A. Barthelon et al. / Tetrahedron Letters 49 (2008) 3208–3211
3211
of allylamine (0.8 mmol, 1 equiv), 88 lL of isobutyraldehyde
(0.8 mmol, 1 equiv), and 120 lL of para-methoxybenzylisonitrile
(0.8 mmol, 1 equiv). The resulting mixture was stirred at 110 °C for
12 h. The solvent was then removed in vacuo. The crude product was
purified by flash chromatography on silica gel (DCM/AcOEt: 95:5) to
give 383 mg (92%) of 2a as a white solid. Mp 116–117 °C. 1H
NMR (400 MHz, CDCl3) d 8.11 (s, 1H), 7.36–7.23 (m, 10H), 6.96 (d,
J = 8.6 Hz, 2H), 6.83 (t, J = 5.3 Hz, 1H), 6.71 (d, J = 8.6 Hz,
2H), 5.87 (ddt, J = 15.6, 10.4, 5.1 Hz, 1H), 5.42 (t, J = 7.1 Hz, 1H),
5.30 (dd, J = 17.2, 10.6 Hz, 2H), 4.29–4.28 (m, 2H), 4.23–4.21 (m,
1H), 4.10–4.06 (m, 1H), 3.76 (s, 3H), 2.02–1.95 (m, 1H), 1.84–1.77
(m, 1H), 1.69–1.62 (m, 1H), 0.98 (d, J = 6.8 Hz, 3H), 0.97 (d,
J = 6.8 Hz, 3H). 13C NMR (100.6 MHz, CDCl3) d 171.8, 159.2, 152.2,
148.8, 141.5, 139.4, 139.3, 134.1, 130.4, 129.9, 129.8, 129.7, 129.2,
128.7, 128.5, 128.5, 127.8, 118.0, 114.4, 56.1, 55.6, 48.1, 43.3,
37.7, 25.3, 22.9. HRMS: calcd for C33H36N4O2 520.2838. Found
520.2839.
References and notes
1. (a) El Ka¨ım, L.; Grimaud, L.; Oble, J. Angew. Chem., Int. Ed. 2005,
44, 7961; (b) El Ka¨ım, L.; Gizolme, M.; Grimaud, L.; Oble, J. J. Org.
Chem. 2007, 72, 4169.
2. El Ka¨ım, L.; Gizolme, M.; Grimaud, L.; Oble, J. Org. Lett. 2006, 8,
4019.
3. For recent reviews of pyrazines, see: (a) Dembitsky, V. M.; Gloriozova,
T. A.; Poroikov, V. V. Mini-Rev. Med. Chem. 2005, 5, 319; (b)
Gryszkiewicz-Wojtkielewicz, A.; Jastrzebska, I.; Morzycki, J. W.;
Romanowska, D. B. Curr. Org. Chem. 2003, 7, 1257; (c) McCullough,
K. J. In Rodd’s Chemistry of Carbon Compounds, 2nd ed.; Sainsbury,
M., Ed.; Elsevier: Amsterdam, 2000; Vol. 4, pp 99–171. Parts I–J; (d)
Sato, N. In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R.,
Rees, C. W., Boulton, A. J., Eds.; Elsevier: Oxford, 1996; Vol. 6, p 233.
4. (a) Maga, J. A. Food Rev. Int. 1992, 8, 479; (b) Buchbauer, G.; Klein,
C. T.; Wailzer, B.; Wolschann, P. J. Agric. Food Chem. 2000, 48, 4273.
5. (a) Betancor, C.; Freire, R.; Perez-Martin, I.; Prange, T.; Suarez, E.
Tetrahedron 2005, 61, 2803; (b) Li, W.; Fuchs, P. L. Org. Lett. 2003, 5,
2849; (c) LaCour, T. G.; Guo, C.; Boyd, M. R.; Fuchs, P. L. Org.
9. The reaction was performed as well in MeOH, CH3CN and in
a 10:1 mixture of toluene:water without any improvement in the
yield.
10. El Ka¨ım, L.; Gizolme, M.; Grimaud, L. Synlett 2007, 465.
11. Typical procedure for 5b: To a solution of 264 mg (1 mmol, 1 equiv) of
5,6-diphenylpyrazine-2-thiol 4a in 1 mL of toluene were added 75 lL
of allylamine (1 mmol, 1 equiv), 108 lL of propanal (1 mmol,
1 equiv), and 110 lL of cyclohexylisonitrile (1 mmol, 1 equiv). The
resulting mixture was stirred at 110 °C for 3 days. The solvent was
then removed in vacuo. The crude product was purified by flash
chromatography on silica gel (DCM/petroleum ether: 60:40) to give
´
Lett. 2000, 2, 33; (d) Buron, F.; Ple, N.; Turck, A.; Gueguiner, G. J.
Org. Chem. 2005, 70, 2616.
6. (a) Fukuwatari, T.; Sugimoto, E.; Shibata, K. Biosci. Biotech.
Biochem. 2002, 66, 1435; (b) Suzuki, Y.; Suzuki, A.; Tamaru, A.;
Katsukawa, C.; Oda, H. J. Clin. Microbiol. 2002, 40, 501; (c) Zhang,
Y.; Permar, S.; Sun, Z. J. Clin. Microbiol. 2002, 40, 42; (d)
Milczarska, B.; Foks, H.; Zwolska, Z. Phosphorus, Sulfur Silicon
Relat. Elem. 2005, 180, 2255; (e) Cynamon, M. H.; Speirs, R. J.;
Welch, J. T. Antimicrob. Agents Chemother. 1998, 42, 462.
7. (a) Fales, H. M.; Blum, M. S.; Southwick, E. W.; William, D. L.;
Roller, P. P.; Don, A. W. Tetrahedron 1988, 44, 5045; (b) Tecle, B.;
Sun, C. M.; Borphy, J. J.; Toia, R. F. J. Chem. Ecol. 1987, 13, 1811;
(c) Wheeler, J. W.; Avery, J.; Olubajo, O.; Shamim, M. T.; Storm, C.
B. Tetrahedron 1982, 38, 1939; (d) Brown, W. V.; Moore, B. P. Insect
Biochem. 1979, 9, 451; (e) Oldham, N. J.; Morgan, E. D. J. Chem.
Soc., Perkin Trans. 1 1993, 2713.
1
169 mg (36%) of 5b as an orange oil. H NMR (400 MHz, CDCl3) d
9.40 (br s, 1H), 8.13 (s, 1H), 7.40–7.26 (m, 10H), 5.96–5.87 (m, 1H),
5.33–5.27 (m, 2H), 5.08 (br s, 1H), 4.52 (dd, J = 18.2, 4.8 Hz, 1H),
4.20–4.07 (m, 2H), 2.47–2.37 (m, 1H), 2.15–2.04 (m, 1H) 1.78–1.60
(m, 2H), 1.43–1.27 (m, 3H), 1.20–1.10 (m, 2H) 1.00 (dd, J = 7.6,
7.0 Hz, 3H), 0.86–0.77 (m, 1H), 0.70–0.60 (m, 1H), 0.52–0.43 (m, 1H).
13C NMR (100.6 MHz, CDCl3) d 200.5, 152.1, 148.1, 141.4, 139.8,
138.9, 134.3, 130.5, 129.9, 129.8, 129.0, 128.8, 128.5, 127.9, 117.7,
67.3, 53.6, 49.0, 31.3, 30.8, 25.4, 24.8, 24.4, 11.7. HRMS: calcd for
8. Typical procedure for 2a: To a solution of 198 mg (0.8 mmol, 1 equiv)
of 5,6-diphenylpyrazin-2-ol 1a in 1 mL of toluene were added 60 lL
C
29H34N4S 470.2504. Found 470.2509.