A R T I C L E S
Saphier et al.
added via a syringe. The mixture was stirred at 0 °C for 15 min and
then allowed to warm to room temperature and stirred for additional
30 min. The reaction was quenched with saturated aq. NH4Cl and
extracted with diethyl ether. The combined organic phase was washed
with brine, dried over MgSO4. Solvents were removed under reduced
pressure. The crude product was purified over silica gel (hexanes-
1-[4′-(Dioxolan-2′′-yl)phenyl]-4-(3′′′-methoxyphenyl)butan-1-ol,
17b. 1H NMR (200 MHz, CDCl3): 7.43 (d, J ) 8.2 Hz, 2H), 7.31 (d,
J ) 8.2 Hz, 2H), 6.73-6.68 (m, 4H), 5.78 (s, 1H), 4.67 (t, J ) 6.9 Hz,
1H), 4.15-4.00 (m, 4H), 3.76 (s, 3H), 2.57 (t, J ) 7.3 Hz, 2H), 1.88-
1.75 (m, 4H). MS (CI): 329.0 (MH+).
1-[4′-(Dioxolan-2′′-yl)phenyl]-4-(3′′′-methoxyphenyl)butan-1-
1
1
ethyl acetate 8:2) to give 17a (580 mg, 64%). H NMR (200 MHz,
one, 18b. H NMR (200 MHz, CDCl3): 7.91 (d, J ) 8.2 Hz, 2H),
CDCl3): 7.43 (d, J ) 8.3 Hz, 2H), 7.31 (d, J ) 8.3 Hz, 2H), 6.30 (m,
3H) 5.78 (s, 1H), 4.67 (t, J ) 6.9 Hz, 1H), 3.97-4.15 (m, 4H), 3.74
(s, 6H), 2.53 (t, J ) 7.2 Hz, 2H), 1.56-1.89 (m, 4H).
7.53 (d, J ) 8.2 Hz, 2H), 7.18 (t, J ) 8.2 Hz, 1H), 6.79-6.71 (m,
3H), 5.83 (s, 1H), 4.17-4.02 (m, 4H), 3.77 (s, 3H), 2.96 (t, J ) 7.2
Hz, 2H), 2.68 (t, J ) 7.3 Hz, 2H), 2.03 (quintet, J ) 7.3 Hz, 2H). MS
(CI): 327.0 (MH+).
1-(4′-Formylphenyl)-4-(3′′-methoxyphenyl)butan-1-one, 19b. 1H
NMR (200 MHz, CDCl3): 10.08 (s, 1H), 8.03 (d, J ) 8.3 Hz, 2H),
7.93 (d, J ) 8.3 Hz, 2H), 7.21-7.13 (m, 1H), 6.79-6.68 (m, 3H),
3.77 (s, 3H), 2.99 (t, J ) 7.1 Hz, 2H), 2.70 (t, J ) 7.1 Hz, 2H), 2.08
(quintet, J ) 7.1 Hz, 2H). MS (CI): 283.1 (MH+).
1-(4′-Hydroxycarbonylphenyl)-4-(3′′-methoxyphenyl)butan-1-
one, 1b. 1H NMR (200 MHz, CDCl3): 8.15 (d, J ) 8.4 Hz, 2H), 7.97
(d, J ) 8.4 Hz, 2H), 7.17 (m, 1H), 6.79-6.69 (m, 3H), 3.77 (s, 3H),
3.00 (t, J ) 7.2 Hz, 2H), 2.72 (t, J ) 7.2 Hz, 2H), 2.08 (quintet, J )
7.2 Hz, 2H). MS (CI): 299.1 (MH+).
1-[4′-(Dioxolan-2′′-yl)phenyl]-4-(3′′′,5′′′-dimethoxyphenyl)butan-
1-one, 18a. PCC (1.99 g, 9.2 mmol) and diatomaceous earth (2 g) were
added to a stirring solution of alcohol 17a (1.65 g, 4.6 mmol) in CH2-
Cl2 (20 mL) at room temperature. After 1 h the brown mixture was
filtered through silica gel and washed with ethyl acetate. The solvents
were removed under reduced pressure and the crude product was
purified by column chromatography (silica gel, hexanes-ethyl acetate
7:3) to give 18a (1.17 g, 72%). 1H NMR (200 MHz, CDCl3): 7.91 (d,
J ) 8.2 Hz, 2H), 7.53 (d, J ) 8.2 Hz, 2H), 6.33 (d, J ) 2.2 Hz, 2H),
6.29 (t, J ) 2.2 Hz, 1H), 5.78 (s, 1H)4.02-4.11 (m, 4H), 3.75 (s, 6H),
2.95 (t, J ) 7.2 Hz, 2H), 2.64 (t, J ) 7.5 Hz, 2H), 2.05 (quintet, J )
7.3 Hz, 2H). MS (CI): 357.2 (MH+).
Ethyl 4-Phenylbutyrate, 15c. (prepared by the esterefication of
1
4-Phenyl-butyric acid) H NMR (200 MHz, CDCl3): 7.31-7.14 (m,
1-(4′-Formylphenyl)-4-(3′′′,5′′′-dimethoxyphenyl)butan-1-one, 19a.
Compound 18a (248 mg, 0.7 mmol) was dissolved in THF (5 mL) and
H2O (0.5 mL). PTSA (50 mg) was added and the mixture was stirred
overnight. Saturated aq. NaHCO3 was added and the mixture was
extracted with diethyl ether. The combined organic phase was washed
with brine, dried over MgSO4 and solvents were removed under reduced
pressure. The crude product was purified by column chromatography
(silica gel, hexanes-ethyl acetate 7:3) to give 19a (180 mg, 78.4%) in
the form of a white solid. 1H NMR (200 MHz, CDCl3): 10.07 (s, 1H),
8.03 (d, J ) 8.2 Hz, 2H), 7.93 (d, J ) 8.2 Hz, 2H), 6.33 (d, J ) 1.7
Hz, 2H), 6.30 (t, J ) 1.7 Hz, 1H), 3.75 (s, 6H), 2.99 (t, J ) 7.1 Hz,
2H), 2.66 (t, J ) 7.4 Hz, 2H), 2.07 (quintet, J ) 7.3, 2H). MS (CI):
313.2 (MH+).
5H), 3.65 (s, 3H), 2.64 (t, J ) 7.4 Hz, 2H), 2.32 (t, J ) 7.3 Hz, 2H),
1.94 (quintet, J ) 7.4 Hz, 2H). MS (CI): 179.0 (MH+). MS (CI): 179.0
(MH+).
4-Phenylbutyraldehyde, 16c.49 1H NMR (200 MHz, CDCl3): 9.74
(t, J ) 1.5 Hz, 1H), 7.32-7.14 (m, 5H), 2.65 (t, J ) 7.3 Hz, 2H), 2.44
(td, J ) 7.7 Hz, 1.4 Hz, 2H), 1.95 (quintet, J ) 7.7 Hz, 2H). MS (CI):
149 (MH+).
1
1-[4′-(Dioxolan-2′′-yl)phenyl]-4-phenylbutan-1-ol, 17c. H NMR
(200 MHz, CDCl3): 7.45 (d, J ) 8.2 Hz, 2H), 7.33 (d, J ) 8.2 Hz,
2H), 7.26-7.12 (m, 5H), 5.80 (s, 1H), 4.70 (t, J ) 6.9 Hz, 1H), 4.14-
4.02 (m, 4H), 2.62 (t, J ) 7.2 Hz, 2H), 1.79-1.63 (m, 4H). MS (CI):
299.2 (MH+).
1-[4′-(Dioxolan-2′′-yl)phenyl]-4-phenylbutan-1-one, 18c. 1H NMR
(200 MHz, CDCl3): 7.90 (d, J ) 8.3 Hz, 2H), 7.53 (d, J ) 8.3 Hz,
2H), 7.32-7.16 (m, 5H), 5.83 (s, 1H), 4.15-3.99 (m, 4H), 2.95 (t, J
) 7.1 Hz, 2H), 2.70 (t, J ) 7.5 Hz, 2H), 2.06 (quintet, J ) 7.1-7.5
Hz, 2H). MS (CI): 297.1 (MH+).
1-(4′-Hydroxycarbonylphenyl)-4-(3′′,5′′-dimethoxyphenyl)butan-
1-one, 1a. A solution of 19a (97 mg, 0.31 mmol) in t-BuOH (2.3 mL)
was diluted with aq. potassium phosphate buffer (1.25 M pH 4, 1.5
mL). Aqueous KMnO4 (1 M, 2.3 mL) was added with vigorous stirring,
the mixture was stirred at room temperature for 10 min and then
quenched by the addition of saturated aq. Na2SO3. The resultant pH of
the mixture was adjusted to 3 with dilute HCl, and extracted with diethyl
ether. The combined organic phase was washed with brine, dried over
MgSO4 and solvents were removed under reduced pressure. The crude
product was purified by column chromatography (silica gel, hexanes-
ethyl acetate 7:3 + 0.5% acetic acid) to give 1 (52 mg, 51%) in the
1-(4′-Formylphenyl)-4-phenylbutan-1-one, 19c. 1H NMR (200
MHz, CDCl3): 10.08 (s, 1H), 8.03 (d, J ) 8.2 Hz, 2H), 7.93 (d, J )
8.2 Hz, 2H), 7.33-7.15 (m, 5H), 2.99 (t, J ) 7.2, 2H), 2.72 (t, J ) 7.5
Hz, 2H), 2.08 (quintet, J ) 7.4 Hz, 2H). MS (CI): 253.1 (MH+).
1-(4′-Hydroxycarbonylphenyl)-4-phenylbutan-1-one, 1c. 1H NMR
(200 MHz, CDCl3): 8.17 (d, J ) 8.3 Hz, 2H), 7.96 (d, J ) 8.3 Hz,
2H), 7.33-7.16 (m, 5H), 2.99 (t, J ) 7.1 Hz, 2H), 2.72 (t, J ) 7.1 Hz,
2H), 2.08 (quintet, J ) 7.1 Hz, 2H). MS (CI): 269.1 (MH+).
Irradiation of 18a. Ketone 18a (676 mg, 1.98 mmol) was dissolved
in acetone (10 mL) under argon, the solution was flushed with argon
for 10 min and then irradiated with a mercury lamp for 7 h. The solvent
was removed under reduced pressure and the residue was separated by
flash column chromatography (silica gel, 2-10% ethyl acetate in
benzene) to give 2 (127 mg, 41%), 20 (165 mg, 45.5%), 21 (33 mg,
4.9%), and 22 (35 mg, 5.2%).
3,5-Dimethoxystyrene, 2. 1H NMR (200 MHz, CDCl3): 6.61-6.70
(dd, J ) 17.4, 10.8 Hz, 1H), 6.55 (d, J ) 2.2 Hz, 2H), 6.37 (t, J ) 2.2
Hz, 1H), 5.71 (d, J ) 17.4 Hz, 1H), 5.23 (d, J ) 10.8 Hz, 1H), 3.79
(s, 6H). MS (CI): 165.0 (MH+).
4-(Dioxolan-2-yl)acetophenone, 20. 1H NMR (200 MHz, CDCl3):
7.95 (d, J ) 8.2 Hz, 2H), 7.55 (d, J ) 8.2 Hz, 2H), 5.85 (s, 1H),
3.00-4.14 (m, 4H), 2.59 (s, 3H). MS (CI): 193.2 (MH+).
cis-1-[4′-(Dioxolan-2′′-yl)phenyl]-2-(3′′′,5′′′-dimethoxyphenyl)cy-
clobutan-1-ol, 21. 1H NMR (200 MHz, CDCl3): 7.30 (d, J ) 8.3 Hz,
1
form of a white solid. H NMR (200 MHz, CDCl3): 8.15 (d, J ) 8.3
Hz, 2H), 7.96 (d, J ) 8.3 Hz, 2H), 6.33 (br s, 2H), 6.30 (br s, 1H),
3.75 (s, 6H), 3.99 (t, J ) 7.1 Hz, 2H), 2.66 (t, J ) 7.4 Hz, 2H), 2.09
(quintet, J ) 7.1 Hz, 2H). MS (CI): 328 (M-).
Physical Data of Similarly Prepared Analogues:
Ethyl 4-(3′-methoxyphenyl)butyrate, 15b.47 This analogue was
prepared from 3-methoxy-1-bromobenzene). 1H NMR (200 MHz,
CDCl3): 7.22-7.14 (m, 1H), 6.77-6.71 (m, 3H), 4.10 (q, J ) 7.4 Hz,
2H), 3.78 (s, 3H), 2.61 (t, J ) 7.3 Hz, 2H), 2.28 (t, J ) 7.3 Hz, 2H),
1.97 (quintet, J ) 7.3 Hz, 2H), 1.23 (t, J ) 7.4 Hz, 3H). MS (CI):
223.2 (MH+).
4-(3′-Methoxyphenyl)butyraldehyde, 16b.48 1H NMR (200 MHz,
CDCl3): 9.74 (br s, 1H), 7.19 (br t, J ) 7.8 Hz, 1H), 6.70 (m, 3H),
3.78 (s, 3H), 2.62 (t, J ) 7.4 Hz, 2H), 2.44 (t, J ) 7.7 Hz, 2H), 1.94
(quintet, J ) 7.5 Hz, 2H). MS (CI): 179.1 (MH+).
(47) Oikawa, Y.; Kurosawa, T.; Yonemitsu, O. Chem. Pharm. Bull. 1975, 23,
2466.
(48) Nagumo, S.; Miyoshi, I.; Akita, H.; Kawahara, N. Tetrahedron Lett. 2002,
43, 2223-2226.
(49) Zelechonok, Y.; Silverman, R. B. J. Org. Chem. 1992, 57, 5785-5787.
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144 J. AM. CHEM. SOC. VOL. 127, NO. 1, 2005