200
T. Fukuhara, S. Hara
LETTER
reaction with IF5. This result supports the view that the
present desulfurizing difluorination reaction proceeds
through the intermediate 3, which was formed by the
Pummerer-type fluorination reaction of 1 (Scheme 4).
Acknowledgment
We are grateful to Asahi Glass Co., Ltd. for their gift of IF5.
References
(1) (a) Welch, J. T. Tetrahedron 1987, 43, 3123. (b) Welch,
J. T.; Eswarakrishnan, S. Fluorine in Bioorganic Chemistry;
Wiley: New York, 1991. (c) Resnati, G. Tetrahedron 1993,
49, 9385. (d) Hiyama, T. In Organofluorine Compounds;
Springer: Berlin, 2000, Chap. 5.
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2002, 2816. (c) Ayuba, S.; Yoneda, N.; Fukuhara, T.; Hara,
S. Bull. Chem. Soc. Jpn. 2002, 75, 1597. As for the review,
see: (d) Dawood, K. M. Tetrahedron 2004, 60, 1435.
(e) Fuchigami, T.; Tajima, T. J. Fluorine Chem. 2005, 126,
181.
Synthesis of Ethyl 2,2-Difluoro-2-phenylacetate (2a)
To a IF5·5CH2Cl2 (0.975g, 1.5 mmol) in a TeflonTM PFA bottle, a
hexane solution (4 mL) of ethyl 2-methylthio-2-phenylacetate (1a,
210 mg, 1.0 mmol) was added at 0 °C, and the mixture was stirred
at r.t. for 2 h. Then, the mixture was poured into aq NaHCO3 and
extracted with Et2O three times. The combined organic phase was
washed with aq Na2S2O3 and dried over MgSO4. Purification by
column chlomatography (SiO2, hexane–Et2O) gave 2a (144 mg) in
72% yield; liquid. IR (liquid film): 2987, 1763, 1267, 1104 cm–1. 1H
NMR (400 MHz, CDCl3): d = 1.31 (t, J = 7.2 Hz, 3 H), 4.30 (q,
J = 7.2 Hz, 2 H), 7.44–7.52 (m, 3 H), 7.61 (d, J = 7.3 Hz, 2 H). 19
F
NMR (376 MHz, CDCl3): d = –104.49 (s, 2 F) (lit5a –103.9). 13C
NMR (100 MHz, CDCl3): d = 13.82, 63.09, 113.36 (t, 1JC–F = 252.9
3
4
Hz), 125.41 (t, JC–F = 6.7 Hz, 2 C), 128.61, 130.96 (t, JC–F = 1.9
2
2
Hz, 2 C), 132.81 (t, JC–F = 25.9 Hz), 164.21 (t, JC–F = 35.5 Hz).
HRMS (EI): m/z calcd for C10H10F2O2 [M+]: 200.0649; found:
200.0645.
(4) (a) Differding, E.; Rüegg, G. M.; Lang, R. W. Tetrahedron
Lett. 1991, 32, 1779. (b) Kotoris, C. C.; Chen, M.-J.; Taylor,
S. D. J. Org. Chem. 1998, 63, 8052. (c) Pravst, I.; Zupan,
M.; Stavber, S. Synthesis 2005, 3140.
(5) (a) Middleton, W. J.; Bingham, E. M. J. Org. Chem. 1980,
45, 2883. (b) Hägele, G.; Haas, A. J. Fluorine Chem. 1996,
76, 15. (c) Lai, G. S.; Pez, G. P.; Pesaresi, R. J.; Prozonic,
F. M.; Cheng, H. J. Org. Chem. 1999, 64, 7048. (d) Singh,
R. P.; Shreeve, J. M. Org. Lett. 2001, 3, 2713. (e) Singh,
R. P.; Shreeve, J. M. J. Org. Chem. 2001, 66, 6263.
(f) Singh, R. P.; Shreeve, J. M. J. Org. Chem. 2003, 68,
6063.
(6) (a) Murakami, S.; Kim, S.; Ishii, H.; Fuchigami, T. Synlett
2004, 815. (b) Murakami, S.; Ishii, H.; Tajima, T.;
Fuchigami, T. Tetrahedron 2006, 62, 3761. (c) Guo, Y.;
Shreeve, J. M. Chem. Commun. 2007, 3583. (d) Nicolaou,
K. C.; Estrada, A. A.; Freestone, G. C.; Lee, S. H.; Alvarez-
Mico, X. Tetrahedron 2007, 63, 6088. (e) Boyer, N.;
Gloznec, P.; Nanteuil, G. D.; Jubault, P.; Quirion, J.-C.
Tetrahedron 2007, 63, 12532. As for the review, see:
(f) Amii, H.; Uneyama, K. In Fluorine-Containing
Synthons; Soloshonok, V. A., Ed.; American Chemical
Society: Washington DC, 2005, 455. (g) Sato, K.; Omote,
M.; Ando, A.; Kumadaki, I. In Fluorine-Containing
Synthons; Soloshonok, V. A., Ed.; American Chemical
Society: Washington DC, 2005, 476. (h) Uneyama, K.
Organofluorine Chemistry; Blackwell: Oxford, 2006, 223.
(i) Wang, X.-J.; Zhang, F.; Liu, J.-T. Tetrahedron 2008, 64,
1731.
2,2-Difluoro-1,2-diphenylethanone (2d)
1
Liquid; IR (liquid film): 1703, 1450, 1256, 1135 cm–1. H NMR
(400 MHz, CDCl3): d = 7.43–7.61 (m, 8 H), 8.02–8.04 (m, 2 H). 19
F
NMR (376 MHz, CDCl3): d = –98.12 (s, 2 F) [lit.11 –98.0 (s, 2 F)].
13C NMR (100 MHz, CDCl3): d = 116.88 (t, JC–F = 253.9 Hz),
1
125.59 (t, 3JC–F = 5.8 Hz, 2 C), 128.62 (2 C), 128.81 (2 C), 130.25
(t, 4JC–F = 2.9 Hz, 2 C), 130.91, 132.10, 133.08 (t, 2JC–F = 24.9 Hz),
2
134.20, 188.94 (t, JC–F = 30.7 Hz). HRMS (EI): m/z calcd for
C14H10F2O [M+]: 232.0700; found: 232.0683.
Ethyl Bromophenyl-2,2-difluoroacetate (2f)
Liquid (a mixture of o- and p-isomers, ratio ortho/para = 1:4). IR
(liquid film): 1767, 1267, 1105 cm–1. 1H NMR (400 MHz, CDCl3):
d = 1.31 (t, J = 7.3 Hz, 2.4 H), 1.33 (t, J = 7.4 Hz, 0.6 H), 4.30 (q,
J = 7.2 Hz, 1.6 H), 4.36 (q, J = 7.2 Hz, 0.4 H), 7.34–7.75 (m, 0.8 H),
7.48 (d, J = 8.4 Hz, 1.6 H), 7.60 (d, J = 8.5 Hz, 1.6 H). 19F NMR
(376 MHz, CDCl3): d = –102.51 (s, 0.4 F), –104.73 (s, 1.6 F). 13
C
NMR (100 MHz, CDCl3): d (ortho) = 13.66, 63.28, 112.68 (t,
1JC–F = 253.0 Hz), 120.24 (t, 3JC–F = 4.8 Hz), 125.59 (t, 4JC–F = 1.9
3
2
Hz), 127.35, 127.58 (t, JC–F = 8.6 Hz), 132.11, 132.74 (t, JC–
2
F = 24.0 Hz), 162.92 (t, JC–F = 34.5 Hz). 13C NMR (100 MHz,
1
CDCl3): d (para) = 13.71, 63.23, 112.92 (t, JC–F = 252.6 Hz),
127.11 (t, 3JC–F = 5.8 Hz, 2C), 131.74 (t, 2JC–F = 26.8 Hz), 131.85 (2
C), 133.93, 163.63 (t, 2JC–F = 35.5 Hz). HRMS (EI): m/z calcd for
C10H9BrF2O2 [M+]: 277.9754; found: 277.9757.
1-(3,4-Difluorophenyl)-2,2-difluoro-2-phenylethanone (2g)
Liquid. IR (liquid film): 1713, 1612, 1263 cm–1. H NMR (400
1
MHz, CDCl3): d = 6.84–6.99 (m, 2 H), 7.45–7.61 (m, 5 H), 7.79–
7.85 (m, 1 H). 19F NMR (376 MHz, CDCl3): d = –100.12 to –100.22
(m, 1 F), –100.61 (d, J = 14.0 Hz, 2 F), –102.62 to –102.75 (m, 1 F).
(7) (a) Ayuba, S.; Fukuhara, T.; Hara, S. Org. Lett. 2003, 5,
2873. (b) Ayuba, S.; Hiramatsu, C.; Fukuhara, T.; Hara, S.
Tetrahedron 2004, 60, 11445.
13C NMR (100 MHz, CDCl3): d = 105.17 (t, JC–F = 25.9 Hz),
2
2
3
1
(8) Hiyama, T. In Organofluorine Compounds; Springer:
Berlin, 2000, Chap. 2, ; and references cited therein.
(9) (a) Kanie, K.; Tanaka, Y.; Suzuki, K.; Kuroboshi, M.;
Hiyama, T. Bull. Chem. Soc. Jpn. 2000, 73, 471. (b)Reddy,
V. P.; Alleti, R.; Perambuduru, M. K.; Welz-Biermann, U.;
Buchholz, H.; Prakash, G. K. S. Chem. Commun. 2005, 654.
(c) Cohen, O.; Rozen, S. Tetrahedron 2008, 64, 5362.
(10) (a) Brigaud, T.; Laurent, E. Tetrahedron Lett. 1990, 31,
2287. (b) Furuta, S.; Kuroboshi, M.; Hiyama, T.
Tetrahedron Lett. 1995, 36, 8243.
111.95 (dd, JC–F = 22.0, JC–F = 3.8 Hz), 116.10 (t, JC–F = 253.9
2
3
3
Hz), 118.73 (dd, JC–F = 12.5, JC–F = 3.8 Hz), 125.78 (t, JC–F
=
6.5 Hz, 2 C), 128.66, 130.98 (t, 4JC–F = 1.9 Hz, 2 C), 132.00 (t,
2JC–F = 25.2 Hz), 132.96–133.16 (m), 162.24 (dd, JC–F = 264.4,
1
2JC–F = 12.5 Hz), 166.15 (dd, 1JC–F = 259.7, 2JC–F = 12.5 Hz), 187.52
2
4
(td, JC–F = 34.0, JC–F = 2.9 Hz). HRMS (EI): m/z calcd for
C14H8F4O [M+]: 268.0511; found: 268.0518.
(11) Rozen, S.; Brand, M. J. Org. Chem. 1986, 51, 222.
Synlett 2009, No. 2, 198–200 © Thieme Stuttgart · New York