Self-Immolative Reduction of Trifluoromethyl Sulfoxides
acid,[25] but quite poorly characterized by 19F NMR spec-
troscopy (δ = –77.6 ppm)[26] as a thermally unstable com-
pound and better used as an in situ formed reagent.[27] The
poor thermal stability and presumed rapid decomposition
giving back trifluoromethanesulfonic acid precluded any
detection in our NMR spectroscopy study. Efforts devoted
to demonstrate the transient presence of this peroxide by
the introduction in the reaction medium of an oxidizable
species (p-bromotrifluoromethylsulfane or an alkene) failed
to give any detectable corresponding oxidized compound.
3Ј-Me), 20.4 (s, 1 C, 2-Me) ppm. HRMS: calcd. for C16H13F6S2
383.0363; found 383.0345 (δ = –4.7 ppm).
[2-Methyl-4-(trifluoromethylsulfanyl)phenyl]-(m-tolyl)-S-trifluoro-
methylsulfonium Trifluoromethanesulfonate (5c): Yield: 560 mg
(81%). Major isomer 85% of the mixture. 1H NMR (300 MHz,
CDCl3): δ = 8.11 (br. s, 1 H, 1-H), 8.03 (m, 1 H, 5-H), 7.96 (d, J
= 8.7 Hz, 1 H, 5Ј-H), 7.85 (dd, J = 8.7, 2.2 Hz, 1 H, 4Ј-H), 7.78
(br. s, 1 H, 2Ј-H), 7.68–7.76 (m, 2 H, 3-H and 4-H), 2.87 (s, 3 H,
Me), 2.52 (s, 3 H, Me) ppm. 19F NMR (188 MHz, CDCl3): δ =
–
–40.4 (s, 3 F, SCF3), –47.9 (s, 3 F, S+CF3), –78.5 (s, 3 F, CF3SO3 )
ppm. 13C NMR (50 MHz, CDCl3): δ = 145.3 (s, 1 C, 2Ј-C), 143.9
(s, 1 C, 3-C), 138.4 (q, J = 1.8 Hz, 1 C, 3Ј-C), 138.3 (s, 1 C, 4-C),
136.0 (q, J = 2.2 Hz, 1 C, 4Ј-C), 134.6 (q, J = 1.1 Hz, 1 C, 5Ј-C),
134.0 (q, J = 1.0 Hz, 1 C, 2-C), 132.4 (s, 1 C, 5-C), 132.0 (s, 1 C,
6Ј-C), 130.1 (q, J = 1.3 Hz, 1 C, 6-C), 128.8 (q, J = 309.3 Hz, 1 C,
SCF3), 123.5 (q, J = 328.6 Hz, 1 C, S+CF3), 120.8 (q, J = 320.4 Hz,
Conclusion
In summary, whatever the nucleophilic species involved,
only attack at oxygen (path b) may result in the formation
of sulfane 6. Although seemingly less favorable, this attack
may be successful because reactions at the other possible
centers are either degenerate or reversible. In both cases, an
unstable intermediate will be formed, which should either
have been detected by NMR spectroscopy (TfOOTf), at le-
ast by its decomposition products, or have escaped any
attempts to detect it (TfOO–, TfOOH) because of its very
fast decomposition into species already present in the reac-
tion medium (TfO–, TfOH). In fact, our results suggests
that reduction of sulfoxide 1c to sulfane 6 under our condi-
tions follows partially the usual reduction route of sulfox-
ides,[28,29] with conventional prior activation, in the present
case with triflic anhydride, followed by a less conventional
reaction with sulfoxide 1c itself (Scheme 2, path b).
–
1 C, CF3SO3 ), 119.3 (s, 1 C, 1Ј-C), 115.4 (s, 1 C, 1-C), 21.5 (s, 1
C, 3-Me), 20.5 (q, J = 0.8 Hz, 1 C, 2Ј-Me) ppm. HRMS: calcd. for
C16H13F6S2 383.0363; found 383.0343 (δ = –5.2 ppm).
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H, 19F, and 13C spectra of compounds 5a–e with
full data and NMR assignments. Enlarged version of Figure 1.
Acknowledgments
Y.M. thanks GlaxoSmithKline and Centre National de la Recher-
che Scientifique (CNRS) for financial support (BDI grant). We
gratefully acknowledge Stephane Germain for technical assistance
and François Metz (Rhodia Company) for the generous gift of flu-
orinated reagents.
Experimental Section
[1] I. L. Baraznenok, V. G. Nenajdenko, E. S. Balenkova, Tetrahe-
dron 2000, 56, 3077–3119 and references cited therein.
[2] For very recent work in this area, see: a) T. Kobatake, S. Yosh-
ida, H. Yorimitsu, K. Oshima, Angew. Chem. Int. Ed. 2010, 49,
2340–2343; b) Z. Moussa, S. A. Ahmed, A. S. ElDouhaibi,
S. Y. Al-Raqa, Tetrahedron Lett. 2010, 51, 1826–1831.
[3] a) B. A. Garcia, J. L. Poole, D. Y. Gin, J. Am. Chem. Soc. 1997,
119, 7597–7598; b) D. Crich, M. Smith, Org. Lett. 2000, 2,
4067–4069; c) D. Crich, M. Smith, J. Am. Chem. Soc. 2001,
123, 9015–9020; d) D. Crich, M. Smith, J. Am. Chem. Soc.
2002, 124, 8867–8869; e) J. D. C. Code, E. J. N. Remy,
R. E. J. N. Litjens, R. den Heeten, H. S. Overkleeft, J. H.
van Boom, G. A. van der Marel, Org. Lett. 2003, 5, 1519–1522;
f) M. A. Fascione, S. J. Adshead, S. A. Stalford, C. A. Kilner,
A. G. Leach, W. B. Turnbull, Chem. Commun. 2009, 5841–
5843.
[4] a) T. Umemoto, S. Ishihara, J. Am. Chem. Soc. 1993, 115,
2156–2164; b) R. L. Kirchmeyer, J.-J. Yang, J. M. Shreeve, J.
Org. Chem. 1998, 63, 2656–2660; c) E. Magnier, J.-C. Blazejew-
ski, M. Tordeux, C. Wakselman, Angew. Chem. Int. Ed. 2006,
45, 1279–1282; d) Y. Macé, B. Raymondeau, C. Pradet, J.-C.
Blazejewski, E. Magnier, Eur. J. Org. Chem. 2009, 1390–1397;
e) C.-P. Zhang, H.-P. Cao, Z.-L. Wang, C.-T. Zhang, Q.-Y.
Chen, J.-C. Xiao, Synlett 2010, 1089–1092.
Typical Procedure for the Preparation of Sulfonium Salts from Sulf-
oxides and Triflic Anhydride: A solution of trifluoromethyl sulfox-
ide 1 (2.58 mmol) in trifluoromethanesulfonic anhydride (2.1 mL,
12.8 mmol, 5 equiv.) was stirred under an atmosphere of argon for
2 to 9 d until total consumption of sulfoxide 1 (followed by 19F
NMR spectroscopic analysis of aliquots). The reaction mixture was
poured onto iced water, and the aqueous layer was extracted with
CH2Cl2 (3ϫ30 mL). Extracts were washed with brine, dried with
MgSO4, and concentrated under reduced pressure. Sulfonium 5 was
isolated by flash chromatography of the residue (SiO2; CH2Cl2/
MeOH, 90:10).
[3-Methyl-4-(trifluoromethylsulfanyl)phenyl]-(o-tolyl)-S-trifluorometh-
ylsulfonium Trifluoromethanesulfonate (5b): Yield: 330 mg (48%).
1H NMR (300 MHz, CDCl3): δ = 8.27 (d, J = 2.1 Hz, 1 H, 2Ј-H),
8.07 and 8.06 (AB system: dd, J = 8.7, 2.1, 1 H, 6Ј-H and d, J =
8.7 Hz, 1 H, 5Ј-H), 7.93 (br. d, J = 8.2 Hz, 1 H, 6-H), 7.80 (td, J
= 7.6, 1.4 Hz, 1 H, 4-H), 7.69 (td, J = 7.9, 1.8 Hz, 1 H, 5-H), 7.62
(dd, J = 7.8, 1.9 Hz, 1 H, 3-H), 2.83 (s, 3 H, 2-Me), 2.64 (s, 3 H,
3Ј-Me) ppm. 19F NMR (188 MHz, CDCl3): δ = –40.8 (s, 3 F,
SCF3), –48.7 (s, 3 F, S+CF3), –79.0 (s, 3 F, CF3SO3 ) ppm. 13C
–
[5] a) Y. Macé, C. Urban, C. Pradet, J. Marrot, J.-C. Blazejewski,
E. Magnier, Eur. J. Org. Chem. 2009, 3150–3153; b) Y. Macé,
C. Urban, C. Pradet, J.-C. Blazejewski, E. Magnier, Eur. J. Org.
Chem. 2009, 5313–5316.
[6] J. B. Hendrickson, S. M. Schwartzman, Tetrahedron Lett. 1975,
16, 273–276.
NMR (75 MHz, CDCl3): δ = 147.3 (q, J = 0.9 Hz, 1 C, 3Ј-C), 145.2
(s, 1 C, 2-C), 138.5 (q, J = 1.1 Hz, 1 C, 5Ј-C), 137.3 (s, 1 C, 4-C),
135.6 (q, J = 2.1 Hz, 1 C, 4Ј-C), 135.0 (q, J = 1.2 Hz, 1 C, 2Ј-C),
134.2 (s, 1 C, 3-C), 131.4 (q, J = 1.5 Hz, 1 C, 6-C), 130.3 (s, 1 C,
5-C), 129.9 (q, J = 309.5 Hz, 1 C, SCF3), 129.9 (q, J = 1.5 Hz, 1 C,
6Ј-C), 123.5 (q, J = 328.8 Hz, 1 C, S+CF3), 120.8 (q, J = 320.4 Hz, 1
[7] a) K. S. Feldman, Tetrahedron 2006, 62, 5003–5034; b) S. Akai,
–
C, CF3SO3 ), 119.0 (s, 1 C, 1-C), 115.8 (s, 1 C, 1Ј-C), 21.4 (s, 1 C,
Y. Kita, Top. Curr. Chem. 2007, 274, 35–76.
Eur. J. Org. Chem. 2010, 5772–5776
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5775