Electrophotocatalytic Decarboxylative C−H Functionalization of Heteroarenes

Abstract

Decarboxylative C−H functionalization reactions are highly attractive methods for forging carbon–carbon bonds considering their inherent step‐ and atom‐economical features and the pervasiveness of carboxylic acids and C−H bonds. An ideal approach to achieve these dehydrogenative transformations is through hydrogen evolution without using any chemical oxidants. However, effective couplings by decarboxylative carbon–carbon bond formation with proton reduction remain an unsolved challenge. Herein, we report an electrophotocatalytic approach that merges organic electrochemistry with photocatalysis to achieve the efficient direct decarboxylative C−H alkylation and carbamoylation of heteroaromatic compounds through hydrogen evolution. This electrophotocatalytic method, which combines the high efficiency and selectivity of photocatalysis in promoting decarboxylation with the superiority of electrochemistry in effecting proton reduction, enables the efficient coupling of a wide range of heteroaromatic bases with a variety of carboxylic acids and oxamic acids. Advantageously, this method is scalable to decagram amounts, and applicable to the late‐stage functionalization of drug molecules.

A 3D-Printed Open Access Photoreactor Designed for Versatile Applications in Photoredox- & Photoelectrochemical Synthesis

“…With the combination of both standardized reactors it was possible to reproduce the decarboxylative C-H functionalization reaction (Scheme 6) from the Xu group. [20] With their custommade LED/electrode setup a yield of 85% after 3.9 F/mol was obtained. A similar yield of 83% after 3 F/mol was isolated using both standardized reactors.…”

Photoelectrocatalytic Cross-Dehydrogenative Coupling of Unactivated Aliphatic Hydrogen Donors with Benzothiazoles: Synthetic Applications and Mechanistic Insights

“…Then, R • added onto the chosen aromatic nucleus Ar-H, ultimately leading to the formation of a new C(sp 3 )-Ar bond via a further oxidation/deprotonation sequence. More recently, the carbamoylation (from oxamate salts) 11 and trifluoromethylation (from Langlois' reagent, CF3SO2 -Na + ) 12 of (hetero)arenes by means of PEC have been likewise reported. Notably, all these strategies rely on the use of easily oxidizable anionic substrates (R-X -), prone to undergo a facile single-electron transfer (SET) with the excited photocatalyst (PC*SET).…”

Hole-Mediated PhotoRedox Catalysis: Tris(p-Substituted)biarylaminium Radical Cations as Tunable, Precomplexing and Potent Photooxidants

“…(38)(39) A third category involves an intimate and synergistic relationship of photo-and electrochemical steps within the same catalytic cycle. (40-51) A variety of nomenclature has been coined in the literature for this sub-category of PEC, such as: "electrophotocatalysis" (45-47,51) "photoelectrocatalysis" (46,50) and "electron-primed photoredox catalysis" (51). We coined the general nomenclature "electrochemically-mediated PhotoRedox Catalysis (e-PRC)" as a blanket term to cover both net-oxidative and net-reductive variants (29) and to avoid misunderstanding with iPEC.…”

“…e-PRC leverages the unique benefits of both parent technologies PRC and SOE in order to i) compile potential and photon energies to achieve photocatalyst excited-state potentials beyond those normally accessible via visible light photons alone (44)(45)(46)51) and to ii) obviate the need for sacrificial oxidants/reductants. (48,50) Pioneering reports on e-PRC realized these benefits in a number of net-reductive/net-oxidative transformations. (44)(45)(46)(47)(48)(49)(50)(51) In the net-oxidative direction , previous examples of electroactivated PhotoRedox Catalysts (e-PRCats) include i) 9-mesityl-10-methylacridinium dye, (44) ii) phenothiazine (40) (Figure 1).…”

“…(48,50) Pioneering reports on e-PRC realized these benefits in a number of net-reductive/net-oxidative transformations. (44)(45)(46)(47)(48)(49)(50)(51) In the net-oxidative direction , previous examples of electroactivated PhotoRedox Catalysts (e-PRCats) include i) 9-mesityl-10-methylacridinium dye, (44) ii) phenothiazine (40) (Figure 1).…”