The direct and scalable electroreduction of triphenylphosphine oxide (TPPO)the stoichiometric byproduct of some of the most common synthetic organic reactionsto triphenylphosphine (TPP) remains an ...unmet challenge that would dramatically reduce the cost and waste associated with performing desirable reactions that are mediated by TPP on a large scale. This report details an electrochemical methodology for the single-step reduction of TPPO to TPP using an aluminum anode in combination with a supporting electrolyte that continuously regenerates a Lewis acid from the products of anodic oxidation. The resulting Lewis acid activates TPPO for reduction at mild potentials and promotes P–O over P–C bond cleavage to selectively form TPP over other byproducts. Finally, this robust methodology is applied to (i) the reduction of synthetically useful classes of phosphine oxides, (ii) the one-pot recycling of TPPO generated from a Wittig reaction, and (iii) the gram-scale reduction of TPPO at high concentration (1 M) with continuous product extraction and in flow at high current density.
Cross-electrophile coupling (XEC) reactions of aryl and alkyl electrophiles are appealing but limited to specific substrate classes. Here, we report electroreductive XEC of previously incompatible ...electrophiles including tertiary alkyl bromides, aryl chlorides, and aryl/vinyl triflates. Reactions rely on the merger of an electrochemically active complex that selectively reacts with alkyl bromides through 1e
processes and an electrochemically inactive Ni
(phosphine) complex that selectively reacts with aryl electrophiles through 2e
processes. Accessing Ni
(phosphine) intermediates is critical to the strategy but is often challenging. We uncover a previously unknown pathway for electrochemically generating these key complexes at mild potentials through a choreographed series of ligand-exchange reactions. The mild methodology is applied to the alkylation of a range of substrates including natural products and pharmaceuticals.
Catalytic hydroarylation of alkenes is a desirable process because it can occur under neutral conditions with regioselectivity complementary to that of acid-catalyzed reactions and stereoselectivity ...derived from the catalyst. We report an intermolecular asymmetric addition of the C–H bonds of indoles, thiophenes, pyrroles, and furans to bicycloalkenes in high yield with high enantiomeric excess. These heteroarene alkylations occur ortho to the heteroatom. This selectivity is observed even with unprotected indoles, which typically undergo alkylation at the C3 position. Initial mechanistic studies revealed that oxidative addition of a heteroarene C–H bond to a neutral IrI species occurs within minutes at room temperature and occurs in the catalytic cycle prior to the turnover-limiting step. Products from syn addition of the C–H bond across the olefin were observed.
Cross-electrophile coupling (XEC) of alkyl and aryl halides promoted by electrochemistry represents an attractive alternative to conventional methods that require stoichiometric quantities of ...high-energy reductants. Most importantly, electroreduction can readily exceed the reducing potentials of chemical reductants to activate catalysts with improved reactivities and selectivities over conventional systems. This work details the mechanistically-driven development of an electrochemical methodology for XEC that utilizes redox-active shuttles developed by the energy-storage community to protect reactive coupling catalysts from overreduction. The resulting electrocatalytic system is practical, scalable, and broadly applicable to the reductive coupling of a wide range of aryl, heteroaryl, or vinyl bromides with primary or secondary alkyl bromides. The impact of overcharge protection as a strategy for electrosynthetic methodologies is underscored by the dramatic differences in yields from coupling reactions with added redox shuttles (generally >80%) and those without (generally <20%). In addition to excellent yields for a wide range of substrates, reactions protected from overreduction can be performed at high currents and on multigram scales.
While the electrooxidative activation of carboxylic acids is an attractive synthetic methodology, the resulting transformations are generally limited to either homocoupling or further oxidation ...followed by solvent capture. These reactions require extensive electrolysis at high potentials, which ultimately renders the methodology incompatible with metal catalysts that could possibly provide new and complementary product distributions. This work establishes a proof-of-concept for a rare and synthetically-underutilized strategy for selective electrooxidation of carboxylic acids in the presence of oxidatively-sensitive catalysts that control reaction selectivity. We leverage the formation of self-adsorbed monolayers of carboxylate substrates at the anode to promote selective oxidation of the adsorbed carboxylate over a more easily-oxidized catalyst. Consequently, reactions operate at lower potentials, greater faradaic efficiencies, and improved catalyst compatibility over conventional approaches, which enables reactions to be performed with inexpensive Fe complexes that catalyze selective radical additions to olefins.
Despite significant efforts to replace Pd-based catalysts with those of Ni, the Ni-catalyzed Mizoroki–Heck coupling of aryl halides and alkenes remains challenging. This work details the development ...of a Mizoroki–Heck reaction of aryl halides and a broad range of alkenes that utilizes electrochemistry as a means to promote Ni-catalyzed coupling under mild conditions. Stoichiometric studies implicate low-valent Ni complexes as key intermediates in route to rapid reactions with even unactivated alkenes. As such, electrochemistry is employed to readily provide the reducing potentials necessary to access these reactive intermediates and render the transformation catalytic. Cyclohexenone was found to be an unreactive substrate but a crucial additive that promotes facile electroreduction of the Ni catalyst and functionalization of other alkenes in high yields. Finally, preliminary mechanistic studies suggest that reactions proceed via an electron-chain transfer process that rapidly terminates but is reinitiated upon electroreduction.
Simple copper salts serve as catalysts to effect C–X bond-forming reactions in some of the most utilized transformations in synthesis, including the oxidative coupling of aryl boronic acids and ...amines. However, these Chan–Lam coupling reactions have historically relied on chemical oxidants that limit their applicability beyond small-scale synthesis. Despite the success of replacing strong chemical oxidants with electrochemistry for a variety of metal-catalyzed processes, electrooxidative reactions with ligandless copper catalysts are plagued by slow electron-transfer kinetics, irreversible copper plating, and competitive substrate oxidation. Herein, we report the implementation of substoichiometric quantities of redox mediators to address limitations to Cu-catalyzed electrosynthesis. Mechanistic studies reveal that mediators serve multiple roles by (i) rapidly oxidizing low-valent Cu intermediates, (ii) stripping Cu metal from the cathode to regenerate the catalyst and reveal the active Pt surface for proton reduction, and (iii) providing anodic overcharge protection to prevent substrate oxidation. This strategy is applied to Chan–Lam coupling of aryl-, heteroaryl-, and alkylamines with arylboronic acids in the absence of chemical oxidants. Couplings under these electrochemical conditions occur with higher yields and shorter reaction times than conventional reactions in air and provide complementary substrate reactivity.
The integration of renewable energy sources into the electric grid requires low-cost energy storage systems that mediate the variable and intermittent flux of energy associated with most renewables. ...Nonaqueous redox-flow batteries have emerged as a promising technology for grid-scale energy storage applications. Because the cost of the system scales with mass, the electroactive materials must have a low equivalent weight (ideally 150 g/(mol·e −) or less), and must function with low molecular weight supporting electrolytes such as LiBF4. However, soluble anolyte materials that undergo reversible redox processes in the presence of Li-ion supports are rare. We report the evolutionary design of a series of pyridine-based anolyte materials that exhibit up to two reversible redox couples at low potentials in the presence of Li-ion supporting electrolytes. A combination of cyclic voltammetry of anolyte candidates and independent synthesis of their corresponding charged-states was performed to rapidly screen for the most promising candidates. Results of this workflow provided evidence for possible decomposition pathways of first-generation materials and guided synthetic modifications to improve the stability of anolyte materials under the targeted conditions. This iterative process led to the identification of a promising anolyte material, N-methyl 4-acetylpyridinium tetrafluoroborate. This compound is soluble in nonaqueous solvents, is prepared in a single synthetic step, has a low equivalent weight of 111 g/(mol·e −), and undergoes two reversible 1e – reductions in the presence of LiBF4 to form reduced products that are stable over days in solution.
A series of small redox‐active organics based on cyclopropenium salts are identified as promising nonaqueous catholytes. Synthetic modification provides access to highly soluble catholytes at all ...redox states (>0.7 m) and that undergo >200 charge–discharge cycles at high potentials (>0.8 V vs Fc/Fc+). The oxidized catholyte is isolable and stable at high concentration for days without degradation.
The oxidative coupling of arenes and alkenes is an attractive strategy for the synthesis of vinylarenes, but reactions with unactivated alkenes have typically occurred in low yield. We report an ...Ir-catalyzed oxidative coupling of furans with unactivated olefins to generate branched vinylfuran products in high yields and with high selectivities with a second alkene as the hydrogen acceptor. Detailed mechanistic experiments revealed catalyst decomposition pathways that were alleviated by the judicious selection of reaction conditions and application of new ligands.
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