Peters Byron K, Rodriguez Kevin X, Reisberg Solomon H, Beil Sebastian B, Hickey David P, Kawamata Yu, Collins Michael, Starr Jeremy, Chen Longrui, Udyavara Sagar, Klunder Kevin, Gorey Timothy J, Anderson Scott L, Neurock Matthew, Minteer Shelley D, Baran Phil S
Department of Chemistry, Scripps Research, La Jolla, CA 92037, USA.
Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
Science. 2019 Feb 22;363(6429):838-845. doi: 10.1126/science.aav5606.
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.
还原性电合成在大规模应用于复杂有机底物方面长期面临挑战。在此，我们展示了数十年来在锂离子电池材料、电解质和添加剂方面的研究如何能为实现用于Birch还原的实际可扩展还原性电合成条件提供灵感。具体而言，我们证明使用牺牲阳极材料（镁或铝），结合廉价、无毒且水溶性的质子源（二甲基脲），以及受电池技术启发的过充保护剂[三（吡咯烷基）磷酰胺]，能够实现多克规模的药学相关结构单元的合成。我们展示了相对于经典的电化学和化学溶解金属还原，这些条件具有非常高的官能团耐受性。最后，我们证明相同的电化学条件可应用于其他溶解金属类型的还原转化，包括McMurry偶联、还原性酮脱氧反应和环氧化物开环反应。
