E
Synlett
Y. Guo et al.
Letter
In summary, trifluoromethyl N-hydroxyimino halide
can be used as a building block for introducing fluoro and
iodo groups into the isoxazole. The incorporated iodo group
can facilitate the synthesis of trifluoromethy isoxazole de-
rivatives, making it useful in synthetic pharmaceutical
chemistry.
(6) (a) Tanaka, K.; Masuda, H.; Mitsuhashi, K. Bull. Chem. Soc. Jpn.
1984, 57, 2184. (b) Gonçalves, R. S. B.; Santos, M. D.; Bernadat,
G.; Delpon, D. B.; Crousse, B. Beilstein J. Org. Chem. 2013, 9, 2387.
7) (a) Waldo, J. P.; Larock, R. C. Org. Lett. 2005, 7, 5203. (b) Waldo, J.
P.; Larock, R. C. J. Org. Chem. 2007, 72, 9643.
8) (a) Yamazaki, T.; Taguchi, T.; Ojima, I. Fluorine in Medicinal
Chemistry and Chemical Biology; Wiley-Blackwell: Chichester,
UK, 2009, 1. (b) Babudri, F.; Farinola, G. M.; Naso, F.; Ragni, R.
Chem. Commun. 2007, 10, 1003. (c) Müller, K.; Faeh, C.;
Diederich, F. Science 2007, 317, 1881. (d) Purser, S.; Moore, P. R.;
Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
(
(
Acknowledgment
The authors thank the National Natural Science Foundation of China
(e) Harper, D. B.; O’Hagan, D. Nat. Prod. Rep. 1994, 11, 123.
(NSFC) (grant number 21172239) and the National Basic Research
(f) Hiyama, T. Organofluorine Compounds, Chemistry and Appli-
Program of China (2012CB821600) for financial support.
cations; Springer: Berlin, 2000, 137. (g) Kirsch, P. Modern Fluo-
roorganic Chemistry: Synthesis, Reactivity, Applications; Wiley-
VCH: Weinheim, 2013, 2nd ed. 1.
Supporting Information
(9) (a) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683.
(
1
6
b) Yang, X.; Wu, T.; Phipps, R. J.; Toste, F. D. Chem. Rev. 2015,
15, 826. (c) Merino, E.; Nevado, C. Chem. Soc. Rev. 2014, 43,
598.
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562115.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
(10) (a) Zhang, M.; Wu, Y.; Li, Y. J. Fluorine Chem. 2006, 127, 218.
(
b) Chen, Z.; Zhu, J.; Xie, H.; Li, S.; Wu, Y.; Gong, Y. Adv. Synth
References and Notes
Catal. 2010, 352, 1296. (c) Chen, Z.; Zhu, J.; Xie, H.; Li, S.; Wu, Y.;
Gong, Y. Org. Lett. 2010, 12, 4376.
(
(
(
1) (a) Sperry, J. B.; Wright, D. L. Curr. Opin. Drug Discovery Dev.
2005, 8, 723. (b) Lakhvich, E. V. K. F. A.; Akhrem, A. A. Chem. Het-
(11) Kemp, M. I. WO 2008135830, 2008.
(12) Chen, W.; Zhang, J.; Wang, B.; Zhao, Z.; Wang, X.; Hu, Y. J. Org.
Chem. 2015, 80, 2413.
(13) Typical Procedure for the Synthesis of Compound 4a
To a dry reaction tube, 2a (147 mg, 1.0 mmol), phenylacetylene
erocycl. Compd. 1989, 25, 359.
2) (a) Müller, G. F.; Eugster, C. H. Helv. Chim. Acta 1965, 48, 910.
(
b) Takemoto, T.; Nakajima, T.; Yokobe, T. J. Pharm. Soc. Jpn.
964, 84, 1232.
3) (a) Simoni, D.; Rondanin, R.; Baruchello, R. J. Med. Chem. 2008,
1, 4796. (b) Daidone, G.; Raffa, D.; Maggio, B.; Plescia, F.;
1
(204 mg, 2.0 mmol), NaHCO (101 mg, 1.2 mmol), NIS (450 mg,
2.0 mmol), and CH
3
5
2
Cl
2
(6 mL) was added successively at room
atmosphere. Then the reaction was
2
Cutuli, V. M. C.; Mangano, N. G.; Caruso, A. Arch. Pharm. Pharm.
Med. Chem. 1999, 332, 50. (c) Van Tol, H. H. M.; Bunzow, J. R.;
Guan, H. C.; Sunahara, R. K.; Seeman, P.; Niznik, H. B.; Civelli, O.
Nature 1991, 350, 610. (d) Ludden, H.; Pritchett, D. B.; Kohler,
M.; Killisch, I.; Keinanen, K.; Monyer, H.; Sprengel, R.; Seeburg,
P. H. Nature 1990, 346, 648.
temperature under N
stirred at room temperature. By the end (monitored by 19
F
NMR), the system was diluted with water, and extracted with
CH
(MgSO
was purified by column chromatography (hexane) affording 4a
(268 mg, yield 79%); white solid; mp 102–103 °C. H NMR (400
MHz, CDCl
NMR (376 MHz, CDCl
CDCl ): δ = 171.35 (s), 157.56 (q, J = 36.5 Hz), 131.70 (s), 129.09
Cl
(3 × 5 mL). The combined organic extracts were dried
) and concentrated under reduced pressure. The residue
2
2
4
1
(4) (a) Rowley, M.; Broughton, H. B.; Collins, I.; Baker, R.; Emms, F.;
Marwood, R.; Patel, S.; Ragan, C. I. J. Med. Chem. 1996, 39, 1943.
1
9
): δ = 8.12–7.93 (m, 2 H), 7.55 (d, J = 6.1 Hz, 3 H).
F
3
13
(b) Frølund, B.; Jørgensen, A. T.; Tagmose, L.; Stensbøl, T. B.;
3
): δ = –63.67 (s, 3 F). C NMR (101 MHz,
Vestergaard, H. T.; Engblom, C.; Kristiansen, U.; Sanchez, C.;
3
Krogsgaard-Larsen, P.; Liljefors, T. J. Med. Chem. 2002, 45, 2454.
(s), 127.92 (s), 126.03 (s), 119.41 (q, J = 272.5 Hz), 49.70 (s).
+
(
c) Tomita, K.; Takahi, Y.; Ishizuka, R.; Kamamura, S.; Nakagawa,
M.; Ando, M.; Nakanishi, T.; Udaira, H. Ann. Sankyo Res. Lab.
973, 1, 25. (d) Talley, J. J. Prog. Med. Chem. 1999, 13, 201.
HRMS (EI): m/z calcd for C10
H
5
F
3
INO [M] : 338.9368; found:
338.9362. IR (KBr): ν = 2956, 1476, 1446, 1255, 1187, 1143,
–1
1
1006, 960 cm .
(
5) (a) Martins, M. A. P.; Siqueira, G. M.; Bastos, G. P.; Bonacorso, H.
G.; Zanatta, N. J. Heterocycl. Chem. 1996, 33, 1619. (b) Katritzky,
A. R.; Wang, M.; Zhang, S. M.; Voronkov, M. V. J. Org. Chem. 2001,
(14) Jiang, Q.; Wang, J.; Guo, C. Synthesis 2015, 47, 2081.
(15) Waldo, J. P.; Mehta, S.; Neuenswander, B.; Lushington, G. H.;
Larock, R. C. J. Comb. Chem. 2008, 10, 658.
66, 6787. (c) Sloop, J. C.; Bumgardner, C. L.; Loehle, W. D. J. Fluo-
rine Chem. 2002, 118, 135.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–E