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The importance of constructing Csp 2 -Csp 3 bonds has motivated the development of electrochemical, photochemical and thermal activation methods to reductively couple abundant aryl and alkyl electrophiles. However, these methodologies are limited to couplings of very specific substrate classes and require specialized sets of catalysts and reaction set-ups. Here we show a consolidation of these myriad strategies into a single set of conditions that enable reliable alkyl-aryl couplings, including those that were previously unknown. These reactions rely on the discovery of unusually persistent organonickel complexes that serve as stoichiometric platforms for C(sp 2 )-C(sp 3 ) coupling. Aryl, heteroaryl or vinyl complexes of Ni can be inexpensively prepared on a multigram scale by mild electroreduction from the corresponding C(sp 2 ) electrophile. Organonickel complexes can be isolated and stored or telescoped directly to reliably diversify drug-like molecules. Finally, the procedure was miniaturized to micromole scales by integrating soluble battery chemistries as redox initiators, enabling a high-throughput exploration of substrate diversity., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase-shaped molecular baskets 4-7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of 4, 6 and 7 change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5-trioxane ( 1 H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes 1 (0.7×0.9 nm), 8 (0.7×1.1 nm;) and 9 (0.7×1.4 nm;) characterized by X-Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

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 0 (phosphine) complex that selectively reacts with aryl electrophiles through 2e - processes. Accessing Ni 0 (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.

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.