M.-Y. Chang et al. / Tetrahedron Letters 51 (2010) 1430–1433
1433
(222 mg, 2.0 mmol) in methanol or dioxane (20 mL) at rt. The reaction mixture
was stirred at reflux for 5 h. Saturated sodium bicarbonate solution (2 mL) was
added to the reaction mixture and the solvent was concentrated. The residue
was extracted with dichloromethane (3 Â 20 mL). The combined organic layers
were washed with brine, dried, filtered, and evaporated to afford crude
product. Purification on silica gel (hexane/AcOEt = 6/1–2/1) afforded
Finally, we examined an extension of the above-mentioned
method to the synthesis of methoxyalcohol 14 and diol 15 (Eq.
3). The selenium dioxide-mediated reaction of exocyclic arylolefin
13 under the above-mentioned condition successfully furnished
the trans-methoxyhydroxylation and dihydroxylation reactions.
The structures of methoxyalcohol 14 and diol 15 were determined
by single-crystal X-ray analysis.14
compounds
2 and 3. For compound 2Aa: Mp= 137–138 °C (recrystallized
from hexane and ethyl acetate); IR (CHCl3) 3519, 2940, 1338, 1168, 1123,
576 cmÀ1; HRMS (ESI, M++1) calcd for C18H22NO4S 348.1270, found 348.1271;
1H NMR (400 MHz): d 7.84–7.81 (m, 2H), 7.66–7.48 (m, 8H), 3.84–3.74 (m, 3H),
3.10 (dd, J = 2.8, 13.2 Hz, 1H), 2.84 (s, 3H), 2.66–2.52 (m, 2H), 2.12 (br s, 1H),
2.08 (br d, J = 14.8 Hz, 1H); 13C NMR (100 MHz): d 142.06, 136.45, 132.95 (2Â),
130.47, 129.18 (2Â), 128.98, 127.55 (2Â), 124.77, 123.72, 77.17, 71.05, 49.67,
48.12, 41.46, 24.27; Anal. Calcd for C18H21NO4S: C, 62.23; H, 6.09; N, 4.03.
Found: C, 62.38; H, 6.21; N, 4.33. For compound 3Aa: Mp= 177–178 °C
(recrystallized from hexane and ethyl acetate); IR (CHCl3) 3489, 2921, 1336,
1169, 1078, 729 cmÀ1; HRMS (ESI, M++1) calcd for C17H20NO4S 334.1113, found
334.1113; 1H NMR (400 MHz): d 7.82–7.78 (m, 3H), 7.70–7.49 (m, 7H), 3.85–
3.74 (m, 3H), 3.11 (dd, J = 1.2, 12.0 Hz, 1H), 2.85 (ddd, J = 2.4, 11.6, 12.8 Hz, 1H),
2.74 (ddd, J = 4.4, 12.8, 13.6 Hz, 1H), 1.74 (br d, J = 13.6 Hz, 1H), 1.68 (br s, 2H);
13C NMR (100 MHz): d 145.53, 136.28, 133.06 (2Â), 129.39, 129.23 (2Â),
128.89, 127.59 (2Â), 124.86, 122.66, 72.11, 70.57, 48.36, 41.79, 31.41; Anal.
Calcd for C17H19NO4S: C, 61.24; H, 5.74; N, 4.20. Found: C, 61.31; H, 5.83; N,
4.41.
3. Conclusion
In summary, we have presented a synthetic method for 4-aryl-
pyridines, 3-hydroxy-4-arylpyridines, and 3,4-diarylpyridines
which involved selenium dioxide-mediated methoxyhydroxylation
of 4-aryl-1,2,3,6-tetrahydropyridines. Considering the utility of
these heterocyclic aromatic compounds, the development of the
general synthetic approaches is significant.
Acknowledgment
7. (a) Misra, M.; Luthra, R.; Singh, K. L.; Sushil, K.. In Comprehensive Natural
Products Chemistry; Barton, D. H. R., Nakanishi, K., Meth-Cohn, O., Eds.;
Pergamon: Oxford, UK, 1999; Vol. 4, p 25; (b) Staunton, J.; Wilkinson, B. Top.
Curr. Chem. 1998, 195, 49; (c) Cardillo, G.; Tomasini, C. Chem. Soc. Rev. 1996,
117; (d) Juaristi, E.; Lopez-Ruiz, H. Curr. Med. Chem. 1999, 6, 983; (e) Wabnitz, T.
C.; Spencer, J. B. Tetrahedron Lett. 2002, 43, 3891; (f) Wabnitz, T. C.; Spencer, J. B.
Org. Lett. 2003, 5, 2141.
The authors would like to thank the National Science Council of
the Republic of China for financial support.
References and notes
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653; (b) Lu, J. Y.; Arndt, H. D. J. Org. Chem. 2007, 72, 4205; (c) Lu, J. Y.; Keith, J.
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therein.
10. CCDC 752928 (2), 752931 (3Ac), 752932 (4Aab) and 752933 (7Aa) contain the
supplementary crystallographic data for this paper. This data can be obtained
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax: 44-1223-336033; e-mail:
deposit@ccdc.cam.ac.uk).
11. Kozikowski, A. P.; Araldi, G. L.; Ball, R. G. J. Org. Chem. 1997, 62, 503.
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5.
A solution of hydrogen peroxide in methanol is prepared from sodium
peroxide. Sodium peroxide is added to an ice-cold dilute solution of 20%
sulfuric acid in methanol, in small doses at a time. Sodium sulfate is removed
by recrystallization, and a dilute solution of hydrogen peroxide in methanol is
obtained. The concentration of the freshly prepared solution of hydrogen
peroxide in methanol was nearly 38–42% (v/v) by titrating with the solution of
potassium permanganate (0.02 M).
14. CCDC 752929 (15) and 752930 (14) contain the supplementary
crystallographic data for this Letter. These data can be obtained free of
Union Road, Cambridge CB2 1EZ, UK; fax: 44-1223-336033; e-mail:
deposit@ccdc.cam.ac.uk).
6. Selenium dioxide-mediated reaction of compound 1 into compounds 2 or 3 is
as follows: A solution of hydrogen peroxide (2 mL) in methanol or water was
added dropwise to a solution of compound 1 (1.0 mmol) with selenium dioxide