Organic Letters
Letter
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silver(I) acetylide (R−CC−Ag) might be the key intermediate
in hydrotrifluoromethylthiolation reactions (see the SI).13
Based on the above results and previous reports,4b,9e,13b we
proposed a plausible mechanism for the anti-Markovnikov-
selective hydrotrifluoromethylthiolation reaction (Scheme 6).
Initially, AgSCF3 is oxidized by K2S2O8 to furnish the ·SCF3
radical through single electron transfer.3e,4c Regioselective
addition of ·SCF3 to the C−C triple bond of silver acetylide
10,13 which is generated in situ from 1a and Ag(I), affords
relatively stable vinyl radical intermediate A. Subsequently, the
hydrogen abstraction from DMF by vinyl radical A gives vinyl-
silver intermediate B.12c,14 Finally, the protonolysis of the alkenyl
C−Ag bond of B with a trace amount of H2O in the DMF
produces the desired product 2a.15
Unfortunately, the exact mechanism of the Markovnikov-
selective hydrotrifluoromethylthiolation of alkoxy-substituted
phenylacetylenes remains unclear, except that we can only
postulate the reaction proceeds through a radical process.
In summary, we have developed a new and efficient method for
the synthesis of vinyl trifluoromethyl thioethers through
hydrotrifluoromethylthiolation of terminal alkynes in the
presence of AgSCF3 and K2S2O8. The Markovnikov and anti-
Markovnikov hydrotrifluoromethylthiolated products are ob-
tained in moderate to good yields by changing the reaction
conditions. Furthermore, the anti-Markovnikov-selective
hydrotrifluoromethylthiolation displays a broad substrate scope
and functional group compatibility. A set of deuterated
experiments provide strong evidence that the two hydrogens in
the anti-Markovnikov product originated from water and DMF,
respectively. Preliminary mechanistic analyses suggest both
Markovnikov and anti-Markovnikov reactions proceed via a
radical process. We anticipate that this strategy may provide an
alternative approach to prepare vinyl trifluoromethyl thioethers
starting from readily available terminal alkynes.
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ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
́
(10) Ferry, A.; Billard, T.; Langlois, B. R.; Bacque, E. Angew. Chem., Int.
Experimental details and spectral data for all products
Ed. 2009, 48, 8551.
(11) The reported 13C NMR spectroscopy chemical shift of C-1 of E-
2a is 142.2 ppm; see ref 7d.
(12) (a) Szostak, M.; Spain, M.; Sautier, B.; Procter, D. J. Org. Lett.
2014, 16, 5694. (b) Lv, L.; Qi, L.; Guo, Q.; Shen, B.; Li, Z. J. Org. Chem.
2015, 80, 12562. (c) Zhou, M.-B.; Song, R.-J.; Ouyang, X.-H.; Liu, Y.;
Wei, W.-T.; Deng, G.-B.; Li, J.-H. Chem. Sci. 2013, 4, 2690. (d) Zhou, D.;
Li, Z.-H.; Li, J.; Li, S.-H.; Wang, M.-W.; Luo, X.-L.; Ding, G.-L.; Sheng,
R.-L.; Fu, M.-J.; Tang, S. Eur. J. Org. Chem. 2015, 1606. (e) Nakao, Y.;
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(13) (a) Fang, G.; Bi, X. Chem. Soc. Rev. 2015, 44, 8124. (b) Weibel, J.-
M.; Blanc, A.; Pale, P. Chem. Rev. 2008, 108, 3149.
(14) The abstraction of hydrogen from DMF can occur at two sites;
see: (a) Xu, X.; Zhang, M.; Jiang, H.; Zheng, J.; Li, Y. Org. Lett. 2014, 16,
3540. (b) He, T.; Li, H.; Li, P.; Wang, L. Chem. Commun. 2011, 47, 8946.
(c) Wang, J.; Li, J.; Zhu, Q. J. Org. Chem. 2016, 81, 3017.
AUTHOR INFORMATION
Corresponding Author
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We are grateful for financial support from the National Natural
Science Foundation of China (Nos. 21472043 and 21272070).
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(15) (a) Shen, T.; Wang, T.; Qin, C.; Jiao, N. Angew. Chem., Int. Ed.
2013, 52, 6677. (b) Li, Y.; Liu, X.; Ma, D.; Liu, B.; Jiang, H. Adv. Synth.
Catal. 2012, 354, 2683.
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