Y. Li, K. A. Wheeler, R. Dembinski
SHORT COMMUNICATION
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mation of three bonds in a sequential procedure. This
method avoids the loss of halogens in the synthetic pathway,
facilitates the regioselective positioning of halogens within
two available β-locations, and also allows for the introduc-
tion of substituents such as cyclopropyl that is not easily
carried out by other methods. Iodofuran was confirmed as
substrate for coupling with lithium N-heterocyclic trialkyl-
borate. The determination of the role of the catalysts and
further optimizations are the subject of further investi-
gations in our laboratory.
[2]
[3]
[4]
Experimental Section
3-Fluoro-4-iodo-5-(4-methylphenyl)-2-phenylfuran (3a):
A 50 mL
round-bottom flask was charged with silyl enol ether 4a (0.0875 g,
0.251 mmol), Selectfluor (0.098 g, 0.28 mmol), and MeCN (5 mL).
The mixture was stirred at ambient temperature (22 °C) and moni-
tored by TLC (hexanes/EtOAc, 8:2; usually for 1 h). The solvent
was removed by rotary evaporation, and the residue was kept under
oil-pump vacuum for 30 min. Dichloromethane (30 mL) was
added, and the mixture was stirred for 10 min. The solid was fil-
tered off (fritted funnel), and the filter cake was washed with
CH2Cl2 (10 mL). The solvent was removed from the combined fil-
trates by rotary evaporation. N-Iodosuccinimide (0.068 g,
0.30 mmol) and anhydrous CH2Cl2 (5.0 mL) were added. The mix-
ture was stirred for a few minutes to become homogeneous, and
anhydrous ground ZnBr2 (0.011 g, 0.049 mmol) was added followed
immediately by AuCl (0.0030 g, 0.013 mmol) in anhydrous CH2Cl2
(3.0 mL). The mixture was stirred vigorously at ambient tempera-
ture for 10 min. The reaction was quenched by adding saturated
aqueous sodium thiosulfate solution (10 mL) and stirring for few
minutes. CH2Cl2 (30 mL) was added. The organic layer was sepa-
rated, dried with MgSO4, filtered, and concentrated under reduced
pressure. Silica gel column chromatography (hexanes) gave 3a
(0.0720 g, 0.190 mmol, 76%) as a white solid, m.p. 115–116 °C.
C17H12FIO (378.18): calcd. C 53.99, H 3.20; found C 54.40, H 3.24.
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IR (KBr): ν = 2963, 1653, 1559, 1262, 938, 816, 668 cm–1. MS (EI):
˜
1
m/z (%) = 378 (100) [M+]. H NMR ([D6]acetone): δ = 8.05–7.97
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(m, 2 H), 7.81–7.75 (m, 2 H), 7.56–7.48 (m, 2 H), 7.39–7.32 (m, 3
H), 2.40 (s, 3 H) ppm. 13C ([D6]acetone): δ = 151.8 (d, J =
250.6 Hz), 149.7 (d, J = 6.0 Hz), 140.2, 136.2 (d, J = 20.9 Hz),
130.3, 130.0, 128.9 (d, J = 5.2 Hz), 128.8, 128.1 (d, J = 1.3 Hz),
126.9, 124.5 (d, J = 5.0 Hz), 56.9 (d, J = 25.1 Hz), 21.4 ppm. 19F
NMR (CDCl3): δ = –156.7 ppm.
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Pd-catalyzed arylation of 3-fluorofurans leads to tetrasubsti-
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Supporting Information (see footnote on the first page of this arti-
1
cle): H, 13C, and 19F NMR spectra for furans 3, 6, and 8.
Acknowledgments
Acknowledgments are made to the donors of the Petroleum Re-
search Fund administered by the American Chemical Society
(ACS) (ACS-PRF#46094) for the support of this research. The
National Science Foundation (NSF) awards (CHE-0821487, CHE-
0722547, and CHE-1048719) are also acknowledged. Y. L. is grate-
ful for the Provost’s Graduate Student Research Award. We thank
Dr. Robert Syvret (Air Products and Chemicals), Dr. Bruno
François (Simafex, France), and Frontier Scientific, Logan, Utah,
for a generous supply of Selectfluor, N-iodosuccinimide, and lith-
ium triisopropoxyborate salts (LTBS), respectively.
[1] a) T. Graening, F. Thrun, “Furans and their benzo derivatives:
Synthesis”, in Comprehensive Heterocyclic Chemistry III (Ed.:
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www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2767–2771