4
Scheme 3. Proposed reaction mechanism for the
trifluoromethylthiolation of β,γ-unsaturated hydrazones.
References and notes
1. (a) Hird, M. Chem. Soc. Rev. 2007, 36, 2070; (b) Leroux, F.;
Jeschke, P.; Schlosser, M. Chem. Rev. 2005, 105, 827; (c) Ondachi,
P.; Castro, A.; Luetje, C. W.; Damaj, M. I.; Mascarella, S. W. J. Med.
Chem. 2012, 55, 6512; (d) Purser, S.; Moore, P. R.; Swallow, S.;
Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320; (e) Ni, C. F.; Hu, M.
Y.; Hu, J. B. Chem. Rev. 2015, 115, 765; (f) Alonso, C.; Marigorta,
E. M.; Palacios, F. Chem. Rev. 2015, 115, 1847; (g) Shen, C.; Xu, J.;
Ying, B. B.; Zhang, P. F. ChemCatChem. 2016, 8, 3560; (h) Xu, J.;
Qiao, L.; Shen, J. B.; Chai, K. J.; Shen, C.; Zhang, P. F. Org. Lett.
2017, 19, 5661. (i) Wang, Q.; Qu, Y.; Tian, H.; Liu, Y. X.; Song, H.
J.; Wang, Q. M. Chem. Eur. J. 2019, 25, 1; (j) Zhang, B.; Fraser, B.
H.; Klenner, M. A.; Chen, Z.; Liang, S. H.; Massi, M.; Robinson, A.
J.; Pascali, G. Chem. Eur. J. 2019, 25, 7613. (k) Wang, X. S.;
Truesdale, L.; Yu, J. Q. J. Am. Chem. Soc. 2010, 132, 3648; (l) Yang,
Z. J.; Liu, C. Z.; Hu, B. L.; Deng, C. L.; Zhang, X. G. Chem.
Commun. 2014, 50, 14554.
Ph
Ph
N
N
I
SO2CF3
N
N
CF3SO2Na
(eq 4)
DME, 15 min, r.t
6
4a,
NR
Ph
N
Ph
TEMPO
NH
SO2CF3
N
N
CF3SO2Na, I2
(eq 5)
DME, 15 min, r.t
1a
Ph
NH
4a,
5% yield
Ph
N
SO2CF3
N
BHT
N
CF3SO2Na, I2
(eq 6)
DME, 15 min, r.t
2. (a) Zhu, S. Q.; Xu, X. H.; Qing, F. L. Eur. J. Org. Chem. 2014,
4453; (b) Bootwicha, T.; Liu, X. Q.; Pluta, R.; Atodiresei, L.;
Rueping, M. Angew. Chem. Int. Ed. 2013, 52, 12856; (c) Zhai, L.; Li,
Y.; Yin, J.; Jin, K.; Zhang, R.; Fu, X.; Duan, C., Tetrahedron. 2013,
69, 10262. (d) Xu, X. H.; Matsuzaki, K.; Shibata, N.; Chem. Rev.
2015, 115, 731; (e) Rouxel, C.; Mongin, O.; Droumaguet, C. L.;
Magnier, E.; Blanchard-Desce, M. Chem. Eur. J. 2012, 18, 12487;
3. (a) Liao, J. H.; Guo, W.; Zhang, Z. M.; Tang, X. D.; Wu, W. Q.;
Jiang, H. F. J. Org. Chem. 2016, 81, 1304; (b) Xing, B.; Ni, C. F.;
Hu, J. B.; Chin. J. Chem. 2018, 36, 206; (c) Hansch, C.; Leo, A.;
Taft, R. W. Chem. Rev. 1991, 91, 165; (d) Huang, P.; Ramphal, J.;
Wei, J.; Liang, C. X.; Jallal, B.; McMahon, G.; Tang, C. Bioorg.
Med. Chem. 2003, 11, 1835; (e) Terrier, F.; Magnier, E.; Kizilian, E.;
Wakselman, C.; Buncel, E. J. Am. Chem. Soc. 2005, 127, 5563; (f)
Yanai, H.; Yoshino, T.; Fujita, M.; Fukaya, H.; Kotani, A.; Kusu, F.;
Taguchi, T. Angew. Chem. Int. Ed. 2013, 52, 1560;
1a
4a,
62% yield
Scheme
4.
Control
experiments
for
the
trifluoromethanesulfonylation of 1a with CF3SO2Na.
Ph
Ph
Ph
NH
NH
N
N
NH
I
I2
N
CF3SO2Na
I
SO2CF3
or CF3SO2I
1a
VIII
IX
I
2 + CF3SO2Na
Ph
Ph
NH
N
N
SO2CF3
N
SO2CF3
X
4a
4. (a) Acker, T. M.; Khatri, A.; Vance, K. M.; Slabber, C.; Bacsa, J.;
Snyder, J. P.; Traynelis, S. F.; Liotta, D. C. J. Med. Chem. 2013, 56,
6434; (b) Acharya, B. N.; Saraswat, D.; Tiwari, M.; Shrivastava, A.
K.; Ghorpade, R.; Bapna, S.; Kaushik, M. P. Eur. J. Med. Chem.
2010, 45, 430; (c) Dardic, D.; Lauro, G.; Bifulco, G.; Laboudie, P.;
Sakhaii, P.; Bauer, A.; Vilcinskas, A.; Hammann, P. E.; Plaza, A.;
Svetamycins, M. P.; J. Org. Chem. 2017, 82, 6032; (d) Kashiwa, M.;
Kuwata, Y.; Sonoda, M.; Tanimori, S. Tetrahedron. 2016, 72, 304;
(e) Padmavathi, V.; Thriveni, P.; Sudhakar Reddy, G.; Deepti, D.
Eur. J. Med. Chem. 2008, 43, 917; (f) Silver, K. S.; Soderlund, D. M.
Pestic. Biochem. Phys. 2005, 81, 136; (g) Huang, Y. Y.; Yang, X.;
Chen, Z.; Verpoort, F.; Shibata, N. Chem. Eur. J. 2015, 21, 12487; (h)
Wu, P.; Hilgraf, R.; Fokin, V. V. Adv. Synth. Catal. 2006, 348, 1079.
5. (a) Wang, L. J.; Ren, P. X.; Qi, L.; Chen, M. M.; Lu, Y. L.; Zhao,
J. Y.; Liu, R.; Chen, J. M.; Li, W. Org. Lett. 2018, 20, 4411; (b)
Chen, M.; Wang, L. J.; Ren, P. X.; Hou, X. Y.; Fang, Z.; Han, M. N.;
Li, W. Org. Lett. 2018, 20, 510.
Scheme 5. Proposed reaction mechanism for the
trifluoromethanesulfonylation of β,γ-unsaturated hydrazones.
Although the precise mechanism of the reaction is unclear at
present, a plausible reaction mechanism is depicted in Scheme 5
based on these observations and previous reports of the iodine-
mediated trifluoromethanesulfonylation of styrenes.12 First,
CF3SO2Na reacts with I2 to form CF3SO2I or I2 which
electrophilically adds to the double bond of 1a to give the three-
membered iodonium ion intermediate VIII. Subsequently,
CF3SO2Na attacks VIII in an anti-Markovnikov manner to give
intermediate IX. Finally, the elimination of HI takes place to
afford CF3SO2-substituted intermediate X, which undergoes
intramolecular ring closure and proton transfer to obtain the final
product 4a.
6. (a) Dong, K. Y.; Qin, H. T.; Liu, F.; Zhu, C.; Eur. J. Org. Chem.
2015, 1419; (b) Duan, X. Y.; Yang, X. L.; Jia, P. P.; Zhang, M.; Han,
B. Org. Lett. 2015, 17, 6022; (c) Liu, R. H.; Wang, Z. Q.; Wei, B. Y.;
Zhang, J. W.; Zhou, B.; Han, B. Org. Lett. 2018, 20, 4183; (d)
Punner, F.; Sohtome, Y.; Sodeoka, M. Chem. Commun. 2016, 52,
14093; (e) Yu, J. M.; Cai, C. Org. Biomol. Chem. 2018, 16, 490.
7. (a) Hu, X. Q.; Feng, G.; Chen, J. R.; Yan, D. M.; Zhao, Q. Q.; Wei,
Q.; Xiao, W. J. Org. Biomol. Chem. 2015, 13, 3457; (b) Hu, X. Q.;
Qi, X.; Chen, J. R.; Zhao, Q. Q.; Wei, Q.; Lan, Y; Xiao, W. J. Nat.
Commun. 2016, 7, 11188; (c) Hu, X. Q.; Chen, J. R.; Wei, Q.; Liu, F.
L.; Deng, Q. H. Angew. Chem. Int. Ed. 2014, 53, 12163; (d) Yang, M.
N.; Yan, D. M.; Zhao, Q. Q.; Chen, J. R.; Xiao, W. J. Org. Lett. 2017,
19, 5208; (e) Zhao, Q. Q.; Hu, X. Q.; Yang, M. N.; Chen, J. R.; Xiao,
W. J. Chem. Commun. 2016, 52, 12749.
In summary, straightforward methods for preparing various
CF3S/CF3SO2-functionalized dihydropyrazole derivatives via the
reaction of AgSCF3/CF3SO2Na with β,γ-unsaturated hydrazones
were developed. Mechanistic studies showed that different
reaction pathways were involved for the trifluoromethylthiolation
and trifluoromethanesulfonylation. Further studies on the
application of AgSCF3/CF3SO2Na as CF3S/CF3SO2 sources are
ongoing in our laboratory.
Acknowledgment
We thank the National Natural Science Foundation of China (Nos.
21991123, 21677094) for financial support.
8. Wei, Q.; Chen, J. R.; Hu, X. Q.; Yang, X. C.; Lu, B.; Xiao, W. J.
Org. Lett. 2015, 17, 4464.
Supplementary data
9. (a) Ruppert, I.; Schlich, K.; Volbach, W., Tetrahedron Lett. 1984,
25, 2195; (b) Chang, B.; Su, Y.; Huang, D.; Wang, K. H.; Zhang,
W.; Shi, Y.; Zhang, X.; Hu, Y. J. Org. Chem. 2018, 83, 4365.
10. Guo, Y.-Q.; Zhao, M.-N.; Ren, Z.-H.; Guan, Z.-H. Org. Lett.
2018, 20, 3337.
Supplementary data (experimental procedures and full
characterization for all compounds) associated with this article can
be found, in the online version, at xxx.
11. The supplementary crystallographic data can be obtained free of
charge from The Cambridge Cryatallographic Data Center via