Selective Preparation of C _2v -Symmetric Hexaphenylbenzene Derivatives through Sequential Suzuki Coupling

Abstract

We have developed effective reaction conditions for the ­Suzuki cross-coupling of chlorinated hexaphenylbenzene derivatives. A chloro group on a hexaphenylbenzene framework exhibits a low reactivity to Suzuki cross-coupling, and only nickel catalysts bearing alkyl-substituted phosphine ligands achieved the coupling. With this as a key step, we succeeded in the selective preparation of a C _2v -symmetric hexaphenylbenzene derivative containing two kinds of aryl group.

Key words

hexaphenylbenzene - Suzuki coupling - cross-coupling - nickel catalysis - aryl chlorides - regioselectivity

• References and Notes

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• 23 Compound 2 A suspension of compound 6 (0.500 g, 0.530 mmol) and TsOH (604 mg, 3.18 mmol) in AcOH (5 mL) was refluxed for 1.5 h. H₂O (5 mL) was then poured into the mixture and the resulting precipitate was collected by filtration and washed with MeOH to afford compound 2 as a colorless solid; yield: 0.346 g (90%); mp >300 °C.¹H NMR (500 MHz, CDCl₃, 298 K): δ = 6.98 (d, J = 8.8 Hz, 4 H), 6.92–6.89 (m, 9 H), 6.83 (d, J = 8.6 Hz, 2 H), 6.78–6.75 (m, 6 H), 6.71 (d, J = 8.6 Hz, 2 H), 6.66 (d, J = 8.6 Hz, 4 H). ¹³C NMR (125 MHz, CDCl₃, 298 K): δ = 140.66, 140.57, 139.91, 139.89, 139.48, 139.43, 139.39, 138.90, 132.98, 132.61, 131.45, 131.25, 130.00, 127.21, 127.08, 125.90, 119.75. HRMS (ESI-TOF): m/z [M]⁺ calcd for C₄₂H₂₇ ⁷⁹Br₂ ³⁵Cl: 724.0182; found: 724.0168.
• 24 Compound 7 A solution of compound 2 (0.200 g, 0.275 mmol, 1.0 equiv), PhB(OH)₂ (0.101 g, 0.825 mmol, 3.0 equiv), K₂CO₃ (0.228 g, 1.65 mmol, 6.0 equiv), and Pd(PPh₃)₄ (31.8 mg, 27.5 µmol, 10 mol%) in THF (2 mL) and H₂O (2 mL) was stirred at 80 °C for 6 h under N₂. The mixture was then extracted with EtOAc (3 × 5mL). The combined organic layer was dried (MgSO₄), filtered, and concentrated in vacuo. The crude product was purified by column chromatography [silica gel, hexane to hexane–EtOAc (20:1)] to give a colorless solid; yield: 0.186 g (93%); mp 284–286 °C. ¹H NMR (500 MHz, CDCl₃, 298 K): δ = 7.44 (d, J = 7.2 Hz, 4 H), 7.33 (t, J = 7.5 Hz, 4 H), 7.24 (t, J = 7.4 Hz, 2 H), 7.13 (d, J = 8.4 Hz, 4 H), 6.90–6.80 (m, 21 H), 6.77 (d, J = 8.6 Hz, 2 H). ¹³C NMR (125 MHz, CDCl₃, 298 K): δ = 140.91, 140.80, 140.55, 140.49, 140.40, 140.31, 139.69, 139.33, 139.27, 137.56, 132.80, 131.90, 131.51, 131.47, 131.29, 128.68, 127.03, 126.92, 126.81, 125.62, 125.50, 125.29. HRMS (ESI-TOF): m/z [M]⁺ calcd for C₅₄H₃₇ ³⁵Cl: 720.2576; found: 724.2584.
• 25 Compound 8 A solution of compound 7 (0.100 g, 0.139 mmol, 1.0 equiv), 4-methoxyphenylboronic acid (42.2 mg, 0.278 mmol, 2.0 equiv), K₃PO₄ (0.118 g, 0.556 mmol, 4.0 equiv), and Ni(PCy₃)₂Cl₂ (9.60 mg, 13.9 µmol, 10 mol%) in THF (1 mL) was stirred at 80 °C for one week under N₂. The mixture was then extracted with EtOAc (3 × 5 mL). The combined organic layer was dried (MgSO₄), filtered, and concentrated in vacuo. The crude product was purified by column chromatography [silica gel, hexane to hexane–EtOAc (10:1)] to give a colorless solid [yield: 48 mg (44%)], together with a mixture of compound 7 and 4,4′-dimethoxybiphenyl. Compound 7 [yield: 30 mg (30%); mp 252–253 °C] was recovered after washing this mixture with hexane. ¹H NMR (500 MHz, CDCl₃, 298 K): δ = 7.45 (d, J = 7.4 Hz, 4 H), 7.38 (d, J = 9.0 Hz, 2 H), 7.33 (t, J = 7.8 Hz, 4 H), 7.24 (t, J = 7.4 Hz, 2 H), 7.13 (d, J = 8.5 Hz, 4 H), 7.09 (d, J = 8.5 Hz, 2 H), 6.90–6.80 (m, 23 H), 3.80 (s, 3 H). ¹³C NMR (125 MHz, CDCl₃, 298 K): δ = 158.97, 140.88, 140.71, 140.69, 140.67, 140.60, 140.30, 140.22, 139.94, 139.21, 137.47, 137.09, 133.45, 132.00, 131.97, 131.61, 128.68, 127.82, 127.01, 126.89, 126.82, 125.40, 125.26, 124.79, 114.11, 55.47. HRMS (ESI-TOF): m/z [M]⁺ calcd for C₆₁H₄₄O: 792.3392; found: 792.3395.