Electrochemical Deconstructive Methoxylation of Arylalcohols-A Synthetic and Mechanistic Investigation.

Herein, we report a mechanistic investigation of a recently developed electrochemical method for the deconstructive methoxylation of arylalcohols. A combination of synthetic, electroanalytical, and computational experiments have been performed to gain a deeper understanding of the reaction mechanism and the structural requirements for fragmentation to occur. It was found that 2-arylalcohols undergo anodic oxidation to form the corresponding aromatic radical cations, which fragment to form oxocarbenium ions and benzylic radical intermediates via mesolytic cleavage, with further anodic oxidation and trapping of the benzylic carbocation with methanol to generate the observed methyl ether products. It was also found that the electrochemical fragmentation of 2-arylalkanols is promoted by structural features that stabilize the oxocarbenium ions and/or benzylic radical intermediates formed upon mesolytic cleavage of the aromatic radical cations. With an enhanced understanding of the reaction mechanism and the structural features that promote fragmentation, it is anticipated that alternative electrosynthetic transformations will be developed that utilize this powerful, yet underdeveloped, mode of substrate activation.

Electrochemical deconstructive functionalization of arylcycloalkanes via fragmentation of anodically generated aromatic radical cations.

This highlight summarises electrochemical approaches for the deconstructive functionalization of arylcycloalkanes via the fragmentation of anodically generated aromatic radical cations. A diverse range of deconstructive functionalization processes is described, including discussion on the electrochemical reaction conditions employed, scope and limitations, and reaction mechanisms, in addition to highlighting future opportunities in this burgeoning area of sustainable synthesis.

Electrochemical Synthesis of C(sp3)-Rich Heterocycles via Mesolytic Cleavage of Anodically Generated Aromatic Radical Cations.

Herein we report an electrochemical deconstructive functionalization approach for the synthesis of C(sp3)-rich heterocycles. The reaction proceeds via the mesolytic cleavage of anodically generated aromatic radical cations and the trapping of formed carbocation intermediates with internal nucleophiles. The method has been demonstrated across various arylalcohol substrates to access a diverse range of C(sp3)-rich heterocycles including tetrahydrofuran, tetrahydropyran, and pyrrolidine scaffolds (26 examples). The electrochemical method was demonstrated on a 5 mmol scale via single pass continuous flow, which utilized lower supporting electrolyte concentration and exhibited increased productivity in relation to the batch process.

Deconstructive Functionalization of Unstrained Cycloalkanols via Electrochemically Generated Aromatic Radical Cations.

Herein we report an electrochemical approach for the deconstructive functionalization of cycloalkanols, where various alcohols, carboxylic acids, and N-heterocycles are employed as nucleophiles. The method has been demonstrated across a broad range of cycloalkanol substrates, including various ring sizes and substituents, to access useful remotely functionalized ketone products (36 examples). The method was demonstrated on a gram scale via single-pass continuous flow, which exhibited increased productivity in relation to the batch process.

Electrochemical generation and utilization of alkoxy radicals.

This highlight summarises electrochemical approaches for the generation and utilization of alkoxy radicals, predominantly focusing on recent advances (2012-present). The application of electrochemically generated alkoxy radicals in a diverse range of transformations is described, including discussion on reaction mechanisms, scope and limitations, in addition to highlighting future challenges in this burgeoning area of sustainable synthesis.

Electrochemical Deconstructive Functionalization of Cycloalkanols via Alkoxy Radicals Enabled by Proton-Coupled Electron Transfer.

Herein, we report a new electrochemical method for alkoxy radical generation from alcohols using a proton-coupled electron transfer (PCET) approach, showcased via the deconstructive functionalization of cycloalkanols. The electrochemical method is applicable across a diverse array of substituted cycloalkanols, accessing a broad range of synthetically useful distally functionalized ketones. The orthogonal derivatization of the products has been demonstrated through chemoselective transformations, and the electrochemical process has been performed on a gram scale in continuous single-pass flow.

Electrochemical oxidative Z-selective C(sp2)-H chlorination of acrylamides.

An electrochemical method for the oxidative Z-selective C(sp2)-H chlorination of acrylamides has been developed. This catalyst and organic oxidant free method is applicable across various substituted tertiary acrylamides, and provides access to a broad range of synthetically useful Z-ß-chloroacrylamides in good yields (22 examples, 73% average yield). The orthogonal derivatization of the products was demonstrated through chemoselective transformations and the electrochemical process was performed on gram scale in flow.