A General and Efficient Protocol for the Synthesis of Biaryl Ethers from Aryl Silyl Ethers Using Cs₂CO₃

Abstract

A general and efficient one-step procedure has been developed for the synthesis of biaryl ethers via direct coupling of electron-deficient arylhalides or aryl triflates to aryl t-butyldimethyl-silyl (TBS) ethers using Cs₂CO₃. The protocol was also applied to electron-rich arylhalides by addition of a catalytic amount of copper(I) iodide. The reaction is rapid and provides good to excellent yields.

Key words

biary ethers - aryl TBS ether - Cs₂CO₃ - copper(I) iodide

References

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5

General Procedure: A mixture of Cs₂CO₃ (1 mmol), aryl TBS ether 2 (1 mmol) and arylhalide or aryl triflate 1 (1 mmol) in DMF (4.0 mL) was stirred at 100 °C under nitrogen until the reaction was finished as indicated by TLC (about 1-2 h). Then the mixture was partitioned between the aqueous and the organic phase (EtOAc). The organic layer was washed with brine, dried over anhyd Na₂SO₄ and evaporated under reduced pressure. The crude product was purified by flash column chromatography over silica gel using EtOAc-hexane (1:20 or 1:3, v/v) as eluent to afford the biaryl ether 3. All data for compound 3l are as follows: white crystals; mp 165 °C. IR (KBr): 2915, 1596, 1499, 1313, 1290, 1256, 1142, 961 cm^-1. ¹H NMR (500 MHz, CDCl₃):
δ = 8.92 (m, 1 H), 8.25 (dd, J = 1.40, 8.35 Hz, 1 H), 7.87 (d, J = 8.83 Hz, 2 H), 7.75 (d, J = 8.17 Hz, 1 H), 7.56 (t, J = 7.83 Hz, 1 H), 7.50 (m, 1 H), 7.39 (d, J = 7.58 Hz, 1 H), 7.11 (d, J = 8.83 Hz, 2 H), 3.05 (s, 3 H) ppm. MS (EI):
m/z = 299 [M⁺].

6

General Procedure: A mixture of Cs₂CO₃ (1 mmol), CuI (0.2 mmol), aryl TBS ether 2 (1 mmol) and arylbromide 1 (1 mmol) in DMF (2.0 mL) was stirred at 100 °C under nitrogen until the reaction was finished as indicated by TLC (about 8 h). Then the mixture was allowed to cool to r.t. and purified by flash column chromatography over silica gel eluted with hexane to afford biaryl ether 3. All data for 3p are as follows: colorless oil. IR (neat): 3022, 2955, 1608, 1590, 1509, 1219, 1110, 1021 cm^-1. ¹H NMR (500 MHz, CDCl₃): δ = 7.14-7.08 (m, 3 H), 7.00 (dd, J = 7.95 Hz, 1 H), 6.94-6.82 (m, 4 H), 3.90 (s, 3 H), 2.30 (s, 3 H) ppm. MS (EI): m/z = 214 [M⁺].