Deconstructive Functionalization of Unstrained Cycloalkanols via Electrochemically Generated Aromatic Radical Cations

Abstract

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.

Ring‐Opening Functionalization/Cyclization Reactions of Cycloalkanols under Transition‐Metal‐Free Conditions

“…In 2023, the group of Morrill reported the electrochemical deconstructive methoxylation of unstrained cycloalkanols to form a diverse array of useful ϵ ‐methoxy ketones employing methanol as nucleophile (Scheme 11). [27] Various substitutes and ring sizes cycloalkanols were compatible with the optimized reaction conditions. Pleasingly, other alcohols, carboxylic acids, and N ‐heterocycles also could be employed as nucleophiles to afford corresponding products.…”

Accessing Alkoxy Radicals via Frustrated Radical Pairs: Diverse Oxidative Functionalizations of Tertiary Alcohols

“…In recent years, pioneering work has led to the development of alternative strategies that can afford access to alkoxy radicals directly from alcohols (Figure a). These reports focused on β-C–C bond cleavage of cycloalkanols via oxidation using a high-valent transition metal (Figure a, approach 1), activation using a hypervalent iodine agent (approach 2), light-induced ligand-to-metal charge transfer (approach 3), and proton-coupled electron transfer by means of photocatalysis (approach 4) or electrochemistry (approach 5) . These approaches have been successful in providing alkoxy radicals directly from free alcohol substrates, although approaches 1 and 2 predominantly require that the alcohol substrates contain strained ring systems and pendant electron-rich arene groups, respectively, which limits their scope.…”