Chemoselective, Metal-free, (Hetero)Arene Electroreduction Enabled by Rapid Alternating Polarity

Abstract

Arene semi-reduction remains a challenge when multiple re-ductively labile functional groups are present or when using heteroarene substrates. Conventional chemical and even elec-trochemical Birch-type reductions suffer from a lack of chemoselectivity due to a reliance on alkali metals or harshly reducing conditions. This study reveals that a simpler avenue is available for such reductions by simply altering the wave-form of current delivery, namely rapid alternating polarity (rAP). The developed method, which proceeds in protic sol-vent and can be easily scaled up, does not require any metal additives or stringently anhydrous conditions. The scope of this dearomatization is broad, tolerating numerous functional groups and providing rapid access to previously challenging molecules. While the mechanism has not been fully deci-phered, the key feature of the rAP reduction is that the main competing process, namely proton reduction, can be sup-pressed. As such, unique arene reductions can be accom-plished even outside solvent electrochemical window or in the presence of Brønsted acids.

Intricacies of Mass Transport during Electrocatalysis: A Journey through Iron Porphyrin-Catalyzed Oxygen Reduction

“…The demonstrated molecular insight under dynamic electrochemical conditions opens possibilities to unravel reactions during AC and voltage-pulse electrosynthesis. 44,45 It also potentially offers an efficient tool for studying reaction kinetics at the electrodes to find optimum conditions and for pairing electrochemical reactions during AC electrolysis. 46−48…”

Scalable Electrochemical Decarboxylative Olefination Driven by Alternating Polarity

“…Electrochemical decarboxylation of secondary, let alone primary carboxylic acids, is considered extremely challenging even in these state-of-the-art protocols. The recently developed rapid alternating polarity (rAP) 16,17 variant of the Kolbe reaction is a notable exception as it enables decarboxylation of primary carboxylic acids with high chemoselectivity; 18 however, this reaction favors carbon radical formation over the carbocation. To the best of our knowledge, a general electrochemical decarboxylative olefination has yet to be described.…”

“…In general, this practical method is applicable to a variety of unactivated secondary, tertiary, and even primary carboxylic acids as illustrated in Table 2. Compatible functional groups include: esters (3, 10, 11, 20), ketals (4), sulfones (5), carbamates (6, 7), amides (10), epoxides (11), arenes (12,16), alcohols (14), alkenes (14,19) and ketones (15). As demonstrated in 3-7, this method offers rapid access to unsaturated six-membered rings with a variety of functional groups.…”

“…The electron-rich alkyl aryl ether prone to electrochemical oxidation was tolerated in the decarboxylative olefination, highlighting the chemoselective nature of the oxidation process. The method also allows facile derivatization of naturally occurring carboxylic acids such as ursolic acid, isosteviol, and dehydroabietic acid to deliver unique olefins with complex polycyclic scaffolds (14)(15)(16). Interestingly, in the case of camphoric acid, the tertiary acid was selectively decarboxylated to afford g,d-unsaturated acid 13.…”

Mild Photochemical Reduction of Alkenes and Heterocycles via Thiol-Mediated Formate Activation

“…Metal-hydride atom transfer (MHAT) is a well-developed alternative for many types of alkene reductions and functionalizations and often favors the formation of the thermodynamic product rather than the kinetic one typically obtained by metal-catalyzed hydrogenation. 5,6 Many electrochemical alkene 7,8 and alkyne 9 reductions have also been developed, as well as the electrochemical Birch-type reductions from the Baran group 10,11 and others. 12 Photochemical reduction of alkenes to their respective radical anions via single-electron transfer is well precedented, and frequently used for further transformations including hydrofunctionalization, 13 cyanation, 14 carboxylation, 15 aminocarboxylation, 16 cyclizations, 17 [2 + 2] 18,19 and [3 + 2] 20 cycloadditions, and others.…”