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.

Key words

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

References and Notes

• 1a Iizuka K. Akahane K. Momose DI. Nakazawa M. Tanouchi T. Kawamura M. Ohyama I. Kajiwara I. Ignchi Y. Okada T. Taniguchi K. Miyamoto T. Hayashi M. J. Med. Chem.  1981,  24:  1139 
• 1b Cozzi P. Carganico G. Fusar D. Grossoni M. Menichincheri M. Pinciroli V. Tonani R. Vaghi F. Salvati P. J. Med. Chem.  1993,  36:  2964 
• 1c Lam PYS. Vincent G. Clark CG. Deudon S. Jadhav PK. Tetrahedron Lett.  2001,  42:  3415 
• 2a Chan DMT. Monaco KL. Wang RP. Winters MP. Tetrahedron Lett.  1998,  39:  2933 
• 2b Lam PYS. Clark CG. Saubern S. Adams J. Winters MP. Chan DMT. Combs A. Tetrahedron Lett.  1998,  39:  2941 
• 3a Collman JP. Zhong M. Org. Lett.  2000,  2:  1233 
• 3b Collman JP. Zhong M. Zeng L. Costano S. J. Org. Chem.  2001,  66:  1528 
• 3c Collman JP. Zhong M. Zhang C. Costanzo S. J. Org. Chem.  2001,  66:  7892 
• 4 Lam PYS. Vincent G. Clark CG. Deudon S. Jadhav PK. Tetrahedron Lett.  2001,  42:  3415 
• 5a Antilla JC. Buchwald SL. Org. Lett.  2001,  3:  2077 
• 5b Sasaki M. Dalili S. Yudin AK. J. Org. Chem.  2003,  68:  2045 
• 6a Kantam ML. Venkanna GT. Sridhar C. Sreedhar B. Choudary BM. J. Org. Chem.  2006,  71:  9522 
• 6b Dai Q. Ran CZ. Harvey RG. Tetrahedron  2006,  62:  1764 
• 6c Tzschucke CC. Murphy JM. Hartwig JF. Org. Lett.  2007,  9:  761 
• 6d Lan JB. Zhang GL. Yu XQ. You JS. Chen L. Yan M. Xie RG. Synlett  2004,  1095 
• 7a Havelková M. Dvorřák D. Hocek M. Synthesis  2001,  1704 
• 7b Havelková M. Hocek M. Cÿesnek M. Dvorřák D. Synlett  1999,  1145 
• 8a Bellina F. Carpita A. Rossi R. Synthesis  2004,  2419 
• 8b Kotha S. Lahiri K. Kashinath D. Tetrahedron  2002,  58:  9633 
• 8c Hassan J. Sevignon M. Gozzi C. Schulz E. Lemaire M. Chem. Rev.  2002,  102:  1359 
• 9 Korenaga T. Kadowaki K. Ema T. Sakai T. J. Org. Chem.  2004,  69:  7340 
• 10a Korenaga T. Kosaki T. Fukumura R. Ema T. Sakai T. Org. Lett.  2005,  7:  4915 
• 10b Chen J. Cammers GA. Tetrahedron Lett.  2003,  44:  1503 
• 10c Takimiya K. Niihara N. Otsubo T. Synthesis  2005,  1589 
• 11a Chanbers RD. Chivers T. J. Chem. Soc.  1965,  3933 
• 11b Frohn HJ. Adomin NY. Bardin VV. Starichenko VF. Z. Anorg. Allg. Chem.  2002,  628:  2834 
• 12a Lam PYS. Clark CG. Saubern S. Adams J. Averill K. Chan DMT. Combs AP. Synlett  2000,  674 
• 12b Evans DA. Katz JL. West TR. Tetrahedron Lett.  1998,  39:  2937 
• 13 Platonov VE. Haas A. Schelvis M. Lieb M. Dvornikova KV. Osina OI. J. Fluorine Chem.  2002,  116:  3 

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.