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.
Original language | English (US) |
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Pages (from-to) | 838-845 |
Number of pages | 8 |
Journal | Science |
Volume | 363 |
Issue number | 6429 |
DOIs | |
State | Published - 2019 |
Bibliographical note
Funding Information:Financial support for this work was provided by NSF (CCI Phase 1 grant 1740656) to M.N., S.D.M., and P.S.B. Financial support was also provided by Pfizer and Asymchem. B.K.P. and K.X.R. acknowledge the Swedish Research Council (Vetenskapsrådet, VR 2017-00362) and National Institutes of Health (PA-18-586), respectively, for funding their postdoc fellowships. Y.K. acknowledges the Hewitt Foundation for a postdoctoral fellowship. S.H.R. acknowledges an NSF GRFP (#2017237151) and a Donald and Delia Baxter Fellowship.
Publisher Copyright:
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