LG

A general strategy has been developed for predictable and robust vinyl halide cross-coupling reactions. This approach demonstrates broad applicability across seven distinct bond-forming transformations, featuring wide electrophile and nucleophile scope, high tolerance for functional groups, and suitability for late-stage functionalization of complex biomolecules. It also enables efficient one-pot, two-step bifunctional transformations.

Abstract

Reliable, broadly applicable cross-coupling conditions that deliver the desired products with minimal optimization are essential in pharmaceutical research, where efficient synthesis accelerates lead discovery and late-stage diversification. Although advances like high-throughput additive screening and commercial catalyst/ligand libraries improve prediction in specific systems, a general strategy for vinyl halide cross-coupling across diverse bond-forming reactions remains elusive. Herein, we report a general and highly predictable method for vinyl halide cross-coupling under photoredox conditions, employing two complementary catalytic systems. In the first, the organic photocatalyst 4CzIPN enables efficient coupling with nucleophiles such as thiols, selenols, sulfinate salts, activated alkenes, phosphorus (III), and boron compounds, affording C(sp²)─S, ─Se, ─C, ─P, and ─B bonds in high yields. In the second, a dual nickelphotoredox catalytic system facilitates coupling with less reactive nucleophiles, including phosphorus (V), nitrogen, and oxygen. This approach enables seven distinct bond-forming reactions, offering broad electrophile and nucleophile scope, high functional group tolerance, and applicability to the late-stage functionalization of complex biomolecules. The simple and consistent conditions enable one-pot, two-step bifunctional transformations by sequentially activating distinct chemical bonds involving nucleophiles and electrophiles.

Using electrochemistry to enact organic molecule transformations offers a potential route towards greener chemical manufacturing. However, such reactions can often be complex with a multitude of factors at play. In their Communication (e202509115), Yanwei Lum et al. performed a systematic study of the impact of electrolyte cations on the selectivity of electrochemical C─H chlorination of cyclohexane. It was found that larger cations increase the propensity towards the formation of chlorine radicals, which then facilitates the formation of chlorocyclohexane through a radical non-chain mechanism.

Herein, electroreductive deoxysilylation of benzylic and allylic alcohols is demonstrated. The cathodic transformation proceeds via carbanionic intermediates and can be extended to aldehydes and ketones. Mechanistic studies reveal that the reaction outcome is dependent on the thermodynamics and kinetics for the coupling step in combination with the reductive stability of the coupling partner, thereby supporting a unified mechanism to that of deoxygenative cross-coupling with CO₂ as electrophile.

Abstract

Alcohols are highly common organic compounds but remain scarce as alkyl donors in synthetic procedures. Here, we describe an electrochemical procedure for their deoxygenative cross-electrophile coupling with hydrosilanes, furnishing organosilane products in good to excellent yields. Mechanistic studies provide insights into the operating pathways of this semi-paired electrolytic transformation, suggesting that silyl ethers are likely reaction intermediates. Furthermore, a unified mechanistic proposal is presented that accounts for observed reactivity differences with analogous deoxygenative electrocarboxylation.

Despite the abundance of oxygen-containing molecules, no unified approach exists that can activate various oxidation states of oxygenated functional groups for deoxygnenative functionalization. Here, we disclose a tandem, one-pot hydrosilylation–electroreduction sequence that enables the conversion of alcohols, aldehydes, ketones, and esters into nucleophilic reagents widely used in cross-coupling chemistry.

Abstract

Oxygen-containing functional groups are prevalent motifs in natural products and feedstock chemicals, but direct methods for their deoxygenative transformation remain rare due to the difficult cleavage of the strong C–O bond. Here, we develop a general activation strategy that employs hydrosilanes as activating reagents for alcohols, carbonyls, and esters to afford a common silyl ether intermediate. Electrochemical reduction of the in situ generated silyl ether results in C–O cleavage to afford a carbanion, which reacts with a number of electrophiles for the construction of C–Si, C–B, C–Ge, and C–Sn bonds.

A continuous-flow electrochemical C–H amination strategy enables efficient and scalable synthesis of (hetero)arylamines from electron-rich and electron-deficient arenes via a pyridination–aminolysis sequence. The method avoids strong oxidants and metal catalysts, delivering over 100 grams of product with broad substrate scope and excellent functional group tolerance.

Abstract

The direct C─H amination of arenes is a powerful strategy for synthesizing arylamines, yet existing methods often suffer from limited substrate scope, poor selectivity, or scalability issues, particularly for electron-deficient arenes. Here, we introduce a continuous flow electrochemical C─H amination via a pyridination-aminolysis sequence, enabling the efficient functionalization of arenes with diverse electronic properties. The method operates under continuous flow electrochemical conditions, avoiding the need for divided cells, strong chemical oxidants, or homogeneous transition-metal catalysts. The broad substrate scope includes a wide range of electron-rich, electron-deficient, and halogenated arenes, as well as heterocycles, demonstrating excellent functional group tolerance. Furthermore, the process is readily scalable, as shown by a 4-day continuous operation in parallel microreactors, producing over 100 grams of aniline product with high efficiency. This study highlights the potential of continuous-flow electrochemistry as a versatile and practical platform for sustainable C─H functionalization in organic synthesis.

ON/OFF switching of PCET. Light and redox-induced PCET ON–OFF switching was investigated in a series of ruthenium complexes. Photosubstitution triggers the conformational from a nonaqua to a PCET-active aqua complex, while oxidation induces a reverse conformational change.

Abstract

We report a reversible ON–OFF proton-coupled electron transfer (PCET) switch based on ruthenium(II) polypyridyl complexes, triggered by both light and redox stimuli. Upon photoirradiation, a carboxylate-ligated Ru(II) complex undergoes photosubstitution to generate a metastable, PCET-active aqua complex. This metastable complex exhibits redox-induced conformational change, regenerating the original carboxylate complex. The switching behavior enables external control of PCET activity, directly modulating electrocatalytic water oxidation. Electrochemical and spectroscopic analyses reveal that the mechanism is governed by a pH-dependent interplay between intramolecular conformational change and bimolecular electron exchange. Importantly, the rate-determining step shifts from unimolecular conformational change near neutral pH to bimolecular electron exchange under acidic conditions. These findings establish a strategy for designing tunable molecular switches and redox-responsive functional materials.