Photoredox-Catalysis-Enabled Ring-Opening Functionalization of Aryl Cyclopropanes

Abstract

Cyclopropanes have long been recognized as privileged synthons in organic synthesis to access 1,3-difunctionalized scaffolds. However, the synthetic potential of aryl cyclopropane, one of the most important subclasses of cyclopropanes, is far less explored. Recently, we uncovered a visible-light promoted strategy for the ring-opening functionalization of a series of aryl cyclopropanes through open-shell intermediates. By leveraging the activation of aryl radical cation derived from the oxidative single-electron-transfer (SET), C–C bond of cyclopropane is weakened and cleaves upon a regio- and stereoselective nucleophilic attack with exogenous nucleophiles to provide a benzyl radical that is readily elaborated to diverse functionalities.

Electrochemical 1,3-Alkyloxylimidation of Arylcyclopropane Radical Cations: Four-Component Access to Imide Derivatives

“…Supported by the above-depicted control experiments, cyclic voltammetry results, and previous reports about the cyclopropane-derived radical cation, − we proposed the reasonable reaction mechanism shown in Scheme . This four-component protocol begins with the direct anodic single electron oxidation of arylcyclopropanes 1a to deliver the key radical cation I , which is quickly captured by nucleophilic MeO – generated from the cathodic reduction of MeOH to produce benzyl radical intermediate II .…”

“…Among the established activation modes, the single-electron oxidation of arylcyclopropane to produce radical cations was proved to be feasible in the 1970s . Over the past few decades, numerous designed modular synthetic strategies for the single-electron oxidation of cyclopropanes by chemical and photochemical process have been developed (Scheme a). For instance, Studer et al achieved a radical-cation-mediated ring-opening 1,3-difunctionalization of arylcyclopropanes with acyl fluorides by merging NHC and organophotoredox catalysis in 2021 .…”

“…Three-component radical-cation-mediated ring-opening 1,3-difunctionalizations of arylcyclopropanes with two nucleophiles have been well established. − In sharp contrast, the similar oxidative four-component ring-opening 1,3-difunctionalization reactions initiated by arylcyclopropane-derived radical cations are still extremely rare due to the difficulties of accurately controlling the reactivity and chemo- and regioselectivity of each reaction component . In this context, Zhang and co-workers developed an unprecedented copper-catalyzed radical-cation-mediated four-component ring-opening 1,3-difunctionalization of arylcyclopropanes, carboxylic acids, nitriles, and N -fluorobenzenesulfonimide (NFSI) (Scheme b) .…”

Visible light-mediated ring opening and cyclization of aryl cyclopropanes: efficient synthesis of pyrrolo[1,2-a]quinoxalin-4(5H)-ones with antineoplastic activity

“…7 In 2016, Lectka's group reported a highly regioselective aminofluorination of aryl cyclopropanes using N -fluorobenzenesulfonimide (NFSI) as an N–F reagent via a photoredox-coupled reaction. 8 Notably, Feng and co-workers did very beautiful work on the photoredox-coupled ring-opening of cyclopropanes, 9 and they recently reported a photoredox-coupled ring-opening deoxygenation of aryl cyclopropanes for synthesizing 1,3/1,5-dioxygenation products. 10 Significantly, König's group reported a facile synthesis of β-chloro ketones via a visible light-mediated multicomponent cascade reaction of aryl cyclopropanes.…”

Visible light mediated regioselective 1,3-oxylallylation of aryl cyclopropanes under redox-neutral conditions

“…2 This strategy has also been successfully applied to the activation of aryl cyclopropanes, 3 refraining from using strong oxidants/electrophiles that were frequently utilized in earlier methods. 4 In 2019, our group reported an aerobic photoredox catalysed ring-opening 1,3-oxoamination of aryl cyclopropanes in which nitrogen-containing heterocycles functioned as nucleophiles (Scheme 1a). 5 Further mechanistic studies suggested that the aryl cyclopropane was first single-electron-oxidized by the excited photocatalyst to give an arylcyclopropane radical cation intermediate, which was predisposed to a regio- and stereospecific three-electron S N 2-like attack of a nitrogen-based nucleophile to produce a benzylic radical intermediate with the opening of the cyclopropane ring.…”