B.V. Ramulu et al. / Tetrahedron 69 (2013) 8305e8315
8313
for Grignard reaction at ꢂ10 ꢀC for 4 h. Purification of the crude
material by silica gel column chromatography (petroleum ether/
ethyl acetate, 90:10e85:15) furnished the alcohol 4abe (243 mg,
75%) as pale yellow viscous liquid. [TLC control (petroleum ether/
ethyl acetate, 85:15), Rf(3ab)¼0.50, Rf(4abe)¼0.40, UV detection].
IR (MIReATR, 4000e600 cmꢂ1): nmax¼3518, 2962, 2933, 2834,
1590, 1510, 1463, 1440, 1254, 1235, 1135, 1025, 752 cmꢂ1. 1H NMR
ArCH), 124.4 (s, ArC), 117.8 (d, ArCH), 107.7 (d, ArCH), 105.9 (d,
ArCH), 100.9 (t, OCH2O), 74.5 [s, ArC(CH3)OH], 43.7 (t, ArCH2), 36.2
[t, ArCCH3(OH)CH2CH2], 30.3 [q, ArC(CH3)OH], 24.3 [t, ArCCH3(OH)
CH2CH2]
ppm.
HRMS
(APCIþ)
m/z
calculated
for
[C18H18BrO2]þ¼[(MþH)eH2O]þ: 345.0485; found: 345.0484.
4.13. 2-(3,4-Dimethoxyphenyl)-2-methylchromane (5abm)
(CDCl3, 400 MHz):
d¼7.47 (dd, 1H, J¼7.8 and 1.0 Hz, ArH), 7.17 (ddd,
1H, J¼7.8, 7.3, and 1.0 Hz, ArH), 7.12 (dd, 1H, J¼7.8 and 2.0 Hz, ArH),
7.02 (ddd, 1H, J¼7.8, 7.3, and 2.0 Hz, ArH), 7.01 (d, 1H, J¼2.0 Hz,
ArH), 6.94 (dd, 1H, J¼8.3 and 2.0 Hz, ArH), 6.85 (d, 1H, J¼8.3 Hz,
ArH), 3.90 (s, 3H, ArOCH3), 3.88 (s, 3H, ArOCH3), 2.74 [dt, 1H, J¼12.7
and 4.9 Hz, ArC(OH)CHaHb(Et)CH2], 2.49 [dt, 1H, J¼11.7 and 4.9 Hz,
ArC(OH)CH2(Et)CHaHb], 2.20e1.96 [m, 2H, ArC(OH)CHaHb(-
CHaHbCH3)CH2], 1.95e1.78 [m, 2H, ArC(OH)CH2(CHaHbCH3)CHaHb],
1.73 (br s,1H, OH), 0.79 [t, 3H, J¼7.3 Hz, ArC(OH)(CH2CH3)CH2] ppm.
GP-5 was carried out with alcohol 4abm (100 mg, 0.27 mmol),
CuI (10.4 mg, 20 mol %), 2,20-bipyridine (8.4 mg, 20 mol %), KOtBu
(90.8 mg, 0.81 mmol), and DMF (3 mL) at 120 ꢀC for 24 h. Purifi-
cation of the crude material by silica gel column chromatography
(petroleum ether/ethyl acetate, 90:10e85:15) furnished the flavan
5abm (63 mg, 82%) as pale yellow viscous liquid. [TLC control
(petroleum ether/ethyl acetate, 85:15), Rf(4abm)¼0.30, Rf(5abm)¼
0.70, UV detection]. IR (MIReATR, 4000e600 cmꢂ1): nmax¼2929,
2834, 1607, 1582, 1512, 1488, 1454, 1372, 1265, 1225, 1179, 1115,
13C NMR (CDCl3, 100 MHz):
d
¼148.6 (s, ArC), 147.5 (s, ArC), 141.8 (s,
ArC), 138.0 (s, ArC), 132.7 (d, ArCH), 130.4 (d, ArCH), 127.5 (d, 2C,
ArCH), 124.3 (s, ArC), 117.6 (d, ArCH), 110.7 (d, ArCH), 109.1 (d,
ArCH), 76.9 [s, ArC(OH)], 55.9 (q, ArOCH3), 55.8 (q, ArOCH3), 42.8 (t,
ArCH2), 35.7 (t, ArCH2CH2), 30.8 [t, ArC(CH2CH3)OH], 7.8 [q,
ArC(CH2CH3)OH] ppm. HRMS (APCIþ) m/z calculated for
[C19H22BrO2]þ¼[(MþH)eH2O]þ: 361.0803; found: 361.0809.
1081, 976, 946, 811, 754 cmꢂ1
.
1H NMR (CDCl3, 400 MHz):
d¼7.12
(ddd, 1H, J¼8.8, 8.3, and 1.5 Hz, ArH), 6.97 (dd, 1H, J¼8.3 and 1.5 Hz,
ArH), 7.00e6.90 (m, 1H, ArH), 6.93 (d, 1H, J¼1.9 Hz, ArH), 6.89 (dd,
1H, J¼8.8 and 1.9 Hz, ArH), 6.81 (ddd, 1H, J¼7.3, 7.3, and 1.5 Hz,
ArH), 6.79 (d, 1H, J¼8.8 Hz, ArH), 3.83 (s, 3H, ArOCH3), 3.81 (s, 3H,
ArOCH3), 2.67 (td, 1H, J¼16.1 and 5.4 Hz, ArCHaHbCH2), 2.56e2.44
(m, 1H, ArCHaHbCH2), 2.34 (td, 1H, J¼16.1 and 5.4 Hz, ArCHaHbCH2),
2.13e2.01 (m, 1H, ArCH2CH2), 1.64 (s, 3H, CH3) ppm. 13C NMR
4.11. 4-(2-Bromophenyl)-1-phenylbutan-1-ol (8aa)
(CDCl3, 100 MHz):
d
¼154.1 (s, ArC), 148.6 (s, ArC), 147.6 (s, ArC),
GP-2 was carried out with ketone 7aa (300.0 mg, 0.99 mmol),
NaBH4 (73.3 mg, 1.98 mmol), and methanol (10 mL) for reduction at
0 ꢀC to room temperature for 2 h. Purification of the crude material
by silica gel column chromatography (petroleum ether/ethyl ace-
tate, 95:5e90:10) furnished the alcohol 8aa (253 mg, 84%) as pale
yellow viscous liquid. [TLC control (petroleum ether/ethyl acetate,
95:5), Rf(7aa)¼0.65, Rf(8aa)¼0.35, UV detection]. IR (MIReATR,
4000e600 cmꢂ1): nmax¼3358, 3061, 3029, 2924, 2855, 1493, 1470,
138.2 (s, ArC), 129.3 (d, ArCH), 127.3 (d, ArCH), 121.6 (s, ArC), 119.9
(d, ArCH), 117.0 (d, ArCH), 116.8 (d, ArCH), 110.9 (d, ArCH), 108.6 (d,
ArCH), 78.0 (s, ArOCMe), 55.8 (q, ArOCH3), 55.7 (q, ArOCH3), 32.9 (t,
ArOCH2CH2), 30.0 (q, CH3), 22.6 (t, ArOCH2CH2) ppm. HRMS
(APCIþ) m/z calculated for [C18H21O3]þ¼[MþH]þ: 285.1485; found:
285.1480.
4.14. 2-(3,4-Dimethoxyphenyl)-2-ethylchromane (5abe)
1454, 1439, 1286, 1061, 1021, 981, 749 cmꢂ1 1H NMR (CDCl3,
.
400 MHz):
d
¼7.50 (d, 1H, J¼7.8 Hz, ArH), 7.40e7.10 (m, 7H, ArH),
GP-5 was carried out with alcohol 4abe (100 mg, 0.26 mmol), CuI
(10.1 mg, 20 mol %), 2,20-bipyridine (8.1 mg, 20 mol %), KOtBu
(87.5 mg, 0.78 mmol), and DMF (3 mL) at 120 ꢀC for 24 h. Purification
of the crude material by silica gel column chromatography (petro-
leum ether/ethyl acetate, 95:5e90:10) furnished the flavan 5abe
(58 mg, 75%) as pale yellow viscous liquid. [TLC control (petroleum
ether/ethyl acetate, 85:15), Rf(4abe)¼0.35, Rf(5abe)¼0.70, UV de-
tection]. IR (MIReATR, 4000e600 cmꢂ1): nmax¼2933, 2834, 1606,
1582, 1511, 1488, 1454, 1346, 1258, 1216, 1179, 1166, 1096, 983, 888,
7.03 (ddd, 1H, J¼8.8, 8.3, and 2.4 Hz, ArH), 4.70 [dd, 1H, J¼6.4 and
5.9 Hz, ArCH(OH)], 2.75 (t, 2H, J¼7.3 Hz, ArCH2), 2.05e1.45 [m, 5H,
ArCH(OH)CH2CH2] ppm. 13C NMR (CDCl3, 100 MHz):
d¼144.6 (s,
ArC), 141.5 (s, ArC), 132.7 (d, ArCH), 130.3 (d, ArCH), 128.5 (d, 2C,
ArCH), 127.6 (d, ArCH), 127.5 (d, ArCH), 127.3 (d, ArCH), 125.9 (d, 2C,
ArCH), 124.4 (s, ArC), 74.4 [d, ArCH(OH)], 38.5 (t, ArCH2), 35.9 [t,
ArCH(OH)CH2CH2], 26.1 [t, ArCH(OH)CH2CH2] ppm. HRMS (APCIþ)
m/z calculated for [C16H19BrN]þ¼[(MþNH4)eH2O]þ: 304.0695;
found: 304.0681.
807, 751, 666 cmꢂ1
.
1H NMR (CDCl3, 400 MHz):
d
¼7.11 (ddd, 1H,
J¼8.8, 7.8, and 1.5 Hz, ArH), 6.96 (d, 1H, J¼8.8 Hz, ArH), 6.92 (d, 1H,
J¼7.8 Hz, ArH), 6.86 (d, 1H, J¼2.0 Hz, ArH), 6.83 (dd, 1H, J¼8.3 and
2.4 Hz, ArH), 6.79 (d,1H, J¼7.8 and 1.5 Hz, ArH), 6.77 (d,1H, J¼8.3 Hz,
ArH), 3.83 (s, 3H, ArOCH3), 3.78 (s, 3H, ArOCH3), 2.61 (td, 1H, J¼15.6
and 4.9 Hz, ArCHaHbCH2), 2.55e2.40 (m, 1H, ArCHaHbCH2),
2.36e2.25 (m, 1H, ArCH2CH2), 2.15e2.03 (m, 1H, ArCH2CH2),
4.12. 2-(1,3-Benzodioxol-5-yl)-5-(2-bromophenyl)pentan-2-ol
(8aem)
GP-3 was carried out with ketone 7ae (300.0 mg, 0.86 mmol),
methylmagnesium iodide (3.44 mmol), and diethyl ether (10 mL)
for Grignard reaction at ꢂ10 ꢀC for 4 h. Purification of the crude
material by silica gel column chromatography (petroleum ether/
ethyl acetate, 85:15e75:25) furnished the alcohol 8aem (266 mg,
85%) as colorless viscous liquid. [TLC control (petroleum ether/ethyl
acetate, 80:20), Rf(7ae)¼0.60, Rf(8aem)¼0.45, UV detection]. IR
(MIReATR, 4000e600 cmꢂ1): nmax¼3428, 2923, 1502, 1487, 1236,
2.01e1.82 (m, 2H, CH2CH3), 0.86 (t, 3H, J¼7.3 Hz, CH2CH3) ppm. 13
C
NMR (CDCl3,100 MHz):
d
¼154.2 (s, ArC),148.6 (s, ArC),147.5 (s, ArC),
136.4 (s, ArC),129.3 (d, ArCH),127.2 (d, ArCH),122.1 (s, ArC),119.8 (d,
ArCH), 117.8 (d, ArCH), 116.8 (d, ArCH), 110.9 (d, ArCH), 109.4 (d,
ArCH), 80.5 (s, ArOCEt), 55.8 (q, 2C, 2ꢁArOCH3), 35.7 (t, ArCH2CH2),
30.9 (t, ArCH2CH2), 22.4 (t, CH2CH3), 7.7 (q, CH2CH3) ppm. HRMS
(APCIþ) m/z calculated for [C19H23O3]þ¼[MþH]þ: 299.1642; found:
299.1643.
1095, 1038, 937, 921, 813, 751, 728, 670 cmꢂ1 1H NMR (CDCl3,
.
400 MHz):
d
¼7.48 (dd, 1H, J¼7.8 and 1.0 Hz, ArH), 7.18 (ddd, 1H,
J¼7.8, 7.8, and 1.0 Hz, ArH), 7.14 (dd, 1H, J¼7.8 and 2.0 Hz, ArH), 7.01
(ddd, 1H, J¼7.8, 7.8, and 2.0 Hz, ArH), 6.92 (d, 1H, J¼2.0 Hz, ArH),
6.85 (dd,1H, J¼8.3 and 2.0 Hz, ArH), 6.74 (d, 1H, J¼8.3 Hz, ArH), 5.93
(s, 2H, OCH2O), 2.67 (t, 2H, J¼7.8 Hz, ArCH2), 2.00e1.53 [m, 5H,
ArC(OH)CH2CH2], 1.51 [s, 3H, ArCCH3(OH)] ppm. 13C NMR (CDCl3,
4.15. 2-Phenyl-2,3,4,5-tetrahydro-1-benzoxepine (9aa)
GP-5 was carried out with alcohol 8aa (100 mg, 0.32 mmol), CuI
(12.5 mg, 20 mol %), 2,20-bipyridine (9.9 mg, 20 mol %), KOtBu
(107.7 mg, 0.96 mmol), and DMF (3 mL) at 120 ꢀC for 24 h. Purifi-
cation of the crude material by silica gel column chromatography
100 MHz):
d
¼147.5 (s, ArC), 146.0 (s, ArC), 142.0 (s, ArC), 141.4 (s,
ArC), 132.7 (d, ArCH), 130.2 (d, ArCH), 127.5 (d, ArCH), 127.3 (d,