H
Synthesis
K. Balaraman et al.
Feature
Benzyl (E)-4-Bromo-4-chloro-3-(4-chlorophenyl)-4-fluorobut-2-
enoate (18)
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561433.
Compound 18 was obtained as a colorless solid in 91% yield (62 mg,
S
u
p
p
ortioIgnfmr oaitn
S
u
p
p
o
nrtogI
i
f
rm oaitn
0.15 mmol) from 2-bromo-2-chloro-1-(4-chlorophenyl)-2-fluo-
roethan-1-one (46 mg, 0.16 mmol) by following the general proce-
dure described above; mp 51–52 °C; R = 0.3 (hexanes/EtOAc, 98:2).
f
References
1
H NMR (400 MHz, CDCl ): δ = 7.36–7.28 (m, 7 H), 7.15–7.10 (m, 2 H),
3
6
.58 (s, 1 H), 5.00 (s, 2 H).
(1) (a) Smith, B. R.; Eastman, C. M.; Njardarson, J. T. J. Med. Chem.
2014, 57, 9764. (b) Wang, J.; Sanchez-Rosello, M.; Acena, J. L.;
del Pozo, C.; Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.;
Liu, H. Chem. Rev. 2014, 114, 2432.
13
C NMR (100 MHz, CDCl ): δ = 163.8 (d, J = 1.6 Hz), 151.6 (d, JC-F
=
3
C-F
1
1
8.8 Hz), 135.4, 134.7, 131.4, 130.8 (d, JC-F = 1.5 Hz), 128.6, 128.5,
28.4, 128.1, 120.6 (d, JC-F = 9.8 Hz), 105.0 (d, JC-F = 310.7 Hz), 67.1.
(2) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.; Zhu, W.; Acena, J. L.;
19
F NMR (376 MHz, CDCl ): δ = –54.71.
3
Soloshonok, V. A.; Izawa, K.; Liu, H. Chem. Rev. 2016, 116, 422.
Anal. Calcd for C17H12BrCl FO : C, 48.84; H, 2.89. Found: C, 48.83; H,
2
2
(3) (a) Hargreaves, M. K.; Barrett, G. C.; Hall, D. M.; Modarai, B.
J. Chem. Soc. C 1971, 279. (b) Hargreaves, M. K.; Modarai, B.
J. Chem. Soc. C 1971, 1013. (c) Doyle, T. R.; Vogl, O. J. Am. Chem.
Soc. 1989, 111, 8510. (d) Doyle, T. R.; Vogl, O. Monatsh. Chem.
2.89.
Ethyl (E)-4-Bromo-4-chloro-4-fluoro-3-phenylbut-2-enoate (19)
1
990, 121, 31.
To a solution of 2-bromo-2-chloro-2-fluoro-1-phenylethan-1-one (50
mg, 0.2 mmol) in anhyd THF was added NaH (10 mg, 0.24 mmol) at
(
4) (a) Yang, Z.-Y. J. Org. Chem. 2003, 68, 4410. (b) Zhao, Y.; Gao, B.;
Hu, J. J. Am. Chem. Soc. 2012, 134, 5790.
0
°C under an inert atmosphere. After stirring for 30 min, triethyl
(
5) (a) Kvicala, J.; Stambasky, J.; Skalicky, M.; Paleta, O. J. Fluorine
Chem. 2005, 126, 1390. (b) Petko, K. I.; Kot, S. Y.; Yagupolskii, L.
M. J. Fluorine Chem. 2008, 129, 1119. (c) Matsnev, A. V.; Qing, S.-
Y.; Stanton, M. A.; Berger, K. A.; Haufe, G.; Thrasher, J. S. Org.
Lett. 2014, 16, 2402. (d) Shiosaki, M.; Inoue, M. J. Fluorine Chem.
phosphonoacetate (0.047 mL, 0.24 mmol) was added. The resulting
solution was stirred for 2 h at 0 °C and quenched with H O. The or-
2
ganic phase was washed with brine, dried (Na SO ), and the solvent
2
4
was removed in vacuo. The crude product was purified by flash chro-
matography on silica gel using hexanes/EtOAc (95:5) as the mobile
phase. Compound 19 was obtained in 95% yield as a colorless liquid
2015, 175, 160.
(
6) Mei, H.; Nie, C.; Acena, J. L.; Soloshonok, V. A.; Roeschenthaler,
G.-V.; Han, J. Eur. J. Org. Chem. 2015, 6401.
7) Prager, J. H.; Ogden, P. H. J. Org. Chem. 1968, 33, 2100.
8) Han, C.; Kim, E. H.; Colby, D. A. J. Am. Chem. Soc. 2011, 133, 5802.
(9) Prakash, G. K. S.; Zhang, Z.; Wang, F.; Munoz, S.; Olah, G. A.
J. Org. Chem. 2013, 78, 3300.
10) (a) Han, C.; Kim, E. H.; Colby, D. A. Synlett 2012, 1559.
(b) Riofski, M. V.; Hart, A. D.; Colby, D. A. Org. Lett. 2013, 15, 208.
11) Li, W.; Zhu, X.; Mao, H.; Tang, Z.; Cheng, Y.; Zhu, C. Chem.
Commun. 2014, 50, 7521.
(
61 mg, 0.19 mmol); R = 0.4 (hexanes/EtOAc, 19:1).
f
1
H NMR (400 MHz, CDCl ): δ = 7.51–7.33 (m, 5 H), 6.53 (s, 1 H), 3.99
3
(
(
(q, J = 7.1 Hz, 2 H), 1.02 (t, J = 7.2 Hz, 3 H).
13
C NMR (100 MHz, CDCl ): δ = 164.3, 152.4 (d, J = 18.5 Hz), 132.6
3
C-F
(d, JC-F = 1.5 Hz), 130.1, 129.0, 127.7, 120.4 (d, JC-F = 9.6 Hz), 105.4 (d, JC-F =
310.5 Hz), 60.9, 13.7.
(
(
(
19
F NMR (376 MHz, CDCl ): δ = –54.3.
3
Anal. Calcd for C12H11BrClFO : C, 44.82; H, 3.45. Found: C, 44.35; H,
2
3.61.
12) (a) Xie, C.; Wu, L.; Mei, H.; Soloshonok, V. A.; Han, J.; Pan, Y. Tet-
rahedron Lett. 2014, 55, 5908. (b) Xie, C.; Wu, L.; Zhou, J.; Mei,
H.; Soloshonok, V. A.; Han, J.; Pan, Y. J. Fluorine Chem. 2015, 172,
Crystallographic Analysis
A single crystal of 3 was obtained by slow evaporation of a solution of
the compound in a mixture of EtOAc and hexanes (5% EtOAc in hex-
anes). Single crystal X-ray analysis was performed at 296 K using a
Siemens platform diffractometer with graphite monochromated Mo-
Kα radiation (λ = 0.71073 Å). Data were integrated and corrected us-
ing the APEX II program. The structures were solved by SHELXT and
refined with full-matrix least-square analysis using SHELX-97-2 soft-
ware. Non-hydrogen atoms were refined with anisotropic displace-
1
3. (c) Xie, C.; Wu, L.; Mei, H.; Soloshonok, V. A.; Han, J.; Pan, Y.
Org. Biomol. Chem. 2014, 12, 7836. (d) Xie, C.; Wu, L.; Han, J.;
Soloshonok, V. A.; Pan, Y. Angew. Chem. Int. Ed. 2015, 54, 6019.
(e) Xie, C.; Dai, Y.; Mei, H.; Han, J.; Soloshonok, V. A.; Pan, Y.
Chem. Commun. 2015, 51, 9149.
(
13) Wu, C.; Li, G.; Sun, W.; Zhang, M.; Hong, L.; Wang, R. Org. Lett.
2
014, 16, 1960.
(
14) (a) Saidalimu, I.; Fang, X.; He, X. P.; Liang, J.; Yang, X. Y.; Wu, F.
H. Angew. Chem. Int. Ed. 2013, 52, 5566. (b) Saidalimu, I.; Fang,
X.; Lv, W.; Yang, X.; He, X.; Zhang, J.; Wu, F. H. Adv. Synth. Catal.
ment parameter. Crystal data: C H ClF O , M = 286.61, colorless
1
0
7
4
3
3
prism, 0.3 × 0.2 × 0.1 mm , monoclnic, space group P2 /c, a =
.0622(11), b = 18.116(2), c = 7.6291(10) Å, V = 1113.3(3) Å , Z = 4. A
1
3
8
2
013, 355, 857.
single crystal of 17 was obtained by slow evaporation of a solution of
the compound in a mixture of EtOAc and hexanes (5% EtOAc in hex-
anes). Single crystal X-ray analysis was performed as described above.
(
15) (a) Zhang, P.; Wolf, W. J. Org. Chem. 2012, 77, 8840. (b) Zhang,
P.; Wolf, W. Angew. Chem. Int. Ed. 2013, 52, 7869.
(16) John, J. P.; Colby, D. A. J. Org. Chem. 2011, 76, 9163.
Crystal data: C 1H BrClFO , M = 433.69, colorless needle, 0.12 × 0.07 ×
2
15
2
(17) Pravst, I.; Zupan, M.; Stavber, S. Tetrahedron 2008, 64, 5191.
(18) The reaction was carried out with 5 equiv of LiBr, 2.5 equiv of
K CO , and 2 equiv of NBS using THF as solvent at r.t. Complete
3
0
8
.05 mm , orthorombic, space group P2 2 2 , a = 5.9238(9), b =
.0989(12), c = 37.622(6) Å, V =1805.0(5) Å , Z = 4.
1
3
1 1
2
3
conversion of 5 was observed within 1 h.
(19) The trapping of chlorofluoro-substituted enolates such as 7
Acknowledgment
with NIS or I is also possible, but the corresponding chlorofluo-
roiodomethyl ketones are considerably less stable than 8 and its
2
We gratefully acknowledge financial support from the National Insti-
tutes of Health (GM106260).
analogues.
©
Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–I