Y. Fujita et al. / Bioorg. Med. Chem. 18 (2010) 1194–1203
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silica gel column chromatography (hexane/EtOAc = 20:1) to afford
5.2.6. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
8 (2.04 g, 7.12 mmol, 75% yield) as a colorless oil.
pyridinyl)-2-propyn-1-ol (9g)
1H NMR (500 MHz, CDCl3) d 10.87 (s, 1H), 9.28 (br d,
J = 8.5 Hz, 1H), 7.96 (d, J = 9.2 Hz, 1H), 7.77 (br d, J = 7.9 Hz,
1H), 7.62 (ddd, J = 8.5, 7.3, 1.5 Hz, 1H), 7.43 (ddd, J = 7.9, 7.3,
1.2 Hz, 1H), 7.06 (d, J = 9.2 Hz, 1H), 1.06 (s, 9H), 0.33 (s, 6H).
FAB-MS m/z 287 (M+H)+.
2-Ethynylpyridine (0.260 mL, 2.57 mmol), n-BuLi (1.60 mL,
2.54 mmol), and 8 (540 mg, 1.89 mmol) afforded 9g (342 mg,
0.878 mmol, 47% yield) as a brown oil.
1H NMR (500 MHz, CDCl3) d 8.59 (d, J = 8.5 Hz, 1H), 8.54–8.53
(m, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 8.5 Hz, 1H), 7.61–7.57
(m, 1H), 7.55–7.52 (m, 1H), 7.39–7.36 (m, 1H), 7.35–7.33 (m,
1H), 7.18 (ddd, J = 7.3, 4.9, 1.2 Hz, 1H), 7.09 (d, J = 8.5 Hz, 1H),
6.68 (d, J = 5.5 Hz, 1H), 3.18 (d, J = 5.5 Hz, 1H), 1.08 (s, 9H), 0.34
(s, 3H), 0.32 (s, 3H). FAB-MS m/z 372 (MꢀOH)+, 389 (M)+, 390
(M+H)+.
5.2.2. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-phenyl-
2-propyn-1-ol (9a)
To a solution of phenylacetylene (0.150 mL, 1.37 mmol) in dry
THF (2 mL) was slowly added n-BuLi (0.700 mL, 1.16 mmol) at
ꢀ78 °C and the mixture was stirred for 40 min under Ar. Then, a
solution of 8 (204 mg, 0.713 mmol) in dry THF (1.5 mL) was slowly
added. Stirring was continued at ꢀ78 °C for 2 h under Ar, then the
reaction was quenched with saturated NH4Cl solution, and the
mixture was extracted with EtOAc. The organic layer was washed
with brine, dried over MgSO4, filtered, and concentrated. The resi-
due was purified by silica gel column chromatography (hexane/
EtOAc = 5:1) to afford 9a (255 mg, 0.656 mmol, 92% yield) as a yel-
low oil.
5.2.7. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-
phenyl-2-propyn-1-one (10a)
A solution of 9a (143 mg, 0.369 mmol) and MnO2 (343 mg,
3.95 mmol) in dry CH2Cl2 (9 mL) was stirred at room temperature
for 23 h and filtered through Celite. The filtrate was concentrated
and the residue was purified by silica gel column chromatography
(hexane/EtOAc = 10:1) to afford 10a (92.9 mg, 0.240 mmol, 65%
yield) as a yellow oil.
1H NMR (500 MHz, CDCl3) d 8.59 (d, J = 8.5 Hz, 1H), 7.79 (d,
J = 7.9 Hz, 1H), 7.72 (d, J = 9.2 Hz, 1H), 7.54 (ddd, J = 8.5, 6.7,
1.2 Hz, 1H), 7.40–7.36 (m, 3H), 7.27–7.24 (m, 3H), 7.09 (d,
J = 9.2 Hz, 1H), 6.63 (d, J = 5.5 Hz, 1H), 3.10 (d, J = 6.1 Hz, 1H),
1.09 (s, 9H), 0.33 (s, 3H), 0.32 (s, 3H). FAB-MS m/z 371 (MꢀOH)+,
388 (M)+, 389 (M+H)+.
1H NMR (500 MHz, CDCl3) d 8.00 (d, J = 8.5 Hz, 1H), 7.83 (d,
J = 8.5 Hz, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.56–7.54 (m, 2H), 7.52–
7.49 (m, 1H), 7.44–7.33 (m, 4H), 7.11 (d, J = 9.2 Hz, 1H), 0.99 (s,
9H), 0.26 (s, 6H). 13C NMR (125 MHz, CDCl3) 181.3, 152.1, 133.1,
132.2, 131.1, 130.5, 128.9, 128.5, 128.1, 127.7, 126.0, 124.4,
123.7, 120.7, 120.4, 91.9, 90.6, 25.7, 18.3, ꢀ4.0. FAB-MS m/z 387
(M+H)+.
Compounds 9b, 9d, 9f, and 9g were prepared using the same
procedure as described for preparing 9a from 8.
5.2.8. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
methylphenyl)-2-propyn-1-one (10b)
5.2.3. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
methylphenyl)-2-propyn-1-ol (9b)
To a solution of 9b (313 mg, 0.777 mmol) in CH2Cl2 (1 mL) was
2-Ethynyltoluene (0.160 mL, 1.23 mmol), n-BuLi (0.780 mL,
1.30 mmol), and 8 (315 mg, 1.10 mmol) afforded 9b (313 mg,
0.777 mmol, 71% yield) as a yellow oil.
added
a
solution of Dess–Martin periodinane (392 mg,
0.923 mmol) in CH2Cl2 (2.5 mL). The mixture was stirred at room
temperature for 15 min, diluted with EtOAc (6 mL), quenched with
0.1 M Na2S2O3 solution (6 mL), and extracted with EtOAc. The or-
ganic layer was washed with brine, dried over MgSO4, filtered,
and concentrated. The residue was purified by silica gel column
chromatography (hexane/EtOAc = 10:1) to afford 10b (202 mg,
0.504 mmol, 65% yield) as a yellow oil.
1H NMR (500 MHz, CDCl3) d 8.68 (d, J = 8.5 Hz, 1H), 7.79 (d,
J = 7.9 Hz, 1H), 7.72 (d, J = 8.5 Hz, 1H), 7.53 (ddd, J = 8.6, 6.7,
1.2 Hz, 1H), 7.40–7.37 (m, 1H), 7.34 (d, J = 7.9 Hz, 1H), 7.18–7.12
(m, 2H), 7.09–7.06 (m, 2H), 6.70 (d, J = 5.5 Hz, 1H), 2.91 (d,
J = 5.5 Hz, 1H), 2.33 (s, 3H), 1.09 (s, 9H), 0.32 (s, 3H), 0.31 (s, 3H).
FAB-MS m/z 385 (MꢀOH)+, 402 (M)+, 403 (M+H)+.
1H NMR (500 MHz, CDCl3) d 8.02 (d, J = 8.5 Hz, 1H), 7.82 (d,
J = 9.2 Hz, 1H), 7.79 (d, J = 8.5 Hz, 1H), 7.52–7.48 (m, 2H), 7.40–
7.37 (m, 1H), 7.32–7.29 (m, 1H), 7.20 (d, J = 7.9 Hz, 1H), 7.15 (dd,
J = 7.6, 7.6 Hz, 1H), 7.11 (d, J = 8.5 Hz, 1H), 2.41 (s, 3H), 0.98 (s,
9H), 0.26 (s, 6H). FAB-MS m/z 401 (M+H)+.
5.2.4. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
fluorophenyl)-2-propyn-1-ol (9d)
1-Ethynyl-2-fluorobenzene (0.180 mL, 1.59 mmol), n-BuLi
(0.900 mL, 1.49 mmol), and 8 (228 mg, 0.797 mmol) afforded 9d
(218 mg, 0.536 mmol, 67% yield) as a yellow oil.
5.2.9. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
fluorophenyl)-2-propyn-1-one (10d)
1H NMR (500 MHz, CDCl3) d 8.61 (d, J = 8.5 Hz, 1H), 7.79 (d,
J = 7.9 Hz, 1H), 7.73 (d, J = 9.2 Hz, 1H), 7.55 (ddd, J = 8.6, 6.7,
1.2 Hz, 1H), 7.40–7.34 (m, 2H), 7.24–7.23 (m, 1H), 7.09 (d,
J = 8.5 Hz, 1H), 7.04–7.00 (m, 2H), 6.67 (d, J = 5.5 Hz, 1H), 3.08 (d,
J = 6.1 Hz, 1H), 1.09 (s, 9H), 0.33 (s, 3H), 0.32 (s, 3H). FAB-MS m/z
389 (MꢀOH)+, 406 (M)+, 407 (M+H)+.
The title compound 10d (142 mg, 0.351 mmol, 65% yield) was
synthesized from 9d (218 mg, 0.536 mmol) and Dess–Martin peri-
odinane (252 mg, 0.576 mmol) as a yellow oil following the same
procedure as described for 10b from 9b.
1H NMR (500 MHz, CDCl3) d 8.02 (d, J = 8.5 Hz, 1H), 7.84 (d,
J = 8.5 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.55–7.50 (m, 2H), 7.44–
7.38 (m, 2H), 7.14–7.08 (m, 3H), 0.99 (s, 9H), 0.27 (s, 6H). FAB-
MS m/z 405 (M+H)+.
5.2.5. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
methoxyphenyl)-2-propyn-1-ol (9f)
2-Ethynylanisole (410 mg, 3.01 mmol), n-BuLi (1.75 mL,
2.78 mmol), and 8 (633 mg, 2.21 mmol) afforded 9f (637 mg,
1.52 mmol, 69% yield) as a yellow oil.
5.2.10. 1-(20-tert-Butyldimethylsilyloxynaphthalen-10-yl)-3-(200-
methoxyphenyl)-2-propyn-1-one (10f)
1H NMR (500 MHz, CDCl3) d 8.73 (d, J = 7.9 Hz, 1H), 7.78 (d,
J = 7.9 Hz, 1H), 7.71 (d, J = 8.5 Hz, 1H), 7.53 (ddd, J = 8.6, 6.7,
1.2 Hz, 1H), 7.39–7.36 (m, 1H), 7.31 (dd, J = 8.0, 1.8 Hz, 1H), 7.26–
7.22 (m, 1H), 7.07 (d, J = 9.2 Hz, 1H), 6.85–6.81 (m, 2H), 6.68 (d,
J = 5.5 Hz, 1H), 3.81 (s, 3H), 2.94 (d, J = 5.5 Hz, 1H), 1.08 (s, 9H),
0.32 (s, 3H), 0.31 (s, 3H). FAB-MS m/z 401 (MꢀOH)+, 418 (M)+,
419 (M+H)+.
To a solution of 9f (637 mg, 1.52 mmol) and t-BuOH (0.150 mL,
1.64 mmol) in CH2Cl2 (1.2 mL) was added a solution of Dess–Mar-
tin periodinane (780 mg, 1.84 mmol) in CH2Cl2 (5.1 mL). The mix-
ture was stirred at room temperature for 20 min, diluted with
EtOAc (8.9 mL), quenched with Na2S2O3ꢂ5H2O (3.38 g, 13.6 mmol)
in saturated NaHCO3 solution (9.9 mL), and extracted with EtOAc.
The organic layer was washed with brine, dried over MgSO4, fil-