M. Carmen de la Fuente, D. Domínguez / Tetrahedron 67 (2011) 3997e4001
4001
flash chromatography (SiO2, 1:9 EtOAc/hexane), affording cyclo-
aduct 2a (20 mg, 79%): mp 120 ꢀC. 1H NMR (CDCl3)
7.71e7.65 (m,
References and notes
d
1. (a) Raasch, M. S. J. Org. Chem. 1980, 45, 856e867; (b) Lee, L.; Snyder, J. K. In
Advances in Cycloaddition; Harmata, M., Ed.; JAI Press: Stamford, CT, 1999; vol. 6,
pp 119e171; (c) Bodwell, G. J.; Li, J. Angew. Chem., Int. Ed. 2002, 41, 3261e3262;
(d) Sasaki, Y.; Kato, D.; Boger, D. L. J. Am. Chem. Soc. 2010, 132, 13533e13544; (e)
Heterocyclic scaffolds II: Indoles: Synthesis, Properties and Applications of Indoles;
Gribble, G. W., Ed. Topics in Heterocyclic Chemistry; Springer: Berlin, Heidel-
berg, 2010; vol. 26, pp 327e396.
2. Siegel, J. B.; Zanghellini, A.; Lovick, H. M.; Kiss, G.; Lambert, A. R.; St.Clair, J. L.;
Gallaher, J. L.; Hilvert, D.; Gelb, M. H.; Stoddard, B. L.; Houk, K. N.; Michael, F. E.;
Baker, D. Science 2010, 329, 309e313.
3. In general, the DA reaction requires opposite electronic features of the sub-
stituents at the diene and the dienophile ends for the reaction to be reasonably
fast. Therefore, the mechanism of these polar DA reactions can be located in the
borderline between a highly asynchronous but concerted mechanism and
a stepwise process with a large ionic character: (a) Domingo, L. R.; Aurell, M. J.;
Perez, P.; Contreras, R. J. Org. Chem. 2003, 68, 3884e3890; (b) Domingo, L. R.;
Aurell, M. J.; Perez, P.; Contreras, R. J. Phys. Chem. A 2002, 106, 6871e6875; (c)
Domingo, L. R.; Saez, J. A. Org. Biomol. Chem. 2009, 7, 3576e3583; (d) Domingo,
L. R.; Chamorro, E.; Perez, P. Org. Biomol. Chem. 2010, 8, 5495e5504.
4. Intermolecular DAs: (a) Wenkert, E.; Moeller, P. D. R.; Piettre, S. R. J. Am. Chem.
Soc. 1988, 110, 7188e7194; (b) Kishbaugh, T. L. S.; Gribble, G. W. Tetrahedron
Lett. 2001, 42, 4783e4785. Intramolecular DAs: (c) Kraus, G. A.; Bougie, D.;
Jacobson, R. A.; Su, Y. J. Org. Chem. 1989, 54, 2425e2428; (d) Lynch, S. M.; Bur, S.
K.; Padwa, A. Org. Lett. 2002, 4, 4643e4645; (e) Boonsombat, J.; Zhang, H.;
Chughtai, M. J.; Hartung, J.; Padwa, A. J. Org. Chem. 2008, 73, 3539e3550.
5. (a) Le Noble, W. J.; Kelm, H. Angew. Chem., Int. Ed. Engl. 1980, 19, 841e856; (b)
Matsumoto, K.; Sera, A.; Uchida, T. Synthesis 1985, 1e26; (c) Matsumoto, K.;
Sera, A. Synthesis 1985, 999e1027.
3H), 7.28e7.25 (m, 1H), 7.20 (d, J¼7.9 Hz, 2H), 7.05e7.00 (m, 2H),
4.55 (t, J¼5.3 Hz, 1H), 2.60e2.45 (m, 2H), 2.58 (d, J¼14.4 Hz, 1H),
2.34 (s, 3H), 2.17 (d, J¼14.4 Hz, 1H), 1.71 (s, 3H), 1.54 (s, 3H), 1.41 (s,
3H). 13C NMR (CDCl3)
d 206.5 (CO), 144.2 (C), 142.9 (C), 134.5 (C),
133.7 (C), 129.6 (2ꢂCH), 129.0 (CH), 127.3 (2ꢂCH), 127.2 (C), 126.4
(C), 124.2 (CH), 124.1 (CH), 115.5 (CH), 65.5 (CH), 63.2 (C), 37.4
(2ꢂCH2), 25.5 (CH3), 21.5 (CH3), 19.1 (CH3), 19.0 (CH3). IR (KBr) 1707,
1671, 1596, 1477, 1459, 1357 cmꢁ1. MS (EI) (m/z): 395 (Mþ, 4), 352
(34), 196 (53), 155 (21), 91 (100). HRMS (EI) calcd for C23H25NO3S:
395.1555, found: 395.1559.
3.2.2. In water. A mixture of 1a (20 mg, 0.064 mmol) and 2,3-di-
methyl-1,3-butadiene (177 mL, 1.53 mmol) in deionized water
(0.3 mL) was heated under Ar in a sealed tube at 250 ꢀC in a sand
bath for 144 h. After cooling to rt the mixture was extracted with
CH2Cl2 (3ꢂ10 mL), washed with brine (3ꢂ10 mL), dried with an-
hydrous Na2SO4 and filtered, and the solvent was evaporated. Pu-
rification by flash chromatography (SiO2, 1:9 EtOAc/hexane)
afforded cycloadduct 2a (22.6 mg, 90%).
3.3. Typical procedure for DA reactions at rt
6. (a) Biolatto, B.; Kneeteman, M.; Mancini, P. M. Molecules 2000, 5, 393e395; (b)
Biolatto, B.; Kneeteman, M.; Paredes, E.; Mancini, P. M. J. Org. Chem. 2001, 66,
3906e3912; (c) Chataigner, I.; Hess, E.; Toupec, L.; Piettre, S. R. Org. Lett. 2001, 3,
515e518; (d) Chretien, A.; Chataigner, I.; L’Helias, N.; Piettre, S. R. J. Org. Chem.
2003, 68, 7990e8002; (e) Chataigner, I.; Panel, C.; Gerard, H.; Piettre, S. R. Chem.
Commun. 2007, 3288e3290.
3.3.1. cis-1-{2,3-Dimethyl-9-[(4-methylphenyl)sulfonyl]-1,4,9,9a-tet-
rahydro-4aH-carbazol-4a-yl}ethanol (3a). A 1 M hexane solution of
Et2AlCl (319
mL, 0.32 mmol) was added dropwise to a stirred solution
7. (a) Peglow, T.; Blechert, S.; Steckhan, E. Chem. Commun. 1999, 433e434; (b)
Perez-Prieto, J.; Stiriba, S.-E.; Gonzalez-Bejar, M.; Domingo, L. R.; Miranda, M. A.
Org. Lett. 2004, 6, 3905e3908; (c) Gonzalez-Bejar, M.; Stiriba, S.-E.; Miranda, M.
A.; Perez-Prieto, J. Org. Lett. 2007, 9, 453e456.
8. Gomez, M. V.; Aranda, A. I.; Moreno, A.; Cossio, F. P.; de Cozar, A.; Diaz-Ortiz, A.;
de la Hoz, A.; Prieto, P. Tetrahedron 2009, 65, 5328e5336.
of 1a (20 mg, 0.064 mmol) and 2,3-dimethyl-1,3-butadiene (177
m
L,
1.53 mmol) in CH2Cl2 (0.5 mL) and the mixture was stirred at rt for
21 h. The reaction was quenched by addition of saturated aqueous
NaHCO3, and the mixture was extracted with CH2Cl2 (3ꢂ10 mL),
washed with brine (3ꢂ10 mL), dried with anhydrous Na2SO4 and
filtered. After evaporation of the solvent, purification by flash chro-
matography (SiO2, 1:9 EtOAc/hexane) afforded 3a (11 mg, 44%) as an
oil containing a 3:2 mixture of diastereomers. 1H NMR(CDCl3)
9. Davies, H. M. L.; Dai, X. J. Org. Chem. 2005, 70, 6680e6684.
10. Kiselev, V. D.; Konovalov, A. I. J. Phys. Org. Chem. 2009, 22, 466e483.
11. Whitney, J. M.; Parnes, J. S.; Shea, K. J. J. Org. Chem. 1997, 62, 8962e8963.
12. (a) Rideout, D. C.; Breslow, R. J. Am. Chem. Soc. 1980, 102, 7816e7817; (b) Blokzijl,
W.; Blandamer, M. J.; Engberts, J. B. F. N. J. Am. Chem. Soc. 1991, 113, 4241e4246.
13. For selected reviews of organic reactions in aqueous media, see: (a) Lindstroem,
U. M. Chem. Rev. 2002, 102, 2751e2771; (b) Li, C.-J. Chem. Rev. 2005, 105,
3095e3165; (c) Chanda, A.; Fokin, V. V. Chem. Rev. 2009, 109, 725e748.
14. For a detailed study of the effects in reactivity of DielseAlder reactions in water
in the presence of alcoholic co-solvents, see: Tiwari, S.; Kumar, A. J. Phys. Chem.
A 2009, 113, 13685e13693.
15. Sternbach, D. D.; Rossana, D. M. J. Am. Chem. Soc. 1982, 104, 5853e5854.
16. Yanai, H.; Saito, A.; Taguchi, T. Tetrahedron 2005, 61, 7087e7093.
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hedron Lett. 1994, 35, 4843e4846.
18. Pawar, S. S.; Phalgune, U.; Kumar, A. J. Org. Chem. 1999, 64, 7055e7060.
19. Waldmann, H. Angew. Chem., Int. Ed. Engl. 1991, 30, 1306e1308.
20. Reymond, S.; Cossy, J. Chem. Rev. 2008, 108, 5359e5406.
d
7.71e7.64 (m, 2.4H), 7.57 (d, J¼8.1 Hz, 0.6H), 7.19 (d, J¼8.1 Hz, 2H),
7.15e7.14 (m, 1H), 7.09e6.93 (m, 2H), 4.29 (t, J¼4.9 Hz, 0.6H), 4.19 (t,
J¼5.1 Hz, 0.4H), 3.45e3.42 (m, 0.6H), 3.22e3.17 (m, 0.4H), 2.66e2.56
(m, 1H), 2.40e2.34 (m, 1.4H), 2.34 (s, 3H), 2.26 (d, J¼14.4 Hz, 0.6H),
2.11 (d, J¼14.4 Hz, 0.6H), 2.06 (d, J¼12.8 Hz, 0.4H),1.70 (s, 3H),1.59 (s,
1.2H), 1.49 (s, 1.8H), 0.82 (d, J¼6.4 Hz, 1.8H), 0.60 (d, J¼6.4 Hz, 1.2H).
13C NMR(CDCl3)
d 143.9 (C), 143.8 (C), 143.1 (C), 142.6 (C), 135.9 (C),
135.4 (C),135.1 (C),135.0 (C),129.5 (CH),129.4 (CH),128.4 (CH),127.4
(CH), 127.2 (CH), 126.8 (C),126.4 (C),126.3 (C),124.2 (CH),123.8 (CH),
123.7 (CH),115.0 (CH),114.5 (CH), 72.7 (CH), 72.6 (CH), 65.3 (CH), 64.8
(CH), 55.3 (C), 55.0 (C), 37.8 (CH2), 37.5 (CH2), 37.2 (CH2), 37.0 (CH2),
21.5 (CH3), 19.3 (CH3), 19.1 (CH3), 17.4 (CH3). IR (CsI) 3542, 1597, 1477,
1458, 1349, 1091 cmꢁ1. MS (EI) (m/z): 397 (Mþ, 2), 352 (12), 300 (10),
197(52),155(19), 91 (100). HRMS(EI)calcd forC23H27NO3S:397.1712,
found: 397.1719.
21. Ward, D. E.; Nixey, T. E.; Gai, Y.; Hrapchak, M. J.; Abaee, M. S. Can. J. Chem. 1996,
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Cha, J. S.; Kim, E. J.; Kwon, O. O.; Kim, J. M. Synlett 1995, 331e332; (e) Cha, J. S.
Bull. Korean Chem. Soc. 2007, 28, 2162e2190; Et3Al or Et2AlCl: Pasynkiewicz, S.;
Sliwa, E. J. Organomet. Chem. 1965, 3, 121e128.
26. Lopez, I.; Silvero, G.; Arevalo, M. J.; Babiano, R.; Palacios, J. C.; Bravo, J. L. Tet-
rahedron 2007, 63, 2901e2906.
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Acknowledgements
Support of this work by the Spanish Ministry of Science and
Innovation (through Project CTQ2008-03253) and by the Xunta de
Galicia through an Isidro Parga Pondal contract to M.C. de la F. is
gratefully acknowledged.
ꢀ
ꢀ
28. In general, DA reactions are faster in water than in ionic liquids at rt: Tiwari, S.;
Kumar, A. Angew. Chem., Int. Ed. 2006, 45, 4824e4825.
Supplementary data
29. Our results are in accordance with a previous related study (Ref. 6e), showing
that best yields are obtained with the trifluoromethanesulfonyl protected
substrate. For the rest of N-substituted derivatives, slightly different reactivities
were observed as a consequence of differences in diene, dienophile and re-
action conditions; with less discrimination at the very high temperature of our
thermal process.
Supplementary data associated with this article can be found in
clude MOL files and InChiKeys of the most important compounds
described in this article.