Taking electrodecarboxylative etherification beyond Hofer–Moest using a radical C–O coupling strategy

Abstract

Established electrodecarboxylative etherification protocols are based on Hofer-Moest-type reaction pathways. An oxidative decarboxylation gives rise to radicals, which are further oxidised to carbocations. This is possible only for benzylic or otherwise stabilised substrates. Here, we report the electrodecarboxylative radical-radical coupling of lithium alkylcarboxylates with 1-hydroxybenzotriazole at platinum electrodes in methanol/pyridine to afford alkyl benzotriazole ethers. The substrate scope of this electrochemical radical coupling extends to primary and secondary alkylcarboxylates. The benzotriazole products easily undergo reductive cleavage to the alcohols. They can also serve as synthetic hubs to access a wide variety of functional groups. This reaction prototype demonstrates that electrodecarboxylative CO bond formation can be taken beyond the intrinsic substrate limitations of Hofer-Moest mechanisms.

Decarboxylation‐Initiated Intermolecular Carbon‐Heteroatom Bond Formation

“…Gooßen and co‐workers disclosed a complementary approach focused on expanding the scope with regard to the carboxylate substrate based on 1‐hydroxybenzotriazoles (HOBts) as the oxygen source (Scheme 37). [111] Distinct from the traditional Hofer‐Moest reaction, this reaction involves a radical C−O coupling. Not only the carboxylate but also the oxygen source, HOBt, is attracted to the anode where it is oxidized to a surface bound .…”

“…However, they typically require the use of solvent‐quantities of the nucleophile (including water, alcohols, carboxylic acids, and nitriles), and are often limited to α‐heteroatom‐substituted, benzylic as well as tertiary acids, since the second oxidation step is favorable only when stabilized carbocations are formed as intermediates. Some of these seemingly inherent limitations have recently been overcome by intricate choice of heteroatom nucleophiles [109–111] and/or additives (e. g. Ag salts), [112] as detailed below, and this reaction type has shifted into the focus of the attention of method developers.…”

(Non-)Kolbe Chemistry Going with the Flow: The Continuous Electrolysis of Biogenic Acids

“…Non-Kolbe flow-cell electrolysis has been the subject to very recent studies, which are comprehensive in their respective field of research and outline the significance of this tool . A prominent example is the development of an online two-dimensional high-performance liquid chromatography system by Wirth for the analysis of enantioselective Hofer–Moest reactions .…”

Electrochemical Generation and Use in Organic Synthesis of C‐, O‐, and N‐Centered Radicals

“…Electrodecarboxylative anodic etherification through radical cross‐coupling C−O reaction between carboxylic acid ( 278 ) and 1‐hydroxybenzotriazole (Bt−OH) ( 279 ) produced O ‐arylated Bt (Scheme 31) [178] . The benzotriazole moiety can be cleaved in reductive conditions affording alcohols or transformed into several functional groups.…”