Copper(II) Acetate Catalyzed Cross-Coupling of Pentafluorophenylboronic Acid with Amines under an Atmosphere of Oxygen

Abstract

Under an atmosphere of oxygen and a catalytic amount of Cu(OAc)₂, pentafluorophenylboronic acid reacted with anilines at room temperature to produce the corresponding N-pentafluoro­phenylanilines in moderate to good yields. In the case of alkyl­amines, unexpected N-alkyl-2,2′,3,3′,4′,5,5′,6,6′-nona-fluoro-biphenyl-4-amines were formed under the similar conditions in moderate yields.

copper acetate - pentafluorophenylboronic acid - amines - N-pentafluorophenylanilines - cross-coupling

References and Notes

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14

Typical Procedure for the Preparation of Compound 3b
Copper(II) acetate (0.2 mmol) was added to a stirred mixture of EtOAc (15 mL) and pentafluorophenylboronic acid (1.5 mmol). The mixture was stirred for 10 min at r.t. then the 4-chlorophenylamine (1.0 mmol) was slowly added to the mixture. The reaction mixture was stirred sequentially for 5 h under the atmosphere of oxygen. The reaction was monitored by TLC and quenched with H₂O (5 mL). The resulting mixture was filtrated through a pad of Celite and the filtrate was extracted with EtOAc (3 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give a crude product, which was purified by column chromatography to give N-(4-chlorophenyl)-2,3,4,5,6-pentafluoroaniline (3b). Light yellow crystals; mp 78.5-79.8 ˚C. IR (KBr): 3417, 3133, 1524, 1495, 1399 cm^-¹. ^¹H NMR (500 MHz, CDCl₃): δ = 5.39 (br, 1 H), 6.75 (d, 2 H, J = 7.5 Hz), 7.23 (d, 2 H, J = 7.0 Hz). ^¹³C NMR [100 MHz, CDCl₃ (except for C₆F₅)]: δ = 117.7 (2 × CH), 126.9, 129.2 (2 × CH), 140.7. ^¹9F NMR (376 MHz, CDCl₃): δ = -158.98 (t, 1 F, J = 21.4 Hz),
-158.57 (dd, 2 F, J ₁ = 21.4 Hz, J ₂ = 21.4 Hz), -145.46 (d, 2 F, J = 19.6 Hz). MS (EI): m/z (%) = 293 (8) [M⁺], 273 (4), 238 (8), 151 (100), 88 (38). HRMS (EI): m/z calcd for C₁₂H₅ClF₅N: 293.0031; found: 293.0030.

15

Typical Procedure for the Preparation of Compound 7a
Copper(II) acetate (1 mmol) was added to a stirred mixture of DMF (25 mL) and pentafluorophenylboronic acid (2 mmol). The mixture was stirred for 10 min at r.t. then the Et₂NH (1.0 mmol) were slowly added to the mixture. The reaction mixture was stirred sequentially for 12 h under the atmosphere of oxygen. The reaction was monitored by TLC and quenched with H₂O (5 mL). The resulting mixture was filtrated through a pad of Celite, and the filtrate was extracted with EtOAc (3 × 15 mL). The combined organic layers were dried over Na₂SO₄, filtered, and concentrated under reduced pressure to give a crude product, which was purified by column chromatography to give N,N-diethyl-2,2′,3,3′,4′,5,5′,6,6′-nonafluorobiphenyl-4-amine (7a). Light yellow crystal; mp 71.6-72.5 ˚C. IR (KBr): 2976, 2917, 1644, 1503, 1384, 1046 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 1.16 (t, 6 H, J = 7.2 Hz), 3.33 (q, 4 H, J = 7.2 Hz). ^¹³C NMR [100 MHz, CDCl₃ (except for C₁₂F₉)]: δ = 13.4 (2 × CH), 46.8 (2 × CH). ^¹9F NMR (376 MHz, CDCl₃): δ = -157.56 to -157.43 (m, 2 F), -147.96 (t, 1 F, J = 21.4 Hz), -145.62 to -145.568 (m, 2 F), -137.16 to
-137.09 (m, 2 F), -133.91 to -133.83 (m, 2 F). MS (EI): m/z (%) = 387 (25) [M⁺], 358 (15), 372 (100), 344 (75). HRMS (EI): m/z calcd for C₁₆H₁₀F₉N: 387.0670; found: 387.0672.