A. Wu et al. / Tetrahedron 68 (2012) 7217e7233
7227
and Q-phos (18 mg, 0.025 mmol) in THF (0.5 mL) was added
ZnBrCH2CO2Et (1M in THF, 1.5 mL) dropwise at room temperature
under argon. The resulting mixture was stirred for 2 h, monitored by
TLC, anddiluted with EtOAc (20 mL). Afterevaporation of the solvent,
the residue was purified by chromatography on a silica gel column.
Elution with hexane/EtOAc (40:1 to 20:1) gave 11b (147 mg, 92%): 1H
DMSO-d6) d 173.3, 157.9, 142.3, 136.5, 133.7, 133.1, 131.3, 130.5, 129.9,
128.7, 128.2, 127.83, 127.75, 127.4, 127.0, 119.5, 106.2, 55.7, 39.1;
HRMS calcd for C19H17O3 [MþH]þ 293.1172, found 293.1143.
5.2.11. 13C2-2-(7-Methoxynaphthalenyl)phenylacetic acid
(
13C2-
11c). 1H NMR (500 MHz, DMSO-d6)
d
12.23 (br s, 1H), 8.00e7.83 (m,
NMR (500 MHz, CDCl3)
d
7.84 (d, J¼8.0 Hz,1H), 7.82 (d, J¼9.0 Hz,1H),
2H), 7.87 (s, 1H), 7.50e7.29 (m, 6H), 7.19 (dd, J¼9.0 and 2.5 Hz, 1H),
7.73 (s, 1H), 7.39e7.48 (m, 4H), 7.35 (dd, J¼8.0 and 1.5 Hz, 1H), 7.21
(dd, J¼8.5 and 2.5 Hz,1H), 7.18 (d, J¼2.5 Hz,1H), 4.11 (q, J¼7.0 Hz, 2H),
3.96 (s, 3H), 3.68 (s, 2H), 1.20 (t, J¼7.0 Hz, 3H); 13C NMR (125.8 MHz,
3.89 (s, 3H), 3.57 (dd, J¼128.5 and 8.0 Hz, 2H); 13C NMR (125.8 MHz,
DMSO-d6)
d
173.2 (d, J¼218.0 Hz), 39.0 (d, J¼218.0 Hz); HRMS calcd
for 13C2-C19H17O3 [MþH]þ 295.1239, found 295.1211.
CDCl3)
d 171.9, 157.9, 142.5, 138.1, 134.3, 132.0, 130.29, 130.25, 129.1,
127.8, 127.5, 127.4, 127.1, 126.9, 125.3, 118.8, 105.8, 60.6, 55.2, 39.0,
5.2.12. 3-Methoxychrysen-5-ol (12e). A suspension of 11c (292 mg,
1 mmol) in MeSO3H was heated at 50 ꢂC for 1 h and monitored by
TLC, then cooled to room temperature, and poured onto crushed ice
(50 g). The solid was filtered off, and dissolved in EtOAc (50 mL).
The solution was washed with brine and water, and dried over
anhydrous Na2SO4. After evaporation of the solvent under reduced
pressure, the residue was chromatographed on a silica gel column.
Elution with hexane/EtOAc (10:1 to 5:1) gave 12e (221 mg, 77%): 1H
14.0; HRMS calcd for C21H21O3 [MþH]þ 321.1485, found 321.1483.
5.2.5. Ethyl 13C2-2-(7-methoxynaphthalenyl)phenylacetate
(
13C2-
7.84 (d, J¼8.0 Hz, 1H), 7.82 (d,
11b). 1H NMR (500 MHz, CDCl3)
d
J¼9.0 Hz, 1H), 7.73 (s, 1H), 7.48e7.39 (m, 4H), 7.35 (dd, J¼8.0 and
1.5 Hz, 1H), 7.21 (dd, J¼8.5 and 2.5 Hz, 1H), 7.18 (d, J¼2.5 Hz, 1H),
4.11 (q, J¼7.0 Hz, 2H), 3.96 (s, 3H), 3.68 (dd, J¼129.0 and 8.0 Hz, 2H),
1.20 (t, J¼7.0 Hz, 3H); 13C NMR (125.8 MHz, CDCl3)
d
172.0 (d,
NMR (500 MHz, acetone-d6)
d
9.79 (s, 1H), 9.62 (d, J¼3.0 Hz, 1H),
J¼228.0 Hz), 39.0 (d, J¼228.0 Hz); HRMS calcd for 13C2-C21H20NaO3
[MþNa]þ 345.1372, found 345.1349.
8.78 (d, J¼11.0 Hz, 1H), 8.72 (d, J¼11.0 Hz, 1H), 8.04 (d, J¼11.5 Hz,
1H), 7.99 (d, J¼11.0 Hz, 1H), 7.82 (d, J¼11.0 Hz, 1H), 7.65e7.45 (m,
3H), 7.33 (dd, J¼8.5 and 2.5 Hz, 1H), 4.00 (s, 3H); 13C NMR
5.2.6. Ethyl 2-(5-methoxynaphthalenyl)phenylacetate (11d). Reaction
of 10a with ZnBrCH2CO2Et gave 11d (93%): 1H NMR (500 MHz, CDCl3)
(125.8 MHz, acetone-d6) d 158.1, 154.4, 133.3, 132.2, 131.5, 129.3,
128.1, 127.9, 126.8, 126.1, 126.0, 123.7, 123.4,119.0, 116.6, 110.2, 108.6,
d
8.36 (d, J¼8.5 Hz,1H), 7.80 (d, J¼1.5 Hz,1H), 7.55e7.35 (m, 7H), 6.89
54.7; HRMS calcd for C19H15O2 [MþH]þ 275.1067, found 275.1062.
(dd, J¼6.5 and 2.0 Hz, 1H), 4.12 (q, J¼7.0 Hz, 2H), 4.07 (s, 3H), 3.68 (s,
2H),1.22 (t, J¼7.0 Hz, 3H); 13C NMR (125.8 MHz, CDCl3)
d
171.9,155.4,
5.2.13. 13C2-3-Methoxychrysen-5-ol (13C2-12e). 1H NMR (500 MHz,
142.4, 139.1, 134.2, 132.0, 130.31, 130.26, 127.6, 127.5, 127.1, 126.8,
126.3, 124.5, 121.9, 120.2, 103.9, 60.6, 55.5, 38.9, 14.0; HRMS calcd for
DMSO-d6)
d
10.87 (s, 1H), 9.51 (d, J¼2.5 Hz, 1H), 8.78 (d, J¼8.5 Hz,
1H), 8.72 (d, J¼9.0 Hz, 1H), 8.04 (d, J¼9.0 Hz, 1H), 8.01 (d, J¼9.0 Hz,
1H), 7.88e7.78 (m, 1H), 7.62e7.42 (m, 3H), 7.33 (dd, J¼9.0 and
C
21H20NaO3 [MþNa]þ 343.1305, found 343.1330.
2.5 Hz, 1H), 3.96 (s, 3H); 13C NMR (125.8 MHz, DMSO-d6)
d 154.9 (d,
5.2.7. Ethyl 2-(6-methoxynaphthalenyl)phenylacetate (11f). Reaction
of 10b with ZnBrCH2CO2Et afforded 11f (90%): 1H NMR (500 MHz,
J¼277.5 Hz), 108.7 (d, J¼277.5 Hz); HRMS calcd for 13C2-C19H14O2
[M]þ 276.1055, found 276.1056.
CDCl3)
4.10 (q, J¼7.0 Hz, 2H), 3.98 (s, 3H), 3.67 (s, 2H), 1.20 (t, J¼7.0 Hz, 3H);
13C NMR (125.8 MHz, CDCl3)
172.0, 157.9, 142.5, 136.4, 133.6, 132.2,
d 7.90e7.70 (m, 3H), 7.50e7.30 (m, 5H), 7.25e7.15 (m, 2H),
5.2.14. 1-Methoxychrysen-5-ol (12a). Similar acid-catalyzed cycli-
d
zation of 11e gave 12a (80%): 1H NMR (500 MHz, acetone-d6)
d 9.66
130.5, 130.4, 129.6, 128.7, 128.1, 127.9, 127.5, 127.2, 126.6, 119.2, 105.6,
60.8, 55.4, 39.1, 14.2; HRMS Calcd for C21H21O3 [MþH]þ 321.1485,
found 321.1517.
(s, 1H), 9.65 (d, J¼8.5 Hz, 1H), 8.86 (d, J¼9.0 Hz, 1H), 8.81 (d,
J¼8.5 Hz,1H), 8.40 (d, J¼9.0 Hz,1H), 7.82 (d, J¼9.0 Hz,1H), 7.65e7.49
(m, 4H), 7.17 (d, J¼7.5 Hz, 1H), 4.09 (s, 3H); 13C NMR (125.8 MHz,
acetone-d6)
d 155.2, 154.3, 133.2, 131.9, 131.3, 126.8, 126.2, 126.01,
5.2.8. 2-(7-Methoxynaphthalenyl)phenylacetic acid (11c). To a solu-
tion of 11b (467 mg, 1.46 mmol) in EtOH (18 mL) and H2O (6 mL)
was added NaOH (175 mg, 4.38 mmol). The resulting mixture was
heated at reflux for 1 h, and reaction was monitored by TLC. This
was evaporated to dryness, and the residue was diluted with water
(50 mL), and acidified with 37% HCl. The solid was filtered off, and
dried to provide 11c (385 mg, 90%): 1H NMR (500 MHz, acetone-d6)
125.96, 124.3, 123.8, 123.4, 121.5, 121.4, 120.5, 109.0, 108.9, 105.2,
55.2; HRMS calcd for C19H15O2 [MþH]þ 275.1067, found 275.1091.
5.2.15. 13C2-1-Methoxychrysen-5-ol (13C2-12a). 1H NMR (500 MHz,
acetone-d6)
d
10.87 (s, 1H), 9.55 (d, J¼9.0 Hz, 1H), 8.86 (d, J¼9.0 Hz,
1H), 8.80 (d, J¼8.5 Hz, 1H), 8.44 (d, J¼9.5 Hz, 1H), 7.82e7.75 (m, 1H),
7.65e7.27 (m, 4H), 7.20 (d, J¼7.5 Hz, 1H), 4.05 (s, 3H); 13C NMR
d
8.02e7.83 (m, 2H), 7.76 (s, 1H), 7.50e7.44 (m, 1H), 7.44e7.29 (m,
(125.8 MHz, acetone-d6)
d
154.8 (d, J¼277.5 Hz),109.1 (d, J¼277.5 Hz);
5H), 7.19 (dd, J¼9.0 and 2.5 Hz, 1H), 3.94 (s, 3H), 3.67 (s, 2H); 13C
HRMS calcd for 13C2-C19H15O2 [MþH]þ 277.1134, found 277.1093.
NMR (125.8 MHz, DMSO-d6) d 173.3, 158.1, 142.4, 139.4, 134.6, 133.2,
131.3, 130.3, 129.6, 127.9, 127.4, 127.0, 125.4, 119.2,106.7, 55.7; HRMS
5.2.16. 2-Methoxychrysen-5-ol (12c). Acid-catalyzed cyclization of
calcd for C19H16O3 [M]þ 292.1094, found 292.1061.
11g gave 12c (87%): 1H NMR (500 MHz, acetone-d6)
d 9.98 (d,
J¼9.5 Hz, 1H), 9.66 (s, 1H), 8.82 (d, J¼9.0 Hz, 1H), 8.76 (d, J¼8.0 Hz,
1H), 8.02 (d, J¼9.0 Hz, 1H), 7.82 (d, J¼7.5 Hz, 1H), 7.60e7.40 (m, 4H),
7.32 (dd, J¼9.5 and 2.5 Hz, 1H), 3.99 (s, 3H); 13C NMR (125.8 MHz,
5.2.9. 2-(5-Methoxynaphthalenyl)phenylacetic
acid
(11e). Hydrolysis of 11d gave 11e (92%): 1H NMR (500 MHz, DMSO-
d6)
d
8.18 (d, J¼9.0 Hz, 1H), 7.77 (s, 1H), 7.60e7.35 (m, 7H), 6.99 (dd,
acetone-d6) d 157.7, 153.9, 134.9, 132.7, 130.8, 129.6, 127.9, 126.3,
J¼5.5 and 3.0 Hz, 1H), 3.99 (s, 3H), 3.60 (s, 2H); 13C NMR
126.2, 126.0, 125.4, 123.8, 123.0, 121.8, 121.4, 117.0, 109.0, 107.6, 54.7;
(125.8 MHz, DMSO-d6)
d
173.2, 155.3,142.1, 139.3, 134.3,133.1,131.4,
HRMS calcd for C19H15O2 [MþH]þ 275.1067, found 275.1085.
130.3, 128.0, 127.7, 127.5, 127.2, 127.0, 124.2, 121.9, 120.6, 105.1, 56.1,
39.1; HRMS calcd for C19H17O3 [MþH]þ 293.1172, found 293.1143.
5.2.17. 13C2-2-Methoxychrysen-5-ol (13C2-12c). This unstable com-
pound was used directly.
5.2.10. 2-(6-Methoxynaphthalenyl)phenylacetic
acid
(11g). Hydrolysis of 11f gave 11g (90%): 1H NMR (500 MHz, DMSO-
5.2.18. 3-Methoxychrysen-5-ol trifluoromethanesulfonate (12f). To
a solution of 12e (180 mg, 0.65 mmol) in CH2Cl2 (10 mL) was added
pyridine (103 mg, 1.3 mmol), and the mixture was stirred for
d6)
d
7.87 (d, J¼8.0 Hz, 1H), 7.75 (s, 1H), 7.45e7.29 (m, 6H), 7.20 (d,
J¼8.0 Hz, 1H), 3.89 (s, 3H), 3.57 (s, 2H); 13C NMR (125.8 MHz,