Electrochemical C-C bond cleavage of cyclopropanes towards the synthesis of 1,3-difunctionalized molecules

Abstract

Electrochemistry has a lot of inherent advantages in organic synthesis and many redox reactions have been achieved under electrochemical condition. However, the electrochemical C-C bond cleavage and functionalization reactions are less studied. Here we develop electrochemical C-C bond cleavage and 1,3-difuntionalization of arylcyclopropanes under catalyst-free and external-oxidant-free conditions. 1,3-difluorination, 1,3-oxyfluorination and 1,3-dioxygenation of arylcyclopropanes are achieved with a high chemo- and regioselectivity by the strategic choice of nucleophiles. This protocol has good functional groups tolerance and can be scaled up. Mechanistic studies demonstrate that arylcyclopropane radical cation obtained from the anode oxidation and the subsequently generated benzyl carbonium are the key intermediates in this transformation. This development provides a scenario for constructing 1,3-difunctionalized molecules.

Fig. 1. 1,3-difunctionalization of cyclopropanes based on radical cation mechanism.

a Thermochemical and photochemical strategy. b Shono’s work. c This work: Electrochemical 1,3-difunctionalization of arylcyclopropanes (PC photoredox catalyst).

Fig. 2. Optimization of the reaction conditions^a.

^aReaction conditions: electrode surface (1.5 × 1.5 cm², J = 7.1 mA/cm²), 16 mA, undivided cell, 1 (0.5 mmol), PhCF₃ (4.8 mL), 2 h, 2.4 F mol⁻¹ (based on 1). ^bGC Yield using biphenyl as internal standard. ^c 1 (0.25 mmol), 1 h. ^dWithout PhCF₃, Bu₄NBF₄ (0.25 mmol) was added as supporting electrolyte (CC Carbon cloth).

Fig. 3. Substrate scope of 1,3-difluorination reaction.

Reaction condition: Cyclopropanes (0.25 or 0.5 mmol), Et₃N·3HF (1.2 mL), PhCF₃ (4.8 mL), 16 mA, 40 min–20 h, isolated yields, electrode surface (1.5 × 1.5 cm², J = 7.1 mA/cm²), undivided cell. ^aNMR yield using 1-fluoronaphthalene as internal standard. ^b0.5 mL DCE was added. ^c0.1 mmol scale, 2–6 h. s.m. starting material. ^dLarge-scale synthesis condition: carbon cloth anode, nickel foam cathode, cyclopropanes (6 or 8 mmol), Et₃N·3HF (2.4 mL), PhCF₃ (9.6 mL), 25–75 h, isolated yields. For more details, see Supplementary Experimental section.

Fig. 4. Substrate scope of 1,3-oxyfluorination and 1,3-dioxygenation reaction.

^aCyclopropanes (0.25 mmol), Et₃N·3HF (0.8 mL), ROH (0.2–0.75 mL), PhCF₃ (4.8 mL), 16 mA, 1–2 h, isolated yields. ^bCyclopropanes (0.5 mmol), Et₃N·3HF (1.2 mL), ether (4.8 mL), 4 h, isolated yields. ^c One milliliter of DCE was added. ^dCyclopropanes (0.25 mmol), Bu₄NBF₄ (0.25 mmol), MeOH (6 mL), 16 mA, 50 min−1h, isolated yields. For more details, see Supplementary Experimental section.

Fig. 5. Mechanistic studies.

a Cyclic voltamemetry studies. b Electrostatic potential surface and charge of phenylcyclopropane radical cation (1^·+). c Trap of benzyl radical intermediate. d Trap of benzyl carbonium intermediate.