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9. A representative two-step synthetic transformation of skeleton 2 or 3 from
olefin 1 is as follows: NBS (200 mg, 1.1 mmol) was added to a solution of olefin
1 (1.0 mmol) in methanol (10 mL) at reflux temperature. The reaction mixture
was stirred at reflux for 2–3 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 ꢀ 20 mL). The combined
organic layers were washed with brine, dried, filtered, and evaporated to
afford the crude product. Purification on silica gel (hexane/AcOEt = 6/1–2/1)
afforded skeleton 4. Representative data for compound 4a: mp = 128–129 °C;
HRMS (ESI, M++1) calcd for C18H21BrNO3S 410.0426, found 410.0428; 1H NMR
(400 MHz): d 7.85–7.82 (m, 2H), 7.64–7.54 (m, 3H), 7.40–7.29 (m, 5H), 4.20
(dd, J = 2.0, 4.4 Hz, 1H), 3.93 (dt, J = 2.0, 12.8 Hz, 1H), 3.85–3.81 (m, 1H), 3.48
(dd, J = 2.0, 12.8 Hz, 1H), 2.83 (s, 3H), 2.77 (dd, J = 4.4, 14.0 Hz, 1H), 2.70 (dt,
J = 2.0, 12.8 Hz, 1H), 2.13 (ddd, J = 2.0, 4.4, 14.0 Hz, 1H); 13C NMR (100 MHz): d
140.55, 137.13, 132.80, 129.08 (2ꢀ), 128.35 (2ꢀ), 128.30, 127.53 (2ꢀ), 126.48
(2ꢀ), 77.18, 53.98, 50.85, 48.78, 41.16, 23.62; anal. calcd for C18H20BrNO3S: C,
52.69; H, 4.91; N, 3.41. Found: C, 52.91; H, 4.83; N, 3.62. DBU (1.5 g, 10.0 mmol)
was added to a solution of 4 (0.8 mmol) in tetrahydrofuran (10 mL) at reflux
temperature. The reaction mixture was stirred at reflux for 10–14 h. Water
(1 mL) was added to the reaction mixture and the solvent was concentrated.
The residue was extracted with ethyl acetate (3 ꢀ 20 mL). The combined
organic layers were washed with brine, dried, filtered, and evaporated to afford
the crude product. Without further purification, a solution of boron trifluoride
etherate (ꢁ4.0 mmol, 0.5 mL) in dichloromethane (5 mL) was added to a stirred
solution of the resulting enamine product in trimethylsilyl cyanide (3 mL) or
allyltrimethylsilane (3 mL) in dichloromethane (10 mL) at rt. The reaction
mixture was stirred at rt for 15 min. Saturated sodium bicarbonate solution
(2 mL) was added to the reaction mixture and the solvent was concentrated
under reduced pressure. The residue was extracted with ethyl acetate
(3 ꢀ 30 mL). The combined organic layers were washed with brine, dried,
filtered, and evaporated to afford crude product under reduced pressure.
Purification on silica gel (hexane/ethyl acetate = 6/1–3/1) afforded skeleton 2 or
3. Representative data for compound 2a: mp = 149–150 °C; HRMS (ESI, M++1)
calcd for C18H17N2O2S 325.1011, found 325.1012; 1H NMR (400 MHz): d 7.94–
7.91 (m, 2H), 7.68–7.56 (m, 3H), 7.39–7.30 (m, 5H), 5.97 (ddd, J = 1.2, 2.4,
5.2 Hz, 1H), 5.41 (ddd, J = 1.2, 2.4, 3.6 Hz, 1H), 4.12 (ddt, J = 1.2, 6.4, 13.2 Hz,
1H), 3.13 (ddd, J = 4.0, 13.2, 17.2 Hz, 1H), 2.84–2.74 (m, 1H), 2.52 (ddd, J = 0.8,
2.4, 17.2 Hz, 1H); 13C NMR (100 MHz): d 140.34, 138.56, 137.49, 133.67, 129.33
(2ꢀ), 128.76, 128.68 (2ꢀ), 127.61 (2ꢀ), 125.34 (2ꢀ), 114.88, 114.76, 44.62,
40.19, 27.32; anal. calcd for C18H16N2O2S: C, 66.64; H, 4.97; N, 8.64. Found: C,
66.89; H, 5.21; N, 8.79. Representative data for compound 3a: Gum; HRMS (ESI,
M++1) calcd for C20H22NO2S 340.1371, found 340.1372; 1H NMR (400 MHz): d
7.87–7.83 (m, 2H), 7.54–7.42 (m, 3H), 7.30–7.21 (m, 3H), 7.16–7.14 (m, 2H),
5.99–5.97 (m, 1H), 5.94–5.83 (m, 1H), 5.14–5.08 (m, 2H), 4.62–4.58 (m, 1H),
4.04–3.98 (m, 1H), 3.29 (ddd, J = 6.0, 10.0, 14.4 Hz, 1H), 2.52–2.44 (m, 2H),
2.18–2.12 (m, 2H); 13C NMR (100 MHz): d 141.33, 140.39, 135.81, 134.11,
132.45, 128.99 (2ꢀ), 128.38 (2ꢀ), 127.53, 126.92 (2ꢀ), 125.05 (2ꢀ), 123.71,
117.99, 53.83, 40.02, 39.01, 25.37.
10. CCDC 776258 (2a) and 783909 (2g) contain the supplementary
crystallographic data for this paper. This data can be obtained free of charge
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk).
11. Amat, M.; Llor, N.; Hidalgo, J.; Escolano, C.; Bosch, J. J. Org. Chem. 2003, 68, 1919.
12. Chiou, W. H.; Schoenfelder, A.; Mann, A.; Ojima, I. Pure Appl. Chem. 2008, 80,
1019.
13. Chang, M.-Y.; Lin, C.-H.; Chen, Y.-L.; Hsu, R.-T.; Chang, C.-Y. Tetrahedron Lett.
2010, 51, 3154.
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16. Chang, M.-Y.; Lin, C.-H.; Chen, Y.-L. Tetrahedron Lett. 2010, 51, 1430.
17. CCDC 789417 (8b) and 783908 (11a) contain the supplementary
crystallographic data for this paper. This data can be obtained free of charge
Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033; e-mail:
deposit@ccdc.cam.ac.uk).