Speciation and Reactivity of Mono- and Binuclear Ni Intermediates in Aminoquinoline-Directed C-H Arylation and Benzylation.

This paper describes detailed organometallic studies of the aminoquinoline-directed Ni-catalyzed C-H functionalization of 2,3,4,5-tetrafluoro-N-(quinolin-8-yl)benzamide with diaryliodonium reagents. A combination of 19F NMR spectroscopy and X-ray crystallography is used to track and characterize diamagnetic and paramagnetic intermediates throughout this transformation. These provide key insights into both the cyclometalation and oxidative functionalization steps of the catalytic cycle. The reaction conditions (solvent, ligands, base, and stoichiometry) play a central role in the observation of a NiII precyclometalation intermediate as well as in the speciation of the NiII products of C-H activation. Both mono- and binuclear cyclometalated NiII species are observed and interconvert, depending on the reaction conditions. Cyclic voltammetry reveals that the NiII/III redox potentials for the cyclometalated intermediates vary by more than 700 mV depending on their coordination environments, and these differences are reflected in their relative reactivity with diaryliodonium oxidants. The oxidative functionalization reaction affords a mixture of arylated and solvent functionalization organic products, depending on the conditions and solvent. For example, conducting oxidation in toluene leads to the preferential formation of the benzylated product. A series of experiments implicate a NiII/III/IV pathway for this transformation.

Visible-Light Photocatalytic C-H Amination of Arenes Utilizing Acridine-Lewis Acid Complexes.

This report describes the development of a visible-light photocatalytic system for C(sp2)-H amination that leverages in situ-generated photocatalysts. We demonstrate that the combination of acridine derivatives and Lewis acids forms potent photooxidants that promote the C-H amination of electronically diverse arenes upon irradiation with visible-light (440 nm). A first-generation photocatalyst composed of Sc(OTf)3 and acridine effects the C-H amination of substrates with oxidation potentials ≤ +2.5 V vs SCE with pyrazole, triazole, and pyridine nucleophiles. Furthermore, the simplicity and modularity of this system enable variation of both Lewis acid and acridine to tune reactivity. This enabled the rapid identification of two second-generation photocatalysts (derived from (i) Al(OTf)3 and acridine or (ii) Sc(OTf)3 and a pyridinium-substituted acridine) that catalyze a particularly challenging transformation: C(sp2)-H amination with benzene as the limiting reagent.

Development of High-Throughput Experimentation Approaches for Rapid Radiochemical Exploration.

Positron emission tomography is a widely used imaging platform for studying physiological processes. Despite the proliferation of modern synthetic methodologies for radiolabeling, the optimization of these reactions still primarily relies on inefficient one-factor-at-a-time approaches. High-throughput experimentation (HTE) has proven to be a powerful approach for optimizing reactions in many areas of chemical synthesis. However, to date, HTE has rarely been applied to radiochemistry. This is largely because of the short lifetime of common radioisotopes, which presents major challenges for efficient parallel reaction setup and analysis using standard equipment and workflows. Herein, we demonstrate an effective HTE workflow and apply it to the optimization of copper-mediated radiofluorination of pharmaceutically relevant boronate ester substrates. The workflow utilizes commercial equipment and allows for rapid analysis of reactions for optimizing reactions, exploring chemical space using pharmaceutically relevant aryl boronates for radiofluorinations, and constructing large radiochemistry data sets.

A Physical Organic Chemistry Approach to Developing Cyclopropenium-Based Energy Storage Materials for Redox Flow Batteries.

ConspectusRedox flow batteries (RFBs) represent a promising modality for electrical energy storage. In these systems, energy is stored via paired redox reactions of molecules on opposite sides of an electrochemical cell. Thus, a central objective for the field is to design molecules with the optimal combination of properties to serve as energy storage materials in RFBs. The ideal molecules should undergo reversible redox reactions at relatively high potentials (for the molecule that is oxidized during battery charging, called the catholyte) or low potentials (for the species that is reduced during battery charging, called the anolyte). Furthermore, anolytes and catholytes must be highly soluble in the electrolyte solution and stable to extended electrochemical cycling in all battery-relevant redox states. The ideal candidates would undergo more than one reversible electron transfer event. Finally, the optimal structures should be resistant to crossover through a selective separator in order to maintain isolation of the two sides of the cell. This Account describes our design and optimization of organic molecules for this application. We first provide background for the metrics and experiments used to characterize anolytes/catholytes and to progress them toward deployment in flow batteries. We then use our studies of aminocyclopropenium-based catholytes to illustrate this workflow and approach.We identified tris(dimethylamino) cyclopropenium hexafluorophosphate as a first-generation catholyte for nonaqueous RFBs based on literature reports from the 1970s describing its reversible chemical and electrochemical oxidation. Cyclic voltammetry and electrochemical cycling experiments in acetonitrile/LiPF6 confirmed that this molecule undergoes oxidation at relatively high potential (0.86 V versus ferrocene/ferrocenium) and exhibits moderate stability toward charge-discharge cycling. Replacing the methyl groups with isopropyl substituents led to enhanced cycling stability but poor solubility of the radical dication (<0.1 M in acetonitrile). Solubility was optimized using quantitative structure-property relationship modeling, which predicted derivatives with ≥10-fold enhanced solubility. Cyclopropeniums with 300-500 mV higher redox potentials were identified by replacing one of the dialkylamino substituents with a less electron-donating thioalkyl or aryl group. Multielectron catholytes were developed by creating hybrid structures that contain a di(amino) cyclopropenium conjugated with a phenothiazine moeity. Finally, oligomeric tris(amino) cyclopropeniums were designed as crossover resistant catholytes. Optimization of their solubility enabled the deployment of these oligomers in high concentration asymmetric redox flow batteries with energy densities that are comparable to the state-of-the-art commercial aqueous inorganic systems.

Benchmarking Trisaminocyclopropeniums as Mediators for Anodic Oxidation Reactions.

This report benchmarks a tris(amino)cyclopropenium (TAC) salt as an electron-transfer mediator for anodic oxidation reactions in comparison to two known mediators: a triarylamine and a triarylimidazole derivative. The three mediators have redox potentials, diffusion coefficients, and heterogeneous electron transfer rates similar to those of glassy carbon electrodes in acetonitrile/KPF6. However, they differ significantly in their performance in two electro-organic reactions: anodic fluorination of a dithiane and anodic oxidation of 4-methoxybenzyl alcohol. These differences are rationalized based on variable stability in the presence of reaction components (e.g., NEt3·3HF, lutidine, and Cs2CO3) as well as very different rates of electron transfer with the organic substrate. Overall, this work highlights the advantages and disadvantages of each mediator and provides a foundation for expanding the applications of TACs in electro-organic synthesis moving forward.

Base-free nickel-catalysed decarbonylative Suzuki-Miyaura coupling of acid fluorides.

The Suzuki-Miyaura cross-coupling of organoboron nucleophiles with aryl halide electrophiles is one of the most widely used carbon-carbon bond-forming reactions in organic and medicinal chemistry1,2. A key challenge associated with these transformations is that they generally require the addition of an exogenous base, the role of which is to enable transmetallation between the organoboron nucleophile and the metal catalyst3. This requirement limits the substrate scope of the reaction because the added base promotes competitive decomposition of many organoboron substrates3-5. As such, considerable research has focused on strategies for mitigating base-mediated side reactions6-12. Previous efforts have primarily focused either on designing strategically masked organoboron reagents (to slow base-mediated decomposition)6-8 or on developing highly active palladium precatalysts (to accelerate cross-coupling relative to base-mediated decomposition pathways)10-12. An attractive alternative approach involves identifying combinations of catalyst and electrophile that enable Suzuki-Miyaura-type reactions to proceed without an exogenous base12-14. Here we use this approach to develop a nickel-catalysed coupling of aryl boronic acids with acid fluorides15-17, which are formed in situ from readily available carboxylic acids18-22. This combination of catalyst and electrophile enables a mechanistic manifold in which a 'transmetallation-active' aryl nickel fluoride intermediate is generated directly in the catalytic cycle13,16. As such, this transformation does not require an exogenous base and is applicable to a wide range of base-sensitive boronic acids and biologically active carboxylic acids.

Zinc-Mediated Radiosynthesis of Unprotected Fluorine-18 Labelled α-Tertiary Amides.

This report describes the development of a Zn(OTf)2 -mediated method for converting α-tertiary haloamides to the corresponding fluorine-18 labelled α-tertiary fluoroamides with no-carrier-added [18 F]tetramethylammonium fluoride. 1,5,7-Triazabicyclo[4.4.0]dec-5-ene is an essential additive for achieving high radiochemical conversion. Under the optimised conditions, radiofluorination proceeds at sterically hindered tertiary sites in high radiochemical conversions, yields, and purities. This method has been successfully automated and applied to access >200 mCi (>7.4 GBq) of several model radiofluorides. Mechanistic studies led to the development of a new, nucleophilic C-H radiofluorination process using N-sulphonyloxyamide substrates.

Characterization and Reactivity of Copper(II) and Copper(III) σ-Aryl Intermediates in Aminoquinoline-Directed C-H Functionalization.

Over the past decade, numerous reports have focused on the development and applications of Cu-mediated C-H functionalization reactions; however, to date, little is known about the Cu intermediates involved in these transformations. This paper details the observation and characterization of CuII and CuIII intermediates in aminoquinoline-directed C(sp2)-H functionalization of a fluoroarene substrate. An initial C(sp2)-H activation at CuII occurs at room temperature to afford an isolable anionic cyclometalated CuII complex. This complex undergoes single-electron oxidation with ferrocenium or AgI salts under mild conditions (5 min at room temperature) to afford C(sp2)-C(sp2) or C(sp2)-NO2 coupling products. Spectroscopic studies implicate the formation of a transient diamagnetic CuIII-σ-aryl intermediate that undergoes either (i) a second C(sp2)-H activation at CuIII followed by C-C bond-forming reductive elimination or (ii) reaction with a NO2- nucleophile and C(sp2)-NO2 coupling.

Room-Temperature Copper-Mediated Radiocyanation of Aryldiazonium Salts and Aryl Iodides via Aryl Radical Intermediates.

Radiocyanation is an attractive strategy for incorporating carbon-11 into radiotracer targets, particularly given the broad scope of acyl moieties accessible from nitriles. Most existing methods for aromatic radiocyanation require elevated temperatures (Cu-mediated reactions of aryl halides or organometallics) or involve expensive and toxic palladium complexes (Pd-mediated reactions of aryl halides). The current report discloses a complementary approach that leverages the capture of aryl radical intermediates by a Cu-11CN complex to achieve rapid and mild (5 min, room temperature) radiocyanation. In a first example, aryl radicals are generated via the reaction of a CuI mediator with an aryldiazonium salt (a Sandmeyer-type reaction) followed by radiocyanation with Cu-11CN. In a second example, aryl radicals are formed from aryl iodides via visible-light photocatalysis and then captured by a Cu-11CN species to achieve aryl-11CN coupling. This approach provides access to radiocyanated products that are challenging to access using other methods (e.g., ortho-disubstituted aryl nitriles).

Indolo[2,3-b]quinoxaline as a Low Reduction Potential and High Stability Anolyte Scaffold for Nonaqueous Redox Flow Batteries.

Redox flow batteries (RFBs) are a promising stationary energy storage technology for leveling power supply from intermittent renewable energy sources with demand. A central objective for the development of practical, scalable RFBs is to identify affordable and high-performance redox-active molecules as storage materials. Herein, we report the design, synthesis, and evaluation of a new organic scaffold, indolo[2,3-b]quinoxaline, for highly stable, low-reduction potential, and high-solubility anolytes for nonaqueous redox flow batteries (NARFBs). The mixture of 2- and 3-(tert-butyl)-6-(2-methoxyethyl)-6H-indolo[2,3-b]quinoxaline exhibits a low reduction potential (-2.01 V vs Fc/Fc+), high solubility (>2.7 M in acetonitrile), and remarkable stability (99.86% capacity retention over 49.5 h (202 cycles) of H-cell cycling). This anolyte was paired with N-(2-(2-methoxyethoxy)-ethyl)phenothiazine (MEEPT) to achieve a 2.3 V all-organic NARFB exhibiting 95.8% capacity retention over 75.1 h (120 cycles) of cycling.

Mechanism-Driven Development of Group 10 Metal-Catalyzed Decarbonylative Coupling Reactions.

Transition-metal-catalyzed cross-coupling reactions are widely used in both academia and industry for the construction of carbon-carbon and carbon-heteroatom bonds. The vast majority of cross-coupling reactions utilize aryl (pseudo)halides as the electrophilic coupling partner. Carboxylic acid derivatives (RC(O)X) represent a complementary class of electrophiles that can engage in decarbonylative couplings to produce analogous products. This decarbonylative approach offers the advantage that RC(O)X are abundant and inexpensive. In addition, decarbonylative coupling enables both intramolecular (between R and X of the carboxylic acid derivative) as well as intermolecular bond-forming reactions (in which an exogeneous nucleophile is coupled with the R group derived from RC(O)X). In these intermolecular reactions, the X-substituent on the carboxylic acid can be tuned to facilitate both oxidative addition and transmetalation, thus eliminating the need for an exogeneous base. This Account details our group's development of a diverse variety of base-free decarbonylative coupling reactions catalyzed by group 10 metals. Furthermore, it highlights how catalyst design can be guided by stoichiometric organometallic studies of these systems.Our early studies focused on intramolecular decarbonylative couplings that transform RC(O)X to the corresponding R-X with extrusion of CO. We first identified Pd and Ni monodentate phosphine catalysts that convert aryl thioesters (ArC(O)SR) to the corresponding thioethers (ArSR). We next expanded this reactivity to fluoroalkyl thioesters, using readily available fluoroalkyl carboxylic acids as the fluoroalkyl (RF) source. A Ni-phosphinoferrocene catalyst proved optimal, and the large bite angle bidentate ligand was necessary to promote the challenging RF-S bond-forming reductive elimination step.We next pursued intramolecular decarbonylative couplings of aroyl halides. Palladium-based catalysts bearing dialkylbiaryl ligands (e.g., BrettPhos) were identified as optimal for converting aroyl chlorides (ArC(O)Cl) to aryl chlorides (ArCl). These ligands were selected based on their ability to facilitate the key C-Cl bond-forming reductive elimination step of the catalytic cycle. In contrast, all attempts to convert aroyl fluorides [ArC(O)F)] to aryl fluorides (ArF) were unsuccessful with either Pd- or Ni-based catalysts. Organometallic studies of the Ni-system show that C(O)-F oxidative addition and CO deinsertion proceed smoothly, but the resulting nickel(II) aryl fluoride intermediate fails to undergo C-F bond-forming reductive elimination.In contrast to its inertness to reductive elimination, this nickel(II) aryl fluoride proved highly reactive toward transmetalation. The fluoride ligand serves as an internal base, such that no additional base is required. We leveraged this "transmetalation active" intermediate to achieve base-free Ni-catalyzed intermolecular decarbonylative coupling reactions between aroyl fluorides and boron reagents to access both biaryl and aryl-boronate ester products. By tuning the electrophile, transmetalating reagent, and catalyst, this same approach also proved applicable to base-free intermolecular decarbonylative fluoroalkylation (between difluoromethylacetyl fluoride and arylboronate esters) and aryl amination (between phenol esters and silyl amines).Moving forward, a key goal is to identify catalyst systems that enable more challenging bond constructions via this manifold. In addition, CO inhibition remains a major issue leading to the requirement for high temperatures and high catalyst loadings. Identifying catalysts that are resistant to CO binding and/or approaches to remove CO under mild conditions will be critical for making these reactions more practical and scalable.

Electroorganic synthesis in aqueous solution via generation of strongly oxidizing and reducing intermediates.

Water is the ideal green solvent for organic electrosynthesis. However, a majority of electroorganic processes require potentials that lie beyond the electrochemical window for water. In general, water oxidation and reduction lead to poor synthetic yields and selectivity or altogether prohibit carrying out a desired reaction. Herein, we report several electroorganic reactions in water using synthetic strategies referred to as reductive oxidation and oxidative reduction. Reductive oxidation involves the homogeneous reduction of peroxydisulfate (S2O82-) via electrogenerated Ru(NH3)62+ at potential of -0.2 V vs. Ag/AgCl (3.5 M KCl) to form the highly oxidizing sulfate radical anion (E0' (SO4˙-/SO42-) = 2.21 V vs. Ag/AgCl), which is capable of oxidizing species beyond the water oxidation potential. Electrochemically generated SO4˙- then efficiently abstracts a hydrogen atom from a variety of organic compounds such as benzyl alcohol and toluene to yield product in water. The reverse analogue of reductive oxidation is oxidative reduction. In this case, the homogeneous oxidation of oxalate (C2O42-) by electrochemically generated Ru(bpy)33+ produces the strongly reducing carbon dioxide radical anion (E0' (CO2˙-/CO2) = -2.1 V vs. Ag/AgCl), which can reduce species at potential beyond the water or proton reduction potential. In preliminary studies, the CO2˙- has been used to homogeneously reduce the C-Br moiety belonging to benzyl bromide at an oxidizing potential in aqueous solution.

Nickel(IV) Intermediates in Aminoquinoline-Directed C(sp2)-C(sp3) Coupling.

We use a ligand design strategy to isolate a cyclometalated nickel(IV) complex that is directly analogous to a key intermediate proposed in aminoquinoline-directed C-H functionalization catalysis. This nickel(IV) complex is formed by oxidative addition of a diaryliodonium reagent to an anionic nickel(II)-picolinate precursor. The nickel(IV) σ-aryl complex is stable at room temperature but undergoes C(sp2)-C(sp3) bond-forming reductive elimination under mild conditions (70 °C, 120 min). Overall, this study demonstrates the accessibility of long-sought-after nickel(IV) intermediates in C-H functionalization catalysis. Furthermore, it demonstrates that LX-type (bidentate, mono-anionic) ligands such as picolinate dramatically stabilize these nickel(IV) species.

Copper-Mediated Radiocyanation of Unprotected Amino Acids and Peptides.

This report describes a copper-mediated radiocyanation of aryl halides that is applicable to complex molecules. This transformation tolerates an exceptionally wide range of functional groups, including unprotected amino acids. As such, it enables the site-specific introduction of [11C]CN into peptides at an iodophenylalanine residue. The use of a diamine-ligated copper(I) mediator is crucial for achieving high radiochemical yield under relatively mild conditions, thus limiting racemization and competing side reactions of other amino acid side chains. The reaction has been scaled and automated to deliver radiolabeled peptides, including analogues of adrenocorticotropic hormone 1-27 (ACTH) and nociceptin (NOP). For instance, this Cu-mediated radiocyanation was leveraged to prepare >40 mCi of [11C]cyano-NOP to evaluate biodistribution in a primate using positron emission tomography. This investigation provides preliminary evidence that nociceptin crosses the blood-brain barrier and shows uptake across all brain regions (SUV > 1 at 60 min post injection), consistent with the known distribution of NOP receptors in the rhesus brain.

A Nonaqueous Redox-Matched Flow Battery with Charge Storage in Insoluble Polymer Beads.

We describe the nonaqueous redox-matched flow battery (RMFB), where charge is stored on redox-active moieties covalently tethered to non-circulating, insoluble polymer beads and charge is transferred between the electrodes and the beads via soluble mediators with redox potentials matched to the active moieties on the beads. The RMFB reported herein uses ferrocene and viologen derivatives bound to crosslinked polystyrene beads. Charge storage in the beads leads to a high (approximately 1.0-1.7 M) effective concentration of active material in the reservoirs while preventing crossover of that material. The relatively low concentration of soluble mediators (15 mM) eliminates the need for high-solubility molecules to create high energy density batteries. Nernstian redox exchange between the beads and redox-matched mediators was fast relative to the cycle time of the RMFB. This approach is generalizable to many different redox-active moieties via attachment to the versatile Merrifield resin.

Theoretical and Experimental Investigation of Functionalized Cyanopyridines Yield an Anolyte with an Extremely Low Reduction Potential for Nonaqueous Redox Flow Batteries.

Cyanopyridines and cyanophenylpyridines were investigated as anolytes for nonaqueous redox flow batteries (RFBs). The three isomers of cyanopyridine are reduced at potentials of -2.2 V or lower vs. ferrocene+/0 (Fc+/0 ), but the 3-CNPy⋅- radical anion forms a sigma-dimer that is re-oxidized at E≈-1.1 V, which would lead to poor voltaic efficiency in a RFB. Bulk electrochemical charge-discharge cycling of the cyanopyridines in acetonitrile and 0.50 M [NBu4 ][PF6 ] shows that 2-CNPy and 4-CNPy lose capacity quickly under these conditions, due to irreversible chemical reaction/decomposition of the radical anions. Density-functional theory (DFT) calculations indicated that adding a phenyl group to the cyanopyridines would, for some isomers, limit dimerization and improve the stability of the radical anions, while shifting their E1/2 only about +0.10 V relative to the parent cyanopyridines. Among the cyanophenylpyridines, 3-CN-6-PhPy and 3-CN-4-PhPy are the most promising as anolytes. They exhibit reversible reductions at E1/2 =-2.19 and -2.22 V vs. ferrocene+/0 , respectively, and retain about half of their capacity after 30 bulk charge-discharge cycles. An improved version of 3-CN-6-PhPy with three methyl groups (3-cyano-4-methyl-6-(3,5-dimethylphenyl)pyridine) has an extremely low reduction potential of -2.50 V vs. Fc+/0 (the lowest reported for a nonaqueous RFB anolyte) and loses only 0.21 % of capacity per cycle during charge-discharge cycling in acetonitrile.

Palladium-catalysed transannular C-H functionalization of alicyclic amines.

Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.

Photochemical C(sp2 )-H Pyridination via Arene-Pyridinium Electron Donor-Acceptor Complexes.

This report describes the development of a photochemical method for C(sp2 )-H pyridination that leverages the photoexcitation of electron donor-acceptor (EDA) complexes. Experimental and DFT studies show that black light (λmax ≈350 nm) irradiation of solutions of protonated pyridines (acceptors) and aromatic C-H substrates (donors) results in single electron transfer to form aryl radical cation intermediates that can be trapped with pyridine nucleophiles under aerobic conditions. With some modification of the reaction conditions, this EDA activation mode is also effective for promoting the oxidatively triggered SN Ar pyridination of aryl halides. Overall, this report represents an inexpensive and atom-economical approach to photochemical pyridination reactions that eliminates the requirement of an exogenous photocatalyst.

Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis.

This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M'). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M' can be avoided by using M' = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H---X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.

Simultaneously Enhancing the Redox Potential and Stability of Multi-Redox Organic Catholytes by Incorporating Cyclopropenium Substituents.

High redox potential, two-electron organic catholytes for nonaqueous redox flow batteries were developed by appending diaminocyclopropenium (DAC) substituents to phenazine and phenothiazine cores. The parent heterocycles exhibit two partially reversible oxidations at moderate potentials [both at lower than 0.7 V vs ferrocene/ferrocenium (Fc/Fc+)]. The incorporation of DAC substituents has a dual effect on these systems. The DAC groups increase the redox potential of both couples by ∼300 mV while simultaneously rendering the second oxidation (which occurs at 1.20 V vs Fc/Fc+ in the phenothiazine derivative) reversible. The electron-withdrawing nature of the DAC unit is responsible for the increase in redox potential, while the DAC substituents stabilize oxidized forms of the molecules through resonance delocalization of charge and unpaired spin density. These new catholytes were deployed in two-electron redox flow batteries that exhibit voltages of up to 2.0 V and no detectable crossover over 250 cycles.