Electrocatalytic Activation of Donor–Acceptor Cyclopropanes and Cyclobutanes: An Alternative C(sp³)−C(sp³) Cleavage Mode

Abstract

We describe the first electrochemical activation of D–A cyclopropanes and D–A cyclobutanes leading after C(sp3)−C(sp3) cleavage to the formation of highly reactive radical cations. This concept is utilized to formally insert molecular oxygen after direct or DDQ‐assisted anodic oxidation of the strained carbocycles, delivering β‐ and γ‐hydroxy ketones and 1,2‐dioxanes electrocatalytically. Furthermore, insights into the mechanism of the oxidative process, obtained experimentally and by additional quantum‐chemical calculations are presented. The synthetic potential of the reaction products is demonstrated by diverse derivatizations.

Friedel–Crafts-Type Reactions with Electrochemically Generated Electrophiles from Donor–Acceptor Cyclopropanes and -Butanes

“…Key to this strategy is the Lewis acid catalyzed formation of the formal zwitterionic species that acts as the electrophile for Friedel–Crafts-type reactions. Recently, we described the first electrochemical activation of D–A cyclopropanes and -butanes via direct anodic SET oxidation (Scheme C) . This concept allows the formation of radical cationic species and was used to form 1,3- and 1,4-oxidized products by the electrocatalytic incorporation of triplet oxygen.…”

“…Since Wenkert and Reissig initially reported on this exceptional reactivity in the late 1970s, different C­(sp 3 )–C­(sp 3 ) cleavage modes for D–A cyclopropanes were developed. While the classic Lewis acid activation concept allows organic transformations such as formal (3 + n )-cycloadditions, rearrangements, and ring-opening reactions, other strategies rely on Brønsted acid, Pd and organocatalysis, radicals, or on photo- or electrochemical means …”

“…To overcome this issue, we screened different potentials and found 6 V to be ideal as the desired product 2a was formed in excellent 93% yield (entry 1, standard conditions). We assume that high overpotentials are generally required to effectively convert D–A cyclopropanes, unless the reaction proceeds via a chain propagating mechanism which can be triggered by the anodic oxidation of a minor amount of starting material at low overpotentials . Efforts to use other solvents such as MeCN or 2,2,2-trifluoroethanol (TFE) led to no product formation, proving the need for HFIP (entries 2 and 3).…”

“…Efforts to convert heteroaromatic cyclopropanes (e.g., 2-thienyl or 2-furyl donors) did not furnish the desired compounds. Our previously described strategy utilizing DDQ to modulate the redox potential was not applicable to electron-rich donors (e.g., p -methoxyphenyl) for this reaction …”

Electricity Driven 1,3‐Oxohydroxylation of Donor‐Acceptor Cyclopropanes: a Mild and Straightforward Access to β‐Hydroxy Ketones

“…While we were in the final stage of preparing this manuscript, similar work was reported by Werz and coworkers. [27] However, unlike their protocol which employs HFIP as the solvent, our methodology encompasses nonhalogenated solvent acetonitrile.…”