Electrochemical oxidation-induced etherification via C(sp ³ )─H/O─H cross-coupling

Abstract

Direct electrochemical construction of C─O bonds through C(sp3)─H functionalization still remains fundamentally challenging. Here, electrochemical oxidation-induced benzylic and allylic C(sp3)─H etherification has been developed. This protocol not only offers a practical strategy for the construction of C─O bonds using nonsolvent amounts of alcohols but also allows direct electrochemical benzylic and allylic C(sp3)─H functionalization in the absence of transition metal catalysis. A series of alcohols and benzylic and allylic C(sp3)─H compounds were compatible with this transformation. Mechanistically, the generation of aryl radical cation intermediates is the key to this C(sp3)─H etherification, as evidenced by radical probe substrate (cyclopropane ring opening) and electron paramagnetic resonance experiments.

Photochemical and Electrochemical Strategies towards Benzylic C−H Functionalization: A Recent Update

“…In 2020, an innovative and interesting electrochemical oxidation-induced benzylic C(sp 3 )À H etherification has been developed by Wang and collabo- rators (Scheme 32). [74] Benzylic substrates were functionalised through anodic oxidation via base promoted SET/proton-transfer/SET sequence to form the carbocation which is subsequently trapped by an alcohol. A wide variety of functional groups on the alcohol side chain were tolerated, including unsaturated bonds, halogens, and ketone.…”

Electrochemical C-C Bond Cleavage of Cyclopropanes towards the Synthesis of 1,3-Difunctionalized Molecules

“…Alcohols such as EtOH, n-BuOH and long-chain primary alcohols (n-C 6 H 13 OH and n-C 8 H 17 OH) were transformed into desired products with good e ciency (40-43). 2-Chloro-1-ethanol afforded the desired product in 40% yield (44). Secondary alcohols (i-PrOH and cyclohexanol) were suitable substrates (45)(46).…”

“…[26][27][28][29][30][31][32][33][34][35][36][37][38] As a main part of preparative electrosynthesis, anode processes such as C-H functionalization, oxidative coupling, decarboxylation and ole n functionalization had been developed. [39][40][41][42][43][44][45][46][47][48] However, electrochemical oxidative C−C bond cleavage and functionalization are rarely developed due to the inertness and weak electronic bias of C−C bonds, which are always encumbered by other bonds. [8-49-50] Herein we developed the electrochemical C−C bond cleavage and 1,3-difunctionalization of arylcyclopropanes under constant current electrolysis based on the following mechanistic proposal (Figure 1b): Firstly, arylcyclopropane is oxidized to the radical cation by anode, which result in the weakness of the C α -C β bond, as the BDE of C α -C β bond decreases more than 30 kcal/mol from the neutral cyclopropane to the corresponding radical cation.…”

A General Strategy for C(sp3)–H Functionalization with Nucleophiles Using Methyl Radical as a Hydrogen Atom Abstractor

“…While access to carbocation intermediates may be accomplished electrochemically, contemporary methodologies are largely limited by the high overpotential required for reactivity, thereby restricting the scope of amenable C(sp 3 )-H and nucleophile coupling partners. 32,33 Whereas C(sp 3 )-H functionalization via HAT-ORPC has been proposed in a recent study from Liu and Chen, the method uses a strong, stoichiometric oxidant and solvent quantities of nucleophile. 7 Here we report a HAT-ORPC platform for C(sp 3 )-H functionalization using a mild, commercially available N-acyloxyphthalimide as HAT precursor.…”

“…Notably, 4-pyridyl diphenylmethane underwent fluorination in 63% yield, demonstrating tolerance to a valuable Nheterocycle scaffold (31). 52 Other heterocycles such as thiophenes, furans, and thiazoles were also tolerated under the reaction conditions (32)(33)(34)(35). Since many bioactive compounds contain heterocyclic fragments, this observation prompted us to evaluate the method for the late-stage derivatization of various pharmaceuticals and complex molecules.…”