Organic Electrochemical Transformations of Resource Small Molecules

Conspectus Resource economical syntheses aim to maximize chemical value from simple, abundant, and inexpensive inputs while minimizing waste, energy consumption, and auxiliary reagents. From this perspective, three interrelated dimensions are particularly critical: (1) the use of readily available feedstocks, (2) the employment of sustainable energy inputs, and (3) the direct generation of high-value products. Electrochemistry is uniquely positioned at the intersection of these principles, as electricity can be regarded as a clean, tunable reagent, ideally compatible with renewable energy sources. When combined with resource small molecules, such as carbon dioxide (CO 2 ), water (H 2 O), and ammonia (NH 3 ), electrochemical strategies enable the direct transformation of traditionally underutilized resources into structurally complex and functionally rich organic molecules. As such, electrochemical transformations of resource small molecules represent a compelling and conceptually aligned platform for advancing resource-economical organic synthesis. Since 2020, our research program has been centered on electrochemical transformations of resource small molecules into high-value organic compounds. These efforts can be broadly classified into three main directions. First, carbon dioxide, an abundant and low-cost feedstock, has been exploited as a carboxyl source for electrochemical carboxylation reactions. Second, water has been employed not only as a hydroxyl source in electrochemical hydroxylation reactions but also as a hydrogen source in reductive hydrogenation processes; notably, substituting water with deuterium oxide enables efficient and economical incorporation of deuterium into organic molecules. Third, ammonia, as the simplest and most direct nitrogen source, has been directly utilized in electrochemical amination reactions. Our studies initially focused on the synthesis of carboxylic acid derivatives that are highly relevant to pharmaceuticals and bioactive molecules. This includes the preparation of aryl carboxylic acids from aryl halides, followed by the more challenging direct carboxylation of simple arenes via C–H activation. Alkenes have also been explored as versatile substrates, allowing selective functionalization–carboxylation through three electrochemical control strategies: electrochemical direct reduction, electrochemical organo-mediated reduction and electrochemical metal-catalyzed reduction. Progressing to even more demanding transformations, C(sp 3 )–H bonds have been directly engaged as starting materials, enabling access to phenylacetic acid and α-amino acid derivatives via linear paired electrolysis. In parallel, water has served as a hydroxyl source for the efficient synthesis of vicinal diols and benzyl alcohol derivatives, while deuterium oxide has enabled the preparation of a diverse array of deuterated compounds. Furthermore, ammonia has been coupled with simple aryl halides to furnish a range of aromatic amines. Meanwhile, methanol acts as a methyl source to realize methylation via electrochemical double dehydroxylative cross-coupling. In addition, it is worth noting that these protocols were successfully applied to scale-up under industrial-grade current density and to the step-economical assembly of bioactive molecules, collectively underscoring the practical utility of the developed electrochemical transformations.