5170
G. D. Cuny / Tetrahedron Letters 45 (2004) 5167–5170
extracts were combined, washed with brine (50 mL), dried
7.06 (m, 2H); 7.11 (d, 2H, J ¼ 7:5 Hz); 7.20–7.24 (m, 3H);
7.49 (d, 2H, J ¼ 7:5 Hz).
over anhydrous Na2SO4, filtered and concentrated. The
product was purified by column chromatography on silica
gel using hexane/ethyl acetate (70:30) as eluant to give
1.31 g of 17 (55%) as a pale yellow oil. 1H NMR
(500 MHz, CDCl3): d 2.32 (s, 3H); 2.56–2.60 (m, 1H);
2.69–2.76 (m, 1H); 3.11–3.22 (m, 2H); 3.57–3.63 (m, 1H);
3.88 (ddd, 1H, J1 ¼ 14:0 Hz, J2 ¼ 6:0 Hz, J3 ¼ 2:0 Hz);
4.65 (b s, 1H); 5.24 (dd, 1H, J1 ¼ 9:5 Hz, J2 ¼ 5:0 Hz); 6.53
(d, 1H, J ¼ 3:0 Hz); 6.62 (dd, 1H, J1 ¼ 8:0 Hz,
J2 ¼ 2:5 Hz); 6.86 (d, 1H, J ¼ 8:5 Hz); 7.03 (d, 2H,
J ¼ 8:5 Hz); 7.10 (d, 2H, J ¼ 8:0 Hz); 7.20 (dt, 1H,
J1 ¼ 7:5 Hz, J2 ¼ 1:5 Hz); 7.39 (dd, 2H, J1 ¼ 7:5 Hz,
J2 ¼ 1:5 Hz); 7.47 (d, 1H, J ¼ 8:0 Hz); 13C NMR
(100.5 MHz, CDCl3): d 21.69, 26.38, 39.50, 43.55, 56.18,
113.63, 114.79, 125.31, 125.47, 127.31, 127.52, 128.58,
129.52, 130.33, 132.34, 132.91, 137.13, 137.28, 143.05,
153.77; HRESMS [M+Na]þ: 494.0396 (calculated for
[C23H22BrNO3S+Na]þ: 494.0396). Compound 16 was
prepared in a similar manner in 51% yield as a white
solid. 1H NMR (400 MHz, d6-acetone): d 2.63–2.81 (m,
2H); 3.15–3.26 (m, 2H); 3.58–3.86 (m, 1H); 4.01–4.06 (m,
1H); 5.33 (dd, 1H, J1 ¼ 9:6 Hz, J2 ¼ 5:2 Hz); 6.66 (dd, 1H,
J1 ¼ 8:0 Hz, J2 ¼ 2:4 Hz); 6.77 (d, 1H, J ¼ 2.4 Hz); 6.87 (d,
1H, J ¼ 8:4 Hz); 7.10–7.23 (m, 3H); 7.47 (dd, 1H,
J1 ¼ 7:6 Hz, J2 ¼ 0:8 Hz); 7.72 (d, 2H, J ¼ 8:8 Hz); 8.14
(d, 2H, J ¼ 8:8 Hz); 8.29 (s, 1H); 13C NMR (100.5 MHz,
d6-acetone): d 26.94, 40.19, 43.48, 57.17, 113.76, 115.70,
124.35, 124.87, 125.34, 128.43, 128.97, 129.50, 130.98,
133.26, 133.44, 137.59, 138.08, 147.17, 150.52, 156.45.
Compound 15 was prepared in a similar manner (eluent
was hexane/ethyl acetate 85:15) in 69% yield as a yellow
oil. 1H NMR (500 MHz, CDCl3): d 2.34 (s, 3H); 2.42–2.47
(m, 1H); 2.59–2.66 (m, 1H); 3.07 (dd, 1H, J1 ¼ 14:0 Hz,
J2 ¼ 6:5 Hz); 3.19 (dd, 1H, J1 ¼ 13:5 Hz, J2 ¼ 6:5 Hz);
3.39–3.45 (m, 1H); 3.56–3.60 (m, 1H); 3.61 (s, 3H); 5.16 (t,
1H, J ¼ 7:0 Hz); 6.23 (d, 1H, J ¼ 3:0 Hz); 6.67 (dd, 1H,
J1 ¼ 8:5 Hz, J2 ¼ 2:5 Hz); 6.87 (d, 1H, J ¼ 8:5 Hz); 7.04–
12. For an example ofa Pd-mediated intramolecular aniline
ortho-arylation utilizing trialkylphosphines see: Hara-
yama, T.; Hori, A.; Abe, H.; Takeuchi, Y. Heterocycles
2003, 60(11), 2429–2434.
13. A mixture of 17 (271 mg, 0.576 mmol), tricyclohexylphos-
phine (69 mg, 0.246 mmol), anhydrous cesium carbonate
(600 mg, 1.84 mmol, finely ground powder) and palladium
acetate (28 mg, 0.123 mmol) in DMA (10 mL) under an
argon atmosphere was heated at 110 ꢁC for 24 h. The
reaction mixture was allowed to cool and then carefully
diluted with 1 N HCl (50 mL). The reaction mixture was
extracted with ethyl acetate (3 · 50 mL). The organic
extracts were combined, washed with brine, dried over
anhydrous Na2SO4, filtered and concentrated. The prod-
uct was purified by column chromatography on silica gel
using CH2Cl2/hexane/ethyl acetate (60:35:5) as eluant to
give 125 mg of 18 (56%) as a white solid. 1H NMR
(500 MHz, CDCl3): d 2.31–2.36 (m, 1H); 2.38 (s, 3H);
2.44–2.47 (m, 1H); 3.03 (t, 1H, J ¼ 13:5 Hz); 3.16 (dd, 1H,
J1 ¼ 14:5 Hz, J2 ¼ 4:0 Hz); 3.24 (dt, 1H, J1 ¼ 12:8 Hz,
J2 ¼ 2:5 Hz); 4.07–4.12 (m, 1H); 4.66 (dd, 1H,
J1 ¼ 14:0 Hz, J2 ¼ 4:5 Hz); 5.31 (b s, 1H); 6.75 (d, 1H,
J ¼ 8:0 Hz); 6.85 (d, 1H, J ¼ 8:0 Hz); 7.23–7.29 (m, 3H);
7.34–7.37 (m, 2H); 7.69 (d, 2H, J ¼ 8:0Þ; 8.15 (d, 1H,
J ¼ 8:0 Hz); 13C NMR (100.5 MHz, CDCl3): d 21.70,
28.24, 37.65, 41.25, 53.72, 116.15, 121.10, 125.86, 127.11,
127.19, 127.39, 127.92, 128.94, 129.16, 130.07, 131.58,
134.20, 136.68, 138.16, 143.54, 151.44; HRESMS
[M+Na]þ: 414.1127 (calculated for [C23H21NO3S+Na]þ:
414.1134).
14. Cacchi, S.; Ciattini, P. G.; Morera, E.; Ortar, G. Tetra-
hedron Lett. 1986, 27(45), 5541–5544.
15. Heathcock, C. H.; Blumenkopf, T. A.; Smith, K. M. J.
Org. Chem. 1989, 54(7), 1548–1562.
16. Bick, I. R. C.; Sevenet, T.; Sinchai, W.; Skelton, B. W.;
White, A. H. Aust. J. Chem. 1981, 34(1), 195–207.