798
Can. J. Chem. Vol. 78, 2000
layers were washed with 1 N HCl (1 × 50 mL) and brine (2
× 25 mL), and were dried over MgSO4. The product was pu-
rified by distillation at normal pressure (bp = 129–139°C) to
give alcohol (3.12 g, 33.9 mmol, 67%). IR (film) (cm–1):
3322, 1101, 1070. 1H NMR (300 MHz, CDCl3) δ: 5.41 (1 H,
t, J = 7.1 Hz), 4.20–4.08 (2 H, m), 1.20 (1 H, m). 13C NMR
(75 MHz, CDCl3) δ : 135.37 (s), 123.76 (d), 58.88 (t), 24.5
(m), 17.0 (m). MS (EI) m/z: 92, 74. HRMS (EI) m/z: Anal.
calcd. for C5H4D6O 92.1108; found: 92.1114.
O-(3-Trideuteriomethyl-4,4,4-trideuterio-2-buten-1-yl)-2-
bromo-phenol (13a)
Diethyl azodicarboxylate (2.96 g, 17.0 mmol) in THF
(2 mL) was added into a mixture of 2-bromophenol (2.78 g,
16.1 mmol), PPh3 (4.20 g, 16.0 mmol), and the above alco-
hol (1.38 g, 15.0 mmol) in THF (40 mL) at 0°C. The tem-
perature was gradually raised to 23°C. After 17.5 h, most of
the solvent was removed under reduced pressure, and
pentane (100 mL) was added to give a precipitate. After the
removal of the precipitate by filtration, the product was puri-
fied by flash chromatography (SiO2, hexanes/Et2O = 10:1)
followed by distillation (bp = 90–98°C at 0.2 mmHg) to give
13a (2.64 g, 10.7 mmol, 71% yield). IR (film) (cm–1): 1476,
O-(3-Trideuteriomethyl-4,4,4-trideuterio-2-buten-1-yl)-2-
iodophenol (13b)
Diethyl azodicarboxylate (2.96 g, 17.0 mmol) in THF
(2 mL) was added into a mixture of 2-iodophenol (3.52 g,
16.0 mmol), PPh3 (4.20 g, 16.0 mmol), and the above prenyl
alcohol-d6 (1.39 g, 15.1 mmol) in THF (35 mL) at 0°C. The
temperature was gradually raised to 23°C. After 16 h, most
of the solvent was removed under reduced pressure, and
pentane (100 mL) was added to give a precipitate. After the
removal of the precipitate by filtration, the product was puri-
fied by flash chromatography (SiO2, hexanes/Et2O = 30:1) to
give 13b (3.05 g, 10.4 mmol, 69% yield). IR (film) (cm–1):
1
1276, 1030, 744 H NMR (300 MHz, CDCl3) δ : 7.54 (1 H,
dd, J = 7.7, 1.6 Hz), 7.24 (1 H, dt, J = 1.6, 7.4 Hz), 6.90
(1 H, dd, J = 8.3, 1.1 Hz), 6.82 (1 H, dt, J = 1.5, 7.7 Hz),
5.51 (1 H, t, J = 6.6 Hz), 4.60 (2 H, d, J = 6.6 Hz). 13C
NMR (75 MHz, CDCl3) δ : 155.11, 137.21, 128.26, 121.60,
119.40, 113.52, 112.19, 65.93, (two CD3 carbons were not
detected). MS (EI) m/z: 248, 246, 228, 188, 186, 175, 173.
HRMS (EI) m/z: Anal. calcd. for C11H7D6BrO 246.0526;
found: 246.0490.
1
1469, 1275, 1239, 1016, 748. H NMR (300 MHz, CDCl3)
General procedure for the reduction of O-prenyl(d6)-2-
halophenol 13a, b by SmI2–HMPA
δ : 7.77 (1 H, dd, J = 7.7, 1.6 Hz), 7.28 (1 H, dt, J = 8.5,
1.6 Hz), 6.82 (1 H, dd, J = 8.2, 0.9 Hz), 6.70 (1 H, dt, J =
1.1, 7.6 Hz), 5.51 (1 H, t, J = 6.5 Hz), 4.58 (2 H, d, J =
6.5 Hz). 13C NMR (75 MHz, CDCl3) δ : 157.38, 139.68,
137.68, 129.30, 122.38, 119.52, 112.57, 86.89, 66.16, (two
CD3 carbons were not detected). MS (EI) m/z: 294, 221, 75.
HRMS (EI) m/z: Anal. calcd. for C11H7D6IO 294.0388;
found: 294.0382.
To SmI2 (0.10 M in THF, 11.0 mL, 1.10 mmol) was added
HMPA (0.85 mL, 4.89 mmol) at 23°C. After 20 min, O-
prenyl(d6)-2-iodophenol (13a) (0.299 g, 1.02 mmol) in THF
(1 mL) was added. After 8 h, dry air was bubbled until the
mixture turned to yellow, and then 0.1 N HCl (15 mL) was
added. After the extraction with Et2O (3 × 10 mL), the com-
bined ether layers were washed with 5% Na2S2O3 (1 ×
10 mL), 0.1 N HCl (1 × 10 mL), and brine (1 × 10 mL), and
were dried over MgSO4. The crude mixture was passed
through a SiO2 column (eluent: hexanes/Et2O = 10:1) to give
a mixture of products (0.130 g). The products ratio was de-
1-[2-(2,3-Dihydrobenzofuran-3-yl)propyl-2-oxy]-2,2,6,6-
tetra-methylpiperidine (12)
HMPA (4.0 mL, 23 mmol) was added to SmI2 (0.1 M in
THF, 44.0 mL, 4.40 mmol) at 23°C. After 14 min, the mix-
ture was cooled to 0°C, and O-prenyl-2-iodophenol (1)
(0.576 g, 2.00 mmol) in THF (2 mL) was added dropwise
over the period of 2 min. After 10 min, TEMPO (0.943 g,
6.04 mmol) in THF (1 mL) was added in one portion. After
1 min, a mixture of sat. potassium sodium tartrate (10 mL),
sat. NaHCO3 (5 mL), and 5% Na2S2O3 (5 mL) was added,
and the mixture was extracted with Et2O (3 × 15 mL). The
combined ether layers were washed with 5% Na2S2O3 (1 ×
15 mL), a mixture of sat. potassium sodium tartrate and sat.
NaHCO3 (5 mL each, 1 ×), H2O (2 × 15 mL), and brine (1 ×
15 mL), and were dried over MgSO4. The product was puri-
fied by flash chromatography (SiO2, hexanes/Et2O = 10:1) to
give 12 (0.122 g, 0.385 mmol, 19% yield). IR (film) (cm–1):
1483, 1460, 1375, 1364, 1234, 1132, 748.; 1H NMR
(300 MHz, CDCl3) δ : 7.33 (1 H, d, J = 7.3 Hz), 7.13 (1 H, t,
J = 7.4 Hz), 6.83 (1 H, t, J = 7.0 Hz), 6.78 (1 H, d, J =
8.0 Hz), 4.73 (1 H, dd, J = 9.5, 5.5 Hz), 4.54 (1 H, t, J =
9.6 Hz), 3.94 (1 H, dd, J = 9.5, 5.4 Hz), 1.68–1.45 (4 H, m),
1.38 (3 H, s), 1.37–1.26 (2 H, m), 1.16 (3 H, s), 1.154 (3
H, s), 1.146 (3 H, s), 1.12 (3 H, s), 1.11 (3 H, s). 13C NMR
(75 MHz, CDCl3) δ : 161.10 (s), 128.75 (s), 128.36 (d),
125.72 (d), 119.99 (d), 109.54 (d), 80.90 (s), 73.34 (t), 59.56
(s), 59.43 (s), 53.25 (d), 40.96 (t), 35.23 (q), 35.13 (q), 23.71
(q), 23.32 (q), 23.71 (q), 23.32 (q), 21.03 (q), 20.90 (q),
17.18 (t). MS (CI) m/z: 318 [M + H], 157, 142.
1
termined by H NMR spectrum of the mixture.
SmI2 reduction of O-prenyl(d6)-2-iodophenol (13a) in
the presence of the ketone 18
HMPA (0.95 mL, 5.5 mmol) was added to SmI2 (0.1 M in
THF, 11.0 mL, 1.10 mmol) at 23°C. After 50 min, a mixture
of O-prenyl(d6)-2-iodophenol (13a) (0.142 g, 0.483 mmol)
and 1,5-diphenylpentan-3-one (18) (0.120 g, 0.504 mmol) in
THF (1 mL) was added in one portion. After 1 h, dry air was
bubbled through the mixture, and then 0.1 N HCl (15 mL)
and brine (5 mL) were added. After the extraction with Et2O
(3 × 10 mL), the combined ether layers were washed with
5% Na2S2O3 (1 × 10 mL), 0.1 N HCl (1 × 10 mL), and brine
(1 × 10 mL), and were dried over MgSO4. The products
were separated by flash chromatography (SiO2, hex-
anes/EtOAc = 10:1 – 5:1) to give a mixture of 3-(2-propyl)-
2,3-dihydrobenzofuran (d6 and d7) (14 and 15) and 3-
(propen-2-yl)-2,3-dihydrobenzofuran (d5) (16) (61.1 mg), a
mixture of 1,5-diphenyl-3-pentanol (20) and 1,5-diphenyl-3-
(2-tetrahydrofuranyl)-3-pentanol (19) (39.1 mg), and 1,5-
diphenyl-3-pentanone (18) (67.0 mg, 56% recovery).
1,5-Diphenyl-3-(tetrahydrofuran-2-yl)pentan-3-ol (19)
The authentic sample of 19 was prepared as follows:
HMPA (0.95 mL, 5.46 mmol) was added to SmI2 (0.1 M in
© 2000 NRC Canada