Electrochemical Arylation Reaction

Review Cite This: Chem. Rev. 2018, 118, 6706−6765

pubs.acs.org/CR

Electrochemical Arylation Reaction Siegfried R. Waldvogel,*,†,‡,§ Sebastian Lips,† Maximilian Selt,†,‡ Barbara Riehl,† and Christopher J. Kampf†,§ †

Institute of Organic Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany Graduate School Materials Science in Mainz, Staudingerweg 9, 55128 Mainz, Germany § Max Planck Graduate Center with Johannes Gutenberg University, Forum universitatis 2, 55122 Mainz, Germany

Chem. Rev. 2018.118:6706-6765. Downloaded from pubs.acs.org by MOUNT ROYAL UNIV on 08/09/18. For personal use only.

‡

ABSTRACT: Arylated products are found in various fields of chemistry and represent essential entities for many applications. Therefore, the formation of this structural feature represents a central issue of contemporary organic synthesis. By the action of electricity the necessity of leaving groups, metal catalysts, stoichiometric oxidizers, or reducing agents can be omitted in part or even completely. The replacement of conventional reagents by sustainable electricity not only will be environmentally benign but also allows significant short cuts in electrochemical synthesis. In addition, this methodology can be considered as inherently safe. The current survey is organized in cathodic and anodic conversions as well as by the number of leaving groups being involved. In some electroconversions the reagents used are regenerated at the electrode, whereas in other electrotransformations free radical sequences are exploited to afford a highly sustainable process. The electrochemical formation of the aryl−substrate bond is discussed for aromatic substrates, heterocycles, other multiple bond systems, and even at saturated carbon substrates. This survey covers most of the seminal work and the advances of the past two decades in this area.

CONTENTS 1. Introduction 2. Preparative Aspects of Electroorganic Synthesis 2.1. Choosing the Appropriate Cell Design 2.2. Preparative Challenges in Electrochemical Arylation 2.3. Scale up of Preparative Electrosynthesis 3. Challenges: Formation of Oligomers, Polymers, and Polycycles Leading to Diversity 4. Aryl−Aryl Bond Formation 4.1. Anodic Conversion 4.1.1. Substrates with Two Leaving Functionalities 4.1.2. Substrates with One Leaving Functionality 4.1.3. Substrates without Leaving Functionality 4.1.4. Template-Directed Conversions 4.2. Cathodic Conversion 4.2.1. Substrates with Two Leaving Functionalities 4.2.2. Substrates with One Leaving Functionality 4.2.3. Substrates without Leaving Functionalities 5. Arylation of Other Carbon Substrates 5.1. Arylation of Olefins 5.1.1. Metal-Catalyzed Electrolysis Involving Leaving Groups © 2018 American Chemical Society

5.1.2. Metal-Mediated Electrolysis without Leaving Functionalities 5.1.3. Metal-Free Electrolysis 5.2. Arylation of Alkynes 5.3. Arylation of sp3 Moieties 5.3.1. Arylation of sp3 Moieties by Anodic Oxidation 5.3.2. Arylation of sp3 Moieties via Cathodic Reduction 5.4. Arylation of Carbon Dioxide 5.4.1. Arylation of Carbon Monoxide 5.4.2. Arylation of Other Carbon Substrates 6. Arylation of Specific Groups 6.1. Arylation of Nitrogen 6.1.1. Amination of Aromatic Compounds 6.1.2. Acetamidation 6.1.3. Arylation of Nitrogen Heterocycles 6.1.4. Synthesis of N-Heterocycles 6.2. Arylation of Oxygen 6.2.1. Synthesis of Aryl Alcohols 6.2.2. Synthesis of Aryl Ethers 6.2.3. Synthesis of Aryl Esters 6.2.4. Synthesis of O-Heterocycles 6.3. Arylation of Sulfur 6.3.1. Arylation of Thiols 6.3.2. Thiocyanation of Aromatic Compounds

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Received: April 9, 2018 Published: July 2, 2018

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DOI: 10.1021/acs.chemrev.8b00233 Chem. Rev. 2018, 118, 6706−6765

Chemical Reviews 6.3.3. Arylation of Sulfonates 6.3.4. Intramolecular C−S Bond Formation 6.4. Arylation of Other Heteroatoms 6.4.1. Arylation of Organoboron Compounds 6.4.2. Arylation of Organosilicon Compounds 6.4.3. Arylation of Organophosphorus Compounds 7. Conclusions Associated Content Special Issue Paper Author Information Corresponding Author ORCID Notes Biographies Acknowledgments Abbreviations References

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as a niche technology and is now evolving to a key technology for sustainable processes.

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2. PREPARATIVE ASPECTS OF ELECTROORGANIC SYNTHESIS This section aims to provide some general information on preparative aspects of synthetic electroconversion being used for the electrochemical arylation reaction: Briefly introducing fundamental principles and considering them in the choice of an appropriate cell design. The most common cell setups, preparative challenges, and viable solutions are outlined.8 Preparative electrochemical conversions can be carried out in two different modes of electrolysis: (1) galvanostatic mode, i.e., applying a constant current density; (2) potentiostatic mode, i.e., maintaining a constant potential at the working electrode throughout the electrolysis. While potentiostatic operation of electrolysis offers maximum selectivity and enables the conversion of specific compounds by applying an electrode potential equal to the redox potential of the substrate of interest, the instrumental setup in potentiostatic mode is more sophisticated compared to galvanostatic electrolysis.9 In galvanostatic mode, the electrode potential adjusts automatically to the species with the least positive oxidation potential (anode) or the species with the least negative oxidation potential (cathode). Although the selectivity of the electrolytic conversion can be hampered using this simple two-electrode setup compared to the three-electrode setup in potentiostatic mode, full substrate conversion usually is achieved faster, because the current density, which in a first approximation is a degree of conversion rate, stays constant throughout the electrolysis. Furthermore, the constant potential approach requires the use of an additional reference electrode and a much more costly electronic periphery. It is noteworthy that the applied voltage is usually much larger than the potential applied to a working electrode. However, the applied voltage represents the data for energy-efficiency considerations of the whole electrolysis, whereas the potential data serve for mechanistic rationals. The electrode arrangement determines the electric field distribution in the electrolysis cell, thereby affecting current density and selectivity. In the coplanar electrode arrangement or a concentric design of electrodes a homogeneous field is provided, which is highly desired. However, the backsides of the electrodes contribute negligibly to synthesis. Generally, the current density between the electrodes is proportional to the density of field lines in the electric field. Therefore, a smaller electric field also induces a lower potential, eventually leading to areas without electroconversion. Furthermore, uneven potential distributions on the electrode surfaces are associated with fluctuations in the current density. Rough electrode surfaces provide higher currents at the peaks, which thus constitute electrochemical hotspots. An inhomogeneous electric field lowers the selectivity of the conversion. Angular electrode configurations should be avoided in electrosynthesis, due to the unbeneficial distribution of the electric field lowering the effective electrode surface area available for conversions.

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1. INTRODUCTION Structural features with aryl moieties occupy an outstandingly important role in modern organic chemistry. The syntheses of these moieties are crucial for synthesis of complex, nonsymmetric structures and therefore contributes to a majority of contemporary areas like material science, biochemistry, and nanotechnology.1−3 Usually, such entities can be synthesized by transition-metal catalysis in combination with prefunctionalized aryls or by application of chemical redox reagents to activate C,H or C,X bonds. All of these approaches give rise to a significant amount of toxic reagent waste or often lack selective bond formation. Consequently, such coupling reactions require leaving functionalities and complex catalysts based on toxic transition metals, such as palladium, nickel, or cobalt. However, electroorganic synthesis is an attractive technique with huge synthetic potential. Therefore, the most striking advantage of electrochemical reactions over conventional chemical processes is the restriction or avoidance of reagent waste. This can be considered as a major diving force why electrosynthesis is currently gaining significant attention.4 Besides typical oxidative or reductive transformations, electrochemical methods can be used as a mild technique and offer a much broader scope of reactivity.5 A number of different methods have been developed to combine common coupling reactions with electrochemical synthesis or to carry out metal- and reagent-free electrochemical coupling reactions.6 In addition to the beneficial environmental aspects, electrosynthetic conversions are driven by the electric field and current applied. Therefore, run-away reactions are not possible, and this technology is considered inherently safe.7 This is of particular interest when dealing with oxidative conversions. The individual sections of the survey are therefore structured into several subsections. Thereby, the first section will deal with anodic electrochemical conversions, whereas the second part deals with cathodic conversions. The individual sections will cover methods that use two leaving functionalities to those following procedures with a modern, atom-economic 2-fold C,H bond activation. In all schemes, the newly formed bonds are indicated in blue. Besides the electrosynthetic application, novel concepts in this area such as cation-pool method and solventdirected cross coupling will be outlined. This review will provide an almost complete and current survey about the electrochemical arylation reaction which was considered for a long time

2.1. Choosing the Appropriate Cell Design

Figure 1 depicts the factors influencing which cell type and mode of operation are appropriate for a specific electrolysis. In general, simple cell designs such as undivided cells (see Figure 2B) are strongly preferred in order to minimize the laboratory effort. However, the reversibility of anodic or 6707


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Scheme 1. Products of Electrochemical Arylation Reactions Have an Extended π-System and Thus Are Prone to Overconversion, Often More Easily than the Starting Material

removed from the solution by sedimentation as a solid, preventing it from being further oxidized at the anode. The significantly lower solubility shifts the electrochemical potential of the product. Electrolyte engineering may help to a certain extent to achieve the precipitation of the product by carefully choosing solvent polarity and mixtures. In flow electrochemistry, the residence time of products can be adjusted in the continuous process, limiting the time for side reactions. So-called quasidivided cells make use of a conversion of solvent molecules at a strongly underdimensioned counter electrode, which is due to a statistical preference for their conversion compared to reaction products or intermediates induced by a strong increase of electrode potential. This conversion of solvent molecules can also be synthetically exploited.13 Finally, sacrificial anodes can be employed to avoid product oxidation and compensate for cathodically formed anions. Mostly Mg, Al, and Zn electrodes are used as sacrificial anodes, which clearly hampers sustainability of this kind of electrochemical setup. Sacrificial electrodes do not represent the green character of electroconversions and are only a viable option for small lab scale.

Figure 1. Influencing factors for the choice of the appropriate cell design.

cathodic transformations at the respective counter electrodes limits the applicability of these simple setups. When substrate, product, or intermediate molecules are not stable toward the “counter half-cell”, i.e., the polarized counter electrode, separator materials have to be introduced into the electrochemical cell, spatially dividing the anolyte and catholyte compartments (see Figure 2A). It should be noted that separators cause a significant voltage drop within the cell. Aside from separator materials for high-temperature applications, which will go beyond the scope of this review, two classes of materials are mainly used: (1) nonfunctionalized glass, ceramic, or polymer (PE, PP) materials, which offer a good take up of electrolyte and a good chemical resistance but suffer from scalability (glass, ceramic) or high voltage drops (polymers); (2) functionalized polymers such as Nafion, with increased conductivity of membranes due to ionic groups and ionselective transfer capabilities. In conclusion, the parameters for the choice of the appropriate cell design are the stability of electrolysis components toward the “counter half-cell” and the selectivity of the electron transfer at the working electrode, as depicted in Figure 1.

2.3. Scale up of Preparative Electrosynthesis

Scaling up electrosynthetic conversions imposes several practical issues including engineering efforts in order to maintain a safe mode of operation, corrosion of electrode contacts, and difficulties in controlling current density and potentials.

2.2. Preparative Challenges in Electrochemical Arylation

Scheme 1 outlines the most prominent preparative issue of electrochemical arylation reactions. Upon the first coupling reaction, the resulting arylated arene inherently exhibits an extended π-system, which is easier to oxidize than the initial substrate. Therefore, strategies to avoid overoxidation of the product need to be exploited. Such strategies include precipitation of the product, flow electrochemistry, quasidivided cells, and sacrificial anodes. The lucky case to avoid side reactions such as overoxidation is the precipitation of the product. In this case, the product is

Figure 3. Schematic drawing of a bipolar electrode stack.

Figure 2. Schematic pictures of different electrochemical cell designs: (A) divided cell, “H-cell”,10 (B) undivided cell,11 and (C) undivided cell with a bipolar electrode stack.12 6708


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Scheme 2. Product Diversity of the Anodic Treatment of 2,4-Dimethylphenol24,25

borates,11 as well as in a direct electrochemical manner using 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) as solvent at borondoped diamond (BDD) anodes (see section 5).26 Nevertheless, the formation of byproducts is still challenging. Under acidic conditions, the formation of quinol (5) or quinone ethers (6) is the major pathway. The group of Ronlán conducted the electrochemical conversion using lead dioxide anodes in diluted sulfuric acid.27 Applying these conditions, the reaction results in the formation of the para-hydroxylated product 5 in yields of 44%. Yields of the corresponding 2,2′-biphenol 4 were rather

Therefore, bipolar setups are preferred over monopolar arrangements of parallel, serial, or stacked electrode cells. On the lab scale, bipolar designs (see Figures 2C and 3) offer a uniform distribution of potential and current density between the electrode plates, without the need to contact each of them individually, whereby the electrode material serves as cathode and anode. This way, the corrosion of electrode contacts is minimized. On the industrial scale, a prominent example for a successful scale up is the combination of a bipolar design with flow electrolysis used in so-called “paired electrosynthesis” utilizing both anode and cathode reactions for the production of added-value products as developed by BASF scientists. Flow electrolysis cells offer the possibility of fast scale up by simply increasing the number of cells or scaling the respective electrolysis parameters, i.e., electrode surface, flow rate, and current density.

Scheme 3. Anodic Conversion of 2,4-Dimethylphenol Using Acidic Conditions27

3. CHALLENGES: FORMATION OF OLIGOMERS, POLYMERS, AND POLYCYCLES LEADING TO DIVERSITY The appearance of 2,2′-biphenols in natural products,14 pharmaceuticals,15 agrochemicals,16 as well as ligand systems17−23 makes such compounds to structural motifs of high significance. However, the application of simple methylsubstituted phenols as substrates for the oxidative 2,2′-biphenol synthesis often suffers from the formation of byproducts, oligomers, and even polymers. In particular, 2,4-dimethylphenol 3 as substrate for electrochemical coupling reactions gained significant attention. This phenol allows the formation of a broad scope of coupling products upon anodic treatment (Scheme 2),24,25 whereby the product distribution can be controlled by the choice of the respective electrolytic conditions. However, the 2,2′-biphenol derivative 4 is selectively accessible with a template-directed method via tetraphenoxy

low with about 18% (Scheme 3). Using phenols with no substituent in position 4 of the phenol, the 1,4-quinone is exclusively formed. In contrast, basic conditions yield a derivative of the Pummerer ketone 7.25 This tricyclic structure is part of different natural products, like calycopterones28 or as reduced form in lunarin.29 Miller et al. also reported that an anodic treatment of p-cresols leads to formation of these ketone in yields up to 37% (Scheme 4).30 The reaction is conducted with a carbon anode in acetonitrile. The authors anticipate that formation of the final product can be explained by a prior ortho−para coupling 6709


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Scheme 4. Synthesis of Pummerer’s Ketone Derivatives by Anodic Coupling of Cresols30

Scheme 5. Synthesis of Pentacyclic Derivatives by Anodic Conversion of 2,4-Dimethylphenol25

Scheme 6. Improved Protocol for Electrosynthesis of Spiropentacyclic Scaffolds Starting from 2,4-Dimethylphenol 331

during electrolysis isolation is very easy to conduct, allowing one to obtain this scaffold in multigram scale by simple filtration of the electrolyte. By thermal or acidic treatment abstraction of one 2,4-dimethylphenol moiety is induced, leading to stereospecific rearrangement that leads to the formation of the desired spiropentacyclic lactone 8 in yields up to 75%. This dehydrotetramer 16 is a key intermediate that allows a high variety of follow-up reactions, for example, installing protecting groups,32 synthesis of propellanes,33 substitution reactions for the installation of amines34 or thiophenoxy moieties,32 elimination reactions,32 and many more (Scheme 7). Noteworthy is the synthesis of dioxa[4.3.3]propellanes. Via the electrochemical pathway, it is possible to construct such complex scaffolds only in two steps.33 After the preliminary anodic synthesis of the dehydrotetramer 16, it is treated with BF4·OEt2 as Lewis acid at low temperatures (Scheme 8). First, the cleavage of the 2,4-dimethylphenoxy moiety leads to a

reaction followed by a subsequent 1,4-addition. The described ortho−para coupling can be explained by a preceding formation of the corresponding phenoxides of the cresols due to the addition of sodium hydroxide. The anodic oxidation of 2,4-dimethylphenol 3 in an electrolyte consisting of Ba(OH)2·8 H2O in methanol promotes the formation of pentacyclic scaffolds (Scheme 5). With a yield of 18%, the spiro lactone 8 is the main pentacyclic product upon workup, whereas compound 9 is obtained in 5% and the benzodioxazole derivatives 10 and 11 in 2% each.25 In addition, the Pummerer ketone derivative 7 and the biphenol 4 are byproducts of this conversion as well. A reinvestigation of the formation and optimization of the protocol for the synthesis of such spiropentacyclic scaffolds revealed an exclusive formation of the corresponding dehydrotetramer 9 of 2,4-dimethylphenol (4) in yields up to 52% (Scheme 6).31 Due to the precipitation of the product 6710


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Scheme 7. Selection of Potential Follow-up Reactions of the Electrochemically Generated Dehydrotetramer 16 of 2,4Dimethylphenol 332−34

Scheme 8. Synthesis of Dioxa[4.3.3]propellanes with Dehydrotetramer 16 as Key Intermediate33

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Scheme 9. Substitution at the Dehydrotetramer 16 by Optically Pure Amines34

stereo- and regioselective generation of a carbocation. Because of the low temperature of −78 °C this cation is stabilized and does not undergo a Wagner−Meerwein rearrangement. Subsequently, a stereoselective Friedel−Crafts-type alkylation takes place between the carbocation and the just liberated 2,4dimethylphenol molecule. Besides, the reaction has a favored diastereoselectivity toward an attack from the Re side. This is due to less steric hindrance as well as stabilization and precoordination via hydrogen bonding. Finally, a BF3-promoted condensation step generates the propellane. By adding different phenols with a higher nucleophilicity than 2,4-dimethylphenol, different dioxa[4.3.3]propellanes are accessible. In a similar fashion, the 2,4-dimethylphenoxy moiety of the dehydrotetramer 16 can be substituted by optically pure α-chiral primary amines (Scheme 9).34 Here, CsF serves as base, which deprotonates the free hydroxyl functionality of 16. This promotes the opening of the hemicetal, which generates an α,β-unsaturated ketone. A subsequent liberation of 2,4dimethylphenolat leads to an o-quinone methide. In the presence of a primary amine as nucleophile a 1,4-addition followed by protonation accomplishes the desired substitution product. The product appears either in a keto or in a hemiketal form, which are both in equilibrium. In contrast to the ketal form, the hemiketal form is more flexible. Therefore, it is the preferred form in the solid state. In solution, the product appears

most likely in the ketal form. In addition, the product is obtained in a mixture of diastereomers. With the elaborated protocol eight different primary amines were converted in overall yields of 67− 84%. Individually, the yields of the diastereomers range from 33% to 44%.

4. ARYL−ARYL BOND FORMATION 4.1. Anodic Conversion

4.1.1. Substrates with Two Leaving Functionalities. In order to achieve specific reactivity for the coupling of biaryls, both coupling components are equipped with sacrificial functionalities. Consequently, for this conversion two leaving functionalities are required, leading to a nucleophilic carbon position. Typical substrates are arylboronic acids, arylboronates, or aryltrifluoroborates. To ensure the C,C coupling reaction of these compounds, employment of palladium catalysts is essential as well. Corresponding work was published by Amatore, Tanaka, and others.35−37 For example, in one electrooxidative method by Amatore et al. an anaerobic protocol using Pd(II) species as catalyst was developed.35 It is used with a catalytic amount of p-benzoquinone serving as ligand for Pd(0) as well as redox catalyst for the Pd(0) species, which is generated in situ. p-Hydroquinone is then oxidized at the anode back to pbenzoquinone, as shown in Scheme 10. As already mentioned, 6712


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region and chemoselectivity within these conversions, can be avoided. Therefore, activation of C,H bonds is necessary. Additionally, the preparation of coupling partners, e.g., introduction of these leaving groups in multistep synthesis, can be circumvented. Therefore, this and the next section will focus on a selection of published work, summarizing different strategies to achieve selective C,H activating coupling reactions of arenes. In a very elegant protocol from Kakiuchi and co-workers the electrochemical C,H iodination with a subsequent arylation of arylpyridines is reported.38 Electrochemical iodination and subsequent arylation via Suzuki coupling are conducted in a onepot synthesis. The concourse of these two reactions is controlled by switching on and off the electric current. Thus, the palladium

Scheme 10. Oxidative Coupling of Arylboronic Acids by Electrooxidative Regeneration of Palladium(II) Species Using p-Benzoqinone35

Scheme 12. Electrochemical C,H Iodination and One-Pot Arylation by Switching on and off Electric Current38

the central disadvantage of this approach is low atom economy and the sophisticated preparation of substrates with conventional methods. Instead of p-benzoquinone the use of TEMPO as organic mediators was successfully applied as well.36,37 When using p-benzoquinone as mediating system constant potential electrolytic conditions (+ 0.75 V) using a carbon cloth anode and a saturated calomel reference electrode were applied35 whereas for TEMPO constant current conditions with low current densities (3.3 mA/cm2) at platinum electrodes were employed.36,37 In both protocols the desired homocoupling products can be obtained in good yields with electronwithdrawing and electron-releasing substituents. The electrolyses have to be carried out in divided cells under exclusion of oxygen. Suitable solvents are water or water/organic solvent Scheme 11. Selection of Biaryls, Synthesized by Electrooxidative Coupling of Arylboronic Acids35−37

catalyst can enter two different catalytic cycles for each reaction, as demonstrated in Scheme 12. The authors were able to demonstrate a broad scope of various aryl groups at the ortho position of arylpyridines. 4.1.3. Substrates without Leaving Functionality. The application of electrochemical synthesis generally opens the field for the development of sustainable processes, as chemical redox reagents can be directly replaced by electric current. To prevent formation of chemical waste throughout coupling reactions, activation of C,H bonds is favorable, as no leaving groups are needed. Additionally, the preparation of coupling partners, e.g., installation of these leaving moieties in multistep sequences, can

mixtures. An overview of isolated products is shown in Scheme 11. 4.1.2. Substrates with One Leaving Functionality. As already indicated, electroorganic chemistry allows one to develop green and sustainable syntheses of well-defined molecular frameworks. This is even more the case if the use of prefunctionalized aryl moieties, which ensure the required 6713


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Scheme 13. Potential Product Portfolio for Oxidative C,H Cross Coupling upon Nonselective Oxidation

Scheme 14. C,H-Activating Anodic Coupling of Aryl Pyridines45

be circumvented. Therefore, modern C,H activating electrochemical coupling reactions are high standard to develop green synthetic processes.39,40 One strategy to accomplish that is the 2fold C,H activation for biaryl formation by anodic treatment of starting materials. The research of such transformations started in the late 20th century.41−44 A major challenge for the cross-coupling reaction two aryls without any leaving groups is the selective synthesis of nonsymmetrical products and avoidance of diverse product mixtures due to unselective oxidation processes, decomposition of oxidized intermediates, and their high tendency to undergo subsequent reactions. Besides homocoupling, direct oxidative C,H/C,H cross coupling of two different arenes is a challenging task as selective oxidation of one coupling partner has to occur. However, in most cases the more electron-rich substrate is often the most nucleophilic component, leading to preferential homocoupling products. Otherwise, statistical formation of homo- and cross-coupling products will take place upon nonselective oxidation processes. This will, in the best case, lead to moderate yields of the desired cross-coupling products. Additionally, due to the extended π-system, overoxidation of the obtained biaryls will lower the overall yield and form oligomeric side products (see Scheme 13). One key to control the reaction pathways is the consideration of oxidation potentials of components involved: The oxidation potentials of starting materials should be lower compared to those of the final products, which is usually not easy to achieve. Therefore, this

section of the review will focus on protocols that achieve selective C,H activating coupling reactions of arenes. Kakiuchi et al. reported a regioselective homocoupling of arylpyridines using anodic oxidation conditions in 2014.45 The electrolysis is carried out in a divided cell with platinum electrodes at a constant current of 20 mA (5.9 mA/cm2). To accomplish the conversion, 10 mol % of Pd(OAc)2 is used within the anodic compartment. In addition, iodine is necessary as redox mediator. Thereby, a broad scope for homocoupling was achieved and occurred at the sterically less hindered ortho position of the arene component due to directed metalation reaction. The regeneration of the catalyst is realized at a platinum anode, Scheme 14. The following examples are dealing with the selective electrochemical formation of 2,2′-biphenols. The challenges coming up when it comes to the coupling phenols have already been described in detail in section 3. In order to obtain the desired 2,2′-biphenol instead of undesired polycyclic compounds a first improved protocol was published in 2006 reporting a chemoselective ortho-coupling reaction of 2,4-dimethylphenol. Key for the described selective coupling reaction was the utilization of boron-doped diamond electrodes instead of platinum. Isolation of the product was possible in yields up to 56%. Adjacent protocols report a broadened scope of symmetric biphenols with yields up to 74% (see Scheme 15). Electrolyses were conducted using a borondoped diamond anode and a nickel cathode in an undivided cell.26 6714


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Torii and co-workers especially investigated the electrooxidative coupling of 2,6-disubstituted phenols, which rather tend to form quinoide dehydrodimers.48 The group was able to apply suitable conditions for a selective coupling of 2,6-di-tertbutylphenol to the corresponding 4,4′-biphenols in yields up to 94%. Key for a defined synthesis of this compounds was the conduction of electrolysis with low voltages with polarity reversals in a divided cell. Iguchi et al. reported the anodic oxidation of 4-allyl-2methoxyphenols as guaiacol derivatives in quantitative yields by using basic conditions (see Scheme 18).49 When instead using isoeugenol as guaiacol derivative in an anodic conversion the corresponding diisoeugenol can be isolated in yields up to 57%.50 Thereby, the diastereoisomer α-diisoeugenol is formed exclusively (see Scheme 19). This high stereoselectivity can be rationalized by a radical chain mechanism, where the initially formed radical intermediate faces a molecular orientation within the HFIP solvate cage. In addition, Johnston reported the coupling of hydroxyacetophenones in yields up to 52%51 and Pearl et al. the selective ortho-coupling of vanilin in yields up to 65%.52 Now, the next few described reactions focus on the electrochemical homocoupling reactions of arenes bearing hydroxyl groups at the aromatic compound. Here, one of the most powerful classes of reagents for the dehydrogenative coupling of aryls is represented by Mo(V) reagents.53−59 However, they have to be used in a stoichiometric manner which is not sustainable. When using molybdenum as an anode in HFIP a compact, conductive, and electroactive layer of higher valent molybdenum species is formed (see Scheme 20). This active anode system can replace Mo(V) reagents for the dehydrogenative coupling of aryls.60 The performance of the reported electrolytic protocol is higher and more environmentally friendly since almost no molybdenum is lost. In contrast to MoCl5, it can be also applied to substrates with nonprotected carboxylic acids.61 Therefore, a broad scope of coupling products based on anisoles and veratrols was presented. Furthermore, by anodic cyclization various rings can be formed including phenanthrenes (Scheme 21). First investigations dealing with the electrochemical coupling of similar electron-rich di- and trimethoxybenzenes already started early in the 1930s.62 Erdtman started to study the formation of complex oxidation and condensation products of phenols. It turned out that upon anodic treatment of 1,2,3trimethoxybenzene the corresponding 2,6-dimethoxybenzene is formed exclusively, whereas when using 1,2,4-trimethoxyben-

Scheme 15. Ortho-Selective Phenol-Coupling Reaction by Anodic Treatment26

An advanced protocol was in addition published in 2011 reporting improved yields and a broadened scope, making coupling of electron-rich and halogenated phenols possible.12 Key for this is a different electrolyte system based on trifluoroacetic acid instead of HFIP. In addition, instead of BDD anodes, less expensive graphite electrodes can be applied (see Scheme 16). Upon transferring this protocol to coupling of guaiacol derivatives with similar electrochemical conditions, not only the formation of symmetrical homocoupling products were observed, but also the corresponding ortho/meta-coupled product (see Scheme 17).46 The concourse of the electrochemical conversion is dependent on the steric demand of the substituent in position 4 of the phenol. These unexpected results indicated that the key step to frameworks like these cannot just consist of simple radical recombination. Otherwise, only the formation of symmetrical biphenols would have been observed. Thus, the mechanism has to be more complex consisting of an oxidation step of the phenol, subsequent nucleophilic attack of the second phenol, and an anodic termination step. The postulation of this mechanistic rationale, which will be presented in more detail on the following pages, allowed us to apply these electrochemical protocols for anodic cross-coupling reactions as well. Coupling of Schiff bases as guaiacol derivatives that are synthesized from o-vanillin, a selective coupling to the dehydrodimers can be observed in yields up to 100%.47 The electroylses were performed using glassy carbon anodes and sodium perchlorate in acetonitrile as electrolyte. Scheme 16. Broadened Scope of Homocoupled Phenols12

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Scheme 17. Anodic Coupling of Guaiacol Derivatives on Boron-Doped Diamond Electrodes46

Scheme 18. Electrochemical Coupling of 4-Allyl-2methoxyphenols49

Scheme 21. Dehydrogenative Coupling Using Active Molybdenum Electrodes60

Scheme 19. Anodic Coupling Isoeugenol50

Scheme 20. Electrocatalytic Dehydrogenative Coupling Reactions Using Molybdenum Anode60

Scheme 22. Anodic Conversion of Trimethoxybenzenes62

zene, the reaction results in formation of the dehydrodimer in yields up to 85% (see Scheme 22). On the basis of these studies Parker et al. investigated the anodic oxidation of differently substituted anisoles aiming on the formation of the corresponding biphenyls.63 It turned out that when using an electrolyte system based on dichloromethane and trifluoroacetic acid (2:1) the best results were achieved (see Scheme 23). The authors clearly demonstrated by cyclovoltametric measurements that the formed products exhibit lower oxidation potentials than the applied substrates. There-

fore, the reaction is carried out with low conversions in order to avoid any overoxidation reactions. In addition, they conclude 6716


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reaction with high yields and a broader scope, which so far delivered only low yields for the desired triphenylenketals (see Scheme 25).67 This optimization was accomplished by using an undivided cell and using a mixture of propylene carbonate and Me4NBF4 as supporting electrolyte. Overoxidation of the final product can be avoided due to the poor solubility in the reported electrolyte. This can be rationalized by the decreased concentration of the final product in the crude electrolysis mixture. According to the Nernst equation the oxidation potentials should be therefore increased (Eox = 1.70 V). Thus, the product can be obtained in yields up to 80% and in good purity. The precipitate thereby floats as very fine particles in the cell. A blocking of the platinum surfaces was not overserved. After electrolysis the authors reported an entire acid-catalyzed cleavage of the ketals yielding the corresponding 2,3,4,7,10,11hexahydroxytriphenylenes. Another remarkable example for an anodic C,H activating homocoupling was published by Osa and co-workers in 1994.68 The authors describe a protocol for the enantioselective anodic coupling of 2-naphthol, 2-methoxynaphthalene, and 10hydroxyphenanthrene at a TEMPO-modified graphite felt anode. The use of equimolar amounts of an enantiomeric pure base, e.g., (−)-sparteine, in combination with the TEMPO-

Scheme 23. Anodic Coupling Anisoles to 4,4′Dimethoxybiphenyls63

that trifluoroacetic acid has a stabilizing influence on the generated radical cations. Scheme 24. Anodic Oxidation of Veratrol Leading to Hexamethoxytriphenylens64

Scheme 26. Enantioselective Anodic Homocoupling of Arenes at TEMPO-Modified Graphite Felt Electrodes68

Thus, the group of Parker was also able to report the first synthesis of triphenylene cations by anodic oxidation of veratrols (see Scheme 24).64 The group of Waldvogel and co-workers developed several electrochemical protocols for the synthesis of these triphenylene ketals. These frameworks are important structures that can be used as novel sensors, e.g., artificial receptors for alkylated oxopurines such as caffeine.55 Waldvogel and co-workers reported a first improved protocol in 2000 enabling the synthesis of these compounds in up to 20 g batches. In this conversion several catechol derivatives were applied leading to high yields up to 62% of the corresponding triphenylenes.65 In 2005 an improved workup procedure was applied and molecular structures and available space for molecular recognition were investigated and discussed.66 Finally, in 2012 the authors were able to optimize electrochemical protocols for this trimerization

modified graphite electrode (24 μmol/cm−3) enables a possible pathway to biaryls in high yields with high enantiomeric excess (Scheme 26).

Scheme 25. Anodic Coupling of Catechols to Triphenylene Ketals67

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Scheme 27. Synthesis of Nonsymmetrical Biaryls by Direct Oxidative Coupling41

Scheme 28. Radical−Cation Pool Method by Yoshida et al.69

Electrolysis was carried out under argon atmosphere and with potential control. The authors also compared the electrochemical formation of 1,1′-binaphthol in the presence of (−)-sparteine at conventional graphite felt and report the TEMPO-modified electrode as a crucial part for this enantioselective oxidative coupling. The first selective electrochemical cross-coupling reactions were reported by Nyberg et al. at the beginning of the 1970s (Scheme 27).41 The coupling of an equimolar amount of naphthalene and pentamethylbenzene yielded the desired cross-coupling products in a yield of 64% when using an undivided cell and a potentiostatic setup. Only 1.6% of the homocoupling product was obtained. The authors explained this extraordinary selectivity of this cross-coupling reaction with differences in oxidation potentials and basicity of involved coupling partners. However, since only similar arenes without prior determination of oxidation potentials by cyclovoltametry measurements for the cross coupling with naphthalenes were applied, no reliable prediction of the concourse of other electrolyses can be stated. Therefore, the selectivity of this early work can be attributed to the significantly lower nucleophilicity of pentamethylbenzene and the steric congestion of the final product. The group of Yoshida et al. accomplished improving the cross-coupling

reaction of naphthalene and pentamethylbenzene which has already been reported by Nyberg by employing an extremely elegant way. Due to the anodic oxidation of naphthalene at low temperatures, the radical cation obtained is stabilized sufficiently long enough so that it can be converted with pentamethylbenzene in a second step (see Scheme 28). The second coupling partner is subsequently added to these reactive intermediates, and the mixture is warmed to room temperature. Due to separation in time and space of the electrochemical oxidation and the coupling event, selective formation of cross-coupling products can be achieved and overoxidation is avoided. The socalled “radical−cation pool” method enables the formation of nonsymmetric biaryls by electrochemical oxidation and ensures an exclusive selectivity of formed biaryls.69 The yield of the reaction is very high with 91%. Furthermore, the two-stage reaction control allows a large number of different substrates for the cross-coupling reaction. Substituents such as halogens, esters, and heteroaryls are tolerated, and the products can be isolated in good to excellent yields. As already indicated, also the group of Waldvogel and coworkers intensively studied the selective cross coupling of arylic compounds. Besides the reported homocoupling reactions also cross-coupling reactions can be accomplished, which was 6718


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Scheme 29. Mechanistic Rationale for the Anodic Aryl−Aryl Coupling Reaction of Phenols with Arenes70

Scheme 30. Source of Selectivity in Anodic Cross-Coupling Reactions of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan2-ol78,79

observed when trying to synthesize biphenols based on guaiacol derivatives. Actually a selective and symmetric coupling ortho to

the phenolic hydroxy group was anticipated, generating a phenoxyl radical stabilized in the ortho position followed by a 6719


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Scheme 31. Anodic C,C Cross-Coupling Reaction of Phenols with Arenes78

electron-rich arenes are cross coupled with phenols. Also, solvates of phenols with different electronic properties differ in their solvate densities: the more electron rich the phenol, the denser the sphere of surrounding solvent should be and, therefore, the less nucleophilic the substrate. Making use of this effect, the yield and selectivity of synthesized cross-coupling products can be increased in many cases by simple addition of water or methanol.78 Besides the nonsymmetric guaicaol derivatives, further investigations for the coupling of phenols with arenes were successfully conducted. Thereby, the direct coupling of phenols with substituted arenes in acceptable yields up to of 69% and partly very good selectivities under mild conditions in an undivided cell was accomplished (Scheme 31).78 Thereafter, the first synthesis of nonsymmetric 2,2′-biphenols using this anodic conversion was published.80 Thereby, a broad scope of phenols and naphthols was employed. An improvement of these protocols with regard to yields and selectivity was achieved by the use of a O-silyl-protected phenol as one coupling

subsequent radical combination. However, the reactions mainly provided the ortho/meta-coupled product. Correspondingly, the following mechanistic rationale was reported (Scheme 29).46,70 The pathway for the cross coupling starts with the anodic generation of a phenoxyl radical I which still represents an electrophile. This open-shell species will experience a nucleophilic attack by an electron-rich coupling component. The intermediates II and III can be oxidized directly or indirectly at the anode to furnish the desired product upon extrusion of a proton. The coupling reaction occurs at the most prone positions for electrophilic conversion. Thus far, this reaction pathway pointed the strategy for a novel anodic crosscoupling reaction exploiting an oxyl spin-center formation, electrophilic arylation, and subsequent anodic termination. BDD has proven to be a very powerful electrode material, since it is chemically inert and can be produced sustainably.71−73 The corresponding source of this selectivity arises from the use of 1,1,1,3,3,3-hexafluoropropan-2-ol as a unique solvent. It is capable of dramatically stabilizing the resulting radicals and being electrochemically stable at the same time.74−77 In addition, solvation by HFIP not only stabilizes reactive intermediates, like radicals and radical−cations to enable a selective reaction in the bulk, but also gives rise to a decoupling of nucleophilicity from the oxidation potential due to a different solvation pattern of the coupling partners making cross coupling possible (Scheme 30).78,79 This can be explained when taking into consideration that in polar solvents solvates of phenols are more pronounced than those of arenes, due to the ability of phenols to participate in hydrogen bonding. Therefore, especially electron-rich phenols are strongly shielded in pure HFIP, which prevents nucleophilic attack on the generated radical cations of the arene. In general, the more electron-rich substrate is therefore selectively oxidized and undergoes undesired homocoupling reactions. The problem is that the electron density (and therefore nucleophilicities) of the individual substrates determines the outcome of the reaction. That means that the oxidation potential and nucleophilicity are directly linked to each other, because the same compounds will enter the reaction sequence for a subsequent nucleophilic attack. Methanol additives act like bases when added to a solution of HFIP. It therefore not only weakens the solvate with phenols but also facilitates deprotonation of phenol by interacting via hydrogen bonding. This results in some cases in a shift of oxidation potentials creating suitable systems and matching pairs for selective anodic cross couplings. In general, shifting of oxidation potential by methanol does not occur when less

Scheme 32. General Overview over Synthesis of 2,2′Biphenols Using Anodic C,C Cross-Coupling Reaction80,81

partner (Scheme 32).81 Another valuable advantage is the fact that extremely electron-rich phenols, which were previously very challenging substrates for the electrochemical cross-coupling reaction, can be converted in the anodic C,C cross-coupling reaction. Because of their high nucleophilicity and therefore low oxidation potentials, these substrates rather tended to homocoupling reactions or mostly to uncontrolled polymerization upon electrolysis. In addition, after coupling the phenol 6720


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Scheme 33. Anodic C,C Cross-Coupling Reaction to Symmetric and Nonsymmetric m-Terphenyl-2,2″-diols83

Scheme 34. Direct Anodic C,C Cross Coupling of Protected Aniline Derivativesa84

a

PG = protective group.

selective cross-coupling reaction employing a different phenol to yield the nonsymmetric target molecule. Besides the coupling reactions of phenols and arenes also the syntheses of cross-coupling products of anilines, thiophenes, and benzofurans were conducted. Anodic treatment of substrates like these usually result in the formation of oligomeric byproducts and uncontrolled polymerization reactions. The reason for that is that especially anilines exhibit low oxidation potentials and are therefore prone to overoxidation. In addition, the solvation of HFIP is very low. With regard to the anilines, both problems can be circumvented with protecting groups based on amides and carbamates. Thereby, the oxidation potentials of anilines can be adjusted to some extent. Furthermore, the amide functional group is able to participate

moiety allows a direct selective modification, whereas the protected moiety allows modification upon deprotection. The yields for this electrochemical conversion were comparable to those obtained by conventional synthesis using metal salts and large amounts of terminal oxidizers.82 In addition, a 2-fold dehydrogenative cross-coupling reaction of a central arene moiety with two phenols leads to symmetric and nonsymmetric m-terphenyl-2,2″-diols (see Scheme 33).83 Symmetric derivatives can be directly obtained by one-pot electrolysis. For nonsymmetric derivatives a phenol−arene is initially synthesized by anodic cross coupling and then isolated. Subsequently, a protecting group is installed to generate an intermediate. This intermediate is then used for a second 6721


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Scheme 35. One- and Two-Fold Metal- and Reagent-Free Anodic C,C Cross Coupling of Phenols with Thiophenes85

Scheme 36. Anodic C,C Cross Coupling of Naphthylamines with Phenols and Naphthols86

Scheme 37. Anodic C,C Cross-Coupling Reaction of Benzofurans with Phenols with a Subsequent Furan Metathesis87

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Scheme 38. Scope for the Electrochemical C,C Cross Coupling at High Current Densitya

a Reactions were carried out with a current density of 35 mA/cm2. For comparison, product yields for electrochemical cross coupling at lower current density from 2.8 to 7.2 mA/cm2 are given in parentheses.88

Scheme 39. Electrochemical Synthesis of Benzofuroindolines89

access to two substance classes of great interest by using thiophene as cross-coupling partner. The successful synthesis of 2-(2′-hydroxyphenyl)thiophenes by 2-fold electrochemical C,H activation and 2,5-bis(2′-hydroxyphenyl)thiophenes by a simple adjustment of electrolysis parameters and applied equivalents was reported (see Scheme 35). Applying similar electrochemical parameters enables also the cross-coupling reaction of naphthylamines with phenols and naphthols (see Scheme 36).86 When using benzofurans in the anodic cross-coupling reaction upon formation of the C,C bond, a subsequent furan metathesis leads to an unique rearrangement; the more electronrich and sterically congested phenolic component is incorporated into the benzofuran skeleton (see Scheme 37).87 So far, the listed cross-coupling reactions reported by Waldvogel and co-workers were conducted within a current density range of 2.8−7.2 mA/cm2. In addition, literature search

in hydrogen bonding as a donor as well as an acceptor. Therefore, the protected anilines experience strong solvation by HFIP. Cyclovoltametry investigations also revealed again a clear shift of oxidation potentials to lower values with an increasing concentration of methanol in HFIP. Thus, by applying these protecting groups the dehydrogenative cross coupling of aniline derivatives to 2,2′-diaminobiaryls was reported.84 After the cross coupling they can be removed selectively at mild conditions, providing quick and efficient access to these important building blocks (see Scheme 34). When it comes to anodic C,C cross-coupling reactions of phenols with thiophenes, this concept describing water or methanol as the source of selectivity for the coupling reactions reaches the limits of its application. Thiophenes are no longer well solvated by these additives. Accordingly, no beneficial effect using these additives was observed for these coupling reactions.85 The reported anodic coupling reaction enables 6723


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Scheme 40. Electrochemical Synthesis of the Precursor for DZ-2384 in Multigram Scale by Anodic Macrocyclization90

reveals that most electroorganic transformations are limited to a low current density of 0.5−5 mA/cm2 or less and can only be operated in a small current density window if decreasing yields or selectivities shall be avoided. A few examples can be found that can be operated at high current densities of ≥20 mA/cm2. Waldvogel’s electrolysis instead shows a unique high stability toward variation in current density. It can be operated in a very wide current density range of more than 2 orders of magnitude while maintaining productivity and selectivity. The electrolysis can be conducted in a very short time with a very high current consumption. This was demonstrated for the cross-coupling reactions toward the synthesis of unprotected and partially protected nonsymmetric biphenols and the synthesis of mterphenyl-2,2″-diols (see Scheme 38).88 The electrochemical phenol cross-coupling reaction with indoles was reported by Lei and co-workers. They conducted an electrooxidative [3 + 2] annulation between these two substrates yielding the corresponding benzofuroindolines with up to 99% yield.89 The protocol allows, depending on the substitution pattern of the indole, the synthesis of benzofuro[3,2-b]indolines and benzofuro[2,3-b]indolines (see Scheme 39). For the coupling an acetyl protecting group at the indole moiety is required. This concept can also be applied for the synthesis of natural products. One nice example was presented by Harran and coworkers.90 An anodic intramolecular macrocyclization of a phenol and an indole moiety was carried out to provide a novel pathway to synthesize a diazonamide-based drug (see Scheme 40). The reaction was carried out in multigram scale (up to 60 g of starting material). Constant potential electrolysis in DMF/ H2O with Et4NBF4 as supporting electrolyte produced the macrocycle in 43% yield (based on recovered starting material). In 2015, Atobe et al. reported the anodic C,C cross coupling of two aryls using a parallel laminar flow in a two-inlet flow microreactor (see Scheme 41).91 They were also focusing on the cross coupling of naphthalenes and alkylbenzenes, especially pentamethylbenzene and naphthalene, the product that was also investigated by Yoshida and Nyberg. By this approach the similar concept of separating the oxidation step from the C,C bond formation was pursued, which has already been investigated for the radical−cation pool. Here, a liquid−liquid parallel laminar flow phase is ensured by the utilized microflow reactor.

Scheme 41. Liquid−Liquid Parallel Laminar Flow in an Electrochemical Microflow Reactor for Arene−Arene Cross Coupling91 a

Liquid−liquid interface of the laminar flow emphasized by dashed line. a

Through the first inlet a solution containing naphthalene is delivered into the microflow reactor, whereas the second inlet provides a solution of the coupling partner. Because of the formation of a liquid−liquid laminar flow, the coupling partner will be prevented from oxidation, which enables the selective oxidation of naphthalene at the anode, forming reactive radical cations. Diffusion of the reactive intermediate into the bulk facilitates the formation of cross-coupling products. Although no isolated yields are presented, comparison with a typical batch cell clearly shows the increase of current yield (determined by HPLC) from 49% to 85% when using this technique. 4.1.4. Template-Directed Conversions. A different approach to avoid overoxidation and the formation of polycyclic byproducts was applied by the group of Waldvogel and coworkers.11,92 In this template-directed coupling reaction substituted phenols were anodically coupled to the corresponding 2,2′-biphenols via tetraphenoxy borates (Scheme 42). The borates fulfill two functions: Bringing the positions ortho in close vicinity for oxidative cyclization. In addition, the negative charge makes these substrates more prone for anodic conversion. The sodium tetraphenoxy borate is easily prepared by a two-step synthesis.92 Besides the role as substrate in the electrolytic conversion the borate also serves as supporting electrolyte. The electrolysis can be conducted in an undivided cell. In addition, a current density of 12.5 mA/cm2 was applied at 40 °C; reversal of the polarity every 60 s avoids deposition on the electrodes. However, a disproportion by ligand exchange seemed to be crucial for a yield up to 85%. This can be proven by combined 11B NMR 6724


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with LiClO4 as supporting electrolyte was applied (see Scheme 44). The use of sacrificial magnesium avoids the anodic generation of bromine.

Scheme 42. Two-Step Synthesis of the Boron-Tethered Phenolates92

Scheme 44. Cathodic Coupling Reactions Using Mg Electrodes93

spectroscopic and CV studies. The irreversible oxidation is only viable on the tetraphenoxyborate. The ligand exchange at the boron is also the reason why this particular method cannot be exploited for cross-coupling reactions. This method is scalable to the multikilogram range. The workup is quite simple; treatment with hot water provides the final biaryls (see Scheme 43).

Besides the two isolated biarlys benzylic mono- and dihalides were also coupled successfully using this method. Although the authors describe the protocol as a viable workaround for Ullmann-type reactions, only a limited scope was reported. Similar to anodic conversions, it is also possible to use transition-metal catalysts, e.g., palladium catalysts. Thereby, the electrochemical coupling of prefunctionalized aryls has been reported. So-called electroreductive coupling of aryl halides by direct or mediated cathodic regeneration of the palladium catalyst is one pathway. The catalytic cycle for the reductive coupling of aryl halides is driven by cathodic regeneration of active palladium complexes (see Scheme 45).

4.2. Cathodic Conversion

4.2.1. Substrates with Two Leaving Functionalities. In analogy to anodic conversions the regioselective formation of the desired carbon−carbon bond is the biggest advantage of electrochemical coupling reactions with two prefunctionalized aryls. In general, these approaches lead to an “Umpolung” of at least one coupling partner which represents the electronwithdrawing substituent an initial carbon electrophile. For cathodic conversions the corresponding protocols mainly focus on the use of aryl halides in addition to sacrificial electrodes or transition-metal catalysts. Similar to the anodic conversions these conversions have the drawback of using toxic transitionmetal complexes such as palladium-based catalysts to form the desired aryl−aryl bonds. Additionally, common methods need prefunctionalization of the coupling partners by installation of leaving functionalities. One example depicting the application of sacrificial electrodes for the direct formation of biaryls was reported by Kim and coworkers.93 They described the electroreductive coupling of aromatic halides by using Mg electrodes. For the cathodic conversions a high current density of about 41 mA/cm2 in THF

Scheme 45. Catalytic Cycle for the Cathodic Coupling of Aryl Halides93

Scheme 43. Template-Directed Anodic Phenol-Coupling Reaction Sequence11,92

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Scheme 46. Selection of Biaryls Synthesized by Electroreductive Coupling of the Corresponding Aryl Bromides94−96

Scheme 47. Electrocatalytic Homocoupling at Palladium Nanoparticles97

halides within the electrolyte. A selection of biaryls synthesized by this approach is depicted in Scheme 46. In order to avoid electrochemical regeneration of soluble palladium species, Rothenberg and co-workers developed a protocol using specific palladium electrodes. This cathodic homocoupling reaction of haloarenes is electrocatalyzed by palladium nanoparticles. By using an ionic liquid as a solvent, a sufficient conductivity during electrolysis is guaranteed and the corresponding metal nanoparticles are stabilized via an ion bilayer mechanism (see Scheme 47).97 The mechanistic rationale implies an initial in-situ formation of palladium nanoparticles. This seems to play a decisive role for the coupling reaction and selective formation of the biaryls in good yields up to 82% by GC analysis. The authors report only for two products isolated yields with a maximum of 55%. The employed ionic liquid is notoriously hygroscopic, and a small amount of water impurity would suffice for closing the cycle by oxidizing the residual water within the ionic liquid into oxygen. In addition, several kinetic studies were conducted to determine reaction rates etc. There is an overall loss of palladium being equivalent to 0.1 mol % referring to aryl halides used. The use of palladium catalysts for biaryl formation provides the option to transform aryl bromides and iodides and different arylboronic acid derivatives as outlined above. With the emergence of transition-metal-catalyzed cross-coupling reac-

Already in 1985 Torri et al. reported an electrochemical conversion of this type.94 The use of palladium precursors like [Pd(PPh3)4] and the direct electroreductive regeneration of Pd(II) to Pd(0) enabled the formation of a variety of homocoupling products. A broad scope of aryl, naphthyl, and pyridyl halides were successfully homocoupled. The authors applied constant current conditions (2.5 mA/cm2) in an H-type divided cell, equipped with a Pb cathode and Pt anode in DMF with Et4NOTs as supporting electrolyte. A tremendous disadvantage is the use of equimolar amounts of palladium. This indicates that the action of the cathode is limited to the Umpolung of a substrate and not the regeneration of the catalytically active species. Further investigations were conducted by Tanaka and coworkers. For the reductive pathway, electrolyses of aryl halides in the presence of a palladium catalyst and either N,N′-dialkyl-4,4bipyridinium salt mediators95 or N-alkyl-4-alkoxycarbonylpyridinium salt mediators96 were conducted. By this variation, the homocoupling of a variety of aryl bromides with electronwithdrawing groups is viable in good yields. When using electron-releasing substituents yields were noticeably lower. However, for successful conversion in the undivided cell sacrificial anodes like Mg or Zn were used in order to avoid undesired oxidation of the reduced mediator species and the 6726


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tions in the 1970s, first attempts were already made to develop nickel-98 and cobalt-meditated99 cathodic coupling reactions of two haloaryls to gain more cost-efficient transformations. The major advantage of this concept is the electrochemical regeneration of low-valent Ni complexes, which have been well known for a long time to enable carbon−carbon bond formation when conventionally applied in equimolar amount. First reports in this area were published by Jennings et al. in 1976 dealing with the coupling of bromobenzene among other organic halides.100 The use of Ni(II) acetylacetonate and PPh3 as a ligand combined with a Cu anode and a Ni cathode at constant potential conditions gave the desired biphenyl in 65% yield. Further insight in this reaction was given by Perichon and co-workers, reporting mechanistic investigations for the electrochemical reduction of Ni(II) complexes to Ni(I) and Ni(0) species and formation of biphenyls by subsequent oxidative addition of chlorobenzene to the reduced catalyst.101 Important improvements on this type of transformation have been published by Fox et al.102 The application of chelating ligands in nickel phosphor complexes (Scheme 48) leads to higher turnover numbers and consequently higher yields due to increased stability of the catalyst.

trolysis using the low valent Ni complex was carried out in simple undivided cells at constant current conditions. The application of a nickel foam cathode with a large surface area in combination with a sacrificial iron anode enabled the application of high electric currents of about 300 mA for a broad variety of different aryl halides (Scheme 49).103 Scheme 49. Selection of Biaryls for Cathodic Coupling of Aryl Halides with Large Surface Cathode and Sacrificial Fe Anode103

Scheme 48. Electroreductive Coupling Using Dichloro(1,2bis(di-2-propylphosphino)benzene)nickel(II) as a Precatalyst102

Besides the listed homocoupling reactions of substrates with two leaving functionalities, quite a lot of protocols for the synthesis of mixed biaryls were investigated. For example, Sibille104 and Gosmini105 achieved high selectivities by a separation of electrochemical metalation and the transitionmetal-catalyzed coupling of both aryl moieties. This gave rise to electrochemical cross-coupling reactions. The key step of the transformation as displayed in Scheme 50 is again the electrochemical reduction of the Ni(II) species to Ni(0), which is required for the oxidative addition to the aryl halide. A follow-up trans metalation by excess of ZnBr2 prevents homocoupling reactions and allows a subsequent Negishi coupling reaction. This provided for the first time also the cross coupling of heteroaryls in good yields and selectivity. However, drawbacks are the need for expensive and toxic metal salts. In addition, due to the two-step protocol the preparative complexity increases as well. Oliviera et al. focused on the formation of bi-, tri-, and terpyridines (Scheme 51).106 Structures like these are of significant interest as ligands for homogeneous catalysis. Reduction on a nickel foam cathode leads to Ni(0) species starting from NiBr2(bpy), which is used for the coupling of 2halopyridines. Because of the structural similarities of the starting materials applied, a significant fraction of homocoupling products is obtained. If two sufficiently different substrates are used in the nickelcatalyzed cross-coupling electrolysis, statistical product mixtures are predominantly obtained. Thereby, only moderate to poor yields were obtained. In addition, over-reduction is particularly challenging (Scheme 52). Nevertheless, isolation and purification of a terpyridine derivative was successful.106 These protocols were extended and optimized for the coupling of other heterocyclic moieties, such as pyrimidines,107,108 pyridazines,109−111 pyridines108 (without the use of organozinc intermediates), and pyrazines.108 Thereby, even the coupling of thiophenes with pyridine derivatives was achieved. By using this cathodic conversion, higher yields were observed in some cases compared to conventional Stille or

Electrolyses were carried out under inert atmosphere in a divided cell. The use of a carbon cloth cathode provides a large surface area leading to low current density. However, the use of a lithium wire as sacrificial anode is untypical and represents in DMSO a safety issue. Potential control was applied to prevent direct reduction of aryl halides at the cathode. The authors report the role of DMSO as a polar solvent with high donor numbers to be crucial for the effective coupling reactions. Reasons outlined are the increased stability of generated Ni(0) catalyst as well as a wide separation of the electrochemical potentials for reduction of aryl halides and propagation of the catalytic cycle in DMSO to prevent a competing dehalogenation reaction. This protocol was employed for the aryl coupling of two distinct substrates like chlorobenzene, 4-chlorotoluene, or 2-bromoaniline, used for intramolecular aryl−aryl coupling reactions and oligomerization of 1,4-dichlorobenzene. Important simplifications in the setup for the application of nickel catalysts have been reported by Troupel and co-workers.103 Further development of earlier studies for the use of nickel-2,2′bipyridine complexes in aprotic solvents like NMP or DMF inspired the authors to investigate electrosynthetic aryl−aryl coupling in low molecular weight alcohols like ethanol/ methanol or ethanol/DMF mixtures, respectively. The elec6727


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Scheme 50. Selection of Biaryls by Cathodic Cross Coupling of Aryl Halides104,105

Scheme 51. Electrochemical Coupling of Halopyridines106

Scheme 52. Cathodic Cross Coupling to Tri- and Terpyridine Derivatives from 2- and 2,6-Dihalopyridines106

Suzuki cross-coupling reactions. The key players in this respective area are Léonel, Gosmini, and Périchon. The electrolyses were carried out in organic solvents and inert

atmosphere. In general, setup of nickel-2,2′-bipyridine complexes as catalysts, a nickel foam cathode, and some type of sacrificial anode (Mg, Zn, Fe, or Fe/Ni) remained unchanged. 6728


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The following scheme gives an overview showing some of the isolated cross-coupling products (Scheme 53).

step to Ni(0) and enters the catalytic cycle. Upon oxidative addition to the aryl halide (2) single electron transfers at the cathode occur followed by oxidative addition of the pyridazine halide (4) and regeneration (6) of Ni(0).111 In addition, Le Gall et al. demonstrated a protocol for the electrochemical coupling of quinoline derivatives with aryl halides using cobalt mediators (26 mol %). Several differently substituted derivatives were used, and good yields in the range 50−81% were obtained (see Scheme 55). However, the toxicity of cobalt is challenging.112 In conclusion, the use of transition-metal-catalyzed methods requires use of an inert atmosphere, which increases the preparative effort. Due to the structural and electronic similarity of the applied starting materials formation of homocoupling derivatives cannot be excluded. In addition, sacrificial anodes are used, making a technical implementation less economically attractive. 4.2.2. Substrates with One Leaving Functionality. As already outlined for the anodic conversions, electroorganic chemistry allows one to develop green and sustainable syntheses of well-defined molecular entities. This is even more the case if the use of prefunctionalized aryl moieties, which ensure in conventional chemistry the required regio- and chemoselectivity, can be avoided. Therefore, activation of C,H bonds is necessary. Additionally, the preparation of coupling partners, e.g., installation of such leaving groups in multistep sequences, can be circumvented. Therefore, this and the next section will focus on a seminal work, summarizing different strategies to achieve selective C,H activating coupling reactions of arenes. In general, only a few attempts for the cathodic coupling of aryls involving a single C,H activation have been carried out. Reductive electrochemical coupling reactions focus on C,H activation of one coupling partner in combination with an aryl halide being the other coupling partner. Gadallah et al. conducted first attempts with one leaving functionality in 1969 by enabling the cross coupling of benzene with substituted aryl component by reducing aryldiazonium and releasing N2.113 Thereby, they replaced the acidic activation by a reduction at 0 V vs SCE, as developed by Claisen and Haase (see Scheme 56).114 The disadvantages of this method are the required initial synthesis of the diazonium compound as well as a lack of control of the resulting isomers within the C,C coupling. Only the electronic and steric features of the substituents used are suitable of influencing the ratio of forming products.

Scheme 53. Synthesized Heterobiaryls by Cathodic Cross Coupling of Aryl Halides Mediated by Nickel107−111

A mechanistic view according to Scheme 54 finally proved that the Ni(II) species is reduced electrochemically in the initial Scheme 54. Simplified Mechanistic Rationale of NickelMediated Reductive Cross-Coupling Reaction111

Scheme 55. Cobalt-Catalyzed Electrochemical Cross Coupling of Phenyl Halides with 4-Chloroquinoline Derivatives112

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Scheme 56. Electrochemically Triggered Gomberg Arylation Reaction113

Scheme 58. Arylation of Pyrroles Using Perylene Bisimide as Mediator117

Early attempts for electrochemical cross-coupling reactions focus on C,H activation of one coupling partner in combination with an aryl halide being the other coupling partner. Protocols following this idea were, for example, published by Thiébault and co-workers for the cross coupling of phenols with aryls and heteroaryls.115 Ongoing investigations lead to the use of different mediators and base additives for this protocol. By focusing on the coupling of 2,4- or 2,6-di-tert-butylphenols with 2-, 3-, or 4-chlorobenzonitrile the formation of regioisomers was avoided. A general reaction scheme and a short selection of coupling products is depicted in Scheme 57. Most of the yields were determined by NMR standard (11− 49%), and the only isolated yield of the model reaction of 4iodotoluene and benzonitrile is rather low (21% with regioisomers o:p = 62:38). Some of the conducted reactions also suffer from low regioselectivities, which likely were responsible for some of the rather low yields. Variations of the electrolysis parameters provide important mechanistic insight pointing the way for further studies. 4.2.3. Substrates without Leaving Functionalities. Schäfer et al. reported the cathodic cyclization of N-(oxoalkyl)pyridinium salts to indolizidines and quinolizidines.119 The intermediary hydroxyalkyl radicals are converted to the final products in high yields and good diastereoselectivities (see Scheme 60).

Scheme 57. General Reaction Scheme and Selection of Biaryls Synthesized by Electrochemically Induced SRN1-Type Coupling115,116

5. ARYLATION OF OTHER CARBON SUBSTRATES The electrochemical attachment of aryl moieties by carbon− carbon bond formation has been investigated for decades. In electrolysis, this can be achieved by either an anodic or a cathodic conversion. The involved intermediates can react in different ways, leading to intra- or intermolecular transformations.120 However, for complete synthetic sequences, many steps which often require leaving groups or metal catalysts are involved. Here, we discuss various reactions of aromatic structural features with olefins, alkynes, sp3 moieties, carbon dioxide, and carbon monoxide.

Zhu and et al. reported the direct arylation of pyrroles using perylene bisimides as an electron-transfer mediator for the first time.117 These compounds are considered to form stable radical anions after a single electron reduction step. The authors anticipate that the formed radical anion reduces the corresponding aryl halides to aryl radicals. The electrolyses were conducted in an undivided cell using a sacrificial zinc anode and a glassy carbon cathode (see Scheme 58). A similar protocol was reported by Atobe and co-workers describing the cross-coupling reaction of aryl halides with arenes in a divided cell (see Scheme 59).118 The authors describe a mechanistic rationale where a radical anion from the iodo arene is generated by a SET. In the next step an aryl radical is formed upon elimintion of I−. Upon formation of the C,C bond by addition of the second aryl a radical anion is generated by deprotonation. Another SET furnishes the final coupling product. The reaction can be considered as a pseudo SRN1 mechanism.

5.1. Arylation of Olefins

Inter- and intramolecular olefin−aryl coupling reactions are important transformations in contemporary C,C bond formation. In particular, in electroorganic synthesis, novel molecular architectures can be generated that are not accessible by conventional methods. This section provides a summary of such electrochemical methods. The reactions can be performed metal catalyzed or metal free. Furthermore, the electrochemical coupling can be carried out directly or mediated. 5.1.1. Metal-Catalyzed Electrolysis Involving Leaving Groups. Nédélec and co-workers investigated the electroreductive coupling of organohalides with enones (Scheme 61). The study reports a simple and mild electrolysis in an undivided 6730


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Scheme 59. Cathodic C,C Cross-Coupling Reaction via Single Electron Transfer118

Scheme 60. Cathodic Cyclization of N-(Oxoalkyl)pyridinium Salts119

Scheme 61. Metal-Catalyzed Addition Reaction to Activated Olefins121,123

cell using a sacrificial iron anode and a nickel cathode. NiBr2 acts as a catalyst in N,N-dimethylformamide (DMF) together with acetonitrile or pyridine as additive. The catalytically active species is formed by electrochemical reduction. However, the reaction is limited to electron-deficient olefins, which react according to an anti-Michael-type reaction mechanism. In addition to nonsubstituted halobenzenes, different moieties such as alkyl, cyano, methoxy groups as well as halogenated naphthalenes are tolerated.121,122 The double bond can be either terminal or nonterminal.123 A similar type of transformation was reported using CoBr2 as catalyst.121 Aryl bromides equipped with electron-withdrawing moieties lead to better yields up to 78% than nonsubstituted bromobenzene. The byproducts of this reaction are nonhalogenated benzenes. Iodo substrates lead to moderate yields up to 22%, whereas aryl chlorides did not react at all. In 2002, Nédélec et al. demonstrated that the nickel-mediated addition reaction can also be applied to heteroaryl halides. Various heterocycles were subjected in this study, providing yields up to 85%, Scheme 62.124

Scheme 62. Metal-Mediated Addition Reaction of Heteroaryl Halides to Activated Olefins124

Drawbacks of this approach are the need for an inert atmosphere and sacrificial anode. Nevertheless, the work of Nédélec et al. shows a very simple electrochemical protocol using a nickel catalyst to perform conjugated addition reactions 6731


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involving aryl, heteroaryl, and alkenyl precursors.125 Furthermore, it is possible to extend this method for the construction of hetero- and carbocyclic medium ring systems.126 5.1.2. Metal-Mediated Electrolysis without Leaving Functionalities. Jutand et al. reported a Pd-mediated C,H olefination of acetanilides by electrochemical oxidation (Scheme 63).127 As electron-transfer mediator they used a catalytic amount of the benzoquinone−hydroquinone redox pair to regenerate the catalyst.

can also be carried out ligand free at room temperature. The applied current also increases the yield, Scheme 65.129 Scheme 65. Electrochemically Assisted Heck Reaction129

Scheme 63. Pd-Mediated Heck-Type Reaction

Hirashima developed another leaving group-free but intramolecular reaction in the 1990s. This reaction consists of a Mn3+-mediated cyclization of 5-arylpent-1-enes with active methylene compounds by an indirect electrooxidation (Scheme 66).130 The mechanism is described by a free-radical cyclization using in-situ-generated Mn3+ as active species.131 5.1.3. Metal-Free Electrolysis. Another possibility to achieve a C,C bond formation between an arene and an olefin is to use anodic oxidation without metal catalysts and leaving groups (Scheme 67). Depending on the substitution pattern, a [3 + 2] or [5 + 2] cycloaddition can be performed. Typically, the mechanism starts by an oxidation step to generate a positively charged phenoxyl ion, followed by nucleophilic attack of the olefin. Finally, an intramolecular cyclization takes place. This can be done via [3 + 2] cycloaddition generating a benzofuran derivative or a bridged bicyclic system via [5 + 2] cycloaddition. The [5 + 2] process is preferred if R1 is a strong electronreleasing group and when R2 is not hydrogen.132−134 Yamamura et al. first carried out a potential-controlled electrolysis of p-methoxyphenol with various vinyl ethers to produce benzofurans (Scheme 68).132,135−137 Swenton et al. investigated a bimolecular oxidative cycloaddition between 4-methoxyphenol and electron-rich styrene and propenylbenzene derivatives in order to receive substituted dihydrobenzofuran derivatives (Scheme 69).138−140 The electrolysis is a promising method to effectively synthesize the corresponding dihydrobenzofurans compared to classical synthesis. Yamamura and co-workers also investigated a regio- and stereoselective method to obtain bioactive natural products such as terpenoids and neolignans.132,136,141−144 The anodic oxidation of phenols serves as a key step for this method, Scheme 70. In both cases, the initial step is an oxidation to a radical cation, which is then attacked by the nucleophilic olefin to form a spirocyclic system. Further investigation by Yamamura et al. revealed that naphthols also serve as suitable substrates, which open up a new electrochemical route to obtain naturally occurring complex molecules.132 The Moeller group faces similar challenges. They developed the intramolecular anodic olefin coupling reactions for constructing polycyclic ring systems (Scheme 71).129,145,146

The catalytic cycle of this transformation is displayed in Scheme 64. The initial step is the C,H activation of the substrate Scheme 64. Proposed Mechanism for the Pd-Mediated HeckType Reaction127,128

by the Pd(II) species, followed by insertion of the olefin and β− H elimination to form the product. Instead of a regeneration using a chemical oxidizer, the mediator is regenerated electrochemically.127,128 Moeller and co-workers reported the site-selective Heck reaction on an electrochemically addressable, semiconducting chip. Compared to classical synthesis, the reaction time can be significantly shortened by this electrochemical approach. The conventional conversion of methyl 4-iodobenzoate with 1pyrenylmethyl acrylate takes place within 18 h, whereas the electrochemical pathway requires only 3 h. The Heck reaction 6732


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Scheme 66. Mn3+-Mediated Intramolecular Coupling Cyclization Reaction131

Scheme 68. Potential-Controlled Electrolysis of pMethoxyphenol with Vinyl Ethers133,135

Scheme 67. Mechanism of [3 + 2] and [5 + 2] Electrochemical Cycloaddition133

Scheme 69. Intermolecular Anodic Oxidation by Swenton139,140

The initial oxidation step has to involve the double bond of the side chain to avoid overoxidation of the final product. By skillfully selecting the substitution pattern, the oxidation potential of the olefin is lowered beyond the oxidation potential of the aromatic ring. In order to fulfill these conditions, phenol ethers were used as substrates and studied in more detail. In 6733


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Scheme 70. Anodic Oxidation of Phenols in Synthesis of Neolignans by Yamamura136

syntheses of heterocycles are described in more detail in section 6.148,149

Scheme 71. Postulated Mechanism of Intramolecular Anodic Olefin Coupling Reaction129

5.2. Arylation of Alkynes

The arylation reaction of alkynes is a rather less explored field in electrosynthesis. Currently, these protocols are used for intramolecular cyclization reactions to obtain polycyclic compounds mostly involving heteroatoms. The group of Hara has shown the aryl radical cyclization to alkynes as well as olefins followed by tandem carboxylation.150−152 As depicted in Scheme 74, a wide range of aryl bromides are suitable for this transformation to obtain the corresponding dicarboxylic acids in up to 71% yield.151 The electrolysis is mediated by methyl 4-tert-butyl benzoate, which serves as a mediator for the generation of aryl radicals. If even more complex substrates with enyen moieties are used, the reaction is still viable and the monocarboxylic acid is formed. A plausible mechanism is outlined in Scheme 75. Initially, the halogenated starting material forms a sigma radical by a mediated one-electron reduction. After cyclization, the radical is reduced to an anionic intermediate, which is attacked by carbon dioxide to generate the final product. Recently, Xu and co-workers established successful electrochemical C,H- and N,H-functionalization for the synthesis of (aza)indoles. This transformation is suitable for a broad range of substrates.152,152,153,153,154 This includes the hydroamidation of alkyls as well as tethered alkynes (Scheme 76). The amidyl radical was initially generated for this purpose, which then triggers the cyclization to highly functionalized indoles and azaindoles.

particular, cyclization involving furans as coupling partners was shown to be excellent to form six- and seven-membered products. Chiba et al. advanced the [3 + 2] cycloaddition of dihydrobenzofuran. They developed a protocol which allows one to use nonactivated alkyl-substitued alkenes. The electrolysis was carried out under controlled potential conditions and inert atmosphere. They used a platinum cathode and poly(tetrafluoroethylene)-fiber-coated (PTFE) glassy carbon anode, which suppresses dehydrodimerization of the phenol (Scheme 72). The special feature of this selective oxidation is the Scheme 72. Anodic Treatment of p-Methoxyphenol with PTFE-Fiber-Coated Glassy Carbon Anode by Chiba133,147

5.3. Arylation of sp3 Moieties

This section is devoted to the electrochemical coupling reaction of arenes with other sp3-hybridized carbon atoms. These arylation reactions can take place in different ways. The transformation can be commenced either by initial oxidation or by reduction of the substrate. By anodic treatment, a radical cation is formed as reactive species, whereas upon cathodic action a radical anion is formed. The subsequent electrochemical transformations are grouped according to this classification. 5.3.1. Arylation of sp3 Moieties by Anodic Oxidation. Scheme 77 depicts a typical reaction pathway of the anodic treatment of aromatic systems. During the electrochemical oxidation of alkyl benzenes a cation is formed. This radical cation is stabilized by mesomeric resonance. These electrophiles are ideally suited to react with other coupling partners, and a C,C bond between aryl components is generated (Scheme 77, path A) Alternatively, the electrolyte allows deprotonation reactions and a benzylic cation is generated. These exquisite electrophiles can also undergo reaction with another aryl component. The latter results in the arylation reaction of a sp3-hybridized carbon (Scheme 77, path B).155,156

highly polar electrolyte solution in combination with the hydrophobic effect of the anode coating. Together with the supporting electrolyte in nitromethane the electron transfer might be promoted and leads to stabilization of the electrogenerated intermediates and thus to exquisite yields.133,147 The electrochemical methods described above are also employed in natural compound synthesis. In the electrochemical synthesis of benzofurans and indole derivatives, a 2-fold Michael-type addition of catechol with 1,3-dicarbonyl compounds can be achieved, Scheme 73. Further electrochemical 6734


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Scheme 73. Electrochemical Synthesis of Benzofuran and Indole Derivatives148,149

Scheme 74. Aryl Radical Cyclization Followed by Tandem Carboxylation under Electroreductive Conditions151

Scheme 75. Mechanism of Tandem Radical Cyclization Followed by Carboxylation of Enynes under Electroreductive Conditions151,152

In the 1970s, Lund et al. intensively studied the various electrochemical coupling conditions as well reactions known for path B (Scheme 77). Some exemplary coupling products are displayed in Scheme 78. All coupling products contain one CH2 unit as a bridge between both arenes.157 The formation of diphenylmethanes is promoted by the use of strong acids in dichloromethane, such as trifluoroacetic acid or trifluoromethanesulfonic acid. By these conditions, a Car,Car coupling can be almost completely suppressed. Maquet et al. demonstrated the advantage of electrochemical oxidation for the alkylation of nitrobenzenes. The classical nucleophilic aromatic substitution has severe drawbacks, in particular, in the alkylation of benzenes equipped with multiple nitro groups. The applicability of this electrochemical method is demonstrated by a broad scope.158 For this transformation two different mechanisms for nucleophilic aromatic substitution were proposed (Scheme 79). Both pathways are initiated by the addition of a nucleophile to the electron-deficient arene. Depending on the substitution pattern, different intermediates are formed and result in the different pathways. The NASH process is first carried out by a single electron oxidation with subsequent proton elimination. Finally, a second single electron oxidation takes place. On the other hand, NASX mechanism can be executed. In this process, only one electron oxidation takes place with subsequent extrusion of the heteroatom as a radical.158

Scheme 76. Electrochemical Hydroamidation of Tethered Alkynes152,153

The synthesis of alkylnitrobenzenes can be realized based on the NASH or NASX mechanism using RLi or RMgCl as reagents. However, NR4− salts have to be used for the synthesis of alkyldinitrobenzenes and alkyltrinitrobenzenes; this synthesis only takes place via the NASH mechanism (Scheme 80). The NR4− anions can be easily electrochemically oxidized to alkyl 6735


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5.3.2. Arylation of sp3 Moieties via Cathodic Reduction. The alkylation can be mechanistically considered as aliphatic nucleophilic substitution. Originally, the mechanism was declared as single electron transfer (SET).155,160−162 The individual steps are outlined in eqs 1−7 and are based on the following assumptions. A represents a compound which forms a stable radical anion, and BX forms an unstable radical anion. First, compound A is reduced at the cathode. Subsequently, a single electron transfer from the nucleophile to the electrophile occurs with a following bond formation. The SN2 reaction involves a synchronous shift of a single electron and a further bond formation. Finally, the generated anions may be protonated.155

Scheme 77. Coupling of Alkyl-Substituted Aromatic Hydrocarbons to Biphenyls or Biphenylmethans Moieties155

Scheme 78. Anodic Oxidation of p-Xylene (236) and Durene (238)157

A + e− F A−•

(1)

A−• + BX → A + B• + X−

(2)

A−• + B• → AB−

(3)

A−• + B• F A + B−

(4)

A−• + BX → AB• + X−

(5)

A−• + AB• F A + AB−

(6)

AB−, B− + H+ → BH, ABH

(7)

A variation of cathodic reduction was often mentioned in the literature.155 In particular, Lund and co-workers carried out the electrolysis with different compounds.160,163,164 In particular, the electrochemical conversion of hydrocarbons such as naphthalene, anthracene, stilbene, and perylene with alkyl halides give alkylated as well as hydrogenated products. In general, the electrolysis is not particularly selective. Instead, complex mixtures of the alkylated product and the hydrogenated product are formed. In the example of stilbene, a 3:2 mixture is obtained from 3,3-dimethyl-1,2-diphenylbutane and 1-phenyl2-(4′-tert-butylphenyl)ethane (Scheme 83). Additionally, naphthalene has been converted with different alkyl chlorides, which is displayed in Scheme 84. The most successful installation was achieved with the tert-butyl system with a yield of 70%. Secondary alkyl chlorides such as cyclohexyl chloride or isopropyl chloride resulted in yields of 40−45%. As expected, primary alkyl chlorides such as butyl chloride could only be isolated in a moderate yield of 22%.160

Scheme 79. Electrochemical SNAr Reaction158 a

5.4. Arylation of Carbon Dioxide

Arylation reactions with carbon dioxide are used in organic synthesis for a wide variety of fine chemicals such as methane, carboxylic acids, and carbonates. However, due to the outstanding thermodynamic stability of carbon dioxide, conversions often require elevated temperatures and high pressure.165,166 This section is devoted to electrochemical methods, wherein CO2 is fixed to an aromatic moiety. The significant advantage of electrochemical carboxylation is the energy efficiency and sustainability in respect to critical resources. Several groups intensively studied the carboxylation of aryl halides to benzoic acids. These investigations involve mainly cyclovoltametry measurements, testing of various cathode materials, and variations in the electrolyte. Gulotta et al. established a protocol for the electrochemical carboxylation of chloroarenes. They could also use substrates with the naphthalene core. An aluminum electrode was employed as sacrificial anode, Scheme 85.167

a

NASX: Nucleophilic aromatic substitution of heteroatom. NASH: Nucleophilic aromatic substation of hydrogen.

radicals. Due to this special feature, the reaction time can be reduced from days to hours. Gubin et al. reported the alkylation of aromatic moieties such as in ferrocene (Scheme 81).159 By anodic Kolbe electrolysis of acetate, methyl radicals can be produced. They react with the ferricinium cation to form an alkylated product (Scheme 82). The single methylated product is obtained in up to 53% yield. In addition, higher alkylated products were found in trace amounts. 6736


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Scheme 80. Electrochemical NASH Reaction of Various Nitrobenzenes158

Scheme 81. Electrochemical Alkylation of Ferrocene159

Scheme 82. Mechanism of the Electrochemical Alkylation of Ferrocene159

Scheme 84. Cathodic Conversion of Naphthalene with Different Alkyl Chlorides160

At the end of the 1980s Troupel commenced the electrochemical carboxylation reaction of aryl chlorides with carbon dioxide. Magnesium served as sacrificial anode and stainless steel as cathode. The electrolysis tolerated different moieties such as alkyl, halide, and various functional groups (Scheme 86).168,169 Périchon et al. was also able to demonstrate the cathodic carboxylation of different organohalides. In addition to the

preparation of benzoic acid, the method could also be applied to heterocycles such as thiophene. As in most electrolyses mentioned above, magnesium served as sacrificial anode. Various aprotic solvents such as DMF or THF are suitable solvents, Scheme 87.170 Nielsen et al. reported a carboxylation reaction of aryl halides in the presence of carbon dioxide on a metal-mediated pathway. For this purpose, catalytic amounts of PdCl2(PPh3)2 are added. The σ-arylpalladium(II) intermediate (ArPd0(PPh3)2−) is

Scheme 83. Cathodic Conversion of Stilbene with tert-Butyl Chloride160a

a

Yields were determined by NMR. 6737


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Scheme 85. Cathodic Carboxylation of Chloroarenes167

conversion of 68% and 71% was observed for m- and pdibromobenzene, respectively. These reactions are not very selective, whereas o-dibromobenzene is predominantly monocarboxylated, which can be attributed to a much larger reduction potential of both reduction events at −1.61 V.172 The work of the Xie lab in 2010 indicates the halogen-free electrochemical dicarboxylation of polycyclic aromatic hydrocarbons with carbon dioxide at high pressure. A simple and efficient electrolysis generates only trans-dicarboxylic acids due to electrostatic repulsion and steric hindrance. The synthetic study covers different cathode materials, solvents, and a scope of substrates combined with cyclovoltametry experiments. Some products are accomplished in yields over 90%, Scheme 89.173 In 2011, Zhang and co-workers described the metal-free chemical carboxylation of different p-alkyl-bromobenzens under mild conditions. Directly after electrolysis, the carboxylates were transformed to methyl esters and then isolated (Scheme 90). However, the authors still use sacrificial anodes and metal bases. In total, a yield of up to 78% of the corresponding methyl carboxylate was isolated.174 Senbuko et al. successfully investigated the electrochemical carboxylation of hexafluorobenzene in 2013. The electrolysis is regio- and stereoselective and polyfluorobenzoic acids are obtained in moderate to high yields (Scheme 91).175 5.4.1. Arylation of Carbon Monoxide. Reductive coupling of aryl compounds with carbon monoxide is a challenging task. Consequently, no electrochemical methods have been reported to form a C,C bond between an aryl carbon atom and carbon monoxide. However, Pèrichon reported a method of the electrochemical conversion of organic halides. In one example phenyl iodide was used as starting material to obtain benzophenone (Scheme 92).176 5.4.2. Arylation of Other Carbon Substrates. In 1977, Lund et al. reported an acetylation of anthracene via electrochemical reduction (Scheme 93). The new feature of this method is that a C,C bond is formed between an aryl carbon atom of anthracene and a carbonyl carbon atom of acetic anhydride. The electrolysis is carried out under mild conditions at room temperature and atmospheric pressure in the presence of oxygen. The product was obtained in a high yield of 75%, and byproducts occur only in traces.177

Scheme 86. Electrochemical Carboxylation of Various Chlorobenzenes169

Scheme 87. Electrochemical Carboxylation of Aryl Halides and Heteroaryl Halides170

6. ARYLATION OF SPECIFIC GROUPS 6.1. Arylation of Nitrogen

Nitrogen-containing aromatic compounds exhibit an utmost importance in chemistry, because they are utterly relevant as structural features in pharmaceuticals,178−180 dyes,181,182 polymers,183−185 natural products,186,187 or functional materials.188 In this section, electrochemical amination, acetamidation, and azolation of aromatic compounds as well as the intermolecular C,N bond formation will be discussed in detail. 6.1.1. Amination of Aromatic Compounds. The direct anodic amination with ammonia or primary amines is not possible or leads in general to overoxidation, because of the low oxidation potentials of the generated products.189,190 Therefore, indirect methods are inevitable. Yoshida et al. used N-arylpyridinium cations as intermediates for the amination of aromatic compounds.191,192 The positive charge of the intermediate protects the intermediate efficiently from overoxidation. Thus, this method is very selective for monoamination. Subsequently, the cation is opened up by the

formed by a single-step two-electron reduction, which will form a free aryl anion. Subsequently, the aryl anion will be attacked nucleophilically from carbon dioxide. Afterwards the carboxylates are obtained.171 In 2002, Lu et al. reported the electrochemical reduction of dibromobenzenes in the presence of carbon dioxide. Different selectivity of individual isomers could be determinated by cyclovoltametry measurements during the carboxylation reaction. In addition, various cathode materials such as Ag, Cu, Ni, and Ti were investigated. The best results are obtained with Ag as cathode material, because of the less negative reduction potential. Nevertheless, there are always three potential products as outlined in Scheme 88. The results only differ in the distribution of the carboxylated products and on the substitution pattern of dibromobenzene: With o-dibromobenzene a conversion of only 49% could be found, but the reaction is more selective (266:267:268) to 86:8:6. In contrast, a moderate 6738


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Scheme 88. Electrochemical Carboxylation of Dibromobenzenes172

Scheme 89. Electrochemical Dicarboxylation of Polycyclic Compounds.173

Scheme 91. Electrochemical Carboxylation of Polyfluoroarenes175

addition of piperidine to liberate the corresponding aniline (Scheme 94). Scheme 90. Electrochemical Carboxylation of Bromobenzenes with Different Substituents174

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Scheme 92. Electrochemical Synthesis of Symmetric Ketones176

Scheme 96. Anodic Synthesis of Highly Functionalized Aryl Alkyl Amines195

Scheme 93. Acetylation of Anthracene via Electrochemical Reduction177

Scheme 94. Anodic Amination of Activated Arenes191,192 Scheme 97. Anodic-Mediated Amination of Benzoxazoles196

Scheme 95. Anodic One- and Two-Fold Amination of Less Activated Arenes193,194 Scheme 98. Ti(IV)/Ti(III)-Mediated Amination of Arenes199,200

perform the first direct electrochemical 2-fold amination of naphthalene with this method. Likewise, diphenylmethane, triphenylmethane, biphenyl, and phenanthrene were 2-fold aminated, whereby different regioisomers were formed.194 The direct coupling of primary amine as a functional group with aromatic compounds is not possible, due to the generally low oxidation potentials of amines. In contrast, N-heterocycles

By this protocol, a broad variety of functional groups are tolerated. However, only activated arenes can be converted. Waldvogel et al. adapted this method and expanded the scope to less activated arenes by using boron-doped diamond (BDD) as anode material (Scheme 95).193 Moreover, it was possible to 6740


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Scheme 99. Ni-Mediated Amination of Aryl Bromides202

Scheme 103. Anodic Synthesis of Pyren-1-yl Azolium Salts213

Scheme 100. Acetamidation of Arenes204 a

Scheme 104. Anodic Arylation of 1-Mesylimidazole Derivatives214

a

Yield of the para-substituted product in parentheses.

Scheme 101. Arylation of 1H-Tetrazole205

Scheme 102. Arylation of Adenine

Scheme 105. Anodic Synthesis of Indole Derivatives via N,OAcetals148

211

represent protected functional groups showing a high nucleophilicity. Thereby, an electrochemical functionalization of arenes is possible. Additionally, cationic intermediates prohibit overoxidation. The group of Yoshida took advantage of these instances to electrochemically synthesize aryl alkyl amines (Scheme 96)195 Initially, the preliminary oxidized arene

will be nucleophilically attacked by the N-heterocycle to form a cationic intermediate. Subsequently, the ring is opened up either by hydrolysis with sodium bicarbonate or by reaction with ethylenediamine. As heterocyclic compounds oxazoles, imida6741


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Scheme 106. Electrochemical Synthesis of 2Methylthioindole Derivatives via N,S-Acetals215

Scheme 108. Electrochemical Synthesis of Functionalized Polycyclic Benzimidazole Derivatives154

zoles, 1,3-oxazines, and pyrimidines are exploitable as well as many functionalized arenes and heteroarenes. An electrochemical method for the amination of benzoxazoles in position 2 was developed by Zeng and Little (Scheme 97).196 Functionalized and nonfunctionalized benzoxazoles can be converted with several cyclic secondary amines as well as acyclic ones. Since this reaction is an iodine-mediated electrochemical dehydrogenative oxidation, the addition of a respective supporting electrolyte is required. In contrast to the anodic aminations outlined above, it is also viable to use transition-metal catalyst in the manner of indirect electrolysis. Lisitsyn et al. studied the amination of benzene and anisole.197,198 The Ti(IV)/Ti(III) redox pair serves as mediator for the cathodic process (Scheme 98).199,200 In addition, they demonstrated a 2-fold amination of arenes by applying this protocol.201 A reductive amination with a Ni catalyst is reported by Baran et al. (Scheme 99).202 A variety of different linear and cyclic secondary amines as well as primary amines were coupled with substituted aryl bromides and heteroaryl bromides under mild conditions. They also demonstrated the scalability of this protocol into the decagram scale. 6.1.2. Acetamidation. In 1974, Parker et al. reported the first example for the anodic acetamidation of anthracene in position 9 with a yield of 82%. It was mandatory that the acetonitrile employed is absolutely dry. Otherwise, the hydroxylation of anthracene is the main reaction pathway.203 Subsequently, Miller et al. reported the acetamidation of several aromatic carbonyl compounds with yields up to 70% for

Scheme 109. Electrochemical Synthesis of Benzoxazole Derivatives via Imines217

acetophenone (Scheme 100).204 However, not only the orthoacetamidated product is formed, but also the para-substituted compound. 6.1.3. Arylation of Nitrogen Heterocycles. Evans et al. successfully coupled 1,4-dimethoxybenzene with 1H-tetrazole via a paired electrolysis. In this process, the C−N bond

Scheme 107. Anodic Synthesis for Pyrimido[4,5-b]indole Derivatives216

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Scheme 110. Anodic Synthesis of Benzoxazoles and Benzothiazoles via Intramolecular C,H Amination218

Scheme 112. Indirect Synthesis of Carbazoles by Electrochemically Regenerated Iodine(III) Species222

Scheme 111. Anodic Benzothiazole Synthesis219,220

Scheme 113. Indirect Synthesis of Carbazoles by Electrochemically Generated Iodine(III)−HFIP Adduct223

formation takes place between a cathodically generated tetrazolide anion and an anodically generated arenium cation. With the application of the tetrabutylammonium salt of tetrazole as supporting electrolyte they were able to obtain an overall yield of 88% of two regioisomeric N-arylated products in a 3:2 ratio (Scheme 101). They also used 1,3,4-trimethoxybenzene in this reaction and achieved similar results.205 Petrosyan et al. also investigated the electrochemical Narylation of tetrazoles as well as pyrazoles and triazoles. However, they obtained complex product mixtures of the ortho- and ipso-substitution products as well as the ipso-double addition product.206−210 Even more complex structures are accessible by electrochemical C−N bond formation. For example, adenine was anodically arylated with dibenzo[a,l]pyrene by anodic oxidation (Scheme 102).211 The arylation in the 3-, 7-, and 6-positions of adenine also occurs, but in very low yields of 2−6%. The adduct formation of guanine with benzo[a]pyrene is also described.212 The electrochemical synthesis of pyren-1-yl azolium salts by anodic coupling of different azole derivatives with pyrene was

reported by Andrieu and Devillers.213 They showed that the C− N bond formation for 1-methylimidazole, 1,2,4-triazole, benzimidazole, and benzothiazole is possible in high yields up to 92% (Scheme 103). In 2014, Yoshida et al. developed a method for the electrochemical arylation of imidazole and related compounds (Scheme 104).214 When using nonprotected imidazoles for this reaction, overoxidation becomes dominant and no desired product is isolated. However, by protecting the imidazole as mesylate, the desired arylated product is obtained in high yields. A subsequent treatment with piperidine is used for deprotection. The transformation exhibits a high tolerance toward various functional groups, and different aromatic substrates are suitable, 6743


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Scheme 114. Synthesis of Quinolinone Derivatives with Electrochemically Generated (Bis(trifluoroacetoxy)iodo)benzene (PIFA)225

Scheme 118. Hydroxylation of Aromatic Carbonyl Compounds204

Scheme 119. Synthesis of 2,3,4-Trimetoxyacetophenone240

Scheme 115. Electrochemical Synthesis of 1,4-Benzoxazin-3ones227

Scheme 120. Methoxylation of 1-Methoxynaphthalene Derivatives241

Scheme 116. Dihydroxylation of Mesitylene

Scheme 121. Co-Mediated Alkoxylation of Benzamides242 a

230

Scheme 117. Electrochemical Synthesis of Phenol231

a

Piv = pivaloyl.

tions. The electrochemical arylation of nitrogen-containing compounds can be a key step for the formation on Nheterocyclic derivatives. A convenient method for the electrochemical synthesis of indole derivatives is the oxidation of catechols in the presence of amines. An example for this is given by the group of Zeng (Scheme 105).148 They oxidized 4-(tert-butyl)catechol as well as

such as substituted benzene derivatives, naphthalene, or perylene. 6.1.4. Synthesis of N-Heterocycles. The synthesis of Nheterocyclic compounds is of high significance, because their appearance in natural products is abundant and they often exhibit a high biological activity. Thus, they are important structural motifs in pharmaceutical and agrochemical applica6744


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Scheme 126. Anodic ortho-Acetoxylation of pMethoxyanisole253

Scheme 122. Anodic Synthesis of Diaryl Ethers243,244

Scheme 127. Anodic Trifluoracetoxylation Reaction of Mono-Substituted Arenes256 a

Scheme 123. Paired Electrolysis in a Microflow Reactor for the Synthesis of Diaryl Ethers247

a

Current yields.

Scheme 128. Anodic Acetoxylation and Trifluoracetoxylation Reaction with Immobilized Base257

248

Scheme 124. Cathodic Diarylether formation

Scheme 125. Anodic Acetoxylation Reaction of Alkylated Benzene Derivatives250

butyl)catechol the final rearomatization step occurs under elimination of the tert-butyl moiety. With 3-methyl- and 3methoxycatechol the substituent still remains in the product but can be in position 4 or 7 of the indole. In a similar fashion, 2methylthioindole derivatives were synthesized. Here, N,Sacetals were used as Michael donors (Scheme 106).215 Recently, Shabani-Nooshabadi et al. developed an electrochemical synthesis for pyrimido[4,5-b]indole derivatives.216 They also take advantage of the catechols and are easily oxidized. However, they use 2,4-diamino-6-hydroxypyrimidine as nucleophile (Scheme 107). Mechanistically, the reaction follows a similar pathway like the previously mentioned examples. Xu et al. reported an electrochemical synthesis of functionalized polycyclic benzimidazoles by intramolecular C−N bond formation.154 A broad variety of different functional groups, such as methyl, methoxy, trifluoromethyl, and halides, are

3-methyl- and 3-methoxycatechol in the presence of different N,O-acetals to form the corresponding indole derivatives. Regarding the mechanism, they propose an initial anodic oxidation of the catechol derivative. The quinone formed is attacked by the acetal via a Michael-type addition reaction. Subsequently, a second oxidation and Michel addition takes place to construct the C−N bond. In the case of 4-(tert6745


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Scheme 129. Anodic Pd-Mediated Acetoxylation of Oximes258

Scheme 133. Anodic Synthesis of Benzofurans with Installation of Various β-Keto Carbonyl Moieties266−270

Scheme 130. Anodic Pd-Catalyzed Electrochemical Perfluoroacyloxylation260

Scheme 134. Two-Fold Michael-Type Addition272

Scheme 131. Anodic Synthesis of 4-Phenylcoumarin264

Scheme 135. Anodic Synthesis of Benzoxazoles273 Scheme 132. Anodic Synthesis of Benzofurans265

the anodically generated quinone undergoes a condensation reaction with the primary amine to form an imine. Subsequently, a cyclization and second oxidation step take place (Scheme 109). With this protocol six different benzoxazoles were synthesized in yields from 72% to 91%.217 A different approach to synthesize benzoxazoles electrochemically is made by Yoshida et al.218 They form the desired structural feature by an intramolecular C−H amination of 2-

tolerated by this method. Altogether, over 40 benzimidazole derivatives were obtained by this method in moderate to high yields. The key step of this reaction is the formation of an amidinyl radical by N−H bond cleavage (Scheme 108). For the synthesis of benzoxazoles by electrochemical Narylation, catecholes can also be used as starting materials. However, in contrast to the examples mentioned above, the mechanistic concourse differs. Instead of a Michal-type reaction, 6746


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Scheme 136. Anodic Synthesis of Benzoxazines276

benzoxazole. Several functional groups, like halides, carbonyl moieties, trifluoromethyl, and cyanide, are tolerated by this method. The protocol can also be applied on 2-pyrimidylthiobenzenes. This results in the corresponding benzothiazoles (Scheme 110). Another access to benzothiazoles is reported by Khodaei and Alizadeh.219,220 They oxidize catechol derivatives in the presence of 2-mercaptobenzimidazole or 2-mercaptoimidazole (Scheme 111). In a similar way, but with 2-thiouracil as nucleophile, Shahrokhian et al. synthesized benzothiazoles.221 Access to carbazoles by intramolecular N-arylation is given by the group of Nishiyama.222 In this indirect process the cyclization of an aminated biaryl is promoted by an electrochemically generated hypervalent iodine mediator (phenyliodine(III) bis(trifluoroethanol)). The protocol was successfully applied to six differently methoxylated biaryl derivatives in yields from 32% to 91% (Scheme 112). This method was adapted by Franke et al. by using a different iodine agent. In their case, the iodine agent serves as redox-active species and supporting electrolyte at the same time. Thereby, it can be recovered very easily. By electrolyzing the iodine(I) precursor in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) they obtain the corresponding iodine(III)−HFIP adduct as oxidizing reagent (Scheme 113).223 It is noteworthy that the mediator generates as byproduct the problematic 1,1,1,3,3,3-hexafluoroacetone. Nishiyama et al. used electrogenerated (bis(trifluoroacetoxy)iodo)benzene (PIFA) for the synthesis of quinolinones.224−226 The principle of the synthesis is similar to the previously introduced reactions with hypervalent iodine compounds. However, they use γ-aryl N-methoxyamides as substrates for the cyclization (Scheme 114). A special characteristic of this reaction is that the moiety in the 2-position (R2) undergoes a rearrangement. In the group of Waldvogel an electrochemical synthesis of 1,4benzoxazin-3-one derivatives by C−H amination was developed.227 The method is based on the formation of Narylpyridinium ions as key intermediates, which is described by Yoshida.192 However, methyl phenoxyacetates were used as starting materials. With this protocol it was possible to convert 12 different substrates with a broad variety of diverse moieties.

Scheme 137. Synthesis of Methyl Aryl Thioethers via Anodically Generated Sulfenium Species277,278

pyrimidyloxybenzenes. The principle of this reaction is the same as for the intermolecular amination of aromatic compounds (see section 6.1.1). As intermediates cationic species are generated anodically, which protects the substrate from overoxidation. A subsequent chemical reaction with piperidine liberates the

Scheme 138. Thiolation of Aromatic Compounds by the Cation Pool Method281

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Scheme 139. Anodic Synthesis of Diaryl Thioethers in a Microflow Reactor282,283

Scheme 140. Cathodic Diarylether Formation248

However, the subsequent reduction of the quinone derivatives gives access to the corresponding hydroquinones. Thus, the anodic oxidation of mesitylene in an electrolyte based on CH3CN, H2O, and H2SO4 gives trimethylbenzoquinol. With a following rearrangement the hydroquinone is obtained in 57% yield (Scheme 116).230 Selective monohydroxylation reaction of aromatic compounds is viable by an indirect pathway. Preliminary anodic treatment of the aromatic compound in the presence of trifluoracetate provides access to aromatic trifluoracetates. The subsequent hydrolysis liberates the corresponding phenol. By this method Nishiguchi et al. were able to obtain phenol from benzene in a yield of 67% (Scheme 117).231 On the basis of this method a variety of substituted benzene derivatives were hydroxylated. However, in most cases different regiosiomers are formed.204,232,233 Miller et al. oxidized aromatic carbonyl compounds in the presence of trifluoracetic acid (TFA) to obtain the corresponding hydroxylation products in yields up to 85% (Scheme 118). The key of this reaction is a preliminary acetoxylation with TFA followed by hydrolyses as well. In the case of benzoic acid and ethyl benzoate the para-hydroxylated product occurs also.204 6.2.2. Synthesis of Aryl Ethers. Like hydroxylation, the alkoxylation of aromatic compounds is challenged by overoxidation. Thus, the formation of quinones or ketals thereof is strongly favored.234−239 By subsequent rearomatization it is possible to obtain the alkoxylated products. For example, 2,3,4trimetoxyacetophenone is accessible by acid-catalyzed elimination of methanol from the intermediate overoxidized product

For example, highly valuable iodine moiety or even bulky 1,1dimethyl ethyl substituents are tolerated (Scheme 115). For the conversion of fluorinated substrates only BDD anodes are suitable. 6.2. Arylation of Oxygen

Oxygen-containing compounds, for instance, alcohols, ethers, or esters, are very common motifs. Therefore, they have high significance in all fields of chemistry. Hence, the electrochemical C,O bond formation is a valuable method for the synthesis of functionalized aromatic compounds.155 6.2.1. Synthesis of Aryl Alcohols. In most cases the direct hydroxylation of aromatic compounds leads to overoxidation, because the oxidation potentials of the phenolic products are lower than those of the corresponding starting materials.228 For example, benzene can be oxidized to benzoquinone at a Pt anode in an aqueous electrolyte consisting of 0.5 M H2SO4.229 Parker et al. extended this method to cresols, xylenols, and mesitol and obtained the corresponding quinones in yields ranging from 44% to 81%.27 Scheme 141. Anodic Synthesis of Monopyrimidyl Thioethers284

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Scheme 142. Anodic Oxidation of Catechols in the Presence of 5-Methyl-2-mercapto-1,3,4-thiadiazoles285

Scheme 143. Anodic Oxidation of Catechols in the Presence of 5-Phenyl-1,3,4-oxadiazole-2-thiol286

Scheme 144. Anodic Oxidation of Catechols in the Presence of 2-Mercaptobenzoxazol.287

Scheme 145. Anodic Thiolation of N,N′-Diphenyl-1,4diamine with Different Heteroaromatic Thiols288

Scheme 146. Anodic Synthesis of Thioethers from Indoles and Thiophenols289

(Scheme 119).240 Interestingly, the elimination is promoted by heating the reaction mixture and simultaneously removing the solvent. In a similar way, 1-methoxynaphthalene derivatives could be successfully methoxylated in the 4-position (Scheme 120).241

In 2017 Ackermann et al. developed a cobalt-catalyzed protocol for the selective electrochemical ortho-alkoxylation of benzamide derivatives (Scheme 121).242 Here, pyridine-Noxide serves as directing group for the cobalt-based mediator. A broad variety of different substrates with various alcohols were converted to over 20 products with yields up to 78%. 6749


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Scheme 147. Anodic Thiocyanation in a Biphasic Mixture292,293

Scheme 150. Anodic Thiocyanation of 5-Membered Hereroarenes297 a

Scheme 148. Direct Anodic Thiocyanation of Substituted Arenes295 a

Yields for constant current electrolysis in parentheses.

reduction with zinc accomplishes the desired diaryl ethers (Scheme 122).243−246 This method has been adapted by Atobe et al. They used a microflow reactor for the conversion of phenols to diaryl ethers. Since it represents a paired electrolysis, no subsequent reduction with zinc is required (Scheme 123).247 In contrast to the oxidative methods, Fuchigami et al. used cathodically generated phenolates as nucleophiles for the formation of diaryl ethers with p-halonitrobenzenes in isolated yields up to 95% (Scheme 124).248 6.2.3. Synthesis of Aryl Esters. In the acyloxylation or more specifically acetoxylation reaction of aromatic compounds the substitution of the core or side chain are competing conversions. This often results in a mixture of different products by oxidative conversion. The presence of acetate as nucleophile can promote the reaction to acetoxylation at the core.249 By adding Pd/C to the electrolyte Eberson and Oberrauch were able to further improve the selectivity toward substitution at the

Nishiyama et al. developed an electrochemical method for the synthesis of diaryl ethers. o,o′-Dihalogenated phenols are anodically treated to the corresponding aryl quinone ethers in the initial step of the sequence. Subsequently, a chemical

Scheme 149. Anodic Thiocyanation of Indole Derivative and Diphenylamine296

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immobilized base can be reused multiple times. Thus, this protocol can be considered as very sustainable.257 In addition to direct electrochemical protocols there are some examples of transition-metal-catalyzed electrochemical acyloxylations reactions. Zhang and Mei reported a palladiumcatalyzed acetoxylation approach of different aromatic oximes (Scheme 129). The electrosynthesis is very ortho selective, because the oxime moiety serves as a directing group by coordinating to the mediator.258 In a similar fashion, Sanford et al. acetoxylated some N-heterocycle-substituted arenes.259 A Pd-catalyzed electrochemical functionalization of 2-phenylpyridine with perfluoroalkyl carboxylic acids has been shown by Budnikova et al. (Scheme 130). With perfluoroheptanoic acid and pentanoic acid yields of 65% and 73% were obtained.260 6.2.4. Synthesis of O-Heterocycles. The synthesis of heterocyclic compound is of special interest, because they represent outstandingly important motifs in natural products and pharmaceutically active compounds.150,261−263 By electrochemical lactonization of 3,3-diphenylacrylic acid it was possible to form 4-phenylcoumarin (Scheme 131).264 The electrochemical oxidation of catechol derivatives in the presence of α,β-diketones leads to the formation of benzofuran derivatives (Scheme 132). In the first step the catechol is anodically oxidized to the corresponding o-quinone. Subsequently, the quinone experiences a nucleophilic attack by the α,β-diketone. This Michael-type addition leads to rearomatization reaction of the quinoidic system. Through a second oxidation step followed by a nucleophilic attack of the enolate the benzofuran is accomplished.265 On the basis of this electrochemically induced Michael addition even larger condensed ring systems are accessible using different Michaeltype donors. By adding a chloro substituent at position 2 of the diketone, the former four-electron oxidation sequence is converted into a two-electron oxidation (Scheme 133).266−271 Even a 2-fold Michael-type addition is viable, whereby a pentacyclic system is formed (Scheme 134).272 In the Waldvogel lab a novel electrochemical synthesis of benzoxazoles has been developed.273,274 The method gives direct access to functionalized benzoxazoles by anodic oxidation of the corresponding anilides (Scheme 135). In the suggested mechanism an anodic amidyl cation formation is the initial step. This cation then undergoes an oxa-Nazarov-type cyclization to form the benzoxazole.275 Electrochemical access to 4H-1,3-benzoxazines is reported by Xu et al.276 In contrast to the benzoxazine synthesis they use Nbenzyl amide derivatives to form a six-membered ring (Scheme 136). With this method they were able to synthesize over 20 different derivatives with yields up to 81%. For one substrate (R1 = OMe, R2 = R3 = Me, R4 = CPh(CH3)2) they demonstrated that this method can also be transferred into electrochemical microflow reactors. With this adaption the yield was increased from 40% to 63% by

Scheme 151. Synthesis of Diaryl Sulfones via Electrogenerated Quinones298

aromatic core. Thereby, Pd/C serves as hydrogenation catalyst to remove acetoxylate moieties from the side chain. With this protocol alkylated arenes such as p-xylene, mesitylene, durene, and isodurene were acetoxylated (Scheme 125).250 The acetoxylation of non- or monosubstituted arenes leads to regioisomers. This is well documented for naphthalene, biphenyl, anisole, and phenyl acetate.251 For a blocked para position the substitution takes place in the ortho position with good yields (Scheme 126). The addition of ZnCl2 as Lewis acid plays a crucial role within this system, since it stabilizes ionic intermediates of this reaction.252,253 In addition to the anodic acetoxylation reaction, there are a few examples for trifluoracetoxylation reported, whereas this method is mostly used for hydroxylation of aromatic componds, since trifluoracetic acid esters are more prone to hydrolysis (see section 6.2.1).254 Even though there are some examples whereby the trifluoracetes are isolated, if there is more than one active position at the aromatic substrate, trifluoracetoxylation, likewise the acetoxylation reaction leads to a regioisomeric mixture. Therein, the distribution of ortho, meta, and para isomers depends on the functionality at the arene substrate (Scheme 127).254−256 A novel method for the acetoxylation and trifluoracetoxylation reaction of aromatic compounds was developed by Tajima et al. (Scheme 128). Immobilized bases like morpholine or pyridine on a silica support promote in situ the formation of acetate or trifluoracetate anions as nucleophiles. In this approach no additional supporting electrolyte is required, and the Scheme 152. Indirect Paired Electrosynthesis of Sulfones298,299

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Scheme 153. Anodic Sulfonylation of Phenol and Aniline Derivatives300,301

Scheme 154. Anodic Sulfonylation of N,N′-Diphenylbenzidine302

Scheme 155. Anodic Sulfonylation of Aminophenols303

electrogenerated arylbis(arylthio)sulfonium cations (aryl = 4fluorobenzene) as Ar−S+ equivalent for the thiolation of three different aromatic substrates (Scheme 138).281 Atobe et al. developed a flow electrochemical method to form diaryl thioethers from different aromatic thiols and catechol.282,283 In contrast to the methods mentioned above, the catechol is anodically oxidized to o-benzoquinone as the initial step. Subsequently, the nucleophilic attack of the thiol will happen in a Michael-type reaction. This protocol was successfully applied to three different substrates. The yields by flow were much higher compared to those obtained in a batchtype cell (Scheme 139). Fushigami et al. report a reductive approach for the synthesis of diaryl thioethers.248 First, thiophenol is cathodically transformed to thiophenolate. Subsequently, it adds onto a 4halonitrobenzene and substitutes the halo moiety. Surprisingly, all halosubstrates are suitable with this protocol and give yields from 95% to 98% (Scheme 140). There are numerous examples for the anodic arylation of heteroaromatic thiols with differently substituted catechol derivatives (Scheme 141). For all those transformations, the general mechanism is quite similar. The catechol derivative is anodically oxidized and then attacked by a thiol as nucleophile to form the thioether. Zeng et al. coupled 2-thiopyrimidine with several catechol derivatives successfully. For catechols exhibiting a substituent in position 4, only the monopyrimidyl thioethers are generated (Scheme 141). However, if the substituent is in position 3, mono- and dipyrimidyl thioethers are observed.284 With the same conditions they coupled different catechols with 5-methyl-2-mercapto-1,3,4-thiadiazole. As in the example above, the selectivity of the reaction strongly depends on the substitution pattern of the catechol too (Scheme 142). Similar results were obtained with 4-amino-3-methyl-5-mercapto-1,2,4triazole as nucleophile.285 Fakhari et al. oxidized 3- or 4-substituted catechols in the presence of 5-phenyl-1,3,4-oxadiazole-2-thiol. Again, the same

simultaneously decreasing the concentration of the supporting electrolyte. Besides, the flow reaction was performed at room temperature, whereas heating to reflux was necessary for the reaction in the batch cell. 6.3. Arylation of Sulfur

6.3.1. Arylation of Thiols. In general, thioethers can be electrochemically formed by the electrophilic action of a sulfenium species onto an aromatic compound, whereby the cation is generated from disulfides by anodic cleavage of the S−S bond. In 1998, Guillanton et al. synthesized several methyl aryl thioethers by oxidizing dimethyl disulfide electrochemically.277,278 Subsequently, the electrolyte was added to a phenol or anisole derivative to form the corresponding thioether. The reaction is very regioselective. Usually, only mono-substitution is observed. However, for 4-methylanisol and 3-methoxyanisol the 2-fold-substituted products are formed in yields of 11% and 26%, respectively (Scheme 137). In a similar fashion, Yoshida et al. synthesized diaryl thioether by taking advantage of the cation pool method.279,280 They used 6752


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Scheme 156. Anodic Sulfonylation of Indoles305

Scheme 157. Anodic Synthesis of 2-Amino-Substituted Benzothiazoles306

Scheme 158. TEMPO-Mediated Anodic Synthesis of Benzothiazoles and Thiazolopyridines307

product distribution is reported. A substituent in position 3 with a concurrent free position in 4 of the catechol results in two different products, hereas in the case of catechol and 4-methyl catechol only a single product is formed (Scheme 143).286 Nematollahi et al. applied this reaction for the arylation of 2mercaptobenzoxazole (Scheme 144).287 They also arylated different heteroaromatic thiols with N,N′diphenyl-1,4-diamine. The concept of the transfromation is almost identical to the conversion with catechol: An electrochemically generated quinonediimine (a strong Michael acceptor) is attacked by the thiol, whereby the thioether is formed. As nucleophiles they used the thiols of pyridine, triazole, tetrazole, benzoxazole, and benzothiazole (Scheme 145).288 Recently, Lei et al. reported a constant current electrochemical reaction for the synthesis of thioethers from indole derivatives and several substituted thiophenols.289 With their elaborated protocol, they synthesized over 25 different thioethers with mostly high yields (Scheme 146). 6.3.2. Thiocyanation of Aromatic Compounds. The electrochemical thiocyanation of aromatic compounds dates back to the 1980s, when Fritz and Ecker studied the reactions of the naphthyl radical cation with nucleophiles.290 Therefore, they

anodically synthesized the radical cationic salt of naphthalene (C10H8)2PF6 at a temperature of −78 °C. Subsequently, these salts were treated with a thiocyanate solution to liberate 1naphthylthiocyanat in a yield of 21%. Isothiocyanates are formed as byproducts in trace amounts. Gurjar et al. developed an electrochemical thiocyanation of aniline and phenol derivatives in a biphasic mixture.291−293 In one layer, consisting of an aqueous solution of ammonium thiocyanate and sulfuric acid, the electrochemical reaction takes place: Initially, thiocyanate anions are oxidized to trithiocyanate. Afterward, trithiocyanate decomposes to thiocyanate and thiocyanogene, which is extracted into the organic layer (CH2Cl2). In the organic fraction the thiocyanation reagent is protected from further decomposition. Subsequently, thiocyanogene reacts with the aromatic compound. This reaction can be either in situ or separated from the electrolysis. However, the 6753


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Scheme 159. Electrochemical Synthesis of Arylboronic Esters311,312

Scheme 160. Electrochemical Synthesis of Aryltrifluoroborates315

Scheme 162. Electrochemical Silylation or Aryls and Heteroaryls322 a

a

Scheme 161. Electrochemical Silylation of Aryl Iodides319,320

HMPA = Hexamethylphosphoramide.

Scheme 163. Products for the Electrochemical Phenylation of White Phosphorus323

Scheme 164. Electrocatalytic Phosphonation Reaction of 2Phenylpyridine324 biphasic operation separates the electrochemical from the chemical conversion (Scheme 147). In 2006, Becker and Gitkis developed a direct, homogeneous, and one-pot electrochemical method for the thiocyanation of anisole. The key step of this sequence is the anodic formation of thiocyanogene as thiocyanation reagent as well. At constant potential conditions, they obtained p-thiocyanoanisole in a yield of 77%. They also carried out the electrolysis under constant current conditions. However, the yields were lower compared to the constant potential electrolysis.294 The elaborated method

then was applied to substituted anisoles, toluene, and aniline derivatives (Scheme 148).295 6754


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also demonstrated the scalability of this electrotransformation. Performing the electrolysis on gram scale resulted almost in no loss of yield (Scheme 158).

Nikoofar and Fotouhi studied the electrochemical thiocyanation reaction of indole under constant current conditions.296 With optimized parameters, they could obtain 3-thiocyanoindole in 95% yield. In addition, substituted indoles, indole-2,3dione, carbazole, as well as diphenylamine are suitable substrates and liberate yields from 55% to 96% (Scheme 149). The reaction is very selective. Only for diphenylamine does the disubstituted product occur as byproduct. Petrosyan et al. thiocyanated several N-heteroaromatic 5membered rings at constant potential as well as constant current conditions (Scheme 150).297 The yields range between 53% and 75% for the constant potential electrolysis. For constant current conditions, the yields are slightly lower but still acceptable and practical. 6.3.3. Arylation of Sulfonates. There are several examples for the electrochemical synthesis of aryl sulfones. For all of them, the mechanistic approach is similar: A hydroquinone or a structurally related compound is anodically transformed to the corresponding quinoidic system. Then this highly electrophilic intermediate is attacked by a sulfonate to accomplish a sulfone. In 2002, Golabi et al. oxidized catechol, 4-methylcatechol, and hydrochinone in the presence of benzenesulfinic acid or 4methylbenzenesulfinic acid and obtained the corresponding sulfones in good yields (Scheme 151).298 Nematollahi et al. developed an indirect, paired electrosynthesis for diaryl sulfones.299 First, 4-nitrocatechol is reduced at the cathode to 4-aminocatechol. At the anode, potassium ferrocyanide is oxidized to potassium ferricyanide. This mediator oxidizes 4-aminocatechol to the corresponding quinone, which is subsequently attacked by a sulfinic acid (Scheme 152). By the same group, 4-morpholino aniline and 4-piperazinyl phenol as substrates were oxidized in the presence of arylsulfinic acids as nucleophiles (Scheme 153).300,301 Recently, Nematollahi and Nikpour synthesized N,N′diphenyl-3-sulfonyl-biphenyl-4,4′-diamines at similar conditions. They oxidized N,N′-diphenylbenzidine with different para-substituted benzenesulfinic acids and obtained the corresponding sulfones in yields up to 90% (Scheme 154).302 In a similar fashion, the group of Zeng converted different aminophenols to the corresponding diaryl sulfones (Scheme 155).303 They also synthesized 6-arylsulfonyl caffeinic acid derivatives with this protocol.304 Recently, Yu and Chen reported a method for the electrochemical α-sulfonylation of indole derivatives.305 Importantly, this is an iodine-mediated process. The protocol shows a broad substrate scope. Regarding the indole derivatives, moieties, such as methyl, methoxy, halide, carbonyl, and carboxyl groups, in different positions of the indole are suitable. In addition, varieties of aromatic and aliphatic sulfonates are applicable (Scheme 156). 6.3.4. Intramolecular C−S Bond Formation. Lei et al. developed an electrochemical synthesis of 2-amino-substituted benzothiazoles by oxidizing aryl isotiocyanates in the presence of secondary amines. With their elaborated protocol, over 20 products were accessible in good yields from 70% to 99%. Cyclic and acyclic secondary amines as well differently substituted aryl isotiocyanates are tolerated by the method (Scheme 157).306 Xu and Song exhibit a TEMPO-mediated method for an intramolecular C−S bond formation.307 With the method, a great product diversity of benzothiazoles as well as thiazolopyridines is accessible. In contrast to the protocol of Lei, they use Narylthioamide derivatives to construct the thiazole ring. They

6.4. Arylation of Other Heteroatoms

6.4.1. Arylation of Organoboron Compounds. Arylboronic acids play an important role in the formation of C−C bonds. A prominent example is the Suzuki reaction.308 Arylboronic acids are conventionally accessible via a Grignard reaction309 or from organolithium compounds.310 In contrast, electrochemical methods provide direct access to arylboronic acids. In the group of Duñach electrosythesis of arylboronic esters of pinacolborane was developed and extended to several different substrates (Scheme 159).311,312 Besides, it was possible to use different organoboron precursors, like trimethyl or triisopropyl borate.313,314 Generally, they used a sacrificial magnesium or aluminum anode, and as cathode either nickel foam or stainless steel is used. Initially, the arylhalides are reduced cathodically and attack as nucleophiles the pinacolborane afterward. A subsequent hydrolysis forms the boronic acids. In the group of Navarro and Menezes an electrochemical synthesis of potassium aryltrifluoroborates was developed.315 The strategy is similar to the examples given by Duñach. An aryl bromide is reduced electrochemically in the presence of triisopropyl borate to construct the C−B bond. A subsequent conversion is followed by the addition of potassium bifluoride to transform the arylboronic esters into the corresponding arylrtifluoroborates. By this protocol differently substituted bromobenzene derivatives as well as 2-naphthyl, 3-pyridyl, and 3-thienyl bromides could be converted (Scheme 160). 6.4.2. Arylation of Organosilicon Compounds. Organosilicon compounds have significant importance in organic chemistry, since they serve as directing or protecting groups or intermediates for cross-coupling reactions.316−318 An electrochemical approach to aryl silanes was established by Kawabata et al. (Scheme 161). They reduced aromatic iodides in the presence of trimethylsilyl chloride. Even heterocyclic compounds could get silylated by this protocol.319,320 In a similar fashion, Dunoguès et al. trimethylsilylated different aryl chlorides as substrates.321 An electrochemical synthesis of arylchlorosilanes has been demonstrated by Bordeau et al. (Scheme 162).322 When using 2,5-dibromothiophene it is even possible to electrosynthesize the silylated compound. In addition to thiophene, different para-substituted bromobenzene derivatives could be successfully silylated, whereas here NiBr2(bpy) was needed as mediator. It was also possible to couple the synthesized mono- or disilylated reagents with other halogenated derivatives. However, the use of a sacrificial anode is inevitable. 6.4.3. Arylation of Organophosphorus Compounds. The electrochemical arylation of phosphorus compounds is a rarely represented topic in the literature. However, there are some examples for such reactions. In 2002, Budnikova et al. investigated the electrochemical arylation of white phosphorus with aryl halides in the presence of Ni(BF4)2bpy2.323 Depending on the anode material and the aryl halide, different products are favored. For iodobenzene and a zinc anode, triphenylphosphane is the main product with a yield of 65%. Using bromobenzene and a magnesium anode, pentaphenylpentaphosphol is obtained with a yield of 60%. Finally, when applying aluminum instead of magnesium as anode material, triphenylphosphinoxide with a yield of 60% is the main product (Scheme 163). 6755


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In the same group electrochemical phosphonation of 2phenylpyridine was developed. In an electrocatalytic process with Pd(OAc)2 as mediator, they obtained the desired product in a yield of 78% (Scheme 164).324

Maximilian Selt obtained his B.Sc. degree in Chemistry in 2014 from the Johannes Gutenberg University Mainz. After working there as undergraduate research assistant in 2014, he obtained his M.Sc. degree in Organic Chemistry in 2016. Currently, he is a Ph.D. student under the supervision of Prof. Dr. S. R. Waldvogel working on electrochemical oxidative homocoupling reactions of phenols.

7. CONCLUSIONS Despite the fact that electroorganic synthesis has been known for more than 150 years, significant progress was made within the past two decades. This particular field has experienced a vivid renaissance, and more research laboratories are focusing on this methodology, since it combines several advantages, which are highly demanded in society and politics, with efficient synthetic applications. The different approach and concepts by the individual research laboratories will bring up vivid progress in electroorganic synthesis which will propel the electrochemical arylation reaction as well. Although the toolbox looks rich and versatile, sill many synthetic challenges remain, such as the selective dehydrogenative coupling of electron-rich substrate with one being electron deficient. However, electrochemical methods in the future should not employ sacrificial electrodes or scarce resources. A clear focus should be given on the sustainable nature of the electrode and electrolyte. Electroorganic synthesis and the electrochemical arylation reaction are currently transforming from a niche technology to a common synthetic tool. The outstanding sustainability of this approach will make this method inevitable on an academic and a technical level.

Barbara Riehl studied Chemistry at the Johannes Gutenberg University Mainz, where she obtained her Bachelor of Science degree in 2014 and Master of Science degree in 2016. She is currently focusing on her Ph.D. work within the research group of Prof. Waldvogel, dealing with anodic C−C cross-coupling reactions. Christopher J. Kampf studied Chemistry in Mainz, Germany, where he also received his Ph.D. degree in Analytical Chemistry in 2012 in the group of Prof. Dr. T. Hoffmann. Afterward he carried out postdoctoral research at the University of Colorado at Boulder (Prof. Dr. R. Volkamer) before starting as a team leader for Analytical Chemistry of Proteins and Organic Aerosols at the Max Planck Institute for Chemistry (Prof. Dr. U. Pöschl) in 2013. Currently, he is heading the Mass Spectrometry Department at the Institute of Organic Chemistry at Mainz University. His research focuses on the development and application of state-of-the-art mass spectrometry methods for the identification and quantification of a variety of analytes ranging from small molecules to (bio-) polymers.

ACKNOWLEDGMENTS S.R.W. thanks the DFG (Wa1276/14-1 and Wa 1276/17-1) for financial support. Support by the Advanced Lab of Electrochemistry and Electrosynthesi- ELYSION (Carl Zeiss Foundation) is gratefully acknowledged. S.L. thanks the Carl Zeiss Foundation for granting a fellowship. C.J.K. and S.R.W. acknowledge support by the Max Planck Graduate Center with the Johannes Gutenberg University Mainz (MPGC). The authors highly appreciate the financial support by the Center for INnovative and Emerging MAterials (CINEMA), the Graduate School Materials Science in Mainz (GSC 266), and the support by BMBF-EPSYLON (FKZ 13XP5016D).

ASSOCIATED CONTENT Special Issue Paper

This paper is an additional review for Chem. Rev. 2018, 118, issue 9, “Electrochemistry: Technology, Synthesis, Energy, and Materials”.

AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected].

ABBREVIATIONS Ac acetyl AcOH acetic acid Ar aryl atm atmosphere BDD boron-doped diamond Bn benzyl Bu butyl DMF dimethylformamide Et ethyl EtOH ethanol HFIP 1,1,1,3,3,3-hexafluoroisopopanol HMPA hexamethylphosphoramide i Pr isopropyl Me methyl MeOH methanol PG protecting group Ph phenyl Piv pivalyl Pr propyl R rest t Bu tert-butyl Tf trifluoromethanesulfonyl, triflyl TFA 2,2,2-trifluoroacetic acid TFE 2,2,2-trifluoroethanol

ORCID

Siegfried R. Waldvogel: 0000-0002-7949-9638 Notes

The authors declare no competing financial interest. Biographies Siegfried R. Waldvogel studied Chemistry in Konstanz and received his Ph.D. degree in 1996 from the University of Bochum/Max-PlanckInstitute for Coal Research with Prof. Dr. M. T. Reetz as supervisor. After postdoctoral research at the Scripps Research Institute in La Jolla, CA (Prof. Dr. J. Rebek, Jr.), he started his research career in 1998 with a habilitation at the University of Münster. In 2004 he moved to the University of Bonn as Professor for Organic Chemistry. In 201, he became Full Professor at the Johannes Gutenberg University Mainz. His main research interests are organic electrochemistry, oxidative coupling reactions with MoV reagents, and supramolecular sensing. Sebastian Lips obtained his B.Sc. degree in Chemistry from the Johannes Gutenberg University Mainz in 2013. After a semester abroad at the University of Massachusetts, Amherst (Prof. Dr. E. Bryan Coughlin), he finished his M.Sc. degree in Biomedical Chemistry in Mainz again. Currently, he is a Ph.D. student under the supervision of Prof. Dr. S. R. Waldvogel, working on electrochemical oxidative coupling reactions of aromatic molecules. The Carl-Zeiss Foundation supports his Ph.D. studies. 6756


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(20) Hawner, C.; Li, K.; Cirriez, V.; Alexakis, A. Copper-Catalyzed Asymmetric Conjugate Addition of Aryl Aluminum Reagents to Trisubstituted Enones: Construction of Aryl-Substituted Quaternary Centers. Angew. Chem., Int. Ed. 2008, 47, 8211−8214. (21) Palais, L.; Mikhel, I. S.; Bournaud, C.; Micouin, L.; Falciola, C. A.; Vuagnoux-d’Augustin, M.; Rosset, S.; Bernardinelli, G.; Alexakis, A. SimplePhos Monodentate Ligands: Synthesis and Application in Copper-Catalyzed Reactions. Angew. Chem. 2007, 119, 7606−7609. (22) Singh, R.; Czekelius, C.; Schrock, R. R.; Müller, P.; Hoveyda, A. H. Molybdenum Imido Alkylidene Metathesis Catalysts that Contain Electron Withdrawing Biphenolates or Binaphtholates. Organometallics 2007, 26, 2528−2539. (23) Vuagnoux-d’Augustin, M.; Kehrli, S.; Alexakis, A. Enantioselective Copper-Catalyzed Conjugate Addition to 2- or 3-Substituted Cyclopent-2-en-1-ones: Construction of Stereogenic Quaternary Carbon Centers. Synlett 2007, 2007, 2057−2060. (24) Waldvogel, S. R. Novel Anodic Concepts for the Selective Phenol Coupling Reaction. Pure Appl. Chem. 2010, 82, 1055−1063. (25) Malkowsky, I. M.; Rommel, C. E.; Wedeking, K.; Fröhlich, R.; Bergander, K.; Nieger, M.; Quaiser, C.; Griesbach, U.; Pütter, H.; Waldvogel, S. R. Facile and Highly Diastereoselective Formation of a Novel Pentacyclic Scaffold by Direct Anodic Oxidation of 2,4Dimethylphenol. Eur. J. Org. Chem. 2006, 2006, 241−245. (26) Kirste, A.; Nieger, M.; Malkowsky, I. M.; Stecker, F.; Fischer, A.; Waldvogel, S. R. Ortho-Selective Phenol-Coupling Reaction by Anodic Treatment on Boron-Doped Diamond Electrode Using Fluorinated Alcohols. Chem. - Eur. J. 2009, 15, 2273−2277. (27) Nilsson, A.; Ronlán, A.; Parker, V. D. Anodic Oxidation of Phenolic Compounds. Part III. Anodic Hydroxylation of Phenols. A Simple General Synthesis of 4-Alkyl-4-hydroxycyclo-hexa-2,5-dienones from 4-Alkylphenols. J. Chem. Soc., Perkin Trans. 1 1973, 1973, 2337− 2345. (28) Wall, M. E.; Wani, M. C.; Fullas, F.; Oswald, J. B.; Brown, D. M.; Santisuk, T.; Reutrakul, V.; McPhail, A. T.; Farnsworth, N. R. Plant Antitumor Agents. 31. The Calycopterones, a New Class of Biflavonoids with Novel Cytotoxicity in a Diverse Panel of Human Tumor Cell Lines. J. Med. Chem. 1994, 37, 1465−1470. (29) Herbert, R. B. The Biosynthesis of Plant Alkaloids and Nitrogenous Microbial Metabolites. Nat. Prod. Rep. 2001, 18, 50−65. (30) Miller, L. L.; Stewart, R. F.; Gillespie, J. P.; Ramachandran, V.; So, Y. H.; Stermitz, F. R. Synthesis of Morphinandienones, a Dihydrophenathrone, and Pummerer’s Ketones by Anodic Coupling. J. Org. Chem. 1978, 43, 1580−1586. (31) Barjau, J.; Königs, P.; Kataeva, O.; Waldvogel, S. Reinvestigation of Highly Diastereoselective Pentacyclic Spirolactone Formation by Direct Anodic Oxidation of 2,4-Dimethylphenol. Synlett 2008, 2008, 2309−2312. (32) Barjau, J.; Schnakenburg, G.; Waldvogel, S. R. Diversity-Oriented Synthesis of Polycyclic Scaffolds by mModification of an Anodic Product Derived from 2,4-Dimethylphenol. Angew. Chem., Int. Ed. 2011, 50, 1415−1419. (33) Barjau, J.; Schnakenburg, G.; Waldvogel, S. Short Domino Sequence to Dioxa[4.3.3]propellanes. Synthesis 2011, 2011, 2054− 2061. (34) Barjau, J.; Fleischhauer, J.; Schnakenburg, G.; Waldvogel, S. R. Installation of Amine Moieties into a Polycyclic Anodic Product Derived from 2,4-Dimethylphenol. Chem. - Eur. J. 2011, 17, 14785− 14791. (35) Amatore, C.; Cammoun, C.; Jutand, A. Pd(OAc)2/pBenzoquinone-Catalyzed Anaerobic Electrooxidative Homocoupling of Arylboronic Acids, Arylboronates and Aryltrifluoroborates in DMF and/or Water. Eur. J. Org. Chem. 2008, 2008, 4567−4570. (36) Mitsudo, K.; Shiraga, T.; Tanaka, H. Electrooxidative HomoCoupling of Arylboronic Acids Catalyzed by Electrogenerated Cationic Palladium Catalysts. Tetrahedron Lett. 2008, 49, 6593−6595. (37) Mitsudo, K.; Shiraga, T.; Kagen, D.; Shi, D.; Becker, J. Y.; Tanaka, H. Pd/TEMPO-Catalyzed Electrooxidative Synthesis of Biaryls from Arylboronic Acids or Arylboronic Esters. Tetrahedron 2009, 65, 8384− 8388.

tetrahydofuran triisopropylsilyl toluenesulfonyl, tosyl

REFERENCES (1) Franke, R.; Selent, D.; Börner, A. Applied Hydroformylation. Chem. Rev. 2012, 112, 5675−5732. (2) Okamoto, K.; Zhang, J.; Housekeeper, J. B.; Marder, S. R.; Luscombe, C. K. C−H Arylation Reaction: Atom Efficient and greener Syntheses of π-Conjugated Small Molecules and Macromolecules for Organic Electronic Materials. Macromolecules 2013, 46, 8059−8078. (3) von Nussbaum, F.; Brands, M.; Hinzen, B.; Weigand, S.; Häbich, D. Antibacterial Natural Products in Medicinal Chemistry - Exodus or Revival? Angew. Chem., Int. Ed. 2006, 45, 5072−5129. (4) Wiebe, A.; Gieshoff, T.; Möhle, S.; Rodrigo, E.; Zirbes, M.; Waldvogel, S. R. Electrifying Organic Synthesis. Angew. Chem., Int. Ed. 2018, 57, 5594−5619. (5) Yan, M.; Kawamata, Y.; Baran, P. S. Synthetic Organic Electrochemical Methods since 2000: On the Verge of a Renaissance. Chem. Rev. 2017, 117, 13230−13319. (6) Möhle, S.; Zirbes, M.; Rodrigo, E.; Gieshoff, T.; Wiebe, A.; Waldvogel, S. R. Modern Electrochemical Aspects for the Synthesis of Value-Added Organic Products. Angew. Chem., Int. Ed. 2018, 57, 6018− 6041. (7) Horn, E. J.; Rosen, B. R.; Baran, P. S. Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method. ACS Cent. Sci. 2016, 2, 302−308. (8) Jörissen, J. Practical Aspects of Preparative Scale Electrolysis. In Organic electrochemistry; Schäfer, H. J., Bard, A. J., Stratmann, M., Eds.; Encyclopedia of electrochemistry 8; Wiley-VCH: Weinheim, 2004; pp 25−72. (9) Fuchigami, T.; Atobe, M.; Inagi, S. Fundamentals and Applications of Organic Electrochemistry: Synthesis, Materials, Devices; John Wiley & Sons Inc: Chichester, West Sussex, 2015; pp 1−238. (10) Kulisch, J.; Nieger, M.; Stecker, F.; Fischer, A.; Waldvogel, S. R. Efficient and Stereodivergent Electrochemical Synthesis of Optically Pure Menthylamines. Angew. Chem., Int. Ed. 2011, 50, 5564−5567. (11) Malkowsky, I. M.; Rommel, C. E.; Fröhlich, R.; Griesbach, U.; Pütter, H.; Waldvogel, S. R. Novel Template-Directed Anodic PhenolCoupling Reaction. Chem. - Eur. J. 2006, 12, 7482−7488. (12) Kirste, A.; Hayashi, S.; Schnakenburg, G.; Malkowsky, I. M.; Stecker, F.; Fischer, A.; Fuchigami, T.; Waldvogel, S. R. Highly Selective Electrosynthesis of Biphenols on Graphite Electrodes in Fluorinated Media. Chem. - Eur. J. 2011, 17, 14164−14169. (13) Hilt, G. Convergent Paired Electrolysis for the ThreeComponent Synthesis of Protected Homoallylic Alcohols. Angew. Chem., Int. Ed. 2003, 42, 1720−1721. (14) In Progress in the Chemistry of Organic Natural Products; Kinghorn, A. D., Falk, H., Gibbons, S., Kobayashi, J., Eds; Springer International Publishing: Cham, Switzerland, 2017; Vol 105, pp 1−88. (15) Markham, A.; Goa, K. L. Valsartan A Review of its Pharmacology and Therapeutic Use in Essential Hypertension. Drugs 1997, 54, 299− 311. (16) Matheron, M. E.; Porchas, M. Activity of Boscalid, Fenhexamid, Fluazinam, Fludioxonil, and Vinclozolin on Growth of Sclerotinia minor and S. sclerotiorum and Development of Lettuce Drop. Plant Dis. 2004, 88, 665−668. (17) Alexakis, A.; Polet, D.; Benhaim, C.; Rosset, S. Biphenol-Based Ligands for Cu-Catalyzed Asymmetric Conjugate Addition. Tetrahedron: Asymmetry 2004, 15, 2199−2203. (18) Alexakis, A.; Polet, D.; Rosset, S.; March, S. Biphenol-Based Phosphoramidite Ligands for the Enantioselective Copper-Catalyzed Conjugate Addition of Diethylzinc. J. Org. Chem. 2004, 69, 5660−5667. (19) Cortez, G. A.; Schrock, R. R.; Hoveyda, A. H. Efficient Enantioselective Synthesis of Piperidines Through Catalytic Asymmetric Ring-Opening/Cross-Metathesis Reactions. Angew. Chem., Int. Ed. 2007, 46, 4534−4538. 6757


Chemical Reviews

Review

(57) Schubert, M.; Franzmann, P.; Wünsche von Leupoldt, A.; Koszinowski, K.; Heinze, K.; Waldvogel, S. R. Over-Oxidation as the Key Step in the Mechanism of the MoCl5-Mediated Dehydrogenative Coupling of Arenes. Angew. Chem., Int. Ed. 2016, 55, 1156−1159. (58) Waldvogel, S. R.; Trosien, S. Oxidative Transformation of Aryls Using Molybdenum Pentachloride. Chem. Commun. 2012, 48, 9109− 9119. (59) Schubert, M.; Waldvogel, S. R. MoV Reagents in Organic Synthesis. Eur. J. Org. Chem. 2016, 2016, 1921−1936. (60) Beil, S. B.; Müller, T.; Sillart, S. B.; Franzmann, P.; Bomm, A.; Holtkamp, M.; Karst, U.; Schade, W.; Waldvogel, S. R. Active Molybdenum-Based Anode for Dehydrogenative Coupling Reactions. Angew. Chem., Int. Ed. 2018, 57, 2450−2454. (61) Wehming, K.; Schubert, M.; Schnakenburg, G.; Waldvogel, S. R. Oxidative Cyclization Reaction of 2-Aryl-Substituted Cinnamates to Form Phenanthrene Carboxylates by Using MoCl5. Chem. - Eur. J. 2014, 20, 12463−12469. (62) Erdtman, H. G. H. Studies on the Formation of Complex Oxidation and Condensation Products of Phenols. Part II. Coupling of Simple Phenols and Quinones to Diphenyl Derivatives. Proc. R. Soc. London, Ser. A 1933, 143, 191−222. (63) Ronlán, A.; Bechgaard, K.; Parker, V. D.; Wennberg, I.; Norbury, A. H.; Swahn, C.-G. Electrochemistry in Media of Intermediate Acidity. Part VI. Coupling Reactions of Simple Aryl Ethers. Acta Chem. Scand. 1973, 27, 2375−2382. (64) Bechgaard, K.; Parker, V. D. Mono-, Di-, and Trications of Hexamethoxytriphenylene. Novel Anodic Trimerization. J. Am. Chem. Soc. 1972, 94, 4749−4750. (65) Waldvogel, S. R.; Mirk, D. Improved Protocol for the Synthesis of Functionalized Triphenylene Ketals. Tetrahedron Lett. 2000, 41, 4769− 4772. (66) Schopohl, M. C.; Faust, A.; Mirk, D.; Fröhlich, R.; Kataeva, O.; Waldvogel, S. R. Synthesis of Rigid Receptors Based on Triphenylene Ketals. Eur. J. Org. Chem. 2005, 2005, 2987−2999. (67) Regenbrecht, C.; Waldvogel, S. R. Efficient Electroorganic Synthesis of 2,3,6,7,10,11-Hexahydroxytriphenylene Derivatives. Beilstein J. Org. Chem. 2012, 8, 1721−1724. (68) Osa, T.; Kashiwagi, Y.; Yanagisawa, Y.; Bobbitt, J. M. Enantioselective, Electrocatalytic Oxidative Coupling of Naphthol, Naphthyl Ether and Phenanthrol on a TEMPO-Modified Graphite Felt Electrode in the Presence of (−)-Sparteine (TEMPO = 2,2,6,6Tetramethylpiperidin-1-yloxyl). J. Chem. Soc., Chem. Commun. 1994, 54, 2535−2537. (69) Morofuji, T.; Shimizu, A.; Yoshida, J.-i. Metal- and ChemicalOxidant-Free C-H/C-H Cross-Coupling of Aromatic Compounds: The Use of Radical-Cation Pools. Angew. Chem. 2012, 124, 7371− 7374. (70) Kirste, A.; Schnakenburg, G.; Stecker, F.; Fischer, A.; Waldvogel, S. R. Anodic Phenol-Arene Cross-Coupling Reaction on Boron-Doped Diamond Eelectrodes. Angew. Chem., Int. Ed. 2010, 49, 971−975. (71) Waldvogel, S. R.; Mentizi, S.; Kirste, A. Boron-Doped Diamond Electrodes for Electroorganic Chemistry. Top. Curr. Chem. 2011, 320, 1−31. (72) In Electrochemistry for the Environment; Comninellis, C.; Chen, G., Eds.; Springer: New York, 2010; pp 1−141. (73) In Synthetic Diamond Films: Preparation, Electrochemistry, Characterization, and Applications; Martínez-Huitle, C. A., Brillas, E., Eds.; The Wiley Series on Electrocatalysis and Electrochemistry; Wiley: Hoboken, NJ, 2011; pp 1−680. (74) Hollóczki, O.; Berkessel, A.; Mars, J.; Mezger, M.; Wiebe, A.; Waldvogel, S. R.; Kirchner, B. The Catalytic Effect of Fluoroalcohol Mixtures Depends on Domain Formation. ACS Catal. 2017, 7, 1846− 1852. (75) Eberson, L.; Hartshorn, M. P.; Persson, O. 1,1,1,3,3,3Hexafluoropropan-2-ol as a Solvent for the Generation of Highly Persistent Radical Cations. J. Chem. Soc., Perkin Trans. 2 1995, 141, 1735−1744. (76) Lucarini, M.; Mugnaini, V.; Pedulli, G. F.; Guerra, M. HydrogenBonding Effects on the Properties of Phenoxyl Radicals. An EPR,

(38) Aiso, H.; Kochi, T.; Mutsutani, H.; Tanabe, T.; Nishiyama, S.; Kakiuchi, F. Catalytic Electrochemical C-H Iodination and One-Pot Arylation by ON/OFF Switching of Electric Current. J. Org. Chem. 2012, 77, 7718−7724. (39) Steckhan, E.; Arns, T.; Heineman, W. R.; Hilt, G.; Hoormann, D.; Jörissen, J.; Kröner, L.; Lewall, B.; Pütter, H. Environmental Protection and Economization of Resources by Electroorganic and Electroenzymatic Syntheses. Chemosphere 2001, 43, 63−73. (40) Frontana-Uribe, B. A.; Little, R. D.; Ibanez, J. G.; Palma, A.; Vasquez-Medrano, R. Organic Electrosynthesis: A Promising Green Methodology in Organic Chemistry. Green Chem. 2010, 12, 2099. (41) Nyberg, K.; Ekström, B.; Sjöberg, B.; Husebye, S.; Klæboe, P.; Swahn, C.-G. Electrolysis in Non-Nucleophilic Media. Part V. Formation of Mixed Biaryls in the Anodic Oxidation of Naphthalene in the Presence of Alkylbenzenes. Acta Chem. Scand. 1973, 27, 503− 509. (42) Nyberg, K.; Kimmel, E. C.; Holm, B.; Widmark, G.; Koskikallio, J.; Kachi, S. Electrolysis in Non-Nucleophilic Media. Part III. Anodic Coupling of Some 5-Alkyl-Substituted m-Xylenes. Acta Chem. Scand. 1971, 25, 2983−2988. (43) Nyberg, K.; Larsen, P. K.; Lemmich, J.; Tørset, O.; Lagerlund, I.; Ehrenberg, L. Anodic Synthesis of Bimesityl by Oxidation of Mesitylene. Acta Chem. Scand. 1971, 25, 534−542. (44) Nyberg, K.; Lindberg, B.; Pilotti, Å.; Lindberg, A. A.; Lamvik, A.; Sunde, E.; Sørensen, N. A. Electrolysis in Non-Nnucleophilic Media. I. Anodic Oxidation of Durene, Mesitylene, and p-Xylene in Methylene Chloride. Acta Chem. Scand. 1970, 24, 1609−1617. (45) Saito, F.; Aiso, H.; Kochi, T.; Kakiuchi, F. Palladium-Catalyzed Regioselective Homocoupling of Arenes Using Anodic Oxidation: Formal Electrolysis of Aromatic Carbon−Hydrogen Bonds. Organometallics 2014, 33, 6704−6707. (46) Kirste, A.; Schnakenburg, G.; Waldvogel, S. R. Anodic Coupling of Guaiacol Derivatives on Boron-Doped Diamond Electrodes. Org. Lett. 2011, 13, 3126−3129. (47) Ohmori, H. Anodic Oxidation of Schiff Bases Derived from 2Hydroxy-3-Methoxybenzaldehyde. J. Electrochem. Soc. 1977, 124, 1849−1854. (48) Torii, S.; Dhimane, A.-L.; Araki, Y.; Inokuchi, T. Electrooxidative Coupling of Phenols. I. Product-Selective Electrosynthesis of 2,2′,6,6′Tetra-Tert-Butyl-1,1′-Biphenol from 2,6-Di-Tert-Butylphenol. Tetrahedron Lett. 1989, 30, 2105−2108. (49) Iguchi, M.; Nishiyama, A.; Terada, Y.; Yamamura, S. Anodic Oxidation of 4-Allyl-2-Methoxyphenol Syntheses of Demethoxyasatone and Demethoxyisoasatone. Chem. Lett. 1978, 7, 451−454. (50) Yamamoto, T.; Riehl, B.; Naba, K.; Nakahara, K.; Wiebe, A.; Saitoh, T.; Waldvogel, S. R.; Einaga, Y. A Solvent-Directed Stereoselective and Electrocatalytic Synthesis of Diisoeugenol. Chem. Commun. 2018, 54, 2771−2773. (51) Johnston, K. M. The Electrolysis of Some Hydroxyacetophenones. Tetrahedron Lett. 1967, 8, 841−844. (52) Vermillion, F. J.; Pearl, I. A. Anodic Reactions of Simple Phenolic Compounds. J. Electrochem. Soc. 1964, 111, 1392. (53) Kramer, B.; Averhoff, A.; Waldvogel, S. R. Highly Selective Formation of Eight-Membered-Ring Systems by Oxidative Cyclization with Molybdenum Pentachloride-An Environmentally Friendly and Inexpensive Access to 2,2′-Cyclolignans. Angew. Chem., Int. Ed. 2002, 41, 2981−2982. (54) Kramer, B.; Waldvogel, S. R. Highly Modular Construction of Differently Substituted Dihydrodibenzo[a,c]cycloheptenes: Fast and Efficient Access to Derivatives of 2,2′-Cyclo-7,8′-Neolignans. Angew. Chem., Int. Ed. 2004, 43, 2446−2449. (55) Waldvogel, S. R.; Fröhlich, R.; Schalley, C. A. First Artificial Receptor for CaffeineA New Concept for the Complexation of Alkylated Oxopurines. Angew. Chem., Int. Ed. 2000, 39, 2472−2475. (56) Schubert, M.; Leppin, J.; Wehming, K.; Schollmeyer, D.; Heinze, K.; Waldvogel, S. R. Powerful Fluoroalkoxy Molybdenum(V) Reagent for Selective Oxidative Arene Coupling Reaction. Angew. Chem., Int. Ed. 2014, 53, 2494−2497. 6758


Chemical Reviews

Review

Kinetic, and Computational Study. J. Am. Chem. Soc. 2003, 125, 8318− 8329. (77) Colomer, I.; Chamberlain, A. E. R.; Haughey, M. B.; Donohoe, T. J. Hexafluoroisopropanol as a Highly Versatile Solvent. Nat. Rev. Chem. 2017, 1, 0088. (78) Kirste, A.; Elsler, B.; Schnakenburg, G.; Waldvogel, S. R. Efficient Anodic and Direct Phenol-Arene C,C Cross-Coupling: The Benign Role of Water or Methanol. J. Am. Chem. Soc. 2012, 134, 3571−3576. (79) Elsler, B.; Wiebe, A.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Source of Selectivity in Oxidative Cross-Coupling of Aryls by Solvent Effect of 1,1,1,3,3,3-Hexafluoropropan-2-ol. Chem. Eur. J. 2015, 21, 12321−12325. (80) Elsler, B.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Metal- and Reagent-Free Highly Selective Anodic Cross-Coupling Reaction of Phenols. Angew. Chem., Int. Ed. 2014, 53, 5210−5213. (81) Wiebe, A.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Selective Synthesis of Partially Protected Nonsymmetric Biphenols by Reagent- and Metal-Free Anodic CrossCoupling Reaction. Angew. Chem., Int. Ed. 2016, 55, 11801−11805. (82) Riehl, B.; Dyballa, K.; Franke, R.; Waldvogel, S. Electro-Organic Synthesis as a Sustainable Alternative for Dehydrogenative CrossCoupling of Phenols and Naphthols. Synthesis 2016, 49, 252−259. (83) Lips, S.; Wiebe, A.; Elsler, B.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Synthesis of meta-Terphenyl-2,2″-diols by Anodic C-C Cross-Coupling Reactions. Angew. Chem., Int. Ed. 2016, 55, 10872−10876. (84) Schulz, L.; Enders, M.; Elsler, B.; Schollmeyer, D.; Dyballa, K. M.; Franke, R.; Waldvogel, S. R. Reagent- and Metal-Free Anodic C-C Cross-Coupling of Aniline Derivatives. Angew. Chem., Int. Ed. 2017, 56, 4877−4881. (85) Wiebe, A.; Lips, S.; Schollmeyer, D.; Franke, R.; Waldvogel, S. R. Single and Twofold Metal- and Reagent-Free Anodic C-C CrossCoupling of Phenols with Thiophenes. Angew. Chem., Int. Ed. 2017, 56, 14727−14731. (86) Dahms, B.; Franke, R.; Waldvogel, S. R. Metal- and Reagent-Free Anodic Dehydrogenative Cross-Coupling of Naphthylamines with Phenols. ChemElectroChem 2018, 5, 1249−1252. (87) Lips, S.; Frontana-Uribe, B. A.; Dörr, M.; Schollmeyer, D.; Franke, R.; Waldvogel, S. R. Metal- and Reagent-Free Anodic C,C Cross-Coupling of Phenols with Benzofurans Leading to a Furan Metathesis. Chem. - Eur. J. 2018, 24, 6057−6061. (88) Wiebe, A.; Riehl, B.; Lips, S.; Franke, R.; Waldvogel, S. R. Unexpected High Robustness of Electrochemical Cross-Coupling for a Broad Range of Current Density. Sci. Adv. 2017, 3, eaao3920. (89) Liu, K.; Tang, S.; Huang, P.; Lei, A. External Oxidant-Free Electrooxidative [3 + 2] Annulation Between Phenol and Indole Dderivatives. Nat. Commun. 2017, 8, 775. (90) Ding, H.; DeRoy, P. L.; Perreault, C.; Larivée, A.; Siddiqui, A.; Caldwell, C. G.; Harran, S.; Harran, P. G. Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide-Based Drug Development Candidate. Angew. Chem., Int. Ed. 2015, 54, 4818−4822. (91) Arai, T.; Tateno, H.; Nakabayashi, K.; Kashiwagi, T.; Atobe, M. An Anodic Aromatic C,C Cross-Coupling Reaction Using Parallel Laminar Flow Mode in a Flow Microreactor. Chem. Commun. 2015, 51, 4891−4894. (92) Malkowsky, I. M.; Fröhlich, R.; Griesbach, U.; Pütter, H.; Waldvogel, S. R. Facile and Reliable Synthesis of Tetraphenoxyborates and Their Properties. Eur. J. Inorg. Chem. 2006, 2006, 1690−1697. (93) Kweon, D.-K.; Jang, Y.-S.; Kim, H.-B. Organic Electrochemical Synthesis Utilizing Mg Electrodes (1) - Facile Reductive Coupling Reactions of Aromatic Halides. Bull. Korean Chem. Soc. 2003, 24, 1049−1050. (94) Torii, S.; Tanaka, H.; Morisaki, K. Pd(O)-Catalyzed ElectroReductive Coupling of Aryl Halides. Tetrahedron Lett. 1985, 26, 1655− 1658. (95) Kuroboshi, M.; Shiba, T.; Tanaka, H. Viologen as Catalytic Organic Reductant: Electro-Reductive Dimerization of Aryl Bromides

in a Pd/Viologen Double Mediatory System. Tetrahedron Lett. 2013, 54, 3666−3668. (96) Tanaka, H.; Kuroboshi, M.; Kataoka, R.; Suzuki, R. ElectroReductive Homo-Coupling Reaction of Aryl Bromides in PdCl2(PPh3)2/Pyridinium Salt Double Mediatory Systems. Electrochemistry 2013, 81, 356−358. (97) Pachón, L. D.; Elsevier, C. J.; Rothenberg, G. Electroreductive Palladium-Catalysed Ullmann Reactions in Ionic Liquids: Scope and Mechanism. Adv. Synth. Catal. 2006, 348, 1705−1710. (98) Meyer, G.; Rollin, Y.; Perichon, J. A Zerovalent Nickel-2,2′Bipyridine Complex: An Efficient Catalyst for Electrochemical Homocoupling of Ortho-Substituted Halides and Their Heterocoupling with Meta- and Para-Substituted Halides. J. Organomet. Chem. 1987, 333, 263−267. (99) Gomes, P.; Fillon, H.; Gosmini, C.; Labbé, E.; Périchon, J. Synthesis of Unsymmetrical Biaryls by Electroreductive CobaltCatalyzed Cross-Coupling of Aryl Halides. Tetrahedron 2002, 58, 8417−8424. (100) Jennings, P. W.; Pillsbury, D. G.; Hall, J. L.; Brice, V. T. CarbonCarbon Bond Formation via Organometallic Electrochemistry. J. Org. Chem. 1976, 41, 719−722. (101) Troupel, M.; Rollin, Y.; Sibille, S.; Perichon, J.; Fauvarque, J.-F. Catalyse par des Complexs σ-Aryl-Nickel de l’Electroreduction en Biaryles des Halogenures Aromatiques. J. Organomet. Chem. 1980, 202, 435−446. (102) Fox, M. A.; Chandler, D. A.; Lee, C. Electrocatalytic Coupling of Aryl Halides with (1,2-Bis(di-2-propylphosphino)benzene)nickel(0). J. Org. Chem. 1991, 56, 3246−3255. (103) Courtois, V.; Barhdadi, R.; Troupel, M.; Périchon, J. Electroreductive Coupling of Organic Halides in Alcoholic Solvents. An Example: The Electrosynthesis of Biaryls Catalysed by Nickel-2,2′ bipyridine Complexes. Tetrahedron 1997, 53, 11569−11576. (104) Sibille, S.; Ratovelomanana, V.; Nédélec, J. Y.; Périchon, J. An Efficient Route to Unsymmetrical Biaryls via the Electrochemical Preparation of Functionalized Aromatic Zinc Organometallics. Synlett 1993, 1993, 425−426. (105) Gosmini, C.; Lasry, S.; Nedelec, J.-Y.; Perichon, J. Electrochemical Cross-Coupling Between 2-Halopyridines and Aryl or Heteroaryl Halides Catalysed by Nickel-2,2′-bipyridine Complexes. Tetrahedron 1998, 54, 1289−1298. (106) Oliveira, J. L.; Silva, M. J.; Florêncio, T.; Urgin, K.; Sengmany, S.; Léonel, E.; Nédélec, J.-Y.; Navarro, M. Electrochemical Coupling of Mono and Dihalopyridines Catalyzed by Nickel Complex in Undivided Cell. Tetrahedron 2012, 68, 2383−2390. (107) Sengmany, S.; Le Gall, E.; Léonel, E. An Electrochemical Synthesis of Functionalized Arylpyrimidines from 4-Amino-6-chloropyrimidines and Aryl Halides. Molecules 2011, 16, 5550−5560. (108) Gosmini, C.; Nédélec, J. Y.; Périchon, J. Electrochemical CrossCoupling Between Functionalized Aryl Halides and 2-Chloropyrimidine or 2-Chloropyrazine Catalyzed by Nickel 2,2′-bipyridine Complex. Tetrahedron Lett. 2000, 41, 201−203. (109) Sengmany, S.; Vitu-Thiebaud, A.; Le Gall, E.; Condon, S.; Léonel, E.; Thobie-Gautier, C.; Pipelier, M.; Lebreton, J.; Dubreuil, D. An Electrochemical Nickel-Catalyzed Arylation of 3-Amino-6-chloropyridazines. J. Org. Chem. 2013, 78, 370−379. (110) Urgin, K.; Barhdadi, R.; Condon, S.; Léonel, E.; Pipelier, M.; Blot, V.; Thobie-Gautier, C.; Dubreuil, D. Some Mechanistic Aspects of a Nickel-Catalyzed Electrochemical Cross-Coupling Between Aryl Halides and Substituted Chloropyridazines. Electrochim. Acta 2010, 55, 4495−4500. (111) Sengmany, S.; Léonel, E.; Polissaint, F.; Nédélec, J.-Y.; Pipelier, M.; Thobie-Gautier, C.; Dubreuil, D. Preparation of Functionalized Aryl- and Heteroarylpyridazines by Nickel-Catalyzed Electrochemical Cross-Coupling Reactions. J. Org. Chem. 2007, 72, 5631−5636. (112) Le Gall, E.; Gosmini, C.; Nédélec, J.-Y.; Périchon, J. CobaltCatalyzed Electrochemical Cross-Coupling of Functionalized Phenyl Halides with 4-Chloroquinoline Derivatives. Tetrahedron Lett. 2001, 42, 267−269. 6759


Chemical Reviews

Review

(113) Gadallah, F. F.; Elofson, R. M. Arylation of Aromatic Compounds by Electrochemical Reduction of Benzenediazonium Tetrafluoroborate in Aprotic Solvents. J. Org. Chem. 1969, 34, 3335− 3338. (114) Claisen, L.; Haase, E. Ueber die Einwirkung von Phenylhydrazin auf Aethoxymethylenmalonsäureäther. Ber. Dtsch. Chem. Ges. 1895, 28, 35−41. (115) Alam, N.; Amatore, C.; Combellas, C.; Thiébault, A.; Verpeaux, J. N. Electrosynthesis of Unsymmetrical Biaryls Using a SRN1 Type Reaction. Tetrahedron Lett. 1987, 28, 6171−6174. (116) Boy, P.; Combellas, C.; Suba, C.; Thiebault, A. Electrosynthesis of Unsymmetrical Polyaryls by a SRN1-Type Reaction. J. Org. Chem. 1994, 59, 4482−4489. (117) Sun, G.; Ren, S.; Zhu, X.; Huang, M.; Wan, Y. Direct Arylation of Pyrroles via Indirect Electroreductive C-H Functionalization Using Perylene Bisimide as an Electron-Transfer Mediator. Org. Lett. 2016, 18, 544−547. (118) Qu, Y.; Tateno, H.; Matsumura, Y.; Kashiwagi, T.; Atobe, M. Cathodic Aromatic C,C Cross-Coupling Reaction via Single Electron Transfer Pathway. Molecules 2017, 22, 413−423. (119) Heimann, J.; Schäfer, H. J.; Fröhlich, R.; Wibbeling, B. Cathodic Cyclisation of N-(Oxoalkyl)pyridinium Salts − Formation of Tricyclic Indolizidine and Quinolizidine Derivatives in Aqueous Medium. Eur. J. Org. Chem. 2003, 2003, 2919−2932. (120) Schäfer, H. J. Anodic and Cathodic CC-Bond Formation. Angew. Chem., Int. Ed. Engl. 1981, 20, 911−934. (121) Gomes, P.; Gosmini, C.; Nédélec, J.-Y.; Périchon, J. Cobalt Bromide as Catalyst in Electrochemical Addition of Aryl Halides onto Activated Olefins. Tetrahedron Lett. 2000, 41, 3385−3388. (122) Condon, S.; Dupré, D.; Falgayrac, G.; Nédélec, J.-Y. NickelCatalyzed Electrochemical Arylation of Activated Olefins. Eur. J. Org. Chem. 2002, 2002, 105−111. (123) Condon-Gueugnot, S.; Leonel, E.; Nedelec, J.-Y.; Perichon, J. Electrochemical Arylation of Activated Olefins using a Nickel Salt as Catalyst. J. Org. Chem. 1995, 60, 7684−7686. (124) Condon, S.; Dupré, D.; Lachaise, I.; Nédélec, J.-Y. Nickel Catalyzed Electrochemical Heteroarylation of Activated Olefins. Synthesis 2002, 2002, 1752−1758. (125) Condon, S.; Nédélec, J.-Y. Overview on Nickel-Catalyzed Electrochemical Conjugate Addition of Organic Halides on ElectronDeficient Olefins. Synthesis 2004, 3070−3078. (126) Métay, E.; Léonel, E.; Condon, S.; Nédélec, J.-Y. Access to a New Family of Medium Ring Aromatic Lactones. Tetrahedron 2006, 62, 8515−8524. (127) Amatore, C.; Cammoun, C.; Jutand, A. Electrochemical Recycling of Benzoquinone in the Pd/Benzoquinone-Catalyzed Heck-Type Reactions from Arenes. Adv. Synth. Catal. 2007, 349, 292−296. (128) Yang, Q.-L.; Fang, P.; Mei, T.-S. Recent Advances in Organic Electrochemical C-H Functionalization. Chin. J. Chem. 2018, 36, 338− 352. (129) Tian, J.; Moeller, K. D. Electrochemically Assisted Heck Reactions. Org. Lett. 2005, 7, 5381−5383. (130) Shundo, R.; Nishiguchi, I.; Matsubara, Y.; Hirashima, T. Mn3+Mediated Coupling-Cyclization of 5-Arylpent-1-enes with Active Methylene Compounds by Electrooxidation. Chem. Lett. 1991, 20, 235−236. (131) Heiba, E. I.; Dessau, R. M. Oxidation by Metal Salts. IX. Formation of Cyclic Ketones. J. Am. Chem. Soc. 1972, 94, 2888−2889. (132) Yamamura, S.; Nishiyama, S. Anodic Oxidation of Phenols Towards the Synthesis of Bioactive Natural Products. Synlett 2002, 2002, 533−543. (133) Quideau, S.; Pouysegu, L.; Deffieux, D. Chemical and Electrochemical Oxidative Activation of Arenol Derivatives for Carbon-Carbon Bond Formation. Curr. Org. Chem. 2004, 8, 113−148. (134) In Organic Electrochemistry, 4th ed., Revised and Expanded; Lund, H., Hammerich, O., Eds.; Marcel Dekker: New York, 2001; pp 1−1391.

(135) Shizuri, Y.; Nakamura, K.; Yamamura, S. Reactions of Alkenes with Unstable Cations Electrogenerated from Phenols. J. Chem. Soc., Chem. Commun. 1985, 0, 530−531. (136) Yamamura, S.; Shizuri, Y.; Shigemori, H.; Okuno, Y.; Ohkubo, M. Natural Products Syntheses Using Anodic Oxidation of Phenols as a Key Step. Tetrahedron 1991, 47, 635−644. (137) Shizuri, Y.; Suyama, K.; Yamamura, S. Total Synthesis of (±)-Helminthosporal. J. Chem. Soc., Chem. Commun. 1986, 0, 63−64. (138) Gates, B. D.; Dalidowicz, P.; Tebben, A.; Wang, S.; Swenton, J. S. Mechanistic Aspects and Synthetic Applications of the Electrochemical and Iodobenzene Bistrifluoroacetate Oxidative 1,3-Cycloadditions of Phenols and Electron-Rich Styrene Derivatives. J. Org. Chem. 1992, 57, 2135−2143. (139) Kerns, M. L.; Conroy, S. M.; Swenton, J. S. Dihydrobenzofuran Derivatives via the Anodic Cycloaddition Reaction of p-Methoxyphenols and Vinyl Sulfides. Tetrahedron Lett. 1994, 35, 7529−7532. (140) Swenton, J. S.; Carpenter, K.; Chen, Y.; Kerns, M. L.; Morrow, G. W. Intramolecular Anodic Carbon-Carbon Bond-Forming Reactions of Oxidized Phenol Intermediates Leading to Spirodienones. Structural Effects on Reactivity and Evidence for a Phenoxonium Ion Intermediate. J. Org. Chem. 1993, 58, 3308−3316. (141) Shizuri, Y.; Yamamura, S. Efficient Synthesis of Several Aniba and Magnolia Neolignans. Tetrahedron Lett. 1983, 24, 5012−5013. (142) Yamamura, S.; Niwa, M. Retro-Diels-Alder Reaction of Asatone: Synthesis of Heterotropanone and Isoheterotropanone. Chem. Lett. 1981, 10, 625−626. (143) Maki, S.; Kosemura, S.; Yamamura, S.; Kawano, S.; Ohba, S. Electrochemical Synthesis of a Tricyclo[5.4.0.01,5]undec-9-en-8,11dione and Its Conversion to a Triqinane-Type Compound. Chem. Lett. 1992, 21, 651−654. (144) El-Seedi, H. R.; Yamamura, S.; Nishiyama, S. Anodic Oxidation of 4-Methoxy-1-naphthol. Tetrahedron Lett. 2002, 43, 3301−3304. (145) Moeller, K. D.; New, D. G. Intramolecular Anodic Olefin Coupling Reactions: Initial Studies Concerning the Use of ElectronRich Aryl Rings. Tetrahedron Lett. 1994, 35, 2857−2860. (146) New, D. G.; Tesfai, Z.; Moeller, K. D. Intramolecular Anodic Olefin Coupling Reactions and the Use of Electron-Rich Aryl Rings. J. Org. Chem. 1996, 61, 1578−1598. (147) Chiba, K.; Fukuda, M.; Kim, S.; Kitano, Y.; Tada, M. Dihydrobenzofuran Synthesis by an Anodic [3 + 2] Cycloaddition of Phenols and Unactivated Alkenes. J. Org. Chem. 1999, 64, 7654−7656. (148) Zeng, C.-C.; Liu, F.-J.; Ping, D.-W.; Hu, L.-M.; Cai, Y.-L.; Zhong, R.-G. One-Pot Electrochemical Synthesis of Fused Indole Derivatives Containing Active Hydroxyl Groups in Aqueous Medium. J. Org. Chem. 2009, 74, 6386−6389. (149) Francke, R. Recent Advances in the Electrochemical Construction of Heterocycles. Beilstein J. Org. Chem. 2014, 10, 2858−2873. (150) Thakur, A.; Singla, R.; Jaitak, V. Coumarins as Anticancer Agents: A Review on Synthetic Strategies, Mechanism of Action and SAR Studies. Eur. J. Med. Chem. 2015, 101, 476−495. (151) Katayama, A.; Senboku, H.; Hara, S. Aryl Radical Cyclization with Alkyne Followed by Tandem Carboxylation in Methyl 4-tertbutylbenzoate-Mediated Electrochemical Reduction of 2-(2Propynyloxy)bromobenzenes in the Presence of Carbon Dioxide. Tetrahedron 2016, 72, 4626−4636. (152) Jiang, Y.; Xu, K.; Zeng, C. Use of Electrochemistry in the Synthesis of Heterocyclic Structures. Chem. Rev. 2018, 118, 4485− 4540. (153) Hou, Z.-W.; Mao, Z.-Y.; Zhao, H.-B.; Melcamu, Y. Y.; Lu, X.; Song, J.; Xu, H.-C. Electrochemical C-H/N-H Functionalization for the Synthesis of Highly Functionalized (Aza)indoles. Angew. Chem., Int. Ed. 2016, 55, 9168−9172. (154) Zhao, H.-B.; Hou, Z.-W.; Liu, Z.-J.; Zhou, Z.-F.; Song, J.; Xu, H.-C. Amidinyl Radical Formation Through Anodic N-H Bond Cleavage and Its Application in Aromatic C-H Bond Functionalization. Angew. Chem., Int. Ed. 2017, 56, 587−590. 6760


Chemical Reviews

Review

(155) Organic Electrochemistry, 5th ed., Revised and Expanded; Hammerich, O.; Speiser, B., Eds.; CRC Press: Boca Raton, London, New York, 2016; pp 1−1716. (156) Svanholm, U.; Parker, V. D. Kinetics and Mechanisms of the Reactions of Organic Cation Radicals and Dications. III. Arylation of Aromatic Hydrocarbon Cation Radicals. J. Am. Chem. Soc. 1976, 98, 2942−2946. (157) Eberson, L.; Nyberg, K.; Sternerup, H.; Hytta, R.; van der Hoeven, M. G.; Swahn, C.-G. Electrolysis in Non-Nucleophilic Media. Part VI. Anodic Coupling of Aromatic Hydrocarbons in Methylene Chloride in the Presence of Strong Acids. Acta Chem. Scand. 1973, 27, 1679−1683. (158) Gallardo, I.; Guirado, G.; Marquet, J. Alkylation of Nitroaromatics with Tetraalkylborate Ion via Electrochemical Ooxidation. J. Org. Chem. 2003, 68, 7334−7341. (159) Zakurin, N. V.; Denisovich, L. I.; Gubin, S. P. Electrochemical Alkylation of Ferrocene. J. Organomet. Chem. 1977, 129, 203−206. (160) Simonet, J.; Michel, M.-A.; Lund, H.; Nimmich, W.; Servin, R.; Sternerup, H. Indirect Electrolysis. Reaction between Alkyl Halides and Electrolytically Generated Anion Radicals. Acta Chem. Scand. 1975, 29b, 489−498. (161) Pross, A.; Shaik, S. S. A Qualitative Valence-Bond Approach to Organic Reactivity. Acc. Chem. Res. 1983, 16, 363−370. (162) Pross, A. The Single Electron Shift as a Fundamental Process in Organic Chemistry: The Relationship Between Polar and ElectronTransfer Pathways. Acc. Chem. Res. 1985, 18, 212−219. (163) Hansen, P. E.; Berg, A.; Lund, H.; Devreux, M.; Vialle, J.; Anthonsen, T. Cathodic t-Butylation of Pyrene. Acta Chem. Scand. 1976, 30b, 267−270. (164) Hobolth, E.; Lund, H.; Harris, G. C.; Sanderson, T. F.; Enzell, C. R.; Berg, J.-E.; Pilotti, A.-M. Reductive Coupling of Anthracene with 1,2- and 1,3-Dihalides. Acta Chem. Scand. 1977, 31b, 395−398. (165) Wang, W.; Wang, S.; Ma, X.; Gong, J. Recent Advances in Catalytic Hydrogenation of Carbon Dioxide. Chem. Soc. Rev. 2011, 40, 3703−3727. (166) Matthessen, R.; Fransaer, J.; Binnemans, K.; De Vos, D. E. Electrocarboxylation: Towards Sustainable and Efficient Synthesis of Valuable Carboxylic Acids. Beilstein J. Org. Chem. 2014, 10, 2484−2500. (167) Silvestri, G.; Gambino, S.; Filardo, G.; Gulotta, A. Sacrificial Anodes in the Electrocarboxylation of Organic Chlorides. Angew. Chem., Int. Ed. Engl. 1984, 23, 979−980. (168) Chaussard, J.; Folest, J.-C.; Nedelec, J.-Y.; Perichon, J.; Sibille, S.; Troupel, M. Use of Sacrificial Anodes in Electrochemical Functionalization of Organic Halides. Synthesis 1990, 1990, 369−381. (169) Heintz, M.; Sock, O.; Saboureau, C.; Perichon, J.; Troupel, M. Electrosynthesis of Aryl-Carboxylic Acids from Chlorobenzene Derivatives and Carbon Dioxide. Tetrahedron 1988, 44, 1631−1636. (170) Sock, O.; Troupel, M.; Perichon, J. Electrosynthesis of Carboxylic Acids from Organic Halides and Carbon Dioxide. Tetrahedron Lett. 1985, 26, 1509−1512. (171) Amatore, C.; Jutand, A.; Khalil, F.; Nielsen, M. F. Carbon Dioxide as a C1 Building Block. Mechanism of Palladium-Catalyzed Carboxylation of Aromatic Halides. J. Am. Chem. Soc. 1992, 114, 7076− 7085. (172) Lan, Y.-C.; Wang, H.; Wu, L.-X.; Zhao, S.-F.; Gu, Y.-Q.; Lu, J.-X. Electroreduction of Dibromobenzenes on Silver Electrode in the Presence of CO2. J. Electroanal. Chem. 2012, 664, 33−38. (173) Yuan, G.; Li, L.; Jiang, H.; Qi, C.; Xie, F. Electrocarboxylation of Carbon Dioxide with Polycyclic Aromatic Hydrocarbons Using Ni as the Cathode. Chin. J. Chem. 2010, 28, 1983−1988. (174) Zhang, J.; Niu, D.; Lan, Y.; Wang, H.; Zhang, G.; Lu, J. Electrocatalytic Carboxylation of Arylic Bromides at Silver Cathode in the Presence of Carbon Dioxide. Synth. Commun. 2011, 41, 3720− 3727. (175) Senboku, H.; Yoneda, K.; Hara, S. Regioselective Electrochemical Carboxylation of Polyfluoroarenes. Electrochemistry 2013, 81, 380−382.

(176) Oçafrain, M.; Devaud, M.; Troupel, M.; Périchon, J. New Electrochemical Synthesis of Ketones from Organic Halides and Carbon Monoxide. J. Chem. Soc., Chem. Commun. 1995, 8, 2331−2332. (177) Lund, H.; Erdtman, H. G. H.; Harris, G. C.; Sanderson, T. F.; Enzell, C. R.; Berg, J.-E.; Pilotti, A.-M. Electrochemical Reductive Acetylation of Anthracene. Acta Chem. Scand. 1977, 31b, 424−425. (178) Bikker, J. A.; Brooijmans, N.; Wissner, A.; Mansour, T. S. Kinase Domain Mutations in Cancer: Implications for Small Molecule Drug Design Strategies. J. Med. Chem. 2009, 52, 1493−1509. (179) Czarnik, A. W. Guest Editorial. Acc. Chem. Res. 1996, 29, 112− 113. (180) Hili, R.; Yudin, A. K. Making Carbon-Nitrogen Bonds in Biological and Chemical Synthesis. Nat. Chem. Biol. 2006, 2, 284−287. (181) Zollinger, H. Color Chemistry: Syntheses, Properties, and Applications of Organic Dyes and Pigments, 3rd Revised ed.; WileyVCH: Weinheim, 2003; pp 1−637. (182) Sousa, M. M.; Melo, M. J.; Parola, A. J.; Morris, P. J. T.; Rzepa, H. S.; de Melo, J. S. S. A Study in Mauve: Unveiling Perkin’s Dye in Historic Samples. Chem. - Eur. J. 2008, 14, 8507−8513. (183) Weissermel, K.; Arpe, H.-J. Industrial Organic Chemistry, 3rd Completely Revised ed.; Wiley-VCH: Weinheim, 2008; pp 1−481. (184) MacDiarmid, A. G.; Epstein, A. J. Polyanilines: A Novel Class of Conducting Polymers. Faraday Discuss. Chem. Soc. 1989, 88, 317−332. (185) MacDiarmid, A. G. Polyaniline and Polypyrrole: Where are we Headed? Synth. Met. 1997, 84, 27−34. (186) Fukuyama, T.; Xu, L.; Goto, S. Total synthesis of (±)-FR900482. J. Am. Chem. Soc. 1992, 114, 383−385. (187) Bowie, A. L.; Hughes, C. C.; Trauner, D. Concise Synthesis of (±)-Rhazinilam Through Direct Coupling. Org. Lett. 2005, 7, 5207− 5209. (188) Yella, A.; Lee, H.-W.; Tsao, H. N.; Yi, C.; Chandiran, A. K.; Nazeeruddin, M. K.; Diau, E. W.-G.; Yeh, C.-Y.; Zakeeruddin, S. M.; Grätzel, M. Porphyrin-Sensitized Solar Cells with Cobalt (II/III)-Based Redox Electrolyte Exceed 12% Efficiency. Science 2011, 334, 629−634. (189) Bourdelande, J. L.; Gallardo, I.; Guirado, G. Inductive vs Solvation Effects in Primary Alkyl Amines: Determination of the Standard Potentials. J. Am. Chem. Soc. 2007, 129, 2817−2821. (190) Mu, S.; Kan, J. Evidence for the Autocatalytic Polymerization of Aniline. Electrochim. Acta 1996, 41, 1593−1599. (191) Morofuji, T.; Shimizu, A.; Yoshida, J.-i. Electrochemical C-H Amination: Synthesis of Aromatic Primary Amines via N-Arylpyridinium Ions. J. Am. Chem. Soc. 2013, 135, 5000−5003. (192) Yoshida, J.-i.; Shimizu, A.; Ashikari, Y.; Morofuji, T.; Hayashi, R.; Nokami, T.; Nagaki, A. Reaction Integration Using Electrogenerated Cationic Intermediates. Bull. Chem. Soc. Jpn. 2015, 88, 763− 775. (193) Herold, S.; Möhle, S.; Zirbes, M.; Richter, F.; Nefzger, H.; Waldvogel, S. R. Electrochemical Amination of Less-Activated Alkylated Arenes Using Boron-Doped Diamond Anodes. Eur. J. Org. Chem. 2016, 2016, 1274−1278. (194) Möhle, S.; Herold, S.; Richter, F.; Nefzger, H.; Waldvogel, S. R. Twofold Electrochemical Amination of Naphthalene and Related Arenes. ChemElectroChem 2017, 4, 2196−2210. (195) Morofuji, T.; Shimizu, A.; Yoshida, J.-i. Heterocyclization Approach for Electrooxidative Coupling of Functional Primary Alkylamines with Aromatics. J. Am. Chem. Soc. 2015, 137, 9816−9819. (196) Gao, W.-J.; Li, W.-C.; Zeng, C.-C.; Tian, H.-Y.; Hu, L.-M.; Little, R. D. Electrochemically Initiated Oxidative Amination of Benzoxazoles Using Tetraalkylammonium Halides as Redox Catalysts. J. Org. Chem. 2014, 79, 9613−9618. (197) Lisitsyn, Y. A.; Grigor’eva, L. V. Electrochemical Amination. Dilute Aqueous Organic Solutions of Sulfuric Acid. Russ. J. Electrochem. 2009, 45, 132−138. (198) Lisitsyn, Y. A.; Kargin, Y. M. Electrochemical Amination: Efficiency of a Radical Substitution. Russ. J. Electrochem. 2004, 40, 977− 980. (199) Lisitsyn, Y. A.; Kargin, Y. M. Electrochemical Amination in the System Ti(IV)−NH2OH−C6H6: The Efficiency of the Process in a 6761


Chemical Reviews

Review

Sulfuric Acid Solution Containing an Organic Solvent. Russ. J. Electrochem. 2004, 40, 864−867. (200) Lisitsyn, Y. A.; Sukhov, A. V. Electrochemical Amination of Benzene in Aqueous-Acetic Solutions of Sulfuric Acid. Russ. J. Gen. Chem. 2017, 87, 929−933. (201) Lisitsyn, Y. A.; Sukhov, A. V. Electrochemical Amination. Selective Introduction of Two Amino Groups into an Aromatic Ring. Russ. J. Gen. Chem. 2017, 87, 16−21. (202) Li, C.; Kawamata, Y.; Nakamura, H.; Vantourout, J. C.; Liu, Z.; Hou, Q.; Bao, D.; Starr, J. T.; Chen, J.; Yan, M.; et al. Electrochemically Enabled, Nickel-Catalyzed Amination. Angew. Chem., Int. Ed. 2017, 56, 13088−13093. (203) Hammerich, O.; Parker, V. D. Reaction of the Anthracene Cation Radical with Acetonitrile. A Novel Anodic Acetamidation. J. Chem. Soc., Chem. Commun. 1974, 1974, 245. (204) So, Y.-H.; Becker, J. Y.; Miller, L. L. Hydroxylation and Amidation of Aromatic Carbonyl Compounds. J. Chem. Soc., Chem. Commun. 1975, 1975, 262. (205) Hu, K.; Niyazymbetov, M. E.; Evans, D. H. Nucleophilic Aromatic Substitution by Paired Electrosynthesis: Reactions of Methoxy Arenes with 1H-Tetrazoles. Tetrahedron Lett. 1995, 36, 7027−7030. (206) Petrosyan, V. A.; Burasov, A. V. Anodic Azolation of 1,2- and 1,3-Dimethoxybenzenes. Russ. Chem. Bull. 2010, 59, 522−527. (207) Petrosyan, V. A.; Burasov, A. V. The Role of Acid Catalysis in the eElectrosynthesis of N-(2,5-Dimethoxyphenyl)azoles. Russ. Chem. Bull. 2008, 57, 292−297. (208) Petrosyan, V. A.; Burasov, A. V. Arenium Cation as the Key Intermediate of the Electrosynthesis of N-(2,5-Dimethoxyphenyl)azoles. A New Approach to the Synthesis of N-(Dimethoxyphenyl)azoles. Russ. Chem. Bull. 2007, 56, 2175−2183. (209) Petrosyan, V. A.; Burasov, A. V.; Vakhotina, T. S. Electrochemical N-Arylation of Azoles in MeOH Using Undivided Electrolysis of their Mixtures with 1,4-Dimethoxybenzene. Russ. Chem. Bull. 2005, 54, 1197−1202. (210) Petrosyan, V. A. Electrosynthesis of N -Arylazoles by Electrolyzing a Mixture of Azole and 1,4-Dimethoxybenzene in a Diaphragmless Cell. Russ. J. Electrochem. 2003, 39, 1211−1220. (211) Li, K. M.; Byun, J.; Gross, M. L.; Zamzow, D.; Jankowiak, R.; Rogan, E. G.; Cavalieri, E. L. Synthesis and Structure Determination of the Adducts formed by Electrochemical Oxidation of Dibenzo[a,l]pyrene in the Presence of Adenine. Chem. Res. Toxicol. 1999, 12, 749− 757. (212) Rogan, E. G.; Cavalieri, E. L.; Tibbels, S. R.; Cremonesi, P.; Warner, C. D.; Nagel, D. L.; Tomer, K. B.; Cerny, R. L.; Gross, M. L. Synthesis and Identification of Benzo[a]pyrene-Guanine Nucleoside Adducts Formed by Electrochemical Oxidation and by Horseradish Peroxidase Catalyzed Reaction of Benzo[a]pyrene with DNA. J. Am. Chem. Soc. 1988, 110, 4023−4029. (213) de Robillard, G.; Makni, O.; Cattey, H.; Andrieu, J.; Devillers, C. H. Towards Sustainable Synthesis of Pyren-1-yl Azoliums via Electrochemical Oxidative C−N Coupling. Green Chem. 2015, 17, 4669−4679. (214) Morofuji, T.; Shimizu, A.; Yoshida, J.-i. Direct C-N Coupling of Imidazoles with Aromatic and Benzylic Compounds via Electrooxidative C-H Functionalization. J. Am. Chem. Soc. 2014, 136, 4496− 4499. (215) Gao, X.-G.; Zhanga, N.-T.; Zeng, C.-C.; Liu, Y.-D.; Hu, L.-M.; Tian, H.-Y. Electrochemical Synthesis of Polyfunctionalized Indoles in Aqueous Medium from Catechols and Ketene N,S-acetals. Curr. Org. Synth. 2014, 11, 141−148. (216) Shabani-Nooshabadi, M.; Moradian, M.; Dadkhah-Tehrani, S. A Practical One-Pot Electrochemical Synthesis of Pyrimido[4,5b]indole Derivatives. Bull. Chem. Soc. Jpn. 2017, 90, 68−73. (217) Salehzadeh, H.; Nematollahi, D.; Hesari, H. An Efficient Electrochemical Method for the Atom Economical Synthesis of Some Benzoxazole Derivatives. Green Chem. 2013, 15, 2441−2446.

(218) Morofuji, T.; Shimizu, A.; Yoshida, J.-i. Electrochemical Intramolecular C-H Amination: Synthesis of Benzoxazoles and Benzothiazoles. Chem. - Eur. J. 2015, 21, 3211−3214. (219) Khodaei, M. M.; Alizadeh, A.; Kanjouri, T. An Efficient, OnePot, Green Synthesis of Tetracyclic Imidazo[2,1-b]thiazoles via Electrochemically Induced Tandem Heteroannulation Reactions. J. Hetercyclic. Chem. 2013, 50, 23−28. (220) Alizadeh, A.; Khodaei, M. M.; Kanjouri, T.; Shamsuddin, M. Electro-Generated ortho-Quinoide Intermediates: Templates for Feasible Construction of a Series of Novel Imidazo[2,1-b]thiazole Derivatives Through One-Pot Five-Step Domino Hetero-Annulation Process. Res. Chem. Intermed. 2015, 41, 6185−6197. (221) Shahrokhian, S.; Hamzehloei, A. Electrochemical Oxidation of Catechol in the Presence of 2-Thiouracil: Application to ElectroOrganic Synthesis. Electrochem. Commun. 2003, 5, 706−710. (222) Kajiyama, D.; Inoue, K.; Ishikawa, Y.; Nishiyama, S. A Synthetic Approach to Carbazoles Using Electrochemically Generated Hypervalent Iodine Oxidant. Tetrahedron 2010, 66, 9779−9784. (223) Broese, T.; Francke, R. Electrosynthesis Using a Recyclable Mediator-Electrolyte System Based on Ionically Tagged Phenyl Iodide and 1,1,1,3,3,3-Hexafluoroisopropanol. Org. Lett. 2016, 18, 5896− 5899. (224) Amano, Y.; Nishiyama, S. Oxidative Synthesis of Azacyclic Derivatives Through the Nitrenium Ion: Application of a Hypervalent Iodine Species Electrochemically Generated from Iodobenzene. Tetrahedron Lett. 2006, 47, 6505−6507. (225) Amano, Y.; Inoue, K.; Nishiyama, S. Oxidative Access to Quinolinone Derivatives with Simultaneous Rearrangement of Functional Groups. Synlett 2008, 2008, 134−136. (226) Inoue, K.; Ishikawa, Y.; Nishiyama, S. Synthesis of Tetrahydropyrroloiminoquinone Alkaloids Based on Electrochemically Generated Hypervalent Iodine Oxidative Cyclization. Org. Lett. 2010, 12, 436−439. (227) Wesenberg, L. J.; Herold, S.; Shimizu, A.; Yoshida, J.-i.; Waldvogel, S. R. New Approach to 1,4-Benzoxazin-3-ones by Electrochemical C-H Amination. Chem. - Eur. J. 2017, 23, 12096− 12099. (228) Weinberg, N. L.; Weinberg, H. R. Electrochemical Oxidation of Organic Compounds. Chem. Rev. 1968, 68, 449−523. (229) Aramata, A. Electrooxidation of Benzene to Benzoquinone on Platinum Group Metals. J. Electroanal. Chem. Interfacial Electrochem. 1985, 182, 197−201. (230) Oberrauch, E.; Eberson, L. An Electrochemical Route to Trimethylhylhydroquinone. J. Appl. Electrochem. 1986, 16, 575−582. (231) Fujimoto, K.; Maekawa, H.; Tokuda, Y.; Matsubara, Y.; Mizuno, T.; Nishiguchi, I. Selective Monohydroxylation of Benzene by Anodic Oxidation. Synlett 1995, 1995, 661−662. (232) Fujimoto, K.; Tokuda, Y.; Maekawa, H.; Matsubara, Y.; Mizuno, T.; Nishiguchi, I. Selective and One-Pot Formation of Phenols by Anodic Oxidation. Tetrahedron 1996, 52, 3889−3896. (233) So, Y.-H.; Miller, L. L. Hydroxylation of Aromatic Compounds. Synthesis 1976, 1976, 468−469. (234) Belleau, B.; Weinberg, N. L. The Electrochemical Methoxylation of Methoxybenzenes and Related Componds. J. Am. Chem. Soc. 1963, 85, 2525−2526. (235) Elgy, G. M.; Jennings, W. B.; Pedler, A. E. The Electrochemical Methoxylation of Dialkoxyaromatic Compounds and the Determination of Isomer Ratios by N.M.R. Spectroscopy. J. Chem. Soc., Perkin Trans. 1 1983, 1983, 1255−1259. (236) Guirado, A.; Barba, F.; Franco, J. A. Electrochemical Methoxylation of Acenaphthylene. A Stereoselective Effect of Anode Material. Electrochim. Acta 1982, 27, 1621. (237) Henton, D. R.; McCreery, R. A.; Swenton, J. S. Anodic Oxidation of 1,4-Dimethoxy Aromatic Compounds. A Facile Route to Functionalized Quinone Bisketals. J. Org. Chem. 1980, 45, 369−378. (238) Nilsson, A.; Ronlán, A.; Parker, V. D. A Novel Synthesis of 4Chloro-4-hethylcyclohexa-2,5-dienone and 4,4-Dimethoxycyclohexa2,5-dienone. Tetrahedron Lett. 1975, 16, 1107−1110. 6762


Chemical Reviews

Review

(239) Margareths, P.; Tissot, P. 3,3,6,6-Tetramethoxy-1,4-cyclohexadiene. Org. Synth. 1977, 57, 92. (240) Hawkes, G. E.; Hawkes, J. E.; Comninos, F. C.M.; Pardini, V. L.; Viertler, H. An Unusual Anodic Methoxylation: 3,4-Dimethoxyacetophenone. Tetrahedron Lett. 1992, 33, 8133−8136. (241) Dolson, M. G.; Swenton, J. S. Product and Mechanistic Studies of the Anodic Oxidation of Methoxylated Naphthalenes. The EECrCp Mechanism. J. Am. Chem. Soc. 1981, 103, 2361−2371. (242) Sauermann, N.; Meyer, T. H.; Tian, C.; Ackermann, L. Electrochemical Cobalt-Catalyzed C-H Oxygenation at Room Temperature. J. Am. Chem. Soc. 2017, 139, 18452−18455. (243) Takahashi, M.; Konishi, H.; Iida, S.; Nakamura, K.; Yamamura, S.; Nishiyama, S. Phenolic Oxidation of o,o′-Dihalogenated Phenols. Tetrahedron 1999, 55, 5295−5302. (244) Nishiyama, S.; Kim, M. H.; Yamamura, S. Syntheses of Isodityrosine, Dityrosine and Related Compounds by Phenolic Oxidation of Tyrosine and Phenylglycine Derivatives Using an Electrochemical Method. Tetrahedron Lett. 1994, 35, 8397−8400. (245) Naito, Y.; Tanabe, T.; Kawabata, Y.; Ishikawa, Y.; Nishiyama, S. Electrochemical Construction of the Diaryl Ethers: A Synthetic Approach to o-Methylthalibrine. Tetrahedron Lett. 2010, 51, 4776− 4778. (246) Tanabe, T.; Doi, F.; Ogamino, T.; Nishiyama, S. A Total Synthesis of Verbenachalcone, a Bioactive Diaryl Ether from Verbena littoralis. Tetrahedron Lett. 2004, 45, 3477−3480. (247) Kashiwagi, T.; Fuchigami, T.; Saito, T.; Nishiyama, S.; Atobe, M. Sequential Paired Electrosynthesis of a Diaryl Ether Derivative Using an Electrochemical Microreactor. Chem. Lett. 2014, 43, 799− 801. (248) Fuchigami, T.; Awata, T.; Nonaka, T.; Baizer, M. M. Esterification, Etherification, and Aldol Condensation Using Cathodically-Generated Organic Olate Anions. Bull. Chem. Soc. Jpn. 1986, 59, 2873−2879. (249) Eberson, L. Electrolytic Substitution Reactions. III. Isomer Distributions and Isotope Effects in Nuclear and Side-Chain Anodic Acetoxylation of Aromatic Compounds. J. Am. Chem. Soc. 1967, 89, 4669−4677. (250) Eberson, L.; Oberrauch, E. Studies on Electrolytic Substitution Reactions. XVII. Selective Nuclear Acetoxylation of Alkylaromatic Compounds. Acta Chem. Scand. 1981, 35b, 193−196. (251) Eberson, L.; Nyberg, K. Studies on Electrolytic Substitution Reactions. I. Anodic Acetoxylation. J. Am. Chem. Soc. 1966, 88, 1686− 1691. (252) Petrosyan, V. A.; Vakhotina, T. S.; Burasov, A. V. Regularities of Anodic Acetoxylation of 1,4-Dimethoxybenzene in Protic and Aprotic Media. Russ. Chem. Bull. 2005, 54, 1580−1584. (253) Burasov, A. V.; Petrosyan, V. A. Electrophilic Components in the Electrochemical Acetoxylation of Substituted Arenes. Mendeleev Commun. 2008, 18, 196−197. (254) Kreh, R. P.; Tadros, M. E.; Hand, H. M.; Cockerham, M. P.; Smith, E. K. Indirect Hydroxylation of Aromatic Rings Using Electrochemical Methods. J. Appl. Electrochem. 1986, 16, 440−446. (255) Bockmair, G.; Fritz, H. P.; Gebauer, H. Electrochemical SynthesesXIII[1]. The Hydroxylation of Chlorobenzene via the Electrosynthesis of Trifluoroacetates. Electrochim. Acta 1978, 23, 21− 23. (256) Blum, Z.; Cedheim, L.; Nyberg, K.; Hörnfeldt, A.-B.; Servin, R.; Sternerup, H. Studies on Electrolytic Substitution Reactions. X. Anodic Trifluoroacetoxylation of Benzene and Deactivated Benzenes. Acta Chem. Scand. 1975, 29b, 715−716. (257) Tajima, T.; Kishi, Y.; Nakajima, A. Anodic Acyloxylation Based on the Acid−Base Reactions Between Acetic Acid or Trifluoroacetic Acid and Solid-Supported Bases. Electrochim. Acta 2009, 54, 5959− 5963. (258) Li, Y.-Q.; Yang, Q.-L.; Fang, P.; Mei, T.-S.; Zhang, D. Palladium-Catalyzed C(sp2)-H Acetoxylation via Electrochemical Oxidation. Org. Lett. 2017, 19, 2905−2908.

(259) Shrestha, A.; Lee, M.; Dunn, A. L.; Sanford, M. S. PalladiumCatalyzed C-H Bond Acetoxylation via Electrochemical Oxidation. Org. Lett. 2018, 20, 204−207. (260) Dudkina, Y. B.; Mikhaylov, D. Y.; Gryaznova, T. V.; Tufatullin, A. I.; Kataeva, O. N.; Vicic, D. A.; Budnikova, Y. H. Electrochemical Ortho Functionalization of 2-Phenylpyridine with Perfluorocarboxylic Acids Catalyzed by Palladium in Higher Oxidation States. Organometallics 2013, 32, 4785−4792. (261) Anand, P.; Singh, B.; Singh, N. A Review on Coumarins as Acetylcholinesterase Inhibitors for Alzheimer’s Disease. Bioorg. Med. Chem. 2012, 20, 1175−1180. (262) Passman, R. S.; Bennett, C. L.; Purpura, J. M.; Kapur, R.; Johnson, L. N.; Raisch, D. W.; West, D. P.; Edwards, B. J.; Belknap, S. M.; Liebling, D. B.; et al. Amiodarone-Associated Optic Neuropathy: A Critical Review. Am. J. Med. 2012, 125, 447−453. (263) Yang, Z.; Hon, P. M.; Chui, K. Y.; Xu, Z. L.; Chang, H. M.; Lee, C. M.; Cui, Y. X.; Wong, H. N.C.; Poon, C. D.; Fung, B. M. Naturally Occurring Benzofuran: Isolation, Structure Elucidation and Total Synthesis of 5-(3-Hydroxypropyl)-7-methoxy-2-(3′-methoxy-4′-hydroxyphenyl)-3-benzo[b]furancarbaldehyde, a Novel Adenosine A1 Receptor Ligand Isolated from Salvia Miltiorrhiza Bunge (Danshen). Tetrahedron Lett. 1991, 32, 2061−2064. (264) Koehl, W. J. Anodic Oxidation of 3,3-Diphenylacrylic Acid and Diphenylacetylene. J. Org. Chem. 1967, 32, 614−618. (265) Fakhari, A. R.; Nematollahi, D.; Shamsipur, M.; Makarem, S.; Hosseini Davarani, S. S.; Alizadeh, A.; Khavasi, H. R. Electrochemical Synthesis of 5,6-Dihydroxy-2-methyl-1-benzofuran-3-carboxylate Derivatives. Tetrahedron 2007, 63, 3894−3898. (266) Grujić, Z.; Tabaković, I.; Trkovnik, M. Electrochemical Syntheses of Heterocyclic Compounds-IV. Syntheses with Nascent Quinones. Tetrahedron Lett. 1976, 17, 4823−4824. (267) Hosseiny Davarani, S. S.; Mashkouri Najafi, N.; Ramyar, S.; Masoumi, L.; Shamsipur, M. An Improved Electrochemical Method for the Synthesis of Some Benzofuran Derivatives. Chem. Pharm. Bull. 2006, 54, 959−962. (268) Nematollahi, D.; Forooghi, Z. Electrochemical Oxidation of Catechols in the Presence of 4-Hydroxy-6-methyl-2-pyrone. Tetrahedron 2002, 58, 4949−4953. (269) Nematollahi, D.; Habibi, D.; Rahmati, M.; Rafiee, M. A Facile Electrochemical Method for Synthesis of New Benzofuran Derivatives. J. Org. Chem. 2004, 69, 2637−2640. (270) Nematollahi, D.; Rafiee, M. Diversity in Electrochemical Oxidation of Dihydroxybenzoic Acids in the Presence of Acetylacetone. A Green Method for Synthesis of New Benzofuran Derivatives. Green Chem. 2005, 7, 638−644. (271) Shamsipur, M.; Davarani, S. S. H.; Nematollahi, D. Electrochemical Oxidation of Catechols in the Presence of Ethyl-2chloroacetoacetate. Synthesis and Mechanistic Study. J. Heterocycl. Chem. 2006, 43, 1673−1677. (272) Hosseiny Davarani, S. S.; Fakhari, A. R.; Fumani, N. S.; Kalatebojdi, M. Electrochemical Synthesis of New Benzodifurans. Electrochem. Commun. 2008, 10, 1765−1768. (273) Gieshoff, T.; Kehl, A.; Schollmeyer, D.; Moeller, K. D.; Waldvogel, S. R. Electrochemical Synthesis of Benzoxazoles from Anilides - a New Approach to Employ Amidyl Radical Intermediates. Chem. Commun. 2017, 53, 2974−2977. (274) Kehl, A.; Gieshoff, T.; Schollmeyer, D.; Waldvogel, S. R. Electrochemical Conversion of Phthaldianilides to Phthalazin-1,4diones by Dehydrogenative N-N Bond Formation. Chem. - Eur. J. 2018, 24, 590−593. (275) Gieshoff, T.; Kehl, A.; Schollmeyer, D.; Moeller, K. D.; Waldvogel, S. R. Insights into the Mechanism of Anodic N-N Bond Formation by Dehydrogenative Coupling. J. Am. Chem. Soc. 2017, 139, 12317−12324. (276) Xu, F.; Qian, X.-Y.; Li, Y.-J.; Xu, H.-C. Synthesis of 4H-1,3Benzoxazines via Metal- and Oxidizing Reagent-Free Aromatic C-H Oxygenation. Org. Lett. 2017, 19, 6332−6335. 6763


Chemical Reviews

Review

(277) Do, Q. T.; Elothmani, D.; Le Guillanton, G. Electrophilic Substitutions with the Electrogenerated Sulfenium Cation R1-S+. Tetrahedron Lett. 1998, 39, 4657−4658. (278) Do, Q. T.; Elothmani, D.; Simonet, J.; Guillanton, G. L. The Electrochemical Oxidation of Dimethyl Disulfide - Anodic Methylsulfanylation of Phenols and Aromatic Ethers. Electrochim. Acta 2005, 50, 4792−4799. (279) Yoshida, J.-i.; Shimizu, A.; Hayashi, R. Electrogenerated Cationic Reactive Intermediates: The Pool Method and Further Advances. Chem. Rev. 2018, 118, 4702−4730. (280) Yoshida, J.-i.; Suga, S. Basic Concepts of “Cation Pool” and “Cation Flow” Methods and Their Applications in Conventional and Combinatorial Organic Synthesis. Chem. - Eur. J. 2002, 8, 2650−2658. (281) Matsumoto, K.; Kozuki, Y.; Ashikari, Y.; Suga, S.; Kashimura, S.; Yoshida, J.-i. Electrophilic Substitution Reactions Using an Electrogenerated ArS(ArSSAr)+ Cation Pool as an ArS+ Equivalent. Tetrahedron Lett. 2012, 53, 1916−1919. (282) Kashiwagi, T.; Amemiya, F.; Fuchigami, T.; Atobe, M. In Situ Electrogeneration of o-Benzoquinone and High Yield Reaction with Benzenethiols in a Microflow System. Chem. Commun. 2012, 48, 2806− 2808. (283) Kashiwagi, T.; Amemiya, F.; Fuchigami, T.; Atobe, M. Continuous In Situ Electrogeneration of o-Benzoquinone in Microreactor: Application to High Yield Reaction with Benzenethiols. J. Flow Chem. 2013, 3, 17−22. (284) Zeng, C.-C.; Ping, D.-W.; Zhang, S.-C.; Zhong, R.-G.; Becker, J. Y. Electrochemical Synthesis of Polyhydroxylated Aromatic Derivatives Substituted with Mono- and Dipyrimidinyl Thioethers in Aqueous Medium. J. Electroanal. Chem. 2008, 622, 90−96. (285) Zeng, C.-C.; Liu, F.-J.; Ping, D.-W.; Hu, L.-M.; Cai, Y.-L.; Zhong, R.-G. Electrochemical Synthesis of 1,3,4-Thiadiazol-2-ylthiosubstituted Catechols in Aqueous Medium. Tetrahedron 2009, 65, 4505−4512. (286) Fakhari, A. R.; Hosseiny Davarani, S. S.; Ahmar, H.; Hasheminasab, K.; Khavasi, H. R. A Facile Electrochemical Method for the Synthesis of 5-Phenyl-1,3,4-oxadiazol-2-ylthio-benzene-1,2-diol Derivatives. J. Heterocycl. Chem. 2009, 46, 443−446. (287) Nematollahi, D.; Tammari, E. Electroorganic Synthesis of Catecholthioethers. J. Org. Chem. 2005, 70, 7769−7772. (288) Nematollahi, D.; Mahdinia, S.; Karimi, P.; Salehzadeh, H.; Kaihani, S. A Green Electrochemical Method for the Synthesis of New N,N′-Diphenylbenzene-1,4-diamine Derivatives. RSC Adv. 2015, 5, 29209−29213. (289) Wang, P.; Tang, S.; Huang, P.; Lei, A. Electrocatalytic OxidantFree Dehydrogenative C-H/S-H Cross-Coupling. Angew. Chem., Int. Ed. 2017, 56, 3009−3013. (290) Fritz, H. P.; Ecker, P. Elektrochemische Synthesen, XVIII: Reaktionen des Naphthalinradikalkations mit Nucleophilen. Chem. Ber. 1981, 114, 3643−3654. (291) Krishnan, P.; Gurjar, V. G. Electrochemical Oxidation of Thiocyanate in a Two-Phase Electrolyte. J. Appl. Electrochem. 1995, 25, 792−796. (292) Krishnan, P.; Gurjar, V. G. Electrochemical Thiocyanation by Two Phase Electrolysis. J. Appl. Electrochem. 1993, 23, 268−270. (293) Krishnan, P.; Gurjar, V. G. A Two Phase Electrochemical Method for Thiocyanation. Synth. Commun. 1992, 22, 2741−2744. (294) Gitkis, A.; Becker, J. Y. A Selective One-Pot Electrochemical Thiocyanation of Methoxybenzene (Anisole). J. Electroanal. Chem. 2006, 593, 29−33. (295) Gitkis, A.; Becker, J. Y. Anodic Thiocyanation of Mono- and Disubstituted Aromatic Compounds. Electrochim. Acta 2010, 55, 5854−5859. (296) Fotouhi, L.; Nikoofar, K. Electrochemical Thiocyanation of Nitrogen-Containing Aromatic and Heteroaromatic Compounds. Tetrahedron Lett. 2013, 54, 2903−2905. (297) Kokorekin, V. A.; Sigacheva, V. L.; Petrosyan, V. A. New Data on Heteroarene Thiocyanation by Anodic Oxidation of NH4SCN. The Processes of Electroinduced Nucleophilic Aromatic Substitution of Hydrogen. Tetrahedron Lett. 2014, 55, 4306−4309.

(298) Nourmohammadi, F.; Golabi, S. M.; Saadnia, A. Electrochemical Synthesis of Organic Compounds: 1. Addition of Sulfinic Acids to Electrochemically Generated o- and p-Benzoquinones. J. Electroanal. Chem. 2002, 529, 12−19. (299) Nematollahi, D.; Varmaghani, F. Paired Electrochemical Synthesis of New Organosulfone Derivatives. Electrochim. Acta 2008, 53, 3350−3355. (300) Nematollahi, D.; Amani, A. Electrochemical Synthesis of the New Substituted Phenylpiperazines. J. Electroanal. Chem. 2011, 651, 72−79. (301) Nematollahi, D.; Esmaili, R. A Green Approach for the Electrochemical Synthesis of 4-Morpholino-2-(arylsulfonyl)benzenamines. Tetrahedron Lett. 2010, 51, 4862−4865. (302) Sharafi-Kolkeshvandi, M.; Nematollahi, D.; Nikpour, F. A Regioselective and Convergent Paired Electrochemical Synthesis of N,N′-Diphenyl-3-sulfonyl-[1,1′-biphenyl]-4,4′-diamines. Synthesis 2017, 49, 1555−1560. (303) Xiao, H.-L.; Yang, C.-W.; Zhang, N.-T.; Zeng, C.-C.; Hu, L.-M.; Tian, H.-Y.; Little, R. D. Electrochemical Oxidation of Aminophenols in the Presence of Benzenesulfinate. Tetrahedron 2013, 69, 658−663. (304) Zeng, C.-C.; Liu, C.-F.; Zeng, J.; Zhong, R.-G. Electrochemical Synthesis of 6-Arylsulfonyl Caffeic Acid Derivatives in Aqueous Medium. J. Electroanal. Chem. 2007, 608, 85−90. (305) Feng, M.-L.; Xi, L.-Y.; Chen, S.-Y.; Yu, X.-Q. Electrooxidative Metal-Free Dehydrogenative α-Sulfonylation of 1 H -Indole with Sodium Sulfinates. Eur. J. Org. Chem. 2017, 2017, 2746−2750. (306) Wang, P.; Tang, S.; Lei, A. Electrochemical Intramolecular Dehydrogenative C−S Bond Formation for the Synthesis of Benzothiazoles. Green Chem. 2017, 19, 2092−2095. (307) Qian, X.-Y.; Li, S.-Q.; Song, J.; Xu, H.-C. TEMPO-Catalyzed Electrochemical C−H Thiolation: Synthesis of Benzothiazoles and Thiazolopyridines from Thioamides. ACS Catal. 2017, 7, 2730−2734. (308) Suzuki, A. Recent Advances in the Cross-Coupling Reactions of Organoboron Derivatives with Organic Electrophiles. J. Organomet. Chem. 1999, 576, 147−168. (309) Hawkins, R. T.; Lennarz, W. J.; Snyder, H. R. Arylboronic Acids. V. Methyl-Substituted Boronic Acids, Borinic Acids and Triarylborons. J. Am. Chem. Soc. 1960, 82, 3053−3059. (310) Yamashita, H.; Amano, K.; Shimada, S.; Narasaka, K. Synthesis of Terphenylboronic Acid Derivatives and Recognition of Anomers of 2-Deoxyribofuranoside. Chem. Lett. 1996, 25, 537−538. (311) Laza, C.; Pintaric, C.; Olivero, S.; Duñach, E. Electrochemical Reduction of Polyhalogenated Aryl Derivatives in the Presence of Pinacolborane: Electrosynthesis of Functionalised Arylboronic Esters. Electrochim. Acta 2005, 50, 4897−4901. (312) Laza, C.; Duñach, E. New Electrosynthesis of Arylboronic Esters from Aromatic Halides and Pinacolborane. Adv. Synth. Catal. 2003, 345, 580−583. (313) Laza, C.; Duñach, E. Nouvelle Méthode de Synthèse d’Acides et d’Esters Arylboroniques par Electroréduction de Dérivés Aromatiques Halogénés en Présence d’Agents Boratants. C. R. Chim. 2003, 6, 185− 187. (314) Laza, C.; Duñach, E.; Serein-Spirau, F.; Moreau, J. J. E.; Vellutini, L. Novel Synthesis of Arylboronic Acids by Electroreduction of Aromatic Halides in the Presence of Trialkyl Borates. New J. Chem. 2002, 26, 373−375. (315) Nascimento, W.; Oliveira, J.; Freitas, J.; Navarro, M.; Menezes, P. Electrochemical Synthesis of Potassium Aryltrifluoroborates. Synthesis 2014, 46, 2579−2584. (316) Ottosson, H.; Steel, P. G. Silylenes, Silenes, and Disilenes: Novel Silicon-Based Reagents for Organic Synthesis? Chem. - Eur. J. 2006, 12, 1576−1585. (317) Sahoo, A. K.; Oda, T.; Nakao, Y.; Hiyama, T. Cross-Coupling of Triallyl(aryl)silanes with Aryl Bromides and Chlorides: An Alternative Convenient Biaryl Synthesis. Adv. Synth. Catal. 2004, 346, 1715−1727. (318) Horn, K. A. Regio- and Stereochemical Aspects of the Palladium-Catalyzed Reactions of Silanes. Chem. Rev. 1995, 95, 1317−1350. 6764


Chemical Reviews

Review

(319) Yoshida, J.; Muraki, K.; Funahashi, H.; Kawabata, N. Electrochemical Synthesis of Organosilicon Compounds. J. Org. Chem. 1986, 51, 3996−4000. (320) Yoshida, J.-i.; Muraki, K.; Funahashi, H.; Kawabata, N. Electrochemical Synthesis of Organosilicon Compounds. J. Organomet. Chem. 1985, 284, C33−C35. (321) Bordeau, M.; Biran, C.; Pons, P.; Leger-Lambert, M. P.; Dunogues, J. The Electrochemical Rreductive Trimethylsilylation of Aryl Chlorides: A Good Route to Aryltrimethylsilanes and a Novel Route to Tris(trimethylsilyl)cyclohexadienes. J. Org. Chem. 1992, 57, 4705−4711. (322) Moreau, C.; Serein-Spirau, F.; Bordeau, M.; Biran, C. Electrochemical Synthesis of Functional Aryl- and Heteroarylchlorosilanes. Application to the Preparation of Donor−Acceptor or Donor−Donor Organosilicon Molecules. Organometallics 2001, 20, 1910−1917. (323) Yakhvarov, D. G.; Budnikova, Y. H.; Tazeev, D. I.; Sinyashin, O. G. The Influence of the Sacrificial Anode Nature on the Mechanism of Electrochemical Arylation and Alkylation of White Phosphorus. Russ. Chem. Bull. 2002, 51, 2059−2064. (324) Grayaznova, T. V.; Dudkina, Y. B.; Islamov, D. R.; Kataeva, O. N.; Sinyashin, O. G.; Vicic, D. A.; Budnikova, Y. H. Pyridine-Directed Palladium-Catalyzed Electrochemical Phosphonation of C(sp2)−H Bond. J. Organomet. Chem. 2015, 785, 68−71.

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