Research Article

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

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Science  22 Feb 2019:
Vol. 363, Issue 6429, pp. 838-845
DOI: 10.1126/science.aav5606

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Scaled-up sodium-free Birch reductions

The so-called Birch reduction is frequently used by chemists despite its daunting conditions: Pyrophoric sodium is dissolved in pure liquified ammonia to achieve partial reduction of aromatics. Peters et al. surveyed and then optimized small-scale electrochemical alternatives to devise a safer protocol that can work on a larger scale with a broad range of functionally complex substrates.

Science, this issue p. 838

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.

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