D
G.-C. Yang et al.
Letter
Synlett
S
S
I
I–I
I
NH
NH
C
1
O
S
O
Ph
S
O
S
O
O
O
I2
I
Ph
S
+
R
I
Ph
S O Na
– NaI
NH
O
A
2
B
D
O
I
O
Ph
S
O
O
S
S
Ph
NaI + S + PhSO2H +
I
N
N
H
+Na O-
3
E
S
O
Ph
2
Scheme 2 Proposed mechanism
In accordance with the above experimental results and
reports in the literature,15–18 a plausible reaction pathway is
proposed, as shown in Scheme 2. Reaction of the sodium
sulfinate 2 with I2 generates iodide intermediate A, which
undergoes homolysis to give an iodide radical and the sul-
fonyl radical B. Intermediate C is formed by the reaction of
the quinoline-2-(1H)-thione 1 with diiodine. Intermediate
C reacts with the sulfonyl radical B to give the radical inter-
mediate D, which couples with an iodine radical to form in-
termediate E. Finally, the sodium sulfinate 2 reacts with E
to remove NaI and elemental sulfur, giving the required
product 3.
In conclusion, we have developed a convenient and effi-
cient strategy for the direct I2-mediated C–S bond cleav-
age/sulfonylation of quinoline-2-(1H)-thiones using sodi-
um sulfinates as sulfonating reagents. A wide range of quin-
oline-2-(1H)-thiones and sodium arenesulfinates reacted
smoothly under the optimized conditions. This method
provides a novel alternative for the synthesis of quinoline
sulfones.19
(2) Michael, J. P. Nat. Prod. Rep. 2008, 25, 166.
(3) (a) Shang, X.-F.; Morris-Natschke, S. L.; Liu, Y.-Q.; Guo, X.; Xu,
X.-S.; Goto, M.; Li, J.-C.; Yang, G.-Z.; Lee, K.-H. Med. Res. Rev.
2018, 38, 775. (b) Puri, S. C.; Verma, V.; Amna, T.; Qazi, G. N.;
Spiteller, M. J. Nat. Prod. 2005, 68, 1717. (c) Tabassum, S.;
Kumara, T. H. S.; Jasinski, J. P.; Millikan, S. P.; Yathirajan, H. S.;
Ganapathy, P. S. S.; Sowmya, H. B. V.; More, S. S.; Nagendrappa,
G.; Kaur, M.; Josea, G. J. Mol. Struct. 2014, 1070, 10.
(4) Marson, A.; Ernsting, J. E.; Lutz, M.; Spek, A. L.; van Leeuwen, P.
W. N. M.; Kamer, P. C. J. Dalton Trans. 2009, 621.
(5) (a) Gorka, A. P.; de Dios, A.; Roepe, P. D. J. Med. Chem. 2013, 56,
5231. (b) Rouffet, M.; de Oliveira, C. A. F.; Udi, Y.; Agrawal, A.;
Sagi, I.; McCammon, J. A.; Cohen, S. M. J. Am. Chem. Soc. 2010,
132, 8232. (c) Bhalla, V.; Vij, V.; Kumar, M.; Sharma, P. R.; Kaur,
T. Org. Lett. 2012, 14, 1012. (d) Kim, J. I.; Shin, I.-S.; Kim, H.; Lee,
J.-K. J. Am. Chem. Soc. 2005, 127, 1614. (e) Xu, H.; Chen, R.; Sun,
Q.; Lai, W.; Su, Q.; Huang, W.; Liu, X. Chem. Soc. Rev. 2014, 43,
3259. (f) Velusamy, M.; Chen, C.-H.; Wen, Y. S.; Lin, J. T.; Lin, C.-
C.; Lai, C.-H.; Chou, P.-T. Organometallics 2010, 29, 3912.
(g) Olah, G. A.; Mathew, T.; Prakash, G. K. S. Chem. Commun.
2001, 1696.
(6) Deeming, A. S.; Russell, C. J.; Willis, M. C. Angew. Chem. Int. Ed.
2016, 55, 747.
(7) (a) El-Awa, A.; Noshi, M. N.; du Jourdin, X. M.; Fuchs, P. L. Chem.
Rev. 2009, 109, 2315. (b) Hassner, A.; Ghera, E.; Yechezkel, T.;
Kleiman, V.; Balasubramanian, T.; Ostercamp, D. Pure Appl.
Chem. 2000, 72, 1671.
(8) Jiang, N.; Zhai, X.; Li, T.; Liu, D.; Zhang, T.; Wang, B.; Gong, P.
Molecules 2012, 17, 5870.
(9) (a) Varma, R. S.; Naicker, K. P. Org. Lett. 1999, 1, 189. (b) Jana, N.
K.; Verkade, J. G. Org. Lett. 2003, 5, 3787. (c) Piscitelli, F.;
Coluccia, A.; Brancale, A.; La Regina, G.; Sansone, A.; Giordano,
C.; Balzarini, J.; Maga, G.; Zanoli, S.; Samuele, A.; Cirilli, R.; La
Torre, F.; Lavecchia, A.; Novellino, E.; Silvestri, R. J. Med. Chem.
2009, 52, 1922.
(10) (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Parisi, L. M.; Bernini,
R. J. Org. Chem. 2004, 69, 5608. (b) Bandgar, B. P.; Bettigeri, S. V.;
Phopase, J. Org. Lett. 2004, 6, 2105.
Funding Information
We are grateful for the financial support from the National Nature
Science Foundation of China (No. 21562036) and the Scientific and
Technological Innovation Engineering Program of Northwest Normal
University (NWNU-LKQN-15-1).
N
orht
w
est
N
orm
a
lU
n
i
v
ersity(N
W
N
U-L
K
Q
N-15-1)
Supporting Information
Supporting information for this article is available online at
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
(11) Aziz, J.; Messaoudi, S.; Alami, M.; Hamze, A. Org. Biomol. Chem.
2014, 12, 9743.
References and Notes
(12) (a) Reddy, A. M.; Reddy, S. P.; Sreedhar, B. Adv. Synth. Catal.
2010, 352, 1861. (b) Li, Y.; Cheng, K.; Lu, X.; Sun, J. Adv. Synth.
Catal. 2010, 352, 1876. (c) Rao, H.; Yang, L.; Shuai, Q.; Li, C.-J.
(1) Boucherle, B.; Haudecoeur, R.; Queiroz, E. F.; De Waard, M.;
Wolfender, J.-L.; Robins, R. J.; Boumendjel, A. Nat. Prod. Rep.
2016, 33, 1034.
© 2020. Thieme. All rights reserved. Synlett 2020, 31, A–E