Synlett 2003(2): 0253-0255
DOI: 10.1055/s-2003-36789
LETTER
© Georg Thieme Verlag Stuttgart · New York

A New Route to 5-Aryl and 5-Heteroaryl-2-pyrones via Suzuki Coupling of a 2-Pyrone-5-boronate ester

Edward C. Gravetta, Philip J. Hiltonb, Keith Jones*a, Jean-Marie Pérona
a School of Chemical and Pharmaceutical Sciences, Kingston University, Kingston-upon-Thames, Surrey, KT1 2EE, UK
Fax: +44(20)85477562; e-Mail: keith.jones@kingston.ac.uk;
b St. Thomas’ Hospital, London SE1 7EH, UK
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Publikationsverlauf

Received 12 November 2002
Publikationsdatum:
22. Januar 2003 (online)

Abstract

The synthesis of the 2-pyrone-5-boronate ester 5 is described along with its palladium-catalysed coupling reactions with a range of aryl and heteroaryl halides and triflates.

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Preparation of(5): A mixture of 5-bromo-2-pyrone (13 g, 74 mmol), pinacolborane (16.2 mL, 14.7 g, 111 mmol), triethylamine (31 mL, 22.1 g, 222 mmol) and PdCl2(PPh3)2 (1.56 g, 2.2 mmol) in dry tolune (100 mL) was heated to reflux under a N2 atmosphere for 6 hours. After this time, TLC analysis showed no remaining 5-bromo-2-pyrone. The dark solution was filtered through a short plug of silica and this was further eluted with dichloromethane (250 mL). The solvent was removed under reduced pressure to give a dark crystalline solid. Flash column chromatography using dichloromethane as eluent gave the 2-pyrone-5-boronate 5 (13.6 g, 61.4 mmol, 83%) as a pale yellow crystalline solid, mp 91-93 °C. This material was used in all coupling reactions. An analytically pure sample with the same mp could be obtained as white crystals by sublimation at 0.7 mm Hg pressure. δH (CDCl3, 300 MHz) 1.29 (6 H, s), 6.27 (1 H, dd, J = 9.6 and 1.2 Hz), 7.50 (1 H, dd, J = 9.6 and 2.1 Hz) and 7.84 (1 H, dd, J = 2.1 and 1.2 Hz); δC (CDCl3, 75 MHz) 24.8, 84.5, 96.9, 115.6, 146.3 and 160.1; HRMS calcd for C11H15 11BO4: 222.1063; found: 222.1059. Anal. Calcd for C11H15BO4: C, 59.50; H, 6.81. Found: C, 59.66; H, 6.83.

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Typical procedure for Suzuki coupling: Phenyl triflate (50 mg, 0.22 mmol), 2-pyrone-5-boronate 5 (55 mg, 0.25 mmol), and PdCl2(dppf) (20 mg, 0.022 mmol) were dissolved in dry DMF (4 mL) under a N2 atmosphere. Finely crushed K3PO4 (180 mg, 0.82 mmol) was added to the DMF solution and this slurry was heated to 60 °C for 6 hours. The DMF was removed under reduced pressure to give a dark solid that was initially purified by dissolving in dichloromethane and filtering through a plug of silica, followed by washing with dichloromethane (30 mL). The solvent was removed under reduced pressure to give a solid that was further purified by flash column chromatography (10% ethyl acetate in dichloromethane) to yield 5-phenyl-2-pyrone (30.2 mg, 0.172 mmol, 80%). δH (CDCl3, 300 MHz) 6.38 (1 H, dd, J = 9, 1 Hz, H-3), 7.35 (5 H, m, aromatic-H), 7.56 (1 H, dd, J = 9, 3 Hz), 7.62 (1 H, dd, J = 3, 1 Hz); δC (CDCl3, 75 MHz) 116.5, 120.6, 126.0, 128.4, 129.3, 133.5, 144.0, 148.3, 161.2; m/z 172 (M+, 90%), 144(38), 115(100), 89(12), 63(10). These data match those reported. [7]