Scalable and safe synthetic organic electroreduction inspired by Li-ion battery chemistry

Abstract

Reductive electrosynthesis has faced long-standing challenges in applications to complex organic substrates at scale. Here, we show how decades of research in lithium-ion battery materials, electrolytes, and additives can serve as an inspiration for achieving practically scalable reductive electrosynthetic conditions for the Birch reduction. Specifically, we demonstrate that using a sacrificial anode material (magnesium or aluminum), combined with a cheap, nontoxic, and water-soluble proton source (dimethylurea), and an overcharge protectant inspired by battery technology [tris(pyrrolidino)phosphoramide] can allow for multigram-scale synthesis of pharmaceutically relevant building blocks. We show how these conditions have a very high level of functional-group tolerance relative to classical electrochemical and chemical dissolving-metal reductions. Finally, we demonstrate that the same electrochemical conditions can be applied to other dissolving metal–type reductive transformations, including McMurry couplings, reductive ketone deoxygenations, and epoxide openings.

Site-specific electrodeposition enables self-terminating growth of atomically dispersed metal catalysts

“…We considered whether we could synthesize ADMCs by simply using the room-temperature electrodeposition (ED) method. Owing to its facile operation, mildness, large scalability, low cost, and precision 8 , ED has been extensively used for the fabrication of nanomaterials and industrial applications (e.g., electroplating) 9 , 10 . However, this process leads to the inevitable formation of multilayer bulk structures with nonuniform coverage (Fig.…”

Organic Electrosynthesis: Applications in Complex Molecule Synthesis

“…Cathodic Birch‐type reduction of aromatic rings to afford dearomatized products is an interesting approach that avoids the synthetically inconvenient use of liquid ammonia and stoichiometric use of metals . Recently, Baran and coworkers developed a fast and scalable protocol for transformation that enabled the synthesis of dearomatized derivatives of natural products (Scheme ) . The reaction conditions were also demonstrated to work well for other reaction types, such as benzyl‐group deprotection and reductive cyclizations.…”

Electrochemically Driven Desaturation of Carbonyl Compounds

“…Our prior experiences for electrochemical reaction development served as a template for this study. [26][27][28][29][30][31][32][33] A myriad of electrolytes, electrodes, and solvents were evaluated. First, an electrolyte screen revealed that inorganic non-nucleophilic salts proved optimal (entries 4-7) with NaSbF6 ($0.56/gram) delivering the highest conversion.…”