Fe/CuBr₂-Catalyzed Benzylation of Arenes and Thiophenes with Benzyl Alcohols

Abstract

An inexpensive and relatively nontoxic Fe/CuBr₂-catalyzed benzylation of arenes and thiophenes with benzyl alcohols has been developed. The reaction can be carried out under mild conditions to afford diarylmethane derivatives in high yields and good ­selectivity.

Key words

benzylation - benzyl alcohols - iron - cupric bromide - ­diarylmethanes

Reference and Notes

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26

Typical Procedure for the Benzylation of Arenes
Benzyl alcohol (1 mmol), arene (1 mL), CuBr₂ (10 mol%,
0.1 mmol), reductive Fe powder (20 mol%, 0.2 mmol), and DCE (5 mL) were put into a flask fitted with a pressure-equalized addition funnel (containing a cotton plug and 1 g of CaH₂ and acting as a Soxhlet extractor) surmounted by a reflux condenser. After stirring for 20 h at 84 ˚C, the reaction was quenched with H₂O. The stirring bar was removed and washed with CH₂Cl₂. The aqueous phase was extracted three times with CH₂Cl₂. The combined organic layers were dried over MgSO₄, and the solvents were evaporated. The product was purified by silica gel column chromatography (200-300 mesh; n-hexane-EtOAc, 50:1).
2-Benzyl-3,4-dibromothiophene (3u) ^¹H NMR (400 MHz, CDCl₃, 25 ˚C): δ = 7.34-7.28 (m, 2 H, Ar), 7.25-7.21 (m, 3 H, Ar), 7.17 (s, 1 H, Ar), 4.16 (s, 2 H, ArCH₂). HRMS: m/z calcd for C₁₁H₈SBr₂: 329.8713; found: 329.8714.
General Procedure for the Benzylation of Thiophene Benzyl alcohol (1 mmol), thiophene (1 mL), CuBr₂ (10 mol%, 0.1 mmol), reductive Fe powder (20 mol%, 0.2 mmol), and DCE (5 mL) were put into a flask fitted with a pressure-equalized addition funnel (containing a cotton plug and 1 g of CaH₂ and acting as a Soxhlet extractor) sur-mounted by a reflux condenser. After stirring for 20 h at 84 ˚C, the reaction was quenched with H₂O. The stirring bar was removed and washed with CH₂Cl₂. The aqueous phase was extracted three times with CH₂Cl₂. The combined organic layers were dried over MgSO₄, and the solvents were evaporated. The product was purified by silica gel column chromatography (200-300 mesh; n-hexane-EtOAc, 50:1).
2-Furyl-2-thienylmethane (6g) ^¹H NMR (400 MHz, CDCl₃, 25 ˚C): δ = 7.33 (s 1 H, Ar), 7.15 (d J = 4.8 Hz, 1 H, Ar), 6.93 (dt J = 2.8, 5.2 Hz, 1 H, Ar), 6.86 (d, J = 2.8 Hz, 1 H, Ar), 6.29 (s, 1 H, Ar), 6.08 (d, J = 2.8 Hz, 1 H, Ar), 4.15 (s, 2 H, ArCH₂). MS (EI): m/z = 164 [M⁺].