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.

Keywords: C(sp3)−C(sp3) cleavage; cyclobutanes; cyclopropanes; donor-acceptor systems; synthetic electrochemistry.

Scheme 1

Overview of known strategies A)–C) for the activation of D–A cyclopropanes and D) our alternative electrochemical approach.

Figure 1

Cyclic voltammograms of D–A cyclopropanes 1 a, 1 d, 1 f and 1 j recorded in HFIP (solid line) and MeCN (dashed lines); NBu₄BF₄ (0.02 m) as electrolyte.

Scheme 2

Scope of the electrosynthesis of β‐hydroxy ketones 2. [a] Yield when constant current electrolysis I=10 mA was applied. Conditions A=standard conditions A: cyclopropane (150 μmol), TBABF₄ (0.02 m), HFIP (3 mL), O₂‐atm., GC/GC, U=+2.40 V, rt; Conditions B=standard conditions B: cyclopropane (150 μmol, 1.0 equiv.), DDQ (1.0 equiv.), TBABF₄ (0.02 m), MeCN (6 mL), O₂‐atm., GC/GC, U=+1.30 V, rt; Conditions C: cyclopropane (150 μmol, 1.0 equiv.), DDQ (1.0 equiv.), TBABF₄ (0.02 m), HFIP (3 mL), O₂‐atm., GC/GC, U=+1.30 V, rt. No reference electrode was used to set the cell voltage.

Scheme 3

Scope of the electrosynthesis of 1,2‐dioxanes 4 and γ‐hydroxy ketones 5. [a] Yield for an one‐pot approach from 3 to 5. No reference electrode was used to set the cell voltage.

Scheme 4

Mechanistic proposal for the direct anodic oxidation.

Scheme 5

Experimental investigation of the mechanistic proposals.

Scheme 6

Results of quantum‐chemical calculations (DFT/TPSSh/def2‐TZVP) for the direct electrolysis of 1 a. Optimized intermediates are shown according to the proposed mechanism (Scheme 4). Spin densities are represented in orange isosurfaces. The contribution to the total charge deviation compared to 1 a is shown for the phenyl (green), cyclopropyl (blue) and the methyl ester (red) parts (contribution of added dioxygen shown in gray). Change in enthalpy and activation energies for each reaction step is given in the table.

Scheme 7

Derivatization of oxidized products 2 a, 4 a and 5 a.