Organic Letters
Letter
Accession Codes
On the basis of the above experiments and the previous
literature reports,12,18 a plausible reaction mechanism for this
one-pot synthesis is illustrated in Scheme 8. Reaction pathway
tallographic data for this paper. These data can be obtained
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Scheme 8. Plausible Mechanism for Thiochromenone 3
AUTHOR INFORMATION
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Corresponding Author
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank IIT Madras for financial support (IRDA project no.:
CHY/17-18/RFIR/GSEK). S.S. thanks IIT Madras for a
senior research fellowship.
1 is initiated by 2′-iodochalcone 1 with xanthate in the
presence of copper acetate, and it expels the desired product
thiochromanone 2 along with Cu-catalyst and potassium
iodide (KI) as byproduct.12c Then, the byproduct KI is
converted to HI on reacting with H2SO4, and further, the HI is
oxidized to I2 in situ in DMSO solvent.
The reaction pathway 2 is initiated by in situ generated I2
with enol tautomer 6 of thiochromanone 2 to yield 3-
iodothioflavanone intermediate 7 (Scheme 8). The inter-
mediate 7 produces desired product 3 by eliminating HI. The
elimination product HI is further oxidized to iodine by DMSO,
which is already presented in the reaction medium as solvent.
Also, the plausible mechanistic pathway for the formation of 8a
from 3a through 5a is described.17 However, further
mechanistic study and applications of this one-pot reaction
are currently underway in our laboratory.
In summary, we have disclosed an efficient Cu-catalyzed
one-pot strategy for the synthesis of 2-arylthiochromenones
from easily accessible 2′-halochalcones using xanthate as sulfur
surrogate through 2-arylthiochromanones. To the best of our
knowledge, this is the first example that takes advantage of
oxidation of cross-coupled product 2-arylthiochromanone to 2-
arylthiochromenone in the same pot using in situ generated
halogen I2, which is generated from byproduct KI of upstream
cross-coupling reaction. In this reaction, the DMSO solvent
oxidizes the byproduct KI into I2, which avoids the use of any
external oxidant. Importantly, the use of byproduct as useful
reagent improves the atom-economy and obviated external
iodine. Further, the one-pot methodology is extended for the
synthesis of 3,3′-methylenebisthiochromenone using dimethyl
sulfoxide as methylene source and Cu catalyst, which is
expelled from upstream reaction.
REFERENCES
■
(1) (a) Sheldon, R. A. Pure Appl. Chem. 2000, 72, 1233−1246.
(b) Anastas, P.; Eghbali, N. Chem. Soc. Rev. 2010, 39, 301−312.
(c) He, M.; Sun, Y.; Han, B. Angew. Chem., Int. Ed. 2013, 52, 9620−
9633.
(2) (a) Trost, B. M. Acc. Chem. Res. 2002, 35, 695−705.
(b) Kobayashi, S.; Manabe, K. Acc. Chem. Res. 2002, 35, 209−217.
(c) Miao, W.; Chan, T. H. Acc. Chem. Res. 2006, 39, 897−908.
(3) (a) Ishikawa, H.; Suzuki, T.; Hayashi, Y. Angew. Chem., Int. Ed.
2009, 48, 1304−1307. (b) Guha, S.; Rajeshkumar, V.; Kotha, S. S.;
Sekar, G. Org. Lett. 2015, 17, 406−409. (c) Hayashi, Y. Chem. Sci.
2016, 7, 866−880.
(4) (a) Cao, J.-J.; Zhou, F.; Zhou, J. Angew. Chem., Int. Ed. 2010, 49,
4976−4980. (b) Chen, L.; Du, Y.; Zeng, X. P.; Shi, T. D.; Zhou, F.;
Zhou, J. Org. Lett. 2015, 17, 1557−1560. (c) Guo, Y.; Meng, C.; Liu,
X.; Li, C.; Xia, A.; Xu, Z.; Xu, D. Org. Lett. 2018, 20, 913−916.
(5) (a) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev.
(Washington, DC, U. S.) 2008, 108, 3054−3131. (b) Beletskaya, I.
P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596−1636. (c) Brown, J.
M. Angew. Chem., Int. Ed. 2015, 54, 5003.
(6) (a) Nussbaumer, P.; Lehr, P.; Billich, A. J. Med. Chem. 2002, 45,
4310−4320. (b) Horvath, A.; Nussbaumer, P.; Wolff, B.; Billich, A. J.
Med. Chem. 2004, 47, 4268−4276. (c) Kataoka, T.; Watanabe, S. i.;
Mori, E.; Kadomoto, R.; Tanimura, S.; Kohno, M. Bioorg. Med. Chem.
2004, 12, 2397−2407.
(7) Kitani, S.; Sugawara, K.; Tsutsumi, K.; Morimoto, T.; Kakiuchi,
K. Chem. Commun. 2008, 2103−2105.
(8) Zhang, F. L.; Chen, Z. B.; Liu, K.; Yuan, Q.; Jiang, Q.; Zhu, Y. M.
Synlett 2018, 29, 621−626.
(9) (a) Yang, X.; Li, S.; Liu, H.; Jiang, Y.; Fu, H. RSC Adv. 2012, 2,
6549−6554. (b) Gu, Z. Y.; Cao, J. J.; Wang, S. Y.; Ji, S. J. Chem. Sci.
2016, 7, 4067−4072.
(10) (a) Inami, T.; Baba, Y.; Kurahashi, T.; Matsubara, S. Org. Lett.
2011, 13, 1912−1915. (b) Inami, T.; Kurahashi, T.; Matsubara, S.
Org. Lett. 2014, 16, 5660−5662.
ASSOCIATED CONTENT
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S
* Supporting Information
(11) (a) Shen, C.; Spannenberg, A.; Wu, X. F. Angew. Chem., Int. Ed.
2016, 55, 5067−5070. (b) Zhang, F. L.; Chen, Z. B.; Liu, K.; Yuan,
Q.; Jiang, Q.; Zhu, Y.-M. Synlett 2018, 29, 621−626.
The Supporting Information is available free of charge on the
(12) (a) Prasad, D. J. C.; Sekar, G. Org. Lett. 2011, 13, 1008−1011.
(b) Prasad, D. J. C.; Sekar, G. Org. Biomol. Chem. 2013, 11, 1659−
1665. (c) Sangeetha, S.; Muthupandi, P.; Sekar, G. Org. Lett. 2015, 17,
6006−6009. (d) Muthupandi, P.; Sundaravelu, N.; Sekar, G. J. Org.
Chem. 2017, 82, 1936−1942. (e) Sangeetha, S.; Sekar, G. Org. Lett.
2017, 19, 1670−1673.
Details of the synthetic experimental procedure, and
1HNMR and 13CNMR spectra and characterization data
of all the compounds (PDF)
D
Org. Lett. XXXX, XXX, XXX−XXX