Shannon S. Stahl

Iron-metalated nitrogen-doped carbon (Fe-N-C) materials rival platinum-based electrocatalysts for the oxygen reduction reaction (ORR) in fuel cells, and O2 reduction is proposed to occur at atomically dispersed Fe atoms coordinated by nitrogen within the graphitic material (FeNx). In recent years, similar catalysts have been shown to be effective for aerobic oxidation of organic substrates, often under non-aqueous conditions that are very different from electrocatalytic ORR conditions. Such reactions have been the focus of limited mechanistic attention, and little is known about the active sites and/or catalyst features that contribute to improved activity. Here, we investigate Fe-NC-catalyzed aerobic oxidation of hydroquinone to benzoquinone and two other organic reactions. The FeNx site density is found to have little influence over catalytic activity. Instead, we find that the basicity of nitrogen atoms in the Fe-N-C surface is the dominant feature that correlates with catalytic activity, with diagnostic insights gained from binding isotherm measurements with pivalic acid. Fe-N-C catalytic activity is shown to correlate directly with the pivalic acid binding constant (Kads) across a series of different catalysts. These insights provide a valuable foundation for future development and optimization of improved aerobic oxidation catalysts.

Thermochemical redox reactions with heterogeneous catalysts often proceed by an "electrochemical" mechanism that features coupled redox half-reactions. Studies supporting this mechanism have typically been performed with water as the solvent; however, many organic oxidation reactions feature non-aqueous solvent. Here, we analyze the aerobic oxidation of hydroquinone with iron-containing nitrogen-doped carbon (Fe-N-C) catalysts in acetonitrile. Addition of proton buffers significantly accelerates the reaction, and mechanistic data indicate the buffers support proton transfer between the two redox half-reactions, proton-coupled oxidation of the hydroquinone and O2 reduction, which take place at different active sites on the catalyst surface. Kinetic studies of the thermochemical aerobic oxidation reaction are complemented by electrochemical studies, including linear-sweep voltametric analysis of both independent half-reactions. Collectively, the data provide a selfconsistent mechanistic picture that highlights the importance of proton management in supporting thermal heterogeneous catalytic redox reactions in non-aqueous solvent.

Direct methylidenation of carbonyl compounds represents an appealing route to terminal alkenes. Existing methods for this transformation typically rely on stoichiometric phosphorus ylides (methylene Wittig) or organotitanium complexes (Tebbe or Petasis reagents). Here, we report a Cp2TiCl2-catalyzed method that uses CH2Br2 as a readily available carbene precursor and Zn as the reductant for methylidenation of alkyl ketones. The reaction is proposed to proceed via the in situ generation of an alkyl–Zn species, which then generates a Ti–carbene intermediate. Alkali metal salts, such as KBF4 and LiPF6, improve the reaction efficiency. Cyclic voltammetry studies implicate the alkali metal ions in promoting dissociation of chloride from Ti and enhancing reactivity with the alkyl–Zn reagent. The resulting protocol is operationally simple and offers a practical alternative to the use of stoichiometric methylidenation reagents.

Electrosynthetic organic reactions have advanced significantly in recent years, but their adoption for large-scale applications remains limited. Here, we report an automated experimental platform designed to facilitate translation of small-scale chemical and electrochemical redox reactions into robust larger-scale electrochemical processes. This platform, which integrates a commercial chemical synthesis workstation, peristaltic pumps, and a potentiostat, is equipped to conduct an automated sequence of batch experiments to optimize standard variables, such as stir rate and temperature, in addition to variables unique to electrosynthesis, such as applied current and total charge passed. Analysis of these variables using a design-of-experiment (DoE) approach accelerates identification of optimal reaction conditions and translation of mg-to-multigram operations. To evaluate the DoE optimization protocol and experimental platform, four Ni-catalyzed C(sp2)–C(sp3) cross-electrophile coupling reactions were selected from the literature that were originally conducted on a 0.2–0.4 mmol scale with chemical or electrochemical reduction methods. Each reaction was successfully scaled by a factor of 30–250, delivering up to 20 g (100 mmol) of isolated product. These results show how small-scale redox reactions may be rapidly translated to scalable electrosynthetic processes.

Well-defined (TTP)TiII (TTP = 5,10,15,20-tetratolylporphyrin) complexes have been shown to promote stoichiometric deoxygenation of organic molecules, such as sulfoxides and epoxides, forming a stable (TTP)TiIV=O product. Here, we explore strategies to promote catalytic deoxygenation reactivity by regenerating (TTP)TiII through chemical or electrochemical reduction. A survey of Lewis acids revealed the effectiveness of B(OPh)3 in promoting activation and loss of the Ti-oxo group, enabling TiII-mediated reductive oxygen-atom transfer (OAT) of diphenyl sulfoxide. Cyclic voltammetry, coulometry, EPR spectroscopy, and X-ray crystallography have been used to probe and characterize TiIII and TiII species from the electroreductive deoxygenation of the TiIV=O complex. The data implicate a Lewis-acid-coupled electron-transfer deoxygenation pathway for TiIV=O turnover. These fundamental studies are complemented by electrochemical reactions demonstrating catalytic reductive oxygen-atom transfer from sulfoxides, pyridine N-oxides, and epoxides.

Electrochemical synthesis is an increasingly attractive approach for sustainable chemical manufacturing, offering precise control over reaction pathways and the potential to replace stoichiometric reagents with electricity. Membrane-separated electrochemical reactors are particularly valuable for enabling independent optimization of anodic and cathodic environments while suppressing undesired crossover of reactive species. However, the scalability of membrane-separated electrosynthesis in non-aqueous solvents remains limited by membrane stability and selectivity. Ion-exchange membranes originally developed for aqueous electrochemical systems, such as perfluorosulfonic acid polymers, often undergo solvent-induced swelling, mechanical deformation, and loss of selectivity in polar aprotic media, leading to performance drift and reduced operational lifetimes.

Selective oxidation of alkanes to oxygenated products remains a fundamental challenge, particularly if the goal is to promote C-C bond cleavage while minimizing formation of CO₂. Oxidation conditions that use O₂ and nitrogen oxides (NO_x) have been shown to be very effective in promoting radical-mediated functionalization and oxidative carbon-carbon cleavage in saturated hydrocarbon polymers, such as polyethylene. Here, we investigate the mechanism of O₂/NO-mediated oxidation of n-decane as a prototypical linear alkane substrate. These reactions enable identification and quantification of reactive intermediates, including nitrites, nitrates, alcohols, and ketones. Under the reaction conditions, these species convert into common ketone intermediates that evolve into α-diketones and other α-functionalized ketones, which undergo further conversion into carboxylic acids. Infrared (IR) spectroscopy indicates that HDPE oxidation proceeds through similar key intermediates. Together, these findings establish a mechanistic framework for NO_x-mediated alkane oxidation and provide a foundation for the development of broadly applicable oxidative transformations.