Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method

Abstract

While preparative electrolysis of organic molecules has been an active area of research over the past century, modern synthetic chemists have generally been reluctant to adopt this technology. In fact, electrochemical methods possess many benefits over traditional reagent-based transformations, such as high functional group tolerance, mild conditions, and innate scalability and sustainability. In this Outlook we highlight illustrative examples of electrochemical reactions in the context of the synthesis of complex molecules, showcasing the intrinsic benefits of electrochemical reactions versus traditional reagent-based approaches. Our hope is that this field will soon see widespread adoption in the synthetic community.

Figure 1

Synthesis of dixiamycin B by Baran and co-workers.

Figure 2

Synthesis of pentacyclosqualene and β-onoceradiene by Corey and co-workers using Kolbe electrolysis.

Figure 3

Moeller’s synthesis of alliacol A via an intermolecular anodic coupling.

Figure 4

Synthesis of diazonamide-inspired drug development candidate DZ-2384 by Harran and co-workers.

Figure 5

Synthesis of NS5A inhibitor intermediate and reduction of cyclosporin A analogue by Waldvogel and co-workers.

Figure 6

(a) Electrochemical allylic oxidation by Baran and co-workers. (b) Process greenness score (PGS) for Cr, Ru, and electrochemistry. (c) 100 g scale allylic oxidation conducted in a bucket. Panels b and c reprinted with permission from ref (45). Copyright 2016 Nature Publishing Group.

Figure 7

Electrochemical arene amination by Yoshida.

Figure 8

(a) Electrochemical fluoroalkylation of heterocycles by Baran and Blackmond and co-workers. (b) Formation of 29 using ^tBuOOH and electrochemical protocols. Reprinted with permission from ref (64). Copyright 2014 WILEY-VCH Verlag GmbH & Co. KGaA.

Figure 9

Synthesis of functionalized polycyclic lactams by Aubé and co-workers using a repurposed mobile phone charger. Reprinted with permission from ref (65). Copyright 2015 WILEY-VCH Verlag GmbH & Co. KGaA.

Figure 10

Suggested topics for further reading. Reprinted with permission from refs (−75). Copyright 2002, 2010, and 2014 WILEY-VCH Verlag GmbH & Co. KGaA. Copyright 1983, 2012, and 2015 American Chemical Society. Copyright 2014 Royal Society of Chemistry. Copyright 1988 Elsevier B.V. Copyright 1996 Springer.