9054
N. Kawai et al. / Tetrahedron 63 (2007) 9049–9056
on silica gel eluted with 10% EtOAc in hexane gave the
corresponding tetrahydropyran.
under an oxygen atomosphere. Evaporation of the solvent
under vacuo and purification of the residue by column chro-
matography on silica gel eluted with 20% EtOAc in hexane
gave phenyl ketone.
4.6.1. Compound 5a. Compound 5a was obtained in 92%
yield from 6a. White amorphous solid; [a]2D1ꢀ6.5 (c 0.73,
CHCl3);Rf¼0.6(35%EtOAcinhexane);1HNMR(300 MHz,
CDCl3) d 7.44–7.19 (m, 10H), 6.83 (d, 1H, J¼16.0 Hz), 6.28
(dd, 1H, J¼16.0, 5.9 Hz), 4.99 (dd, 1H, J¼11.5, 2.5 Hz), 4.70
(m, 1H), 4.41 (quint, 1H, J¼3.0 Hz), 1.98–1.75 (m, 4H); 13C
NMR (75 MHz, CDCl3) d 142.7, 137.0, 130.4, 130.2, 128.5,
128.3, 127.5, 127.4, 126.5, 126.0, 73.7, 72.6, 64.8, 40.5,
38.7; IR (film, cmꢀ1) 3320, 2948, 2853, 1450, 1060, 748;
MS (FAB) m/z 303 (M+Na+). HRMS calcd for C19H20O2Na
(M+Na+): 303.1361; found: m/z 303.1352.
4.7.1. Compound 1. Compound 1 was obtained from 5a in
37% yield along with a recovery of 5a in 50% yield. Colorless
amorphous solid; [a]D24 ꢀ21.4 (c 0.8, CHCl3); Rf¼0.35 (40%
EtOAc in hexane); 1H NMR (300 MHz, CDCl3) d 7.97 (dd,
2H, J¼7.5, 1.5 Hz), 7.55 (tt, 1H, J¼7.1, 1.5 Hz) 7.45 (td, 2H,
J¼7.5, 1.3 Hz), 7.31–7.22 (m, 5H), 4.95 (dd, 1H, J¼11.9,
2.0 Hz), 4.65 (dddd, 1H, J¼11.5, 6.8, 5.8, 2.0 Hz), 4.37 (q,
1H, J¼3.0 Hz), 3.41 (dd, 1H, J¼15.9, 6.8 Hz), 3.06 (dd,
1H, J¼15.9, 5.8 Hz), 1.97 (ddd, 1H, J¼13.8, 3.0, 2.0 Hz),
1.94 (ddd, 1H, J¼13.8, 3.0, 2.0 Hz), 1.76 (ddd, 1H, J¼13.8,
11.9, 3.0 Hz), 1.75–1.67 (br, 1H), 1.68 (ddd, 1H, J¼13.8,
11.5, 3.0 Hz); 13C NMR (75 MHz, CDCl3) d 198.3, 142.6,
137.3, 133.0, 128.5, 128.3, 128.2, 127.2, 126.8, 73.8, 66.0,
64.6, 45.1, 40.0, 38.4; IR (KBr, cmꢀ1) 3329, 2922, 1680,
1451, 1062; MS (EI) m/z 296 (M+). HRMS calcd for
C19H20O3 (M+): 296.1412; found: m/z 296.1414. Under a
microwave in sealed tube at 70 ꢁC for 4 h, the reaction of
5a gave 1 in 56% yield and 27% recovery of 5a.
4.6.2. Compound 5b. Compound 5b was obtained from 6b
in 86% yield. White amorphous solid; [a]2D2 ꢀ82.8 (c 0.65,
CHCl3); Rf¼0.48 (35% EtOAc in hexane); 1H NMR
(300 MHz, CDCl3) d 7.48–7.21 (m, 10H), 6.66 (dd, 1H,
J¼15.9, 1.1 Hz), 6.39 (dd, 1H, J¼15.9, 5.7 Hz), 5.30 (t,
1H, J¼4.4 Hz), 4.28 (dddd, 1H, J¼9.2, 5.7, 4.8, 1.1 Hz),
4.07 (dddd, 1H, J¼9.2, 9.1, 4.4, 4.0 Hz), 2.54 (ddd, 1H,
J¼14.4, 4.4, 4.0 Hz), 2.09 (ddd, 1H, J¼12.8, 4.8, 4.0 Hz),
1.96 (ddd, 1H, J¼14.4, 9.1, 4.4 Hz), 1.63 (dt, 1H, J¼12.8,
9.2 Hz); 13C NMR (75 MHz, CDCl3) d 140.6, 136.8, 130.5,
129.9, 128.6, 128.5, 127.6, 127.2, 126.5, 126.3, 72.0, 70.5,
64.6, 40.4, 36.9; IR (KBr, cmꢀ1) 3364, 2944, 1492, 1477,
1046, 968; MS (FAB) m/z 303 (M+Na+). HRMS calcd for
C19H20O2Na (M+Na+): 303.1361; found: m/z 303.1352.
4.7.2. Compound 14. Compound 14 was obtained from 13 in
55% yield along with a recovery of 13 in 35% yield. Colorless
oil; [a]2D1 28.9 (c 0.79, CHCl3); Rf¼0.24 (15% EtOAc in hex-
1
ane); H NMR (300 MHz, CDCl3) d 7.96 (dd, 2H, J¼7.2,
1.8 Hz), 7.57 (tt, 1H, J¼7.7, 1.9 Hz), 7.46 (t, 2H, J¼7.5 Hz),
7.36–7.22 (m, 5H), 5.16 (t, 1H, J¼4.4 Hz), 4.70 (s, 2H), 4.24
(dddd, 1H, J¼9.4, 7.1, 5.8, 3.1 Hz), 3.91 (dddd, 1H, J¼9.7,
9.4, 4.3, 3.8 Hz), 3.44 (dd, 1H, J¼15.9, 7.1 Hz), 3.38 (s,
3H), 3.21 (dd, 1H, J¼15.9, 5.8 Hz), 2.52 (ddd, 1H, J¼13.4,
4.4, 3.8 Hz), 2.10 (ddd, 1H, J¼12.8, 3.8, 3.12 Hz), 1.98
(ddd, 1H, J¼13.4, 9.7, 4.9 Hz), 1.59 (dt, 1H, J¼12.8,
9.4 Hz); 13C NMR (75 MHz, CDCl3) d 198.2, 140.3, 137.0,
133.1, 128.6, 128.5, 128.2, 127.1, 126.3, 94.9, 72.3, 69.5,
67.1, 55.3, 44.6, 37.5, 34.4; IR (film, cmꢀ1) 2929, 1685,
1448, 1037, 754; MS (FAB) m/z 341 (M+H+). HRMS calcd
for C21H25O4 (M+H+): 341.1753; found: m/z 341.1745.
4.6.3. Compounds 18 and 19. Compound 17 gave 18 in 47%
yield and 19 in 49% yield, after purification of the residue by
column chromatography on silica gel eluted with 50%
CH2Cl2 in hexane. Compound 18: white amorphous solid;
1
[a]2D3 ꢀ5.8 (c 1.00, CHCl3); Rf¼0.38 (CH2Cl2); H NMR
(300 MHz, CDCl3) d 7.42–7.19 (m, 10H), 6.65 (d, 1H, J¼
16.0 Hz), 6.29 (dd, 1H, J¼16.0, 5.8 Hz), 4.47 (dd, 1H, J¼
11.0, 1.5 Hz), 4.21 (ddt, 1H, J¼11.2, 5.8, 1.5 Hz), 4.04(dddd,
1H, J¼11.0, 10.8, 6.4, 4.6 Hz), 2.26–2.14 (m, 2H), 1.68 (br s,
1H), 1.16–1.43 (m, 2H); 13C NMR (75 MHz, CDCl3) d 141.8,
136.7, 130.5, 129.5, 128.5, 128.4, 127.6(2C), 126.5, 126.0,
77.7, 76.4, 68.4, 42.8, 41.1; IR (film, cmꢀ1) 3321, 2923,
1450, 1058, 747; MS (FAB) m/z 303 (M+Na+). HRMS calcd
for C19H20O2Na (M+Na+): 303.1361; found: m/z 303.1353.
Compound 19: light yellow amorphous solid; [a]2D4 ꢀ30.9
4.7.3. Compound 3. Compound 3 was obtained from 18 in
63% yield along with a recovery of 18 in 17% yield. White
amorphous solid; [a]D25 ꢀ11.6 (c 0.54, CHCl3); Rf¼0.23
(30% EtOAc in hexane); 1H NMR (300 MHz, CDCl3)
d 7.95 (d, 2H, J¼7.2 Hz), 7.53 (t, 1H, J¼7.3 Hz), 7.46 (t,
2H, J¼7.5 Hz), 7.35–7.17 (m, 5H), 4.39 (dd, 1H, J¼11.5,
1.8 Hz), 4.15 (dddd, 1H, J¼11.2, 6.6, 6.0, 4.8 Hz), 4.02
(dddd, 1H, J¼11.0, 10.8, 6.4, 4.4 Hz), 3.46 (dd, 1H,
J¼16.5, 6.0 Hz), 3.08 (dd, 1H, J¼16.5, 6.6 Hz), 2.22–2.17
(m, 2H), 1.59 (br, 1H), 1.54–1.22 (m, 3H); 13C NMR
(75 MHz, CDCl3) d 198.0, 141.7, 137.2, 133.2, 128.5,
128.3, 128.2, 127.5, 125.9, 77.5, 72.5, 68.2, 44.8, 42.5,
40.9; IR (film, cmꢀ1) 3408, 2920, 1684, 1449, 1063, 754;
MS (FAB) m/z 297 (M+H+). HRMS calcd for C19H21O3
(M+H+): 297.1491; found: m/z 297.1496.
1
(c 1.05, CHCl3); Rf¼0.28 (CH2Cl2); H NMR (300 MHz,
CDCl3+TMS) d 7.41–7.23 (m, 10H), 6.65 (dd, 1H, J¼16.3,
1.8 Hz), 6.36 (dd, 1H, J¼16.3, 4.2 Hz), 4.97 (m, 1H), 4.74
(dd, 1H, J¼11.4, 2.2 Hz), 4.17 (dddd, 1H, J¼11.2, 11.1,
6.6, 4.4 Hz), 2.27 (ddd, 1H, J¼12.8, 4.2, 2.0 Hz), 2.17 (ddd,
1H, J¼12.2, 4.4, 2.2 Hz), 1.88 (ddd, 1H, J¼12.8, 11.2,
5.9 Hz), 1.69–1.62 (br, 1H), 1.62 (dd, 1H, J¼12.2, 11.4 Hz);
13C NMR (75 MHz, CDCl3) d 142.0, 136.5, 132.0, 129.2,
128.6, 128.4, 127.8, 127.6, 126.4, 126.0, 73.2, 71.8, 64.9,
43.2, 37.7; IR (film, cmꢀ1) 3314, 2922, 1671, 1449, 1051;
MS (FAB) m/z 303 (M+Na+). HRMS calcd for
C19H20O2Na (M+Na+): 303.1361; found: m/z 303.1354.
4.7.4. Compound 4. Compound 4 was obtained from 19
in 57% yield along with a recovery of 19 in 25% yield.
Amorphous solid; [a]2D5 9.0 (c 0.39, CHCl3); Rf¼0.19
(30% EtOAc in hexane); 1H NMR (300 MHz, CDCl3)
d 7.96 (d, 2H, J¼7.3 Hz), 7.58 (t, 1H, J¼7.5 Hz), 7.47 (t,
2H, J¼7.7 Hz), 7.35–7.26 (m, 5H), 4.89 (m, 1H), 4.74 (dd,
4.7. General procedure of Wacker oxidation
A mixture of alkene (0.05 mmol), PdCl2 (4.4 mg,
0.025 mmol), and CuCl (7.4 mg, 0.075 mmol) in DMF
(0.6 mL) and H2O (0.6 mL) was stirred at 50 ꢁC for 3 days