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Recent Applications of Homogeneous Catalysis in Electrochemical Organic Synthesis

2021; Chinese Chemical Society; Volume: 4; Issue: 4 Linguagem: Inglês

10.31635/ccschem.021.202101451

2096-5745

Xu Cheng, Aiwen Lei, Tian‐Sheng Mei, Hai‐Chao Xu, Kun Xu, Cheng‐Chu Zeng,

Conducting polymers and applications

Open AccessCCS ChemistryMINI REVIEW1 Apr 2022Recent Applications of Homogeneous Catalysis in Electrochemical Organic Synthesis Xu Cheng†, Aiwen Lei†, Tian-Sheng Mei†, Hai-Chao Xu†, Kun Xu† and Chengchu Zeng† Xu Cheng† *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] E-mail Address: [email protected] School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023 †X. Cheng, A. Lei, T. Mei, H. Xu, K. Xu, and C. Zeng contributed equally to this work.Google Scholar More articles by this author , Aiwen Lei† College of Chemistry and Molecular Sciences, Institute for Advanced Studies (IAS), Wuhan University, Wuhan 430072 †X. Cheng, A. Lei, T. Mei, H. Xu, K. Xu, and C. Zeng contributed equally to this work.Google Scholar More articles by this author , Tian-Sheng Mei† State Key Laboratory of Organometallic Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032 †X. Cheng, A. Lei, T. Mei, H. Xu, K. Xu, and C. Zeng contributed equally to this work.Google Scholar More articles by this author , Hai-Chao Xu† State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005 †X. Cheng, A. Lei, T. Mei, H. Xu, K. Xu, and C. Zeng contributed equally to this work.Google Scholar More articles by this author , Kun Xu† Faculty of Environment and Life, Beijing University of Technology, Beijing 100124 †X. Cheng, A. Lei, T. Mei, H. Xu, K. Xu, and C. Zeng contributed equally to this work.Google Scholar More articles by this author and Chengchu Zeng† Faculty of Environment and Life, Beijing University of Technology, Beijing 100124 †X. Cheng, A. Lei, T. Mei, H. Xu, K. Xu, and C. Zeng contributed equally to this work.Google Scholar More articles by this author https://doi.org/10.31635/ccschem.021.202101451 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Although the combination of electrochemistry and homogeneous catalysis has proven to be a powerful strategy for achieving a diverse array of novel transformations, some challenges such as controlling the diffusion of catalyst-related species and the instability of catalysts at electrodes remain to be overcome. Herein, we review recent advances in electrochemical homogeneous catalysis, focusing on electrochemical noble-transition-metal catalysis, photoelectrochemical catalysis, and electrochemical enantioselective catalysis. The topics discussed include: (1) how the noble metal catalyst works in the presence of cathodic hydrogen evolution, (2) how the photocatalyst gets enhanced redox property, and (3) how the enantioselectivity is regulated in a catalytic electrochemical reaction. Download figure Download PowerPoint Introduction Catalysts are chemicals that alter reaction pathways by interacting with reactants at specific sites to form transition states that ultimately lower the energy input required for the pathway. Therefore, catalytic reactions are useful for green chemistry and chemical engineering applications.1 Among the various catalytic strategies, extensive progress has been achieved in homogeneous catalysis recently, and its use in organic synthesis permits control of the chemo-, regio-, and enantioselectivities of reactions.2 Electrochemical processes were first observed in biological systems and electrochemical cells in the late-eighteenth century,3 and the first organic electrochemical syntheses were achieved by Faraday4 and Kolbe5,6 in the first half of the nineteenth century. The use of electrochemistry for organic synthesis has witnessed sustained growth in recent years (Figure 1).7 When electricity is used as a driving force to activate inert compounds, they can undergo various transformations readily, which are otherwise challenging. In particular, multiple electron transfers can occur rapidly at electrodes, whereas such transfers are hard to achieve by other methods. Figure 1 | Annual numbers of publications on electrochemical organic synthesis, 2016–2020. Download figure Download PowerPoint Merging homogeneous catalysis and electrochemical synthesis can provide a new driving force for catalytic cycles, generate reactive intermediates at electrodes, and reduce the demand for reagents such as external oxidants (Figures 2a–2c). For transition-metal catalysis, in particular, electron transfer at the electrodes generates catalysts with more valence states, and thus, enables unprecedented catalytic pathways. However, under electrochemical conditions, homogeneous catalysis presents some challenges. For example, solution-phase catalysts can undergo electron transfer at the electrodes. Because this is an interfacial process, diffusion of mass, which has only marginal relevance under homogeneous conditions, becomes an essential factor in catalytic electrochemical synthesis (Figure 2d). In addition, transition metals can take part in multiple electron transfers at the cathode, resulting in the generation of M0, followed by deactivation and precipitation of the metal (Figure 2f). Moreover, a number of ligands developed for homogeneous catalysis (e.g., phosphines) can be irreversibly oxidized at the anode, which limits the choice of ligands used for electrochemical synthesis (Figure 2e). Figure 2 | (a–f) Advantages and challenges of electrochemical homogeneous catalysis. Download figure Download PowerPoint Seminal reviews and accounts of electrochemical organic synthesis have been addressed in recent years.8–28 Herein, we review advances in the design of homogeneous electrochemical catalysis for organic synthesis, focusing on electrochemical noble-transition-metal catalysis, photoelectrochemical catalysis, and electrochemical enantioselective catalysis. Electrochemical Noble-Transition-Metal Catalysis Transition-metal complexes have been extensively used in electrochemical reactions as mediators and catalysts; recent reviews have documented the rapid progress in this field.21,22,29–31 One particularly useful electrochemical reaction is the cathodic hydrogen evolution reaction (HER) because it eliminates the need to use stoichiometric oxidants in various X–H bond-functionalization reactions. However, coupling HER with transition-metal catalysis is challenging. Transition metals have different standard reduction potentials, but ions of active metals (e.g., Fe, Mn, Ni, and Co) are relatively stable to cathodic reduction; thus, they are compatible with catalytic cycles involving the HER. Tremendous progress on HER-coupled electrochemical reactions catalyzed by Mn, Fe, Ni, and Co complexes has been achieved. These reactions, particularly electrochemical C–H functionalization reactions, have been reviewed recently.20,32,33 Four examples are shown in Figure 3. First, Lin’s group34 achieved a breakthrough by developing a protocol for electrochemical diazidation of alkenes 3-1 with catalysis by MnBr2 [E2+/0 = −1.17 V vs normal hydrogen electrode (NHE)] in the absence of an added ligand (Figure 3a). The initially formed MnII azide underwent anodic oxidation to form a MnIII azide. Then alkenes 3-1 were azidated twice by MnIII azide via intermediates 3-A to afford diazides 3-2 and regenerate a MnII salt. In the second example, a cobalt-catalyzed electrochemical C–H alkylation reaction, Ackermann’s group35 used CoII complex 3-B as a precursor for a CoI/CoIII cycle involving the formation of intermediates 3-C, 3-D, and 3-E at the anode (Figure 3b). This cycle was coupled smoothly with a cathodic HER, which eliminated the need for an external oxidant. The third example involved homogeneous Fe catalysis, which, despite the various advantages of Fe as a catalyst, has not been extensively used for electrochemical synthesis. Ackermann’s group36 accomplished Fe-catalyzed arylation of 3-6 with Grignard reagent 3-7 to afford arylated products 3-8 (Figure 3c). A computational study of this transformation revealed that an electron transfer could happen at multiple stages in the catalytic cycle and that FeIII intermediates 3-F were generated without the need for an external oxidant such as dichloroisobutane. In the fourth example, Jiao’s group37 recently reported the oxidation of sulfides 3-9 to sulfoxides 3-11 with oxygen generated in situ from water splitting catalyzed by Ni(OTf)2/bipyridine 3-10 (Figure 3d). At the cathode, the NiII catalyst was reduced to NiI, which underwent complexation with oxygen to form 3-G. This complex underwent a cathodic reduction to generate 3-H, followed by oxidation of the substrate to afford products 3-11, with the generation of NiII from Ni0 at the anode. Figure 3 | (a–d) Electrochemical homogeneous catalysis with Mn, Co, Fe, and Ni complexes. Download figure Download PowerPoint In contrast, the inclusive list of salts of noble metals38 such as Cu, Ru, Rh, Pd, Ag, Re, Os, Ir, Pt, and Au have low standard reduction potentials; hence, they tend to undergo reduction before protonic species. One straightforward way to overcome this challenge is to conduct reactions in a divided cell to prevent contact between the metal and the cathode. However, using a divided cell increases the cost of the process and slows down the mass transfer. Thus, it would be advantageous to carry out electrochemical reactions catalyzed by these metals in an undivided cell. In this section, we describe recent examples of the design of electrochemical reactions in undivided cells to stabilize Cu, Ru, Rh, Pd, Ir, and Au catalysts. In 2018, Mei and co-workers39 reported Cu-catalyzed electrochemical dehydrogenative cross-coupling reactions of the aromatic Csp2–H bonds of substrates 4-1 with secondary amines 4-2 in an undivided cell at room temperature to afford products 4-3 with good conversion yield (Figure 4a). Because Cu species tend to be reduced at the cathode, a divided cell was used as a preference. In their work, Mei’s group used iodide to mediate a Cu3+/Cu2+/Cu+ catalytic cycle with a relatively low anodic potential. The Cu3+ facilitates C–H amination at room temperature, and cathodic reduction of a ligated Cu+–substrate complex [Ered = −0.44 V vs standard hydrogen electrode (SHE)] may be less favorable than the HER. Another advantage of iodine mediation is that the diffusion barrier is overcome by using a substoichiometric amount of inexpensive iodide instead of a catalytic amount of Cu. These C–H amination reactions are thought to proceed by the mechanism shown in Figure 4b. The NHCO-2-Py moiety of 4-1 acts as a directing group, and amines 4-2 serve as nitrogen sources. In 2019, Kathiravan and co-workers40 reported a similar Cu-catalyzed electrochemical C–H amination approach with a quinoline moiety as a chelating group (Figure 4c). These investigators found that at a 20 mol % catalyst loading, direct anodic oxidation of the Cu complex is adequate to drive the catalytic cycle. In addition, Ackermann’s group41 used a Cu catalyst and a directing group for alkyne annulation via a C–H alkynylation pathway (Figure 4d). Xie and co-workers42 achieved the first example of Cu-catalyzed electrochemical B–H oxygenation reactions of o-carboranes by introducing an 8-aminoquinoline as a directing group at room temperature (Figure 4e). The use of a chelating directing group for Cu-catalyzed electrochemical bromination reactions was reported by Mei’s group,43 who used NH4Br as a bromine source (Figure 4f); the Cu catalyst accelerates the bromination reaction by the formation of CuI species 4-A. Figure 4 | (a–f) Cu-catalyzed electrochemical C–H functionalization with chelation in an undivided cell. Download figure Download PowerPoint In 2021, the Sevov group44 reported ligand-free catalysis with a Cu salt, a process that tended to be challenging because of the potential for reductive deposition of Cu0 at the cathode, avoided in Cu catalysis with ligands. Sevov and co-workers44 carried out electrochemical homogeneous Chan–Lam coupling reactions between amines 5-1 and aryl boronic acids 5-2 with Cu(OAc)2 as a catalyst and Fc+ as an anodic mediator and obtained moderate to excellent yields of anilines 5-3 (Figure 5a). The mediator serves several functions: (1) it mediates the CuI/CuII cycle in the coupling reaction; (2) it shields the amine from anodic oxidation; and (3) it regenerates Cu2+ from Cu0 deposited on the cathode surface (Figure 5b). Figure 5 | (a and f) Ligand-free Cu-catalyzed electrochemical homogeneous Chan–Lam coupling reactions. Download figure Download PowerPoint Ruthenium is another inexpensive transition metal used for innovative homogeneous catalysis.45 Ruthenium compounds exist in a variety of valence states. Compared with a proton, Ru3+ exhibits a stronger tendency to accept an electron, giving Ru2+ or Ru0.46 These varying features complicate the design of electrochemical homogeneous catalytic methods involving Ru complexes. However, in 2018, Xu and co-workers47 reported a method for [RuCl2(p-cymene)]2-catalyzed electrochemical alkyne annulation reactions in an undivided cell (Figure 6a). With anilines 6-1 and alkyne 6-2 as starting materials, [3+2] annulation products 6-3 were obtained in good yields at reflux temperature. In the proposed mechanism, thermal C–H activation gives Ru2+ complex 6-A, and subsequent coordination ( 6-B), insertion ( 6-C), and reductive elimination yield 6-3. The Ru0 complex generated by the elimination reaction ( 6-D) is stabilized by the neutral p-cymene ligand during the anodic oxidation step that regenerates the Ru2+ catalyst (Figure 6b). Following this report, Ru2+ catalysts with p-cymene as a ligand found a wide array of applications in electrochemical homogeneous catalysis. For example, Ackermann’s group48 carried out alkyne annulation reactions of aryl carbamates or phenols using [RuCl2(p-cymene)]2 as a catalyst precursor in an undivided cell (Figure 6c), and the same precursor was used for C–H/O–H annulation reactions (Figure 6d).49 In addition, these investigators used [(p-cymene)Ru(OAc)2] as a catalyst and aryl iodide as a mediator to realize ortho C–H oxygenation of various substituted arenes and proposed a catalytic cycle involving p-cymene-coordinated Ru4+ species 6-E (Figure 6e).50 In 2019, Tang’s group51 reported Ru-catalyzed electrochemical dehydrogenative double [4+2] annulation of benzamides and diphenylacetylene (Figure 6f). In 2020, Zhong and co-workers52 achieved rutheniumelectro-catalyzed mono- and diacyloxylation of aryl C–H bonds (Figure 6g). That same year, Ackermann’s group53 reported alkyne annulation reactions that involve alkenylic C–H and N–H bonds and proceeded via a key azaruthena(II)-bicyclo[3.2.0]heptadiene intermediate (Figure 6h). These investigators proposed a Ru2+/Ru3+/Ru+ pathway in which anodic oxidation regenerated the catalyst and induced reductive elimination. Calculations revealed that the reductive elimination transition state for the Ru3+ to Ru+ process was 8.6 kcal/mol lower than that for the Ru2+ to Ru0 process, which supported an oxidation-induced reductive elimination mechanism. Figure 6 | (a–h) Ru-catalyzed alkyne annulation reactions involving Ru4+/Ru3+/Ru2+/Ru+ intermediates. Download figure Download PowerPoint Rhodium salts are also extensively used as catalysts in electrochemical transformations. The fact that Rh3+ is readily reduced to Rh0 in aqueous media (0.76 V vs NHE) must be considered in designing methods for Rh-catalyzed electrochemical synthesis. The first Rh-catalyzed electrochemical C–H functionalization reactions were reported by Ackermann’s group,54 accomplished by α-alkenylation of aromatic carboxylic acids 7-1 with electron-deficient alkenes 7-2 (Figure 7a). In this transformation, a Cp* not only acted as an anionic ligand but also stabilized [RhCp*Cl2]2 against cathodic reduction (Ered = −0.35 V vs SHE). In addition, KOAc and products 7-3 influenced the in situ generated Rh3+ species. It was proposed that in these reactions, Cp*Rh+ species 7-A underwent direct anodic oxidation to regenerate Cp*Rh3+ catalyst 7-B (Figure 7b). Using a Cp*Rh3+ complex, the same research group extended this C–H functionalization chemistry to C–C alkenylation (Figure 7c),55 C–H/C–N/alkyne annulation in an electroflow cell (Figure 7d),56 annulative polycyclic arene synthesis (Figure 7e),57 annulative syntheses of aza-polycyclic aromatic hydrocarbons (Figure 7f),58 C–H olefination of benzamides (Figure 7g),59 synthesis of chromones (Figure 7h),60 and [5+2] annulation reactions (Figure 7i).61 Xu and co-workers62 used [Cp*RhCl2]2 in a scalable protocol for aryl C–H phosphorylation in which anodic oxidation induced a reductive elimination (Figure 7j). In a study of [Cp*RhCl2]2-catalyzed electrochemical vinylic C–H annulation reactions between acrylamides and alkynes, Mei’s group63 obtained annulation products generated by two different pathways. A computational study indicated that the substituent on the nitrogen of the amide substrate determines whether the reaction proceeds via a stepwise ionic pathway or a concerted neutral pathway (Figure 7k). Chang’s group64 investigated electrochemical aryl C–H oxygenation by using Cp*Rh+ catalysis in an undivided cell at room temperature (Figure 7l) and found that anodic oxidation of a rhodacyclic carboxylate intermediate enabled the reductive elimination. Figure 7 | (a–l) Stabilization of Rh catalysts by Cp* ligands in electrochemical reactions. Download figure Download PowerPoint Recently, Gooßen’s group65 reported a method for RhCl3-catalyzed electrochemical dehydrogenative C–H/C–H coupling of benzoic acids (Figure 8). These investigators found that in dimethylformamide (DMF), RhCl3.3H2O provides a higher yield than [Cp*RhCl2]2. Cyclic voltammetry measurement showed that in DMF, RhCl3 accepted electrons stepwise at 0.12 and −0.38 V versus SHE, a behavior that differed from that in aqueous media. Figure 8 | RhCl3-catalyzed electrochemical coupling of benzoic acids. Download figure Download PowerPoint In 2021, Ackermann’s group66 reported electrochemical C–H oxygenation reactions catalyzed by a dimetallic Rh complex. Instead of a Cp*Rh complex, [Rh(OAc)2]2, with a stable dimeric structure, was used as the catalyst, and the product selectivity was controlled by varying the quantity of electricity. From amides or ketones 9-1, products 9-3 were obtained with 2.2–2.5 F/mol electricity, whereas the reaction of N-Me amides 9-2 at 4.0 F/mol gave annulated products 9-4 (Figure 9a). In the proposed reaction pathway (Figure 9b), [Rh(OAc)2]2 was presumed to be oxidized at the anode to give Rh3+/Rh3+ dimer 9-A. Subsequent cleavage of the aryl C–H bond by Rh3+ afforded the intermediate 9-B, which reacted with CF3CO2− to give 9-C; and a reductive elimination reaction of 9-C generated products 9-3. The N-methyl product underwent Shono oxidation and intramolecular annulation to give 9-4. Figure 9 | (a and b) [Rh(OAc)2]2-catalyzed electrochemical bimetallic C–H oxygenation. Download figure Download PowerPoint Palladium (Pd) is well-known for its high reduction potential, even in an acidic aqueous solution with a coordinative anionic ligand (EPdCl4/Pd = 0.62 V vs SHE in HCl). In the pioneering work on electrochemical Pd homogeneous catalysis, many of the reported reactions in organic media required a divided cell configuration.67–78 However, in 2019, Mei’s group79 reported a method for Pd-catalyzed electrochemical aryl C–H alkylation reactions in an undivided cell in an aqueous solution. By employing 2-aryl pyridines 10-1 as substrates and potassium trifluoroalkylborates 10-2 as alkylation reagents, these investigators obtained the corresponding alkylated products 10-3 in up to 70% yields (Figure 10a). The reactions were carried out in a mixed acidic solvent using Pt as the cathode to facilitate the HER instead of Pd2+ reduction. In the proposed reaction pathway, the intermediate 10-A (generated by Pd insertion into the aryl C–H bond of a 10-1–Pd(OAc)2 complex) underwent anodic oxidation and transmetalation with 10-2 to form key Pd3+ or Pd4+ complexes ( 10-B or 10-C, respectively). Then a subsequent reductive elimination yielded the products and regenerated the Pd2+ catalyst, as shown in Figure 10b. Figure 10 | (a and b) Pd-catalyzed electrochemical C–H alkylation of 2-aryl pyridines in an undivided cell. Download figure Download PowerPoint The use of phosphine ligands in electrochemical transformations is hampered by their tendency to undergo anodic oxidation; therefore, a sacrificial anode is necessary. Since many phosphine ligands have been developed for Pd catalysis, studying electrochemical transformations involving Pd–phosphine complexes and inert electrodes is important. One such study was reported by Lei and co-workers,80 who investigated Pd-catalyzed electrochemical oxidative aminocarbonylation of terminal alkynes 11-1 with CO and a nitrogen source (Figure 11). Considering mixing CO and an oxidant raises safety issues, it was necessary to develop a dehydrogenative protocol in an undivided cell in the absence of air, required for conventional aminocarbonylation reactions. Lei’s group80 used ammonium salts, primary amines, and secondary amines as nitrogen sources to prepare amides 11-2, 11-3, and 11-4, respectively (Figure 11a). Quick-scanning X-ray absorption fine-structure spectroscopy (Q-XAFS) supported the involvement of a Pd0/Pd2+ catalytic cycle at the anode and an HER at the cathode (Figure 11b). Given that the standard potential for the Pd2++ 2e = Pd0 half-reaction is 0.92 V versus SHE (0.72 V vs Ag/AgCl), reduction of Pd2+ at the cathode was possible at room temperature. A series of cyclic voltammetry experiments revealed that the phosphine ligand (PAr3), CO, and the nBuOH solvent all play important roles in stabilizing the Pd2+ species involved in the reaction. The combined effects of these factors shift the Ered of the Pd complex to −1.84 V versus Ag/AgCl, which was beyond the reduction potential window of the reaction (Figure 11c). Figure 11 | (a–c) Pd-catalyzed electrochemical oxidative aminocarbonylation of terminal alkynes with hydrogen evolution. Download figure Download PowerPoint In aqueous solutions, reduction of Ir cations to Ir0 (Ered = 0.77–1.16 V vs NHE) is more likely than proton reduction. However, in organic solvents, coordination of Ir species with suitable compounds can stabilize the metal against cathodic reduction. In 2018, Ackermann’s group81 reported a method for Ir-catalyzed electro-oxidative Csp2–H annulation reactions (Figure 12a). An Ir complex with an anion derived from pentamethyl cyclopentadiene as a ligand (EIII/II = −1.86 V vs Fc+/0) catalyzed intermolecular formation of C–O, and C–C bonds via a base-assisted internal electrophilic-type substitution pathway. During catalyst regeneration, benzoquinone, and its redox couple hydroquinone ( 12-A) shuttled an electron from IrI species 12-B to the anode to furnish IrIII species 12-C (Figure 12b). Using the same catalyst precursor, Mei’s group82,83 achieved electrochemical Ir-catalyzed vinylic C–H functionalization (Figure 12c)82 and regioselective annulation of benzoic acids with internal alkynes (Figure 12d).83 In addition, Shi and co-workers84 reported a method for Ir-catalyzed electrochemical aryl C–H alkynylation reactions (Figure 12e). Figure 12 | (a–e) Electrochemical reactions catalyzed by Cp*-stabilized cationic Ir. Download figure Download PowerPoint Gold is highly stable, with a remarkably high EAu+/Au value of 1.8 V versus SHE; Shi and co-workers85 found that their attempts to achieve Au-catalyzed electrochemical cross-coupling of terminal alkynes were hampered by cathodic decomposition of the Au catalyst. To overcome this unwanted side process, they used excess acid to enhance the HER at the Pt cathode. For example, using a 1,2,3-triazole (TA)–Au complex as a catalyst, they accomplished homo coupling of terminal aromatic alkynes 13-1 in an undivided cell in a mixture of MeCN/HOAc to obtain products 13-2 in excellent yields (Figure 13a). Using this dehydrogenative electrochemical protocol, these investigators carried out hetero cross-coupling reactions between aromatic alkynes 13-3 and aliphatic alkynes 13-4, catalyzed by Au complexes bearing phosphine and phenanthroline ligands and obtained good product yields 13-5. In the proposed reaction pathway (Figure 13b), Au+–alkynyl complexes 13-A underwent two-electron oxidations at the anode to give Au3+ complexes 13-B. Then a ligand exchange gave 13-C, followed by reductive elimination, giving cross-coupling products and regeneration of the Au+ catalyst. Figure 13 | (a and b) Gold-catalyzed electrochemical dehydrogenative cross-coupling of terminal alkynes. Download figure Download PowerPoint Photoelectrochemical catalysis One of the advantages of electrochemistry is that the potential required for a specific transformation could be dialed in. However, in some difficult redox processes, a high electrode potential can limit functional group tolerance because of undesired overoxidation or -reduction. However, the merger of electrochemistry with photocatalysis allows access to strongly oxidizing or reducing species at low electrode potentials because some of the energy is provided by photoirradiation (Figures 14a and 14b). For example, the excited Fukuzumi86 photocatalyst Mes-Acr+ is a strong oxidant [Ered = 2.06 V vs saturated calomel electrode (SCE)]. For a photoelectrochemical transformation catalyzed by Mes-Acr+ turning over at the anode, the electrode potential can be kept substantially lower than 2.06 V, as the oxidation potential of Mes-Acr• is around −0.60 V versus SCE (estimated from the reduction potential of Mes-Acr+).87 In another example, combining cathodic reduction of dicyanoanthracene (DCA) with photoexcitation of the resulting DCA•− allowed access to the strongly reducing excited radical anion [DCA•−]* (Eoxd = −3.2 V). In this case, the electrode potential was kept at a value more positive than −3.2 V because DCA was reduced at −0.82 V.88 In addition, the selectivity of the transient excited state was expected to be different from that of a persistent electrode or mediator. As a result, synthetic photoelectrochemistry is a potentially powerful tool for overcoming some of the limitations associated with electrochemistry or photochemistry alone. Electrochemistry and photochemistry were first to be merged for organic synthesis in 1979 when Moutet and Reverdy89 reported photoinduced oxidation reactions with electrochemically generated organic radical cations; however, after these early studies, synthetic photoelectrochemistry did not receive much attention until very recently.90,91 Figure 14 | (a and b) Redox window of photocatalysts for electrochemical reactions. Download figure Download PowerPoint In early 2019, Xu and co-workers92 reported efficient photoelectrocatalytic Minisci C–H alkylation reactions of various heteroarenes 15-1 with primary, secondary, and tertiary organotrifluoroborates 15-2 with catalysis by Mes-Acr+ (Figures 15a and 15b). The reactions were conducted in an undivided cell at a constant current of 2 mA under irradiation with blue light-emitting diodes (LEDs). Mechanistically, irradiation of Mes-Acr+ induced electron transfer from the organotrifluoroborate to excited Mes-Acr+* ( 15-A) to generate reduced catalyst Mes-Acr• ( 15-B) and alkyl radical 15-C. The persistent radical Mes-Acr• was reoxidized to Mes-Acr+ to complete the catalytic cycle. Meanwhile, the addition of 15-C to protonated heteroarene gave 15-D; subsequent rearomatization, likely assisted by Mes-Acr+, afforded the final alkylated heteroarene product. Due to the bulk production of alkyl radical solution away from the electrode, anodic oxidation of the radical to a carbocation was avoided, even though electron-rich alkyl radicals were readily oxidized (e.g., Ep/2 (t-Bu•) = 0.09 V vs SCE). At the cathode, electrons and protons were able to combine to generate H2. The combination of anodic regeneration of the ground-state catalyst and a cathodic HER obviated the need for external chemical oxidants. Figure 15 | (a and b) Photoelectrocatalytic C–H functionalization of heteroarenes with organotrifluoroborates. Download figure Download PowerPoint Using the Langlois reagent, Ackermann’s group93 accomplished undirected trifluoromethylation reactions of aromatic C–H bonds under electrophotocatalytic