992
S. S. Mikhailichenko et al. / Tetrahedron Letters 51 (2010) 990–993
S
S
(CF2)4H
CF3SO3H
n-Hexane
- CF3SO3 H3N(p-Tol)
2d
(CF2)4H
NH2(p-Tol)
H
4
30%
CF3SO3
3d
Scheme 5. Ref. 25.
13. Bouillon, J. P.; Shermolovich, Y. G.; Portella, C. Tetrahedron Lett. 2001, 42, 2133–
2135.
14. Pfund, E.; Lequeux, T.; Vazeux, M.; Masson, S. Tetrahedron Lett. 2002, 43, 2033–
2036.
15. For a recent book see: Microwaves in Organic Synthesis; Loupy, A., Ed.; Whiley-
VCH Gmbh: KGaA, Weinhein, 2006.
Compared to its congeners, the behavior of compound 2d bear-
ing a longer perfluoroalkyl substituent was slightly different.
Under analogous conditions, 2d afforded first the corresponding
salt 3d which underwent spontaneous desamination into 2H-thio-
pyran 4 (Scheme 5).25 Influence of ammonium and octafluorobutyl
substituents (which is more electron-withdrawing than trifluoro-
methyl one) would probably facilitate deprotonation of intermedi-
ate 3d. To the best of our knowledge, compound 4 is one of the first
examples of the 6-perfluoroalkyl-2H-thiopyrans. Only one highly
fluorinated compound of this type was already described in the
literature using a complex thermal rearrangement of 2,3-diaza-
bicyclo[3.2.0]heptadiene.26
16. For recent reviews see: (a) Caddick, S.; Fitzmaurice, R. Tetrahedron 2009, 65,
3325–3355; (b) Kappe, C. O.; Dallinger, D. Mol. Div. 2009, 13, 71–193; (c) De la
Hoz, A.; Diaz-Ortiz, A.; Moreno, A. Chem. Soc. Rev. 2005, 34, 164–178.
17. Complete description of instrument and methodology was published in:
Ferguson, J. D. Mol. Div. 2003, 7, 281–286.
18. Focused microwave irradiations were carried in pressurized (0–20 bar) sealed
vials (0–20 bar, tubes of 10 mL, sealed with a septum) with a CEM Discover™
focused microwave reactor (monomode system).17 Power input (0–400 W)
was monitored by computer as infrared measurement and continuous
feedback temperature control. The experiments were performed using
stirring option whereby the contents of a vessel are stirred by means of a
rotating plate located below the floor of the microwave cavity and a Teflon-
coated magnetic stir bar in the vessel. In all experiments a target temperature
was selected together with a power. The target temperature was reached with
a ramp of 2 min and the chosen microwave power stay constant to hold the
mixture at this temperature. The time of the reaction does not include the
ramp period.
3. Conclusion
In conclusion, we have described the first microwave-assisted
hetero-Diels–Alder reactions of perfluoroalkanethioamides 1a–e
with 2,3-dimethylbutadiene affording new 3,6-dihydro-2H-thio-
pyrans 2a–e. The use of rapid and controlled microwave heating
in sealed vials allowed good conditions of work and reproducibil-
ity. We also observed that the nature of perfluoroalkyl chains
and substituents on the nitrogen atom of thioamides have a signif-
icant influence on the yields of 2. Treatment of cycloadducts 2a,c,e
with trifluoromethanesulfonic acid gave the corresponding
ammonium salts 3a,c,e in almost quantitative yields, except for
2-octafluorobutyl-substituted derivative 3d which underwent a
spontaneous desamination reaction. Investigation of the scope
and limitations of these novel hetero-Diels–Alder reactions in the
presence of various thioamides and other electron-rich 1,3-dienes
(symmetrical and unsymmetrical) is actually in course in our
laboratories.
19. For recent examples of the use of NMP under microwaves see: (a) Lamazzi, C.;
Dreau, A.; Bufferne, C.; Flouzat, C.; Patrick Carlier, P.; ter Halle, R.; Besson, T.
Tetrahedron Lett. 2009, 50, 5402–5405; (b) Pereira, M.; De, F.; Thiéry, V.;
Besson, T. Tetrahedron Lett. 2007, 48, 7657–7659.
20. Typical procedure for the preparation of cycloadduct 2a:
a mixture of
perfluorothioamide 1a (1.0 mmol) and 2,3-dimethylbutadiene (2.5 mmol) in
N-methylpyrrolidone (5 mL) in the presence of pieces of Weflon™ (Weflon™ is
Teflon™ filled with graphite) was heated 30 min at 180 °C under irradiation
(400 W) in a microwave oven. After 30 min of heating, 2,3-dimethylbutadiene
(2.5 mmol) was added to the cooled reaction mixture, then the mixture was
again heated for 30 min. This procedure was repeated three times (total
heating time: 2.5 h, 1,3-diene: 12.5 equiv). After cooling, the reaction mixture
was poured into water (50 mL) and extracted three times with
dichloromethane (3 ꢀ 30 mL). The combined organic phases were washed
with water (30 mL), dried over MgSO4, filtered, and evaporated under reduced
pressure. The residue was purified by flash column chromatography on silica
gel, eluting with a mixture (9:1) of petroleum ether and ethyl acetate affording
121 mg (yield: 43%) of cycloadduct 2a (Scheme 3, Table 2).
21. Spectral data of 4-(4,5-dimethyl-2-trifluoromethyl-3,6-dihydro-2H-thiopyran-
2-yl)morpholine (2a). Oil. Rf (petroleum ether/ethyl acetate (9:1)) = 0.37 (TLC-
development: ethanolic phosphomolybdic acid solution). 1H NMR (CDCl3, d
Acknowledgments
2
ppm): 1.71 (s, 3H, Me), 1.75 (s, 3H, Me), 2.44 (d, JH,H = 17.5 Hz, 1H, CHAHB),
2.69 (m, 2H, NCH2), 2.79 (d, 2JH,H = 16.4 Hz, 1H, SCHAHB), 2.83 (d, 2JH,H = 17.5 Hz,
The authors thank Institut Normand de Chimie Moléculaire,
Médicinale et Macromoléculaire (INC3M, FR 3038) and Ambassade
de France at Kiev (S.S.M.) for financial support.
2
1H, CHAHB), 3.13 (m, 2H, NCH2), 3.23 (d, JH,H = 16.4 Hz, 1H, SCHAHB), 3.59 (m,
4H, O(CH2)2). 19F NMR (CDCl3, d ppm): ꢁ71.3 (s, 3F, CF3). 13C NMR (CDCl3, d
ppm): 18.9 (s, CH3), 20.0 (s, CH3), 30.4 (s, CH2S), 35.2 (q, 3JC,F = 1.1 Hz, CH2), 47.2
2
(s, CH2N), 68.1 (s, CH2O), 71.0 (q, JC,F = 24.9 Hz, CCF3), 122.5 (s, Cq), 123.9 (s,
1
Cq), 126.6 (q, JC,F = 293.1 Hz, CF3). GC–MS: m/z = 281 [M+]. HRMS (ESI+): calcd
References and notes
for C12H18F3KNOS m/z 320.0698, found 320.0692.
22. Typical procedure for the preparation of ammonium salt 3a:
a mixture of
compound 2a (1.0 mmol) and trifluoromethanesulfonic acid (1.0 mmol) in n-
hexane (15 mL) was stirred for 16 h at room temperature. After completion of
the reaction, the solution was decanted and the product was dried in vacuo
affording 0.40 g (yield: 92%) of ammonium salt 3a (Scheme 4).
1. Shermolovich, Y. G.; Slyusarenko, E. I.; Markovski, L. N. Zh. Org. Khim. (Russ.)
1988, 24, 1931–1934.
2. Schuler, B.; Sundermeyer, W. Tetrahedron Lett. 1989, 30, 4111–4112.
3. Schuler, B.; Sundermeyer, W. Chem. Ber. 1990, 123, 177–184.
4. Markovski, L. N.; Slyusarenko, E. I.; Shermolovich, Y. G. Zh. Org. Khim. (Russ.)
1990, 26, 912–914.
5. Middleton, W. J. J. Org. Chem. 1965, 30, 1390–1394.
6. Schwab, M.; Sundermeyer, W. Chem. Ber. 1986, 119, 2458–2465.
7. Timoshenko, V. M.; Bouillon, J. P.; Shermolovich, Y. G.; Portella, C. Tetrahedron
Lett. 2002, 43, 5809–5812.
8. Middleton, W. J.; Howard, E. G.; Sharkey, W. H. J. Am. Chem. Soc. 1961, 83, 2589–
2590.
9. Gradel, J.; Sundermeyer, W. Chem. Ber. 1992, 125, 1889–1894.
10. Shermolovich, Yu. G.; Slyusarenko, Y. I.; Timoshenko, V. M.; Roshenko, A. B.;
Markovski, L. N. J. Fluorine Chem. 1991, 55, 329–333.
11. Portella, C.; Shermolovich, Y. G.; Tschenn, O. Bull. Soc. Chim. Fr. 1997, 134, 697–
702.
23. Spectral data of (4,5-dimethyl-2-trifluoromethyl-3,6-dihydro-2H-thiopyran-2-
yl)morpholinium trifluoromethane sulfonate (3a). Oil. 1H NMR (CDCl3, d ppm):
2
1.84 (s, 3H, Me), 1.87 (s, 3H, Me), 2.76 (d, JH,H = 14.5 Hz, 1H, CHAHB), 2.95 (d,
2
2JH,H = 15.5 Hz, 1H, SCHAHB), 3.00 (d, JH,H = 14.5 Hz, 1H, CHAHB), 3.58 (d,
2JH,H = 15.5 Hz, 1H, SCHAHB), 3.44 (m, 2H, NHCH2), 3.80 (m, 2H, NHCH2), 4.13
(m, 4H, O(CH2)2). 19F NMR (CDCl3, d ppm): ꢁ67.9 (s, 3F, CF3), ꢁ79.1 (s, 3F,
CF3SO 3ꢁ). Anal. Calcd for C13H19F6NO4S2: C, 36.19; H, 4.44; N, 3.25; S, 14.87.
Found3: C, 35.94; H, 4.65; N, 3.38; S, 17.92.
24. Markovski, L. N.; Shermolovich, Yu. G.; Slusarenko, E. I.; Timoshenko, V. M.
Japan Patent 06100555, 1994; Chem. Abst. 121: 108523.
25. Spectral data of 3,4-dimethyl-6-(1,1,2,2,3,3,4,4-octafluorobutyl)-2H-thiopyran
(4). This compound was purified by flash column chromatography on silica gel
(eluent: petroleum ether). Rf (petroleum ether) = 0.51. Oil. 1H NMR (CDCl3, d
ppm): 1.84 (s, 3H, Me), 1.92 (s, 3H, Me), 3.22 (s, 2H, SCH2), 6.08 (tt,
12. Laduron, F.; Nyns, C.; Janousek, Z.; Viehe, H. G. J. Prakt. Chem/Chem-Ztg. 1997,
339, 697–707.
3
2JH,F = 52.2 Hz, JH,F = 5.6 Hz, 1H, HCF2), 6.50 (s, 1H, CH@). 19F NMR (CDCl3, d