Organic Letters
Letter
a
zenethiols with both electron-donating and electron-with-
drawing groups are tolerated, affording the desired products in
moderate to high yields in most cases.
Table 2. Synthesis of 3-Methylthiochroman-4-ones
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
Experimental procedures and full characterization of new
AUTHOR INFORMATION
Corresponding Authors
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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Support by the Loker Hydrocarbon Research Institute is
gratefully acknowledged. H.V. thanks Colorado College for
granting pretenure sabbatical leave.
REFERENCES
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(1) Bondock, S.; Metwally, M. A. J. Sulfur Chem. 2008, 29, 623.
(2) Dalla Via, L.; Marciani Magno, S.; Gia, O.; Marini, A. M.; Da
Settimo, F.; Salerno, S.; La Motta, C.; Simorini, F.; Taliani, S.; Lavecchia,
A.; Di Giovanni, C.; Brancato, G.; Barone, V.; Novellino, E. J. Med.
Chem. 2009, 52, 5429.
(3) Fang, B.; Ma, Z.; Yang, G.; Wang, G.; Tian, W.; Li, L. Int. J. Chem.
2010, 2, 143.
(4) Song, Y.-L.; Wu, F.; Zhang, C.-C.; Liang, G.-C.; Zhou, G.; Yu, J.-J.
Bioorg. Med. Chem. Lett. 2015, 25, 259.
(5) Geng, H.-J.; Xing, Z.-B.; Luo, W.; Cong, L.; Li, x-U.; Guo, C. Lett.
Drug Des. Discovery 2012, 9, 797.
(6) Xiao, W.-J.; Alper, H. J. Org. Chem. 1999, 64, 9646.
(7) Zhao, J.; Li, C.; Suo, H.; Wang, Y.; Yang, C.; Ma, Z.; Liu, Y. Global.
Adv. Res. J. Med. Med. Sci. 2014, 3, 240−250.
a
Reactions were carried out with methacrylic acid 2a (1.18 mmol) and
thiophenol (1.18 mmol) in CH2Cl2 (0.5 mL) and CF3SO3H (1.5 mL).
(8) Holshouser, M. H.; Loeffler, L. J.; Hall, I. H. J. Med. Chem. 1981, 24,
853−858.
too deactivated to participate in a Friedel−Crafts acylation.
Formation of the carbenium−carboxonium dication 8 is a crucial
step, which is possible under the superacidic condition provided
by triflic acid (Scheme 2).18
(9) Li, J.-T.; Li, H.-Y.; Li, H.-Z.; Xiao, L.-W. J. Chem. Res. 2004, 6, 394.
(10) Xiao, L.-W.; Li, H.-Z. Chin. J. Org. Chem. 2006, 26, 979.
(11) Chu, S.-L.; Chang, C.-C. Huaxue Xuebao 1958, 24, 87. Chu, S.-L.;
Chang, C.-C. Chem. Abstr. 1959, 53, 39911.
(12) (a) Sen, A. B.; Arora, S.L. J. Indian Chem. Soc. 1958, 35, 197.
(b) Sen, A. B.; Kulkarni, Y.D. J. Indian Chem. Soc. 1957, 34, 687.
(13) Cui, D.-M.; Kawamura, M.; Shimada, S.; Hayashi, T.; Tanaka, M.
Tetrahedron Lett. 2003, 44, 4007.
In summary, we have developed an efficient direct route to
both 2- and 3-methylthiochroman-4-ones (3 and 6) via
superacid-catalyzed sequential alkylation/cyclic acylation. Ben-
(14) Clayton, S. E.; Gabbutt, C. D.; Hepworth, J. D.; Heron, B. M.
Tetrahedron 1993, 49, 939.
Scheme 2. Proposed Mechanism
(15) Dougherty, G.; Hammond, P. D. J. Am. Chem. Soc. 1935, 57, 117.
(16) (a) Prakash, G. K. S.; Paknia, F.; Vaghoo, H.; Rasul, G.; Mathew,
T.; Olah, G. A. J. Org. Chem. 2010, 75, 2219. (b) Prakash, G. K. S.;
Paknia, F.; Narayanan, A.; Rasul, G.; Mathew, T.; Olah, G. A. J. Fluorine
Chem. 2012, 143, 292.
(17) (a) Krystenansky, J. L.; Cotteril, I. Curr. Opin. Drug Discovery Dev.
2000, 3, 454. (b) Larhed, M.; Hallberg, A. Drug Discovery Today 2001, 6,
406. (c) Microwave Methods in Organic Synthesis; Larhead, M., Olofsoon,
K., Eds.; Springer: Berlin, 2006. (d) Dallinger, D.; Kappe, C. O. Chem.
Rev. 2007, 107, 2563. (e) Larhed, M.; Moberg, C.; Hallberg, A. Acc.
Chem. Res. 2002, 35, 717. (f) Roberts, B. A.; Strauss, C. R. Acc. Chem. Res.
2005, 38, 653. (g) Polshettiwar, V.; Varma, R. S. Acc. Chem. Res. 2008,
41, 629. (h) Microwaves in Organic Synthesis, 3rd ed.; de la Hoz, A.,
C
Org. Lett. XXXX, XXX, XXX−XXX