55.4, 42.3, 28.2 ppm. HRMS (FAB): M2 + Na+, found 515.3130.
(C16H22O2)2Na requires 515.3132.
preparation of 6a. Purification of the residue by column
chromatography (SiO2, hexanes = 100%) gave 6b (0.906 g, 60%)
as a light yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.05 and
6.78 (AA’BB’, JAB = 8.7 Hz, 4H, ArH), 5.92-5.89 (m, 2H,
CH=CH), 2.69 (tt, J = 11.2, 3.2 Hz, 1H, H5), 2.36-2.27 (m, 2H),
2.24-2.14 (m, 2H), 1.93-1.85 (m, 2H), 1.55-1.44 (m, 2H), 1.01 (s,
9H, t-Bu), 0.22 (s, 6H, SiMe2); 13C NMR (100 MHz, CDCl3) δ
153.7, 142.2, 132.7, 127.6, 120.0, 49.7, 35.1, 28.1, 25.9, 18.4, -
4.2 ppm.
ACCEPTED MANUSCRIPT
4.1.3 5-(4-t-Butyldimethylsilyloxyphenyl)nona-1,8-dien-5-ol 4b
The reaction of methyl 4-t-butyldimethylsilyloxybenzoate (5.000
g, 0.0188 mmol) with the Grignard reagent generated from 4-
bromo-1-butene (11.5 mL, 0.113 mol) was carried out in a
fashion similar to the preparation of 4a, to give 4b as a colorless
oil (5.208 g, 80%). 1H NMR (400 MHz, CDCl3) δ 7.23 and 6.82
(AA’BB’, JAB = 8.6 Hz, 4H, ArH), 5.85-5.73 (m, 2H, CH=CH2),
5.01-4.86 (m, 4H, CH=CH2), 2.13-1.80 (m, 9H), 1.01 (s, 9H, t-
Bu), 0.22 (s, 6H, SiMe2); 13C NMR (100 MHz, CDCl3) δ 154.2,
139.1, 138.5, 126.5, 119.7, 114.7, 77.0, 42.2, 28.2, 25.8, 18.3, -
4.2 ppm.
4.1.8 4-(4-Methoxyphenyl)cycloheptanol 7a
To a solution of 6a (1.24 g, 5.67 mmol) in freshly distilled THF
(25 mL) at 0 °C under N2, was added dropwise a solution of BH3-
THF (1M in THF, 11.3 mL, 11.3 mmol). The solution was
warmed to room temperature and stirred for 20 h. The reaction
mixture was cooled to 0 °C, and water (440 mL) was slowly
added followed by 30% H2O2 (8.50 mL) and 1N NaOH (14.5
mL). The resulting mixture was stirred at room temperature for
30 min, extracted several times with ethyl acetate, and the
combined extracts concentrated. The residue was purified by
column chromatography (SiO2, hexanes–ethyl acetate = 60:40) to
give 7a (1.150 g, 93%) as a yellow oil. This product was
determined to be a mixture of cis- and trans-stereoisomers by
4.1.4 1-(4-Methoxyphenyl)-4-cyclohepten-1-ol 5a
To a solution of 4a (1.015 g, 4.126 mmol) in dry CH2Cl2 (415
mL, 0.01 M) at 40 °C was slowly added via syringe pump over a
10 h period, a solution of Grubbs I catalyst (0.136 g, 0.165 mmol,
4%) in CH2Cl2. The mixture was heated for an additional 12-18
h. After cooling to room temperature, the mixture was quenched
with DMSO (50 eq, 0.600 mL) and stirred for another 12 h. The
mixture was concentrated and the residue was purified by column
chromatography (SiO2, hexanes–diethyl ether = 4:1) to give 5a
(0.675 g, 75%) as a green oil. 1H NMR (400 MHz, CDCl3) δ
7.43 and 6.87 (AA’BB’, JAB = 9.0 Hz, 4H, ArH), 5.86-5.83 (m,
2H, CH=CH), 3.80 (s, 3H, OMe), 2.55-2.44 (m, 2H), 2.10-1.97
(m, 4H), 1.90-1.82 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
158.4, 142.4, 132.12, 125.9, 113.6, 76.7, 55.4, 40.2, 23.2 ppm.
HRMS (FAB): M + Na+, found 241.1202. C14H18O2Na requires
241.1199.
1
NMR spectroscopy. H NMR (400 MHz, CDCl3) δ 7.11 and 7.09
(2 x d, J = 8.3 Hz, 2H total, ArH), 6.83 (d, J = 8.2 Hz, 2H, ArH),
4.06-4.00 and 3.99-3.90 (m, 1H, CHOH), 3.78 (s, 3H, OMe),
2.72-2.56 (m, 1H, H4), 2.15-2.05 (m, 1H), 2.02-1.50 (m, 11H);
13C NMR (100 MHz, CDCl3) δ 157.7, 141.5, 127.7, 113.9, 72.9,
71.8, 55.4, 46.4, 46.1, 38.4, 37.8, 37.3, 37.1, 37.0, 35.8, 31.9,
29.7, 23.4, 21.5 ppm. HRMS (FAB): M + Na+, found 243.1358.
C14H20O2Na requires 243.1356.
4.1.9 4-(4-t-Butyldimethylsilyloxyphenyl)cycloheptanol 7b
4.5 1-(4-((tert-Butyldimethylsilyl)oxy)phenyl)cyclohept-4-en-1-ol
5b
The hydroboration/oxidation of 6b (0.906 g, 2.99 mmol) with
BH3-THF (1M in THF, 6.0 mL, 6.0 mmol) was carried out in a
fashion similar to the preparation of 7a. Purification of the
residue by column chromatography (SiO2, hexanes-ethyl acetate
= 80:20) gave 7b (0.880 g, 93%) as a yellow oil. This was
determined to be a mixture of cis- and trans-stereoisomers by
NMR spectroscopy. 1H NMR (400 MHz, CDCl3) δ 7.01 (m, 2H,
ArH), 6.74 (m, 2H, ArH), 4.06-3.99 and 3.98-3.90 (m, 1H,
CHOH), 2.69-2.53 (m, 1H, H4), 2.14-1.49 (m, 11H), 0.97 (s, 9H,
t-Bu), 0.18 (s, 6H, SiMe2); 13C NMR (100 MHz, CDCl3) δ 153.6,
142.2, 142.1, 127.6, 119.9, 73.0, 71.9, 46.4, 46.1, 38.3, 37.8,
37.3, 37.1, 37.0, 35.9, 31.8, 29.8, 25.9, 23.5, 21.5, 18.4, -4.2
ppm. HRMS (FAB): M + Na+, found 343.2064. C19H32O2SiNa
requires 343.2064.
The ring closing metathesis of 4b (0.313 g, 0.903 mmol) in dry
CH2Cl2 (100 mL, 0.01 M) with Grubbs I catalyst (0.029 g, 0.032
mmol, 4%) was carried out in a fashion similar to the preparation
of 5a. Purification of the residue by column chromatography
(SiO2, hexanes–diethyl ether = 4:1) gave 5b (0.247 g, 86%) as a
colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.35 and 6.79
(AA’BB’, JAB = 8.7 Hz, 4H, ArH), 5.86-5.79 (m, 2H, CH=CH),
2.54-2.43 (m, 2H), 2.10-1.94 (m, 4H), 1.90-1.82 (m, 2H), 1.73 (s,
1H), 0.99 (s, 9H, t-Bu), 0.20 (s, 6H, SiMe2); 13C NMR (100
MHz, CDCl3) δ 154.5, 142.9, 132.3, 125.9, 119.7, 76.7, 40.3,
25.8, 23.2, 18.3, -4.2 ppm. HRMS (FAB): M + Na+, found
325.1959. C19H30OSiNa requires 325.1958.
4.1.6 5-(4-Methoxyphenyl)cycloheptene 6a
4.1.10 4-(4-Methoxyphenyl)cycloheptanone (±)-8a
To a solution of 5a (1.720 g, 7.880 mmol) in dry CH2Cl2 (50 mL)
was added triethylsilane (1.4 mL, 0.22 mmol), followed by TFA
(6.2 mL, 79 mmol). The mixture was stirred at room temperature
To a solution of 7a (0.787 g, 3.58 mmol) in CH2Cl2 (38 mL) at
room temperature, was added Dess–Martin periodinane (4.55 g,
10.7 mmol) and water (0.2 mL). The mixture was stirred at room
temperature for 6 h, and then quenched with 50:50 sodium
thiosulfate:sodium bicarbonate. The resulting solution was stirred
at room temperature for 30 min and then extracted several times
with ethyl acetate, dried (MgSO4), and concentrated. The residue
was purified by column chromatography (SiO2, hexanes– ethyl
acetate = 80:20) to give 8a (0.389 g, 55%) as a colorless oil. 1H
NMR (400 MHz, CDCl3) δ 7.10 and 6.84 (AA’BB’, JAB = 8.7
Hz, 4H, ArH), 3.79 (s, 3H, OMe), 2.77-2.53 (m, 4H), 2.16-1.52
(m, 7H); 13C NMR (100 MHz, CDCl3) δ 215.0, 157.9, 139.9,
127.4, 113.9, 55.3, 47.9, 43.8, 42.9, 38.6, 32.2, 23.8 ppm. The
spectral data obtained for this compound were consistent with the
literature values.16 Oxidation of 7a with either PCC/silica gel or
for 48
disappearance of the starting material, the solution was
concentrated to bilayer oil and purified by column
h
while monitoring by TLC.
After complete
a
chromatography (SiO2, hexanes–ethyl acetate = 50:50) to give 6a
as a brown oil (1.433 g, 90%). 1H NMR (400 MHz, CDCl3) δ
7.11 and 6.84 (AA’BB’, JAB = 8.6 Hz, 4H, ArH), 5.91-5.87 (m,
2H, CH=CH), 3.79 (s, 3H, OMe), 2.69 (tt, J = 11.3, 3.2 Hz, 1H,
H5), 2.35-2.25 (m, 2H), 2.23-2.13 (m, 2H), 1.91-1.83 (m, 2H),
1.54-1.43 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 157.8, 141.7,
132.7, 127.7, 113.9, 55.4, 49.6, 35.1, 28.1 ppm.
4.1.7 5-(4-t-Butyldimethylsilyloxyphenyl)cycloheptene 6b
The ionic reduction of 5b (1.601 g, 5.026 mmol) in anhydrous
CH2Cl2 (20 mL) with triethylsilane (0.8 mL, 1.02 mmol) and
TFA (4.0 mL, 20 mmol) was carried out in a fashion similar to
n-propylmagnesium
bromide/1,1’-(azodicarbonyl)dipiperidine
gave 8a (55% or 20% respectively).