G. Kumaraswamy et al. / Tetrahedron 66 (2010) 9814e9818
9817
23
silica gel (hexanes/EtOAc: 75/25) to give 4c (1.14 g, 91% yield). [
a
]
(s,1H, ArH), 6.36 (s,1H,]CH), 5.80 (s,1H, CHOH), 5.05 (s, 2H, OCH2),
4.98 (s, 2H, OCH2); 13C NMR (75 MHz, CDCl3):
158.0, 156.7, 156.0,
D
þ6.9 (c 1.5, CHCl3); Rf (30% EtOAc/Hex) 0.45; 1H NMR (300 MHz,
d
CDCl3):
d
7.34(d, J¼8.49 Hz, 2H, ArH), 7.08e7.01(m, 2H, ArH), 6.84
152.6, 140.3, 136.7, 128.4, 128.0, 127.5, 127.4, 126.7, 101.8, 96.0, 89.8,
70.5, 70.4, 70.1; MS (ESI) m/z 459 (MþNa)þ; HRMS (ESI) m/z
459.1588 (calcd for C29H24NaO4: 459.1572); IR (neat): 3442, 3032,
(d, J¼8.6 Hz, 2H, ArH), 6.69 (dd, J¼2.2, 6.4 Hz, 1H, ArH), 6.40 (s,
1H,]CH), 5.84 (s, 1H, CHOH), 3.95 (s, 3H, OMe), 3.78 (s, 3H, OMe),
2.65 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3):
d
159.5, 159.2, 145.3,
2927, 2325, 1615, 1498, 1154, 1030, 738 cmꢁ1
.
144.3, 132.4, 129.1, 128.2, 123.5, 114.0, 113.5, 106.4, 104.2, 70.1, 55.9,
55.2; MS (ESI) m/z 307 (MþNa)þ; HRMS (ESI) m/z 307.0960 (calcd
for C17H16NaO4: 307.0946); IR (neat): 3418, 2932, 2841, 1612, 1513,
4.3.9. (R)-(5-tert-Butylbenzofuran-2-yl)(phenyl)methanol (4i). The
crude residue was purified by column chromatography on silica gel
(hexanes/EtOAc: 90/10) to give 4i (675 mg, 86% yield); Rf (10%
1248, 1031, 732 cmꢁ1
.
EtOAc/Hex) 0.55; 1H NMR (300 MHz, CDCl3):
d 7.44e7.40 (m, 3H,
ArH), 7.36e7.24 (m, 5H, ArH), 6.41 (s, 1H,]CH), 5.85 (s, 1H, CHOH),
4.3.4. (R)-(4-Chlorophenyl)(7-methoxybenzofuran-2-yl)methanol
(4d). The crude residue was purified by column chromatography
2.48 (br s, 1H, OH), 1.34 (s, 9H, t-Bu); 13C NMR (75 MHz, CDCl3):
d
158.5, 153.0, 145.8, 140.3, 128.6, 128.3, 127.6, 126.7, 122.2, 117.2,
on silica gel (hexanes/EtOAc: 85/15) to give 4d (800 mg, 87% yield).
110.5, 104.1, 70.7, 34.6, 31.8; MS (ESI) m/z 281 (MþH)þ; IR (neat):
23
[
a]
þ10.5 (c 4.0, CHCl3); Rf (15% EtOAc/Hex) 0.35; 1H NMR
D
3412, 2922, 2838, 1609, 1502, 1248, 1026, 728 cmꢁ1
.
(300 MHz, CDCl3):
d
7.42 (d, J¼8.4 Hz, 2H, ArH), 7.33 (d, J¼8.4 Hz,
2H, ArH), 7.26 (d, J¼7.7 Hz,1H, ArH), 6.73 (dd, J¼1.7, 7.1 Hz,1H, ArH),
6.40 (s, 1H,]CH), 5.90 (s, 1H, CHOH), 3.97 (s, 3H, OMe), 2.59 (s, 1H,
4.3.10. (R)-(5,7-Di-tert-butylbenzofuran-2-yl)(phenyl)methanol
(4j). The crude residue was purified by column chromatography on
silica gel (hexanes/EtOAc: 90/10) to give 4j (559 mg, 78% yield).
OH); 13C NMR (75 MHz, CDCl3):
d 158.3, 145.3, 144.2, 138.6, 133.8,
129.5, 128.6, 128.0, 126.7, 123.5, 113.4, 106.5, 104.4, 69.6, 55.8; MS
(ESI) m/z 311 (MþNa)þ; HRMS (ESI) m/z 311.0459 (calcd for
C16H13NaO3Cl: 295.0746); IR (neat): 3367, 2936, 2842, 1592, 1490,
23
[a
]
ꢁ97.5 (c 0.4, CHCl3); Rf (10% EtOAc/Hex) 0.45; 1H NMR
D
(300 MHz, CDCl3): d 7.49e7.45 (m, 2H, ArH), 7.37e7.28 (m, 4H, ArH),
1270, 1091, 779 cmꢁ1
.
7.14 (d, J¼1.8 Hz, 1H, ArH), 6.42 (s, 1H,]CH), 5.91 (d, J¼3.7 Hz, 1H,
CHOH), 2.31 (d, J¼4.3 Hz, 1H, OH), 1.45 (s, 9H, t-Bu), 1.34 (s, 9H, t-
Bu); 13C NMR (75 MHz, CDCl3):
d 157.8, 145.7, 140.7, 133.7, 128.3,
4.3.5. (R)-(4-Fluorophenyl)(7-methoxybenzofuran-2-yl)methanol
128.1, 126.8, 124.0, 122.5, 118.9, 115.1, 103.8, 70.6, 34.7, 34.3, 31.8,
(4e). The crude residue was purified by column chromatography on
29.0; MS (ESI) m/z 359 (MþNa)þ; IR (neat): 3415, 2924, 2833, 1605,
23
silica gel (hexanes/EtOAc: 85/15) to give 4e (730 mg, 84% yield). [a]
D
1499, 1027, 738 cmꢁ1
.
ꢁ3.8 (c 3.0, CHCl3); Rf (20% EtOAc/Hex) 0.35; 1H NMR (300 MHz,
CDCl3):
d
7.33 (dd, J¼5.4, 8.4 Hz, 2H, ArH), 7.06e6.91 (m, 4H, ArH),
4.3.11. (R)-(5-Bromobenzofuran-2-yl)(phenyl)methanol (4l). The
crude residue was purified by column chromatography on silica
6.67 (dd, J¼1.3, 7.3 Hz,1H, ArH), 6.32 (s,1H,]CH), 5.81 (s,1H, CHOH),
3.87 (s, 3H, OMe), 3.52 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3):
23
gel (hexanes/EtOAc: 90/10) to give 4l (760 mg, 95% yield). [a]
D
d
164.1, 160.8, 158.6, 145.1, 136.0, 135.9, 129.5, 128.6, 128.4, 123.5,
ꢁ7.3 (c 1.5, CHCl3); Rf (10% EtOAc/Hex) 0.30; 1H NMR (300 MHz,
115.4,115.1,113.4,106.4,104.2, 69.7, 55.8; MS (ESI) m/z 295 (MþNa)þ;
HRMS (ESI) m/z 295.0756 (calcd for C16H13NaO3F: 295.0746); IR
CDCl3):
d
7.58 (d, J¼1.8 Hz, 1H, ArH), 7.51 (dd, J¼1.5, 5.2 Hz, 1H,
(neat): 3388, 2936, 2844, 1599, 1500, 1222, 1094, 730 cmꢁ1
.
ArH), 7.46e7.31 (m, 5H, ArH), 7.29 (d, J¼1.8 Hz, 1H, ArH), 6.42 (s,
1H,]CH), 5.84 (s, 1H, CHOH); 13C NMR (75 MHz, CDCl3):
d
160.0,
139.9, 139.7, 129.6, 128.7, 127.1, 126.7, 123.8, 122.9, 112.7, 104.2,
4.3.6. (R)-(4-(Benzyloxy)phenyl)(7-methoxybenzofuran-2-yl)metha-
nol (4f). The crude residue was purified bycolumn chromatography
on silica gel (hexanes/EtOAc: 80/20) to give 4f (1.05 g, 92% yield).
103.3, 70.6; HRMS (ESI) m/z 324.9838 (calcd for C15H11NaO2Br:
324.9840); IR (neat): 3432, 3028, 2927, 1611, 1498, 1150, 748 cmꢁ1
.
[
a]
23 þ5.3 (c 1.5, CHCl3); Rf (30% EtOAc/Hex) 0.35; 1H NMR (300 MHz,
D
4.3.12. (R)-Naphtho[2,1-b]furan-2-yl(phenyl)methanol (4m). The
crude residue was purified by column chromatography on silica
CDCl3):
d 7.41e7.24 (m, 15H, Ar), 7.05e7.02 (m, 2H, ArH), 6.93 (d,
J¼8.6 Hz, 2H, ArH), 6.71 (dd, J¼2.4, 6.4 Hz,1H, ArH), 6.42 (s,1H,]CH),
23
gel (hexanes/EtOAc: 85/15) to give 4m (716 mg, 90% yield). [a]
D
5.86 (s, 1H, CHOH), 5.05 (s, 2H, OCH2), 3.98 (s, 3H, OMe), 2.38 (br s,
ꢁ10.3 (c 2.0, CHCl3); Rf (20% EtOAc/Hex) 0.60; 1H NMR (300 MHz,
1H, OH); 13C NMR (75 MHz, CDCl3):
d 159.2,158.8,145.3,144.2,136.9,
CDCl3):
d
7.98 (d, J¼8.1 Hz, 1H, ArH), 7.85 (d, J¼7.9 Hz, 1H, ArH),
132.6,129.9,128.5,128.2,127.9,127.4,123.4,114.8,113.4,106.2,104.0,
70.0, 69.9, 55.8; MS (ESI) m/z 383 (MþNa)þ; HRMS (ESI) m/z
383.1266 (calcd for C23H20NaO4: 383.1259); IR (neat): 3409, 3034,
7.68e7.61 (m, 1H, ArH), 7.55 (d, J¼8.8 Hz, 1H, ArH), 7.51e7.45 (m,
2H, ArH), 7.40e7.23 (m, 5H, ArH), 6.92 (s, 1H,]CH), 5.97 (s, 1H,
CHOH), 2.62 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3):
d 157.8,
2933, 1609, 1502, 1309, 1237, 1173, 1017, 784 cmꢁ1
.
152.6, 140.4, 130.3, 128.7, 128.6, 128.4, 127.7, 126.8, 126.3, 125.3,
124.5, 123.3, 112.4, 103.2, 70.8; MS (ESI) m/z 297 (MþNa)þ; IR
4.3.7. (R)-Benzofuran-2-yl(2,4-dimethoxyphenyl)methanol
(4g). The crude residue was purified by column chromatography
on silica gel (hexanes/EtOAc: 75/25) to give 4g (1.42 g, 91% yield);
(neat): 3416, 3058, 2924, 1630, 1454, 1049, 804, 745 cmꢁ1
.
Rf (20% EtOAc/Hex) 0.30; 1H NMR (300 MHz, CDCl3):
d 7.65e7.36
4.3.13. (S)-(7-Methoxybenzofuran-2-yl)(thiophen-2-yl)methanol
(4n). The crude residue was purified by column chromatography on
(m, 3H, ArH), 7.22e7.11 (m, 2H, ArH), 6.55e6.46 (m, 1H, ArH), 6.44
23
silica gel (hexanes/EtOAc: 85/15) to give 4n (716 mg, 90% yield). [
a
]
D
(s, 2H, ArH), 6.05 (s, 1H, CHOH), 3.83 (s, 3H, OMe), 3.80 (s, 3H,
ꢁ10.3 (c 2.0, CHCl3); Rf (20% EtOAc/Hex) 0.40; 1H NMR (300 MHz,
OMe), 2.81 (s, 1H, OH); 13C NMR (75 MHz, CDCl3):
d 160.5, 157.7,
CDCl3):
d
7.22 (d, J¼3.7 Hz,1H, ArH), 7.05 (d, J¼2.2 Hz,1H, ArH), 7.03 (s,
156.3, 156.2, 129.1, 127.6, 125.1, 124.7, 123.3, 120.9, 111.5, 110.9,
105.0, 100.6, 66.7, 55.6, 55.4; MS (ESI) m/z 307 (MþNa)þ; HRMS
(ESI) m/z 307.0956 (calcd for C17H16NaO4: 307.0946); IR (neat):
1H, ArH), 7.00 (d, J¼3.0 Hz, 1H, ArH), 6.90 (dd, J¼3.0, 4.5 Hz, 1H, ArH),
6.69 (dd, J¼3.7, 6.0 Hz, 1H, ArH), 6.55 (s,1H,]CH), 6.09 (s, 1H, CHOH),
3.91 (s, 3H, OMe), 3.36(brs,1H, OH);13C NMR (75MHz,CDCl3):
d 157.7,
3565, 2932, 2841, 1609, 1459, 1209, 1034, 750 cmꢁ1
.
145.2, 143.7, 291.5, 126.6, 125.7, 125.6, 123.5, 113.5, 106.2, 104.2, 66.5,
57.0; MS (ESI) m/z 283 (MþNa)þ; IR (neat): 3394, 2924, 2848, 1591,
4.3.8. (R)-(4,6-Bis(benzyloxy)benzofuran-2-yl)(phenyl)methanol
(4h). The crude residue was purified by column chromatography
1491, 1267, 1176, 778, 703 cmꢁ1
.
on silica gel (hexanes/EtOAc: 70/30) to give 4h (580 mg, 89% yield).
23
ꢁ6.7 (c 2.3, CHCl3); Rf (35% EtOAc/Hex) 0.45; 1H NMR
4.3.14. (S)-Benzofuran-2-yl(thiophen-2-yl)methanol
crude residue was purified by column chromatography on silica
(4o). The
[a]
D
(300 MHz, CDCl3): d 7.43e7.26 (m, 15H, ArH), 6.59 (s, 1H, ArH), 6.48