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Analyzing mechanisms in Co(i) redox catalysis using a pattern recognition platform

TOC graphic for D0SC06725CTianhua Tang, Christopher Sandford, Shelley D. Minteer, and Matthew S. Sigman

DOI: 10.1039/D0SC06725C

Analyzing mechanisms in Co(i) redox catalysis using a pattern recognition platform

Redox catalysis has been broadly utilized in electrochemical synthesis due to its kinetic advantages over direct electrolysis. The appropriate choice of redox mediator can avoid electrode passivation and overpotential, which strongly inhibit the efficient activation of substrates in electrolysis. Despite the benefits brought by redox catalysis, establishing the precise nature of substrate activation remains challenging. Herein, we determine that a Co(I) complex bearing two N,N,N-tridentate ligands acts as a competent redox catalyst for the reduction of benzyl bromide substrates. Kinetic studies combining electroanalytical techniques with multivariable linear-regression analysis were conducted, disclosing an outer-sphere electron-transfer mechanism, which occurs in concert with C–Br bond cleavage. Furthermore, we apply a pattern recognition platform to distinguish between mechanisms in the activation of benzyl bromides, found to be dependent on the ligation state of the cobalt(I) center and ligand used.

Advances in Electrochemical Modification Strategies of 5‐Hydroxymethylfurfural

 

Olja Simoska, Zayn Rhodes, Samali Weliwatte, Jaime R. Cabrera‐Pardo, Erin M. Gaffney, Koun Lim, Shelley D. Minteer

DOI: 10.1002/cssc.202100139

Advances in Electrochemical Modification Strategies of 5‐Hydroxymethylfurfural

The development of electrochemical catalytic conversion of 5‐hydroxymethylfurfural (HMF) has recently gained attention as a potentially scalable approach for both oxidation and reduction processes yielding value‐added products. While the possibility of electrocatalytic HMF transformations has been demonstrated, this growing research area is in its initial stages. Additionally, its practical applications remain limited due to low catalytic activity and product selectivity. Understanding the catalytic processes and design of electrocatalysts are important in achieving a selective and complete conversion into the desired highly valuable products. In this Minireview, an overview of the most recent status, advances, and challenges of oxidation and reduction processes of HMF was provided. Discussion and summary of voltammetric studies and important reaction factors (e. g., catalyst type, electrode material) were included. Finally, biocatalysts (e. g., enzymes, whole cells) were introduced for HMF modification, and future opportunities to combine biocatalysts with electrochemical methods for the production of high‐value chemicals from HMF were discussed.

Solvent molecules form surface redox mediators in situ and cocatalyze O2 reduction on Pd

 

Jason S. Adams, Ashwin Chemburkar, Pranjali Priyadarshini, Tomas Ricciardulli, Yubing Lu, Vineet Maliekkal, Abinaya Sampath, Stuart Winikoff, Ayman M. Karim, Matthew Neurock, David W. Flaherty 

DOI: 10.1126/science.abc1339 

Solvent molecules form surface redox mediators in situ and cocatalyze O2 reduction on Pd

Solvent molecules influence the reactions of molecular hydrogen and oxygen on palladium nanoparticles. Organic solvents activate to form reactive surface intermediates that mediate oxygen reduction through pathways distinct from reactions in pure water. Kinetic measurements and ab initio quantum chemical calculations indicate that methanol and water cocatalyze oxygen reduction by facilitating proton-electron transfer reactions. Methanol generates hydroxymethyl intermediates on palladium surfaces that efficiently transfer protons and electrons to oxygen to form hydrogen peroxide and formaldehyde. Formaldehyde subsequently oxidizes hydrogen to regenerate hydroxymethyl. Water, on the other hand, heterolytically oxidizes hydrogen to produce hydronium ions and electrons that reduce oxygen. These findings suggest that reactions of solvent molecules at solid-liquid interfaces can generate redox mediators in situ and provide opportunities to substantially increase rates and selectivities for catalytic reactions.

Effect of Structural Ordering on the Charge Storage Mechanism of p-Type Organic Electrode Materials

TOC for acsami.0c19622Brian M. Peterson, Cara N. Gannett, Luis Melecio-Zambrano, Brett P. Fors, and Héctor Abruña

DOI: 10.1021/acsami.0c19622

Effect of Structural Ordering on the Charge Storage Mechanism of p-Type Organic Electrode Materials

Understanding the properties that govern the kinetics of charge storage will enable informed design strategies and improve the rate performance of future battery materials. Herein, we study the effects of structural ordering in organic electrode materials on their charge storage mechanisms. A redox active unit, N,N′-diphenyl-phenazine, was incorporated into three materials which exhibited varying degrees of ordering. From cyclic voltammetry analysis, the crystalline small molecule exhibited diffusion-limited behavior, likely arising from structural rearrangements that occur during charge/discharge. Conversely, a branched polymer network displayed surface-controlled kinetics, attributed to the amorphous structure which enabled fast ionic transport throughout charge/discharge, unimpeded by sluggish structural rearrangements. These results suggest a method for designing new materials for battery electrodes with battery-like energy densities and pseudocapacitor-like rate capabilities. 

Organic Electrode Materials for Fast-Rate, High-Power Battery Applications

 TOC for j.matre.2021.01.003

Cara N. Gannett, Luis Melecio-Zambrano, Monica Theibault, Brian M. Peterson, Brett P. Fors, Héctor D. Abruña

DOI: 10.1016/j.matre.2021.01.003

Organic Electrode Materials for Fast-Rate, High-Power Battery Applications

The development of new battery materials with fast charging/discharging capabilities is necessary to meet the growing demands of modern technologies. While counter ion transport in inorganic materials (generally by de/intercalation) currently limits charge/discharge rates in lithium-ion batteries, the weak intermolecular forces in organic materials result in flexible, spacious structures that offer improved ion transport capabilities. Herein, we present the principles which enable fast rate capabilities in organic electrode materials, accompanied by specific literature examples illustrating exceptional rate performances. We discuss approaches to material design which support electron and/or ion transport and the limitations associated with each. This review aims to highlight the unique characteristics of organic materials as high-power density electrodes and inspire continued work in the field. 

Carbonyl Desaturation: Where Does Catalysis Stand?

TOC for acscatal.0c04712

Samer Gnaim, Julien C. Vantourout, Fabien Serpier, Pierre-Georges Echeverria, and Phil. S. Baran

DOI: 10.1021/acscatal.0c04712

Carbonyl Desaturation: Where Does Catalysis Stand?

There is a strong parallel between simple alcohol oxidation and carbonyl desaturation from both strategic and tactical vantage points. As they both seek to extract hydrogen from an organic substrate, they are deceptively simple looking transformations that have been addressed over the past 70+ years through stoichiometric means. The past decade has seen an intensifying level of interest in rendering both of these simple reactions catalytic. In this Perspective, recent advances from the past 5 years are highlighted featuring both transition-metal-catalyzed and metal-free approaches to carbonyl desaturation. Through a historical overview and a detailed look at each of these new developments, we seek to address the question of in what context a catalytic strategy emerges as ideal. 

Electroreductive Olefin–Ketone Coupling


TOC for jacs.0c11214

 

Pengfei Hu, Byron K. Peters, Christian A. Malapit, Julien C. Vantourout, Pan Wang, Jinjun Li, Lucas Mele, Pierre-Georges Echeverria, Shelley D. Minteer, and Phil S. Baran

DOI: 10.1021/jacs.0c11214

Electroreductive Olefin–Ketone Coupling

A user-friendly approach is presented to sidestep the venerable Grignard addition to unactivated ketones to access tertiary alcohols by reversing the polarity of the disconnection. In this work a ketone instead acts as a nucleophile when adding to simple unactivated olefins to accomplish the same overall transformation. The scope of this coupling is broad as enabled using an electrochemical approach, and the reaction is scalable, chemoselective, and requires no precaution to exclude air or water. Multiple applications demonstrate the simplifying nature of the reaction on multistep synthesis, and mechanistic studies point to an intuitive mechanism reminiscent of other chemical reductants such as SmI2 (which cannot accomplish the same reaction). 

Biphasic Bioelectrocatalytic Synthesis of Chiral β-Hydroxy Nitriles

TOC for jacs.0c01890

  Fangyuan Dong, Hui Chen, Christian A. Malapit, Matthew B. Prater, Min Li, Mengwei Yuan, Koun Lim, and Shelley D. Minteer

DOI: 10.1021/jacs.0c01890

Biphasic Bioelectrocatalytic Synthesis of Chiral β-Hydroxy Nitriles

Two obstacles limit the application of oxidoreductase-based asymmetric synthesis. One is the consumption of high stoichiometric amounts of reduced cofactor. The other is the low solubility of organic substrates, intermediates, and products in the aqueous phase. In order to address these two obstacles to oxidoreductase-based asymmetric synthesis, a biphasic bioelectrocatalytic system was constructed and applied. In this study, the preparation of chiral β-hydroxy nitriles catalyzed by alcohol dehydrogenase (AdhS) and halohydrin dehalogenase (HHDH) was investigated as a model bioelectrosynthesis, since they are high-value intermediates in statin synthesis. Diaphorase (DH) was immobilized by a cobaltocene-modified poly(allylamine) redox polymer on the electrode surface (DH/Cc-PAA bioelectrode) to achieve effective bioelectrocatalytic NADH regeneration. Since AdhS is a NAD-dependent dehydrogenase, the diaphorase-modified biocathode was used to regenerate NADH to support the conversion from ethyl 4-chloroacetoacetate (COBE) to ethyl (S)-4-chloro-3-hydroxybutanoate ((S)-CHBE) catalyzed by AdhS. The addition of methyl tert-butyl ether (MTBE) as an organic phase not only increased the uploading of COBE but also prevented the spontaneous hydrolysis of COBE, extended the lifetime of DH/Cc-PAA bioelectrode, and increased the Faradaic efficiency and the concentration of generated (R)-ethyl-4-cyano-3-hydroxybutyrate ((R)-CHCN). After 10 h of reaction, the highest concentration of (R)-CHCN in the biphasic bioelectrocatalytic system was 25.5 mM with 81.2% enantiomeric excess (eep). The conversion ratio of COBE achieved 85%, which was 8.8 times higher than that achieved with the single-phase system. Besides COBE, two other substrates with aromatic ring structures were also used in this biphasic bioelectrocatalytic system to prepare the corresponding chiral β-hydroxy nitriles. The results indicate that the biphasic bioelectrocatalytic system has the potential to produce a variety of β-hydroxy nitriles with different structures. 

Selective Electroenzymatic Oxyfunctionalization by Alkane Monooxygenase in a Biofuel Cell

TOC for ange.202003032

Mengwei Yuan Dr. Sofiene Abdellaoui Dr. Hui Chen Matthew J. Kummer Dr. Christian A. Malapit Dr. Chun You Prof. Shelley D. Minteer

DOI: 10.1002/anie.202003032

Selective Electroenzymatic Oxyfunctionalization by Alkane Monooxygenase in a Biofuel Cell

Aliphatic synthetic intermediates with high added value are generally produced from alkane sources (e.g., petroleum) by inert carbon–hydrogen (C−H) bond activation using classical chemical methods (i.e. high temperature, rare metals). As an alternative approach for these reactions, alkane monooxygenase from Pseudomonas putida (alkB) is able to catalyze the difficult terminal oxyfunctionalization of alkanes selectively and under mild conditions. Herein, we report an electrosynthetic system using an alkB biocathode which produces alcohols, epoxides, and sulfoxides through bioelectrochemical hydroxylation, epoxidation, sulfoxidation, and demethylation. The capacity of the alkB binding pocket to protect internal functional groups is also demonstrated. By coupling our alkB biocathode with a hydrogenase bioanode and using H2 as a clean fuel source, we have developed and characterized a series of enzymatic fuel cells capable of oxyfunctionalization while simultaneously producing electricity. 

Electrochemical Reduction of [Ni(Mebpy)3]2+: Elucidation of the Redox Mechanism by Cyclic Voltammetry and Steady‐State Voltammetry in Low Ionic Strength Solutions

 

Koushik Barman, Martin A. Edwards, David P. Hickey, Christopher Sandford, Yinghua Qiu, Rui Gao, Shelley D. Minteer, Henry S. White

DOI: 10.1002/celc.202000171

Electrochemical Reduction of [Ni(Mebpy)3]2+: Elucidation of the Redox Mechanism by Cyclic Voltammetry and Steady‐State Voltammetry in Low Ionic Strength Solutions

Bipyridine complexes of Ni are used as catalysts in a variety of reductive transformations. Here, the electroreduction of [Ni(Mebpy)3]2+ (Mebpy=4,4′‐dimethyl‐2,2′‐bipyridine) in dimethylformamide is reported, with the aim of determining the redox mechanism and oxidation states of products formed under well‐controlled electrochemical conditions. Results from cyclic voltammetry, steady‐state voltammetry (SSV) and chronoamperometry demonstrate that [Ni(Mebpy)3]2+ undergoes two sequential 1e reductions at closely separated potentials (E10’=−1.06±0.01 V and E20’=−1.15±0.01 V vs Ag/AgCl (3.4 M KCl)). Homogeneous comproportionation to generate [Ni(Mebpy)3]+ is demonstrated in SSV experiments in low ionic strength solutions. The comproportionation rate constant is determined to be >106 M−1 s−1, consistent with rapid outer‐sphere electron transfer. Consequentially, on voltammetric time scales, the 2e reduction of [Ni(Mebpy)3]2+ results in formation of [Ni(Mebpy)3]+ as the predominant species released into bulk solution. We also demonstrate that [Ni(Mebpy)3]0 slowly loses a Mebpy ligand (∼10 s−1). 

Ionic Liquid Stabilized 2,2,6,6-Tetramethylpiperidine 1-Oxyl Catalysis for Alcohol Oxidation

TOC for Li, M.; Klunder, K.; Blumenthal, E.; Prater, M.B.; Lee, J.; Matthiesen, J.E.; Minteer, S.D. Ionic Liquid Stabilized 2,2,6,6-Tetramethylpiperidine 1-Oxyl Catalysis for Alcohol Oxidation. ACS Sustainable Chem. Eng. 2020, in press (doi: 10.1021/acssuschemeng.9b07650)

Min Li, Kevin Klunder, Emmy Blumenthal, Matthew B. Prater, Jack Lee, John E. Matthiesen, and Shelley D. Minteer

DOI: 10.1021/acssuschemeng.9b07650

Ionic Liquid Stabilized 2,2,6,6-Tetramethylpiperidine 1-Oxyl Catalysis for Alcohol Oxidation

N-Oxyl reagents, particularly 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO), have been extensively used for alcohol oxidations. While TEMPO-mediated oxidations are kinetically and thermodynamically favorable in high-pH electrolytes, base-induced degradation often results in significant loss of catalytic activity. Herein, we demonstrate enhanced alkaline stability of a TEMPO derivative in ionic liquids (ILs). By incorporating TEMPO in an imidazole-anchored IL, no loss of current was observed at pH 10.0 after 2.0 h during the oxidation of butanol and glycerol, while TEMPO in polycaprolactone (PCL), a patternable binder material, degraded 58.5% and 67.1%, respectively. The stability enhancement was further demonstrated by analyzing the conversion of glycerol in an 800 μL electrochemical cell using bulk chemical analysis techniques. Successive cycles of glycerol oxidation indicated 14-fold stability enhancement by applying IL in a TEMPO electrode composite in comparison to PCL. The strategy demonstrated here provides an opportunity to prepare catalytic systems with enhanced stability. Further, this method provides the ability to convert what are typically homogeneous catalysts to heterogeneous systems. 

Bioelectrocatalytic Conversion from N2 to Chiral Amino Acids in a H2/α-Keto Acid Enzymatic Fuel Cell

TOC for Chen, H.; Prater, M.B.; Cai, R.; Dong, F.; Chen, H; Minteer, S.D. Bioelectrocatalytic Conversion from N2 to Chiral Amino Acids in a H2/alpha-Keto Acid Enzymatic Fuel Cell. Journal of the American Chemical Society 2020, 142, 4028-4036.

Hui Chen, Matthew B. Prater, Rong Cai, Fangyuan Dong, Hsiaonung Chen, and Shelley D. Minteer

DOI: 10.1021/jacs.9b13968

Bioelectrocatalytic Conversion from N2 to Chiral Amino Acids in a H2/α-Keto Acid Enzymatic Fuel Cell

Enzymatic electrosynthesis is a promising approach to produce useful chemicals with the requirement of external electrical energy input. Enzymatic fuel cells (EFCs) are devices to convert chemical energy to electrical energy via the oxidation of fuel at the anode and usually the reduction of oxygen or peroxide at the cathode. The integration of enzymatic electrosynthesis with EFC architectures can simultaneously result in self-powered enzymatic electrosynthesis with more valuable usage of electrons to produce high-value-added chemicals. In this study, a H2/α-keto acid EFC was developed for the conversion from chemically inert nitrogen gas to chiral amino acids, powered by H2 oxidation. A highly efficient cathodic reaction cascade was first designed and constructed. Powered by an applied voltage, the cathode supplied enough reducing equivalents to support the NH3 production and NADH recycling catalyzed by nitrogenase and diaphorase. The produced NH3 and NADH were reacted in situ with leucine dehydrogenase (LeuDH) to generate l-norleucine with 2-ketohexanoic acid as the NH3 acceptor. A 92% NH3 conversion ratio and 87.1% Faradaic efficiency were achieved. On this basis, a H2-powered fuel cell with hyper-thermostable hydrogenase (SHI) as the anodic catalyst was combined with the cathodic reaction cascade to form the H2/α-keto acid EFC. After 10 h of reaction, the concentration of l-norleucine achieved 0.36 mM with >99% enantiomeric excess and 82% Faradaic efficiency. From the broad substrate scope and the high enzymatic enantioselectivity of LeuDH, the H2/α-keto acid EFC is an energy-efficient alternative to electrochemically produce chiral amino acids for biotechnology applications. 

The progress and outlook of bioelectrocatalysis for the production of chemicals, fuels and materials

Bioelectrocatalysis is a green, sustainable, efficient method to produce value-added chemicals, clean biofuels and degradable materials. As an alternative approach to modern biomanufacturing technology, bioelectrocatalysis fully combines the merits of both biocatalysis and electrocatalysis to realize the green, efficient production of target products from electricity. Here, we review the development status of bioelectrocatalysis, discussing the current challenges and looking toward future development directions. First, we detail the structure, function and modification methods of bioelectrocatalysis. Next, we describe the mechanism of electron transfer, including mediated electron transfer and directed electron transfer. Third, we discuss the impact of the electrode on bioelectrocatalysis. Then we analyse and summarize the application of bioelectrocatalysis methods in the production of chemicals, biofuels and materials. Finally, we detail future developments and perspectives on bioelectrocatalysis for electrosynthesis. 

A Survival Guide for the “Electro-curious”

 

TOC for Kingston, C.; Palkowitz, M. D.; Takahira, Y.; Vantourout, J. C.; Peters, B. K.; Kawamata, Y.; Baran, P. S. A Survival Guide for the “Electro-curious”. Accounts of Chemical Research 2020, 53, 72-83.

 

Cian Kingston, Maximilian D. Palkowitz, Yusuke Takahira, Julien C. Vantourout, Byron K. Peters, Yu Kawamata, and Phil S. Baran

DOI: 10.1021/acs.accounts.9b00539

A Survival Guide for the “Electro-curious”

The appeal and promise of synthetic organic electrochemistry have been appreciated over the past century. In terms of redox chemistry, which is frequently encountered when forging new bonds, it is difficult to conceive of a more economical way to add or remove electrons than electrochemistry. Indeed, many of the largest industrial synthetic chemical processes are achieved in a practical way using electrons as a reagent. Why then, after so many years of the documented benefits of electrochemistry, is it not more widely embraced by mainstream practitioners? Erroneous perceptions that electrochemistry is a “black box” combined with a lack of intuitive and inexpensive standardized equipment likely contributed to this stagnation in interest within the synthetic organic community. This barrier to entry is magnified by the fact that many redox processes can already be accomplished using simple chemical reagents even if they are less atom-economic. Time has proven that sustainability and economics are not strong enough driving forces for the adoption of electrochemical techniques within the broader community. Indeed, like many synthetic organic chemists that have dabbled in this age-old technique, our first foray into this area was not by choice but rather through sheer necessity.

The unique reactivity benefits of this old redox-modulating technique must therefore be highlighted and leveraged in order to draw organic chemists into the field. Enabling new bonds to be forged with higher levels of chemo- and regioselectivity will likely accomplish this goal. In doing so, it is envisioned that widespread adoption of electrochemistry will go beyond supplanting unsustainable reagents in mundane redox reactions to the development of exciting reactivity paradigms that enable heretofore unimagined retrosynthetic pathways. Whereas the rigorous physical organic chemical principles of electroorganic synthesis have been reviewed elsewhere, it is often the case that such summaries leave out the pragmatic aspects of designing, optimizing, and scaling up preparative electrochemical reactions. Taken together, the task of setting up an electrochemical reaction, much less inventing a new one, can be vexing for even seasoned organic chemists. This Account therefore features a unique format that focuses on addressing this exact issue within the context of our own studies. The graphically rich presentation style pinpoints basic concepts, typical challenges, and key insights for those “electro-curious” chemists who seek to rapidly explore the power of electrochemistry in their research. 

Nitrogenase Bioelectrochemistry for Synthesis Applications

The fixation of atmospheric dinitrogen to ammonia by industrial technologies (such as the Haber Bosch process) has revolutionized humankind. In contrast to industrial technologies, a single enzyme is known for its ability to reduce or “fix” dinitrogen: nitrogenase. Nitrogenase is a complex oxidoreductase enzymatic system that includes a catalytic protein (where dinitrogen is reduced) and an electron-transferring reductase protein (termed the Fe protein) that delivers the electrons necessary for dinitrogen fixation. The catalytic protein most commonly contains a FeMo cofactor (called the MoFe protein), but it can also contain a VFe or FeFe cofactor. Besides their ability to fix dinitrogen to ammonia, these nitrogenases can also reduce substrates such as carbon dioxide to formate. Interestingly, the VFE nitrogenase can also form carbon–carbon bonds. The vast majority of research surrounding nitrogenase employs the Fe protein to transfer electrons, which is also associated with the rate-limiting step of nitrogenase catalysis and also requires the hydrolysis of adenosine triphosphate. Thus, there is significant interest in artificially transferring electrons to the catalytic nitrogenase proteins. In this Account, we review nitrogenase electrocatalysis whereby electrons are delivered to nitrogenase from electrodes. We first describe the use of an electron mediator (cobaltocene) to transfer electrons from electrodes to the MoFe protein. The reduction of protons to molecular hydrogen was realized, in addition to azide and nitrite reduction to ammonia. Bypassing the rate-limiting step within the Fe protein, we also describe how this approach was used to interrogate the rate-limiting step of the MoFe protein: metal-hydride protonolysis at the FeMo-co. This Account next reviews the use of cobaltocene to mediate electron transfer to the VFe protein, where the reduction of carbon dioxide and the formation of carbon–carbon bonds (yielding the formation of ethene and propene) was realized. This approach also found success in mediating electron transfer to the FeFe catalytic protein, which exhibited improved carbon dioxide reduction in comparison to the MoFe protein. In the final example of mediated electron transfer to the catalytic protein, this Account also reviews recent work where the coupling of infrared spectroscopy with electrochemistry enabled the potential-dependent binding of carbon monoxide to the FeMo-co to be studied. As an alternative to mediated electron transfer, recent work that has sought to transfer electrons to the catalytic proteins in the absence of electron mediators (by direct electron transfer) is also reviewed. This approach has subsequently enabled a thermodynamic landscape to be proposed for the cofactors of the catalytic proteins. Finally, this Account also describes nitrogenase electrocatalysis whereby electrons are first transferred from an electrode to the Fe protein, before being transferred to the MoFe protein alongside the hydrolysis of adenosine triphosphate. In this way, increased quantities of ammonia can be electrocatalytically produced from dinitrogen fixation. We discuss how this has led to the further upgrade of electrocatalytically produced ammonia, in combination with additional enzymes (diaphorase, alanine dehydrogenase, and transaminase), to selective production of chiral amine intermediates for pharmaceuticals. This Account concludes by discussing current and future research challenges in the field of electrocatalytic nitrogen fixation by nitrogenase. 

Polycaprolactone-enabled sealing and carbon composite electrode integration into electrochemical microfluidics

TOC graphic for Klunder, K.; Clark, K.M.; McCord, C.; Berg, K.E.; Minteer, S.D.; Henry, C.S. Polycaprolactone-enabled sealing and carbon composite electrode integration into electrochemical microfluidics.  Lab on a Chip 2019 19, 2589-2597

Kevin J. Klunder, Kaylee M. Clark, Cynthia McCord, Kathleen E. Berg, Shelley D. Minteer, Charles S. Henry 

DOI: 10.1039/C9LC00417C

Polycaprolactone-enabled sealing and carbon composite electrode integration into electrochemical microfluidics

Combining electrochemistry with microfluidics is attractive for a wide array of applications including multiplexing, automation, and high-throughput screening. Electrochemical instrumentation also has the advantage of being low-cost and can enable high analyte sensitivity. For many electrochemical microfluidic applications, carbon electrodes are more desirable than noble metals because they are resistant to fouling, have high activity, and large electrochemical solvent windows. At present, fabrication of electrochemical microfluidic devices bearing integrated carbon electrodes remains a challenge. Here, a new system for integrating polycaprolactone (PCL) and carbon composite electrodes into microfluidics is presented. The PCL : carbon composites have excellent electrochemical activity towards a wide range of analytes as well as high electrical conductivity (∼1000 S m−1). The new system utilizes a laser cutter for fast, simple fabrication of microfluidics using PCL as a bonding layer. As a proof-of-concept application, oil-in-water and water-in-oil droplets are electrochemically analysed. Small-scale electrochemical organic synthesis for TEMPO mediated alcohol oxidation is also demonstrated. 

Mechanistic Studies into the Oxidative Addition of Co(I) Complexes: Combining Electroanalytical Techniques with Parameterization

The oxidative addition of organic electrophiles into electrochemically generated Co(I) complexes has been widely utilized as a strategy to produce carbon-centered radicals when cobalt is ligated by a polydentate ligand. Changing to a bidentate ligand provides the opportunity to access discrete Co(III)ñC bonded complexes for alternative reactivity, but knowledge of how ligand and/or substrate structures affect catalytic steps is pivotal to reaction design and catalyst optimization. In this vein, experimental studies which can determine the exact nature of elementary organometallic steps remain limited, especially for single-electron oxidative addition pathways. Herein, we utilize cyclic voltammetry combined with simulations to obtain kinetic and thermodynamic properties of the two-step, halogen-atom abstraction mechanism, validated by analyzing kinetic isotope and substituent effects. Complex Hammett relationships could be disentangled to allow understanding of individual effects on activation energy barriers and equilibrium constants, and DFT-derived parameters used to build predictive statistical models for rates of new ligand/substrate combinations.  

 

 

Hindered dialkyl ether synthesis with electrogenerated carbocations

 

 

Jinbao Xiang, Ming Shang, Yu Kawamata, Helena Lundberg, Solomon H. Reisberg, Miao Chen, Pavel Mykhailiuk, Gregory Beutner, Michael R. Collins, Alyn Davies, Matthew Del Bel, Gary M. Gallego, Jillian E. Spangler, Jeremy Starr, Shouliang Yang, Donna G. Blackmond & Phil S. Baran

DOI: 10.1038/s41586-019-1539-y

Hindered dialkyl ether synthesis with electrogenerated carbocations

Hindered ethers are of high value for various applications; however, they remain an underexplored area of chemical space because they are difficult to synthesize via conventional reactions’–1,–2. Such motifs are highly coveted in medicinal chemistry, because extensive substitution about the ether bond prevents unwanted metabolic processes that can lead to rapid degradation in vivo. Here we report a simple route towards the synthesis of hindered ethers, in which electrochemical oxidation is used to liberate high-energy carbocations from simple carboxylic acids. These reactive carbocation intermediates, which are generated with low electrochemical potentials, capture an alcohol donor under non-acidic conditions; this enables the formation of a range of ethers (more than 80 have been prepared here) that would otherwise be difficult to access. The carbocations can also be intercepted by simple nucleophiles, leading to the formation of hindered alcohols and even alkyl fluorides. This method was evaluated for its ability to circumvent the synthetic bottlenecks encountered in the preparation of 12 chemical scaffolds, leading to higher yields of the required products, in addition to substantial reductions in the number of steps and the amount of labour required to prepare them. The use of molecular probes and the results of kinetic studies support the proposed mechanism and the role of additives under the conditions examined. The reaction manifold that we report here demonstrates the power of electrochemistry to access highly reactive intermediates under mild conditions and, in turn, the substantial improvements in efficiency that can be achieved with these otherwise-inaccessible intermediates.  

Efficient NADH Regeneration by a Redox Polymer-Immobilized Enzymatic System

 TOC for acscatal.9b00513

 
Mengwei Yuan, Matthew J. Kummer, Ross D. Milton, Timothy Quah, and Shelley D. Minteer
 
 

Efficient NADH Regeneration by a Redox Polymer-Immobilized Enzymatic System

Given the high costs and stoichiometric amounts of reduced nicotinamide adenine dinucleotide (NADH) required by the many oxidoreductases used for organic synthesis and the pharmaceutical industry, there is a need for the efficient reductive regeneration of NADH from its oxidized form, NAD+. Bioelectrocatalytic methods for NADH regeneration involving diaphorase and a redox mediator have shown promise; however, strong reductive mediators needed for this system are scarce, generally unstable, and require downstream separation. The immobilization of diaphorase in cobaltocene-modified poly(allylamine) redox polymer is presented which is capable of producing bioactive 1,4-NADH with yields between 97% and 100%, faradaic efficiencies between 78% and 99%, and turnover frequencies between 2091 h–1 and 3680 h–1 over a range of temperatures spanning 20 to 60 °C. By using this system, methanol and propanol production by an NADH-dependent alcohol dehydrogenase were enhanced 7.1- and 5.2-fold, respectively, compared with a negative control. Finally, the efficiency of this approach coupled with its high operational stability (91% of the maximum activity after five experimental cycles) renders it among the most promising means of NADH regeneration yet developed..  

A synthetic chemist's guide to electroanalytical tools for studying reaction mechanisms

 

Christopher Sandford, Martin A. Edwards, Kevin J. Klunder, David P. Hickey, Min Li, Koushik Barman, Matthew S. Sigman,  Henry S. White  and Shelley D. Minteer 

DOI: 10.1039/c9sc01545k

A synthetic chemist's guide to electroanalytical tools for studying reaction mechanisms

Monitoring reactive intermediates can provide vital information in the study of synthetic reaction mechanisms, enabling the design of new catalysts and methods. Many synthetic transformations are centred on the alteration of oxidation states, but these redox processes frequently pass through intermediates with short life-times, making their study challenging. A variety of electroanalytical tools can be utilised to investigate these redox-active intermediates: from voltammetry to in situ spectroelectrochemistry and scanning electrochemical microscopy. This perspective provides an overview of these tools, with examples of both electrochemically-initiated processes and monitoring redox-active intermediates formed chemically in solution. The article is designed to introduce synthetic organic and organometallic chemists to electroanalytical techniques and their use in probing key mechanistic questions.  

Phthalocyanines as a π–π Adsorption Strategy to Immobilize Catalyst on Carbon for Electrochemical Synthesis

In most electrochemical syntheses, reactions are happening at or near the electrode surface. For catalyzed reactions, ideally, the electrode surface would solely contain the catalyst, which then simplifies purification and lowers the amount of catalyst needed. Here, a new strategy involving phthalocyanines (Pc) to immobilize catalysts onto carbon electrode surfaces is presented. The large π structure of the Pc enables adsorption to the sp2-structure of graphitic carbon. TEMPO-modified Pc were chosen as a proof of concept to test the new immobilization strategy. It was found that the TEMPO-Pc derivatives functioned similarly or better than the widely used pyrene adsorption method. Interestingly, the new TEMPO-Pc catalyst appears to facilitate a cascade reaction involving both the anode and the cathode. The first step is the generation of an aryl aldehyde (anode) followed by the reduction of the aryl aldehyde in a pinacol-type coupling reaction at the cathode. The last step is the oxidation of a hydrobenzoin to create benzil. This work demonstrates the unique ability of electrochemistry and bifunctional catalysts to enable multistep chemical transformations, performing both reductive and oxidative transformations in one pot.  

Upgraded Bioelectrocatalytic N2 Fixation: From N2 to Chiral Amine Intermediates

 

Hui Chen, Rong Cai, Janki Patel, Fangyuan Dong, Hsiaonung Chen, Shelley D. Minteer
 
 

Upgraded Bioelectrocatalytic N2 Fixation: From N2 to Chiral Amine Intermediates

Enantiomerically pure chiral amines are of increasing value in the preparation of bioactive compounds, pharmaceuticals, and agrochemicals. ω-Transaminase (ω-TA) is an ideal catalyst for asymmetric amination because of its excellent enantioselectivity and wide substrate scope. To shift the equilibrium of reactions catalyzed by ω-TA to the side of the amine product, an upgraded N2 fixation system based on bioelectrocatalysis was developed to realize the conversion from N2to chiral amine intermediates. The produced NH3 was in situ reacted with l-alanine dehydrogenase to generate alanine with NADH as a coenzyme. ω-TA transferred the amino group from alanine to ketone substrates and finally produced the desired chiral amine intermediates. The cathode of the upgraded N2 fixation system supplied enough reducing power to synchronously realize the regeneration of reduced methyl viologen (MV•+) and NADH for the nitrogenase and l-alanine dehydrogenase. The coproduct, pyruvate, was consumed by l-alanine dehydrogenase to regenerate alanine and push the equilibrium to the side of amine. After 10 h of reaction, the concentration of 1-methyl-3-phenylpropylamine achieved 0.54 mM with the 27.6% highest faradaic efficiency and >99% enantiomeric excess (eep). Because of the wide substrate scope and excellent enantioselectivity of ω-TA, the upgraded N2 fixation system has great potential to produce a variety of chiral amine intermediates for pharmaceuticals and other applications.  

Electrochemical C(sp3)–H Fluorination

 

Yusuke Takahira, Miao Chen, Yu Kawamata, Pavel Mykhailiuk, Hugh Nakamura, Byron K. Peters, Solomon H. Reisberg, Chao Li, Longrui Chen, Tamaki Hoshikawa, Tomoyuki Shibuguchi, Phil S. Baran
 
 

Electrochemical C(sp3)–H Fluorination

A simple and robust method for electrochemical alkyl C–H fluorination is presented. Using a simple nitrate additive, a widely available fluorine source (Selectfluor), and carbon-based electrodes, a wide variety of activated and unactivated C–H bonds are converted into their C–F congeners. The scalability of the reaction is also demonstrated with a 100 gram preparation of fluorovaline.  

Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

 

Yu KawamataJulien Christian VantouroutDavid P. HickeyPeng BaiLongrui ChenQinglong HouWenhua QiaoKoushik BarmanMartin A. EdwardsAlberto F. Garrido-CastroJustine N. deGruyterHugh NakamuraKyle W. KnouseChuanguang QinKhalyd J. ClayDenghui BaoChao LiJeremy T. StarrCarmen Garcia-IrizarryNeal SachHenry S. WhiteMatthew NeurockShelley D. MinteerPhil S. Baran

DOI: 10.1021/jacs.9b01886

Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

C–N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely domi-nated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electro-chemical, computational, kinetic, and empirical experiments the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles, including complex examples on oligopeptides, medicinally-relevant heterocycles, natu-ral products, and sugars. Full disclosure of the current limitations as well as procedures for both batch and flow scale-ups (100 gram) are also described.  

Scalable and Safe Synthetic Organic Electroreduction Inspired by Li-ion Battery Chemistry

 

Byron K. PetersKevin X. RodriguezSolomon H. ReisbergSebastian B. BeilDavid P. HickeyYu KawamataMichael CollinsJeremy StarrLongrui ChenSagar UdyavaraKevin KlunderTimothy J. GoreyScott L. AndersonMatthew NeurockShelley D. Minteer, Phil S. Baran

DOI: 10.1126/science.aav5606

Scalable and Safe Synthetic Organic Electroreduction Inspired by Li-ion Battery Chemistry

Reductive electrosynthesis has faced long-standing challenges in applications to complex organic substrates at scale. Here, we show how decades of research in lithium-ion battery materials, electrolytes, and additives can serve as an inspiration for achieving practically scalable reductive electrosynthetic conditions for the Birch reduction. Specifically, we demonstrate that using a sacrificial anode material (magnesium or aluminum), combined with a cheap, nontoxic, and water-soluble proton source (dimethylurea), and an overcharge protectant inspired by battery technology [tris(pyrrolidino)phosphoramide] can allow for multigram-scale synthesis of pharmaceutically relevant building blocks. We show how these conditions have a very high level of functional-group tolerance relative to classical electrochemical and chemical dissolving-metal reductions. Finally, we demonstrate that the same electrochemical conditions can be applied to other dissolving metal–type reductive transformations, including McMurry couplings, reductive ketone deoxygenations, and epoxide openings. 

Investigating the Role of Ligand Electronics on Stabilizing Electrocatalytically Relevant Low-Valent Co(I) Intermediates

 

David P. Hickey, Christopher Sandford, Zayn Rhodes, Tobias Gensch, Lydia R. Fries, Matthew S. Sigman, and Shelley D. Minteer

DOI: 10.1021/jacs.8b12634

 Investigating the Role of Ligand Electronics on Stabilizing Electrocatalytically Relevant Low-Valent Co(I) Intermediates

Cobalt complexes have shown great promise as electrocatalysts in applications ranging from hydrogen evolution to C–H functionalization. However, the use of such complexes often requires polydentate, bulky ligands to stabilize the catalytically active Co(I) oxidation state from deleterious disproportionation reactions to enable the desired reactivity. Herein, we describe the use of bidentate electronically asymmetric ligands as an alternative approach to stabilizing transient Co(I) species. Using disproportionation rates of electrochemically generated Co(I) complexes as a model for stability, we measured the relative stability of complexes prepared with a series of N,N-bidentate ligands. While the stability of Co(I)Cl complexes demonstrates a correlation with experimentally measured thermodynamic properties, consistent with an outer-sphere electron transfer process, the set of ligated Co(I)Br complexes evaluated was found to be preferentially stabilized by electronically asymmetric ligands, demonstrating an alternative disproportionation mechanism. These results allow a greater understanding of the fundamental processes involved in the disproportionation of organometallic complexes and have allowed the identification of cobalt complexes that show promise for the development of novel electrocatalytic reactions. 

Last Updated: 2/24/21