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Abstract The development of a convergent radical annulation strategy for the synthesis of complex terpenoids from sclareolide is disclosed. This approach employs a 1,3‐diradical synthon to enable rapid C‐ring annulation through inter‐ and intramolecular radical couplings, exemplified in the concise syntheses of serratene and cyclodammarane scaffolds from a common intermediate. Key features include a rapid alternating polarity (rAP) Kolbe electrolysis for onoceradiene assembly, a Co‐electrocatalytic metal‐catalyzed hydrogen atom transfer (MHAT) 7‐endo‐trig cycloisomerization─the first of its kind─to form the serratene core, and a tandem Fe‐mediated reductive olefin coupling/enolate alkylation cascade─also unprecedented─to forge the [4.3.1] propellane motif of cyclodammaranes with complete diastereocontrol over three contiguous quaternary centers. These routes, completed in 5–9 steps, maximize skeletal bond‐forming efficiency, feature unique radical cascades, and highlight the advantages of radical‐based disconnections in terpenoid synthesis. 

Abstract The Cu(II)‐mediated Chan‐Lam coupling reaction offers several benefits for developing point‐of‐care detection devices on microelectrode arrays. However, achieving selectivity on borate ester‐based polymer surfaces has proven difficult due to background reactions. Fluorescence‐based studies were conducted using fluorescently labeled acetylene nucleophiles. Initial experiments revealed significant background fluorescence across the electrode array, indicating selectivity issues. Further investigation uncovered significant background reactions occurring even without copper. To address this, a strategy utilizing an arylbromide‐based polymer was developed, enhancing reaction selectivity by minimizing background non‐specific reactions. Exploration into the confinement mechanism revealed the role of acetylene in forming dimers, facilitating rapid consumption of Cu(II) reagents that escaped from the specific electrodes used. These findings offer a way to construct devices for the multiplex point‐of‐care detection of metabolites, improving performance and accuracy in diagnostic devices. 

Abstract There have been significant advancements in the electrosynthesis of fuels and organic molecules, making it an increasingly sustainable and cost‐effective alternative to traditional chemical redox reagents. Early versions of these systems faced challenges in chemoselectivity due to high applied overpotentials, which have been mitigated with the introduction of molecular electrocatalysts, like metal salens (MSalens). These MSalens reduce the required overpotentials, increase turnover numbers (TON), and have simple modularity within their ligand structure allowing for tunable selectivity. While these MSalen electrocatalysts are typically used homogeneously for engineering simplicity, downstream separations are often costly and time‐consuming. Immobilization of MSalens addresses these issues by enabling synthesis at lower potentials, achieving high selectivity, and facilitating straightforward separations. This review explores the application of MSalens in electrosynthesis and immobilized molecular electrocatalysts in organic electrosynthesis. 

Abstract Electrochemical research often requires stringent combinations of experimental parameters that are demanding to manually locate. Recent advances in automated instrumentation and machine-learning algorithms unlock the possibility for accelerated studies of electrochemical fundamentals via high-throughput, online decision-making. Here we report an autonomous electrochemical platform that implements an adaptive, closed-loop workflow for mechanistic investigation of molecular electrochemistry. As a proof-of-concept, this platform autonomously identifies and investigates anECmechanism, an interfacial electron transfer (Estep) followed by a solution reaction (Cstep), for cobalt tetraphenylporphyrin exposed to a library of organohalide electrophiles. The generally applicable workflow accurately discerns theECmechanism’s presence amid negative controls and outliers, adaptively designs desired experimental conditions, and quantitatively extracts kinetic information of theCstep spanning over 7 orders of magnitude, from which mechanistic insights into oxidative addition pathways are gained. This work opens opportunities for autonomous mechanistic discoveries in self-driving electrochemistry laboratories without manual intervention. 

Abstract C−C linked glutarimide‐containing structures with direct utility in the preparation of cereblon‐based degraders (PROTACs, CELMoDs) can be assessed in a single step from inexpensive, commercial α‐bromoglutarimide through a unique Brønsted‐acid assisted Ni‐electrocatalytic approach. The reaction tolerates a broad array of functional groups that are historically problematic and can be applied to the simplified synthesis of dozens of known compounds that have only been procured through laborious, wasteful, multi‐step sequences. The reaction is scalable in both batch and flow and features a trivial procedure wherein the most time‐consuming aspect of reaction setup is weighing out the starting materials. 

Abstract A mild, scalable (kg) metal‐free electrochemical decarboxylation of alkyl carboxylic acids to olefins is disclosed. Numerous applications are presented wherein this transformation can simplify alkene synthesis and provide alternative synthetic access to valuable olefins from simple carboxylic acid feedstocks. This robust method relies on alternating polarity to maintain the quality of the electrode surface and local pH, providing a deeper understanding of the Hofer‐Moest process with unprecedented chemoselectivity. 

Abstract There is a pressing need, particularly in the field of drug discovery, for general methods that will enable direct coupling of tertiary alkyl fragments to (hetero)aryl halides. Herein a uniquely powerful and simple set of conditions for achieving this transformation with unparalleled generality and chemoselectivity is disclosed. This new protocol is placed in context with other recently reported methods, applied to simplify the routes of known bioactive building blocks molecules, and scaled up in both batch and flow. The role of pyridine additive as well as the mechanism of this reaction are interrogated through Cyclic Voltammetry studies, titration experiments, control reactions with Ni(0) and Ni(II)‐complexes, and ligand optimization data. Those studies indicate that the formation of a BINAPNi(0) is minimized and the formation of an active pyridine‐stabilized Ni(I) species is sustained during the reaction. Our preliminary mechanistic studies ruled out the involvement of Ni(0) species in this electrochemical cross‐coupling, which is mediated by Ni(I) species via a Ni(I)‐Ni(II)‐Ni(III)‐Ni(I) catalytic cycle. 

Abstract Over the last fifty years, the use of nickel catalysts for facilitating organic transformations has skyrocketed. Nickel(0) sources act as useful precatalysts because they can enter a catalytic cycle through ligand exchange, without needing to undergo additional elementary steps. However, most Ni(0) precatalysts are synthesized with stoichiometric aluminum–hydride reductants, pyrophoric reagents that are not atom‐economical and must be used at cryogenic temperatures. Here, we demonstrate that Ni(II) salts can be reduced on preparative scale using electrolysis to yield a variety of Ni(0) and Ni(II) complexes that are widely used as precatalysts in organic synthesis, including bis(1,5‐cyclooctadiene)nickel(0) [Ni(COD)₂]. This method overcomes the reproducibility issues of previously reported methods by standardizing the procedure, such that it can be performed anywhere in a robust manner. It can be transitioned to large scale through an electrochemical recirculating flow process and extended to an in situ reduction protocol to generate catalytic amounts of Ni(0) for organic transformations. We anticipate that this work will accelerate adoption of preparative electrochemistry for the synthesis of low‐valent organometallic complexes in academia and industry. 

Hydrogen isotope exchange (HIE) plays a pivotal role in the synthesis of isotopically labeled compounds, which are widely used in the pharmaceutical industry for drug pharmacokinetic and pharmacodynamic studies. While electrochemical HIE has emerged as a powerful strategy for site-selective labeling of C–H bonds, extending its application to alkyl amine-containing drugs has been hindered by the instability of α-amino radicals and their susceptibility to overoxidation. Here, we report the first electrochemical HIE protocol that enables efficient deuterium (D) labeling of both cyclic and acyclic alkyl amine substrates. The key innovation lies in using 1,3-propanedithiol as the hydrogen atom transfer (HAT) catalyst, which could in situ generate a potent HAT agent─a mercaptothiyl radical─via alternating current electrolysis. This radical benefits from a significantly weakened effective S–H bond dissociation energy of 34 kcal/mol compared to conventional monothiol HAT catalysts (∼80 kcal/mol), driven by exothermic disulfide ring formation. Mechanistic studies and computational analyses reveal a strong structure–activity relationship among dithiols, identifying 1,3-propanedithiol as the optimal catalyst, which is uniquely suited to balance fast HAT kinetics with efficient regeneration of the dithiol. The application of this method to over 30 pharmaceutically relevant compounds achieved up to 3.7 D per molecule. This work addresses a long-standing challenge in electrochemical HIE and introduces a new HAT platform with broad potential in synthetic and biological chemistry. 

Organic electrosynthesis has emerged as a powerful strategy for leveraging electricity in organic synthesis. Despite its growing popularity, the fundamental molecular interactions governing electrochemical systems remain poorly understood. Many electrosynthetic reactions show strong dependence on the identity of the allegedly inert supporting electrolyte, which can significantly impact yields and selectivity, yet the physical origins of these effects are largely unexplored. A mechanistic understanding of electrolyte effects would enable more rational reaction design for applications. Here, we use cyclic voltammetry to investigate cobalt-based metal–carbon bond homolysis and elucidate how common supporting electrolytes influence reaction rates. Bulk electrolysis experiments further reveal how electrolyte choice affects overall selectivity. Peak-ratio analysis indicates that Co(Salen)–benzyl bond cleavage proceeds via a reversible homolysis mechanism that becomes rate-limited by bond dissociation at high substrate concentrations. The reaction rate varies systematically with electrolyte identity, and changes in oxidative addition rates are quantified using simulations. These experimental findings are supported by ab initio and classical molecular dynamics simulations, as well as density functional theory calculations, which provide insights into reaction pathways, energetics, and dynamics. Together, these results demonstrate that electrolyte selection enables rational tuning of reaction rates and downstream selectivity, highlighting the critical role of electrolytes in metal-catalyzed organic electrosynthesis.