Xu et al.
°C. 19F NMR showed all TFDA was consumed. The reaction
mixture was cooled to room temperature, and the product was
obtained by distillation under reduced pressure.
Hz, 2H); 19F NMR δ -75.6 (s, 3F); 13C NMR, δ 22.3, 30.0, 39.2,
67.5, 114.7 (q, J ) 286 Hz), 157.6 (q, J ) 42 Hz), 207.0; HRMS
(EI) calcd for C7H10F3O3 [M + H]+ 199.0582, found 199.0577.
Anal. Calcd for C10H9F3O3: C, 42.43; H, 4.58. Found: C, 42.54;
H, 4.62.
Characterizations of 3a and 3b are provided below, with those
of 3c and 3d appearing in the Supporting Information.
Phenyl 2,2-Difluorocyclopropyl Ketone, 3a.23 Prepared starting
from precursor 1-phenylprop-2-en-1-one:15 liquid, 49%; 1H NMR
δ 1.74-1.86 (m, 1H), 2.37-2.48 (m, 1H), 3.35-3.45 (m, 1H),
7.46-7.53 (m, 2H), 7.59-7.64 (m, 1H), 7.99-8.02 (m, 2H); 19F
NMR, δ -124.4 to -125.1 (m, 1F), -140.3 to-140.9 (m, 1F).
4-Chlorophenyl 2,2-Difluorocyclopropyl Ketone, 3b. Prepared
starting from precursor 1-(4-chlorophenyl)prop-2-en-1-one:24 solid,
1-Phenyl-4-bromo-1-butanone (2b):26 1H NMR δ 2.31 (q, J
) 6.6 Hz, 2H), 3.19 (t, J ) 6.9 Hz, 2H), 3.55 (t, J ) 6.3 Hz, 2H),
7.45-7.60 (m, 3H), 7.96-7.99 (m, 2H).
1-Phenyl-4-trifluoroacetoxy-1-butanone (6b): 1H NMR δ 2.22
(q, J ) 6.6 Hz, 2H), 3.12 (t, J ) 6.9 Hz, 2H), 4.47 (t, J ) 6.3 Hz,
2H), 7.45-7.59 (m, 3H), 7.96-7.99 (m, 2H); 19F NMR δ -75.4
(s, 3F); 13C NMR δ 22.8, 34.3, 67.7, 114.7 (q, J ) 286 Hz), 128.2,
128.9, 133.6, 136.7, 157.7 (q, J ) 42 Hz), 198.6; HRMS (EI) calcd
for C12H12F3O3 [M + H]+ 261.0739, found 261.0733. Anal. Calcd
for C12H11F3O3: C, 55.39; H, 4.26. Found: C, 55.66; H, 4.36.
1
47%; mp 47-48 °C; H NMR δ 1.76-1.88 (m, 1H), 2.36-2.48
(m, 1H), 3.29-3.39 (m, 1H), 7.48 (d, J ) 8.7 Hz, 2H), 7.94 (d, J
) 8.7 Hz, 2H); 19F NMR δ -124.3 to -124.9 (m, 1F), -140.2 to
-140.7 (m, 1F); 13C NMR, δ 16.0 (t, J ) 10 Hz), 29.9 (t, J ) 11
Hz), 111.7 (q, J ) 289 Hz), 129.4, 130.0, 135.5, 140.5, 189.6;
HRMS (EI) calcd for C10H8ClF2O [M + H]+ 217.0232, found
217.0241. Anal. Calcd for C10H7ClF2O: C, 55.45; H, 3.26. Found:
C, 55.15; H, 3.23.
1
4-Bromo-3,3-difluoro-1-phenyl-1-butanone (4a): H NMR δ
3.82 (t, J ) 12.7 Hz, 2H), 3.95 (t, J ) 12.7 Hz, 2H), 7.48-7.54
(m, 2H), 7.60-7.65 (m, 1H), 7.94-7.97 (m, 2H); 19F NMR δ -93.1
(q, J ) 12.4 Hz, 2F); 13C NMR δ 31.4 (t, J ) 32 Hz), 42.6 (t, J )
26 Hz), 120.2 (t, J ) 244 Hz), 128.5, 129.1, 134.3, 136.4, 193.1
(t, J ) 6.0 Hz); HRMS (EI) calcd for C10H10BrF2O [M + H]+
262.9883, found 262.9886. Anal. Calcd for C10H9BrF2O: C, 45.65;
H, 3.46. Found: C, 45.98; H, 3.47.
Typical Procedure for the Reaction of the Cyclopropyl
Ketones with the Ionic Liquid Reagents. Under nitrogen, into a
25 mL round-bottomed flask with stirbar was placed N-pentylpy-
ridinium bromide (2.30 g, 10 mmol), which was heated to 70 °C
until the salt melted, and then either trifluoroactic acid or triflic
acid (10 mmol) was added through a syringe. The mixture was
then stirred at 70 °C for 5 min and cooled to room temperature, at
which time it was still a liquid. Substrate (5mmol) was added in
one portion and then stirred at 70 °C for 10 h. The reaction mixture
was cooled to room temperature, extracted with ethyl ether, washed
with brine, and dried over anhydrous sodium sulfate. After removal
of the solvent, the products 2a-f, 6a-e, 7, 4a-e, and 5 were
isolated by column chromatography, eluting with 10:1 to 5:1
hexane/ethyl acetate.
4-Bromo-3,3-difluoro-1-(4-chlorophenyl)-1-butanone (4b): 1H
NMR δ 3.78 (t, J ) 13.5 Hz, 2H), 3.92 (t, J ) 13.5 Hz, 2H), 7.47
(d, J ) 8.4 Hz, 2H), 7.90 (d, J ) 8.4 Hz, 2H); 19F NMR δ -93.1
(q, J ) 12.4 Hz, 2F); 13C NMR δ 31.2 (t, J ) 32 Hz), 42.6 (t, J )
26 Hz), 120.1 (t, J ) 244 Hz), 129.5, 129.9, 134.8, 140.9, 192.0
(t, J ) 6.0 Hz); HRMS (EI) calcd for C10H9BrClF2O [M + H]+
296.9493, found 296.9512. Anal. Calcd for C10H8BrClF2O: C,
40.37; H, 2.71. Found: C, 40.77; H, 2.65.
Acknowledgment. Support of this research by Fluorotech,
LLC is gratefully acknowledged, and J.S. thanks the Decanato
de Investigacion y Desarrollo (Universidad Simo´n Bolivar,
Caracas) for support of travel expenses.
Characterization data are provided below for 2a,b, 6a,b, and 4a,b
with the data for the remaining compounds appearing in the
Supporting Information.
5-Bromo-2-pentanone (2a):25 1H NMR δ 2.09 (q, J ) 7.2 Hz,
2H), 2.16 (s, 3H), 2.63 (t, J ) 6.9 Hz, 2H), 3.42 (t, J ) 6.6 Hz,
2H).
Supporting Information Available: Proton, carbon, and
fluorine NMR spectra of all new compounds, as well as proton
spectra of previously reported compounds 1f, 2a-f, 3a,e, 5,
and 7. This material is available free of charge via the Internet
5-Trifluoroacetoxy-2-pentanone (6a): 1H NMR δ 2.03 (q, J )
6.6 Hz, 2H), 2.21 (s, 3H), 2.61 (t, J ) 7.2 Hz, 2H), 4.36 (t, J ) 6.0
(23) Jonczyk, A.; Kaczmarczyk, G. Tetrahedron Lett. 1996, 37, 4085–4086.
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(24) Itoh, K.; Nakanishi, S.; Otsuji, Y. Bull. Chem. Soc. Jpn. 1991, 64, 2965–
2977.
(25) Cornish, C. A.; Warren, S. J. Chem. Soc., Perkin Trans. 1 1985, 2585–
2598.
(26) Ahlbrecht, H.; Raab, W.; Vonderheid, C. Synthesis 1979, 127–129.
3538 J. Org. Chem. Vol. 73, No. 9, 2008