indirect reduction of aryl halides with transition-metal mediators.

Figure 45

Cathodic reduction in palladium catalysis.

Figure 46

Electrochemical carboxylation of alkenes, alkynes, and carbonyls.

Figure 47

Electrochemical carboxylation of organohalides.

Figure 48

Reduction of miscellaneous functional groups.

Figure 49

Cathodic generation of oxidants.

Figure 50

Parallel paired electrolysis.

Figure 51

Sequential anodic oxidation and cathodic reduction.

Figure 52

Convergent paired electrolysis.