1090
Vol. 60, No. 8
was stirred for 3h at 50°C. The mixture was then filtered 400MHz) δ: 1.24 (6H, s), 1.99 (1H, t, J=2.6Hz), 2.35 (2H, m),
through celite with EtOAc, and concentrated under reduced 2.43 (2H, m), 2.50 (1H, s), 3.34 (2H, d, J=6.1Hz), 5.90 (1H, td,
pressure. The crude product was purified by flash chromatog- J=1.5, 15.4Hz), 5.99 (1H, brs), 6.88 (1H, td, J=6.5, 15.4Hz).
raphy on silica gel (hexane–EtOAc=1:1 then EtOAc–MeOH= 13C-NMR (CDCl3, 100MHz) δ: 17.59, 27.36, 30.93, 50.42,
100:1) to give the desired compound 3 as a colorless solid 69.34, 71.06, 82.92, 124.42, 142.61, 166.63. +ESI-MS m/z: 218
(461.1mg, 77%). Recrystallization from EtOAc–hexane af- [M+Na]+. HR-ESI-MS m/z: 218.1153 (Calcd for C11H17NO2Na,
1
forded colorless crystals: mp 104.4–106.4°C. H-NMR (CDCl3, 218.1157). IR (KBr) cm−1: 3313, 3284, 1670, 1626, 1548.
200MHz) δ: 1.78 (3H, d, J=6.5Hz), 2.83 (3H, s), 3.67 (2H, d,
A mixture of (E)-N-(2-hydroxy-2-methylpropyl)hept-2-en-6-
J=16.3Hz), 3.84 (2H, d, J=16.3Hz), 5.41 (1H, d, J=17.4Hz), ylamide (646.2mg, 3.31mmol), NBS (648.0mg, 3.64mmol)
5.82 (1H, qd, J=6.5, 15.1Hz), 6.16 (1H, dd, J=10.1, 15.1Hz), and AgNO3 (56.0mg, 0.331mmol) in acetone (16mL) was
6.64 (1H, dd, J=10.1, 17.4Hz). 13C-NMR (CDCl3, 100MHz) stirred for 2h at room temperature. The reaction mixture was
δ: 18.12, 46.71, 61.39, 132.47, 133.42, 144.95, 167.44. +ESI- then filtered through celite with EtOAc, and concentrated un-
MS m/z: 246 [M+Na]+. HR-ESI-MS m/z: 246.0915 (Calcd for der reduced pressure. The crude product was purified by flash
C10H14BNO4Na, 246.0914). IR (KBr) cm−1: 1753, 1647, 1604.
(E)-Hept-2-en-6-ynoic Acid (9) To a stirred solution of the title compound 4 as a colorless solid (884.2mg, 97%). Re-
chromatography on silica gel (hexane–EtOAc=1:3) to give
oxalyl chloride (2.44mL, 28.81mmol) in dichloromethane crystallization from EtOAc–hexane afforded colorless crystals:
1
(60mL) at −60°C was added dimethyl sulfoxide (DMSO) mp 97.5–98.0°C. H-NMR (CDCl3, 400MHz) δ: 1.24 (6H, s),
(4.09mL, 57.60mmol). After 10min, a solution of 4-pentyn- 2.34–2.45 (4H, m), 2.54 (1H, s), 3.35 (2H, d, J=6.1Hz), 5.89
1-ol (8) (2.02g, 24.01mmol) in dichloromethane (20mL) (1H, td, J=1.5, 15.2Hz), 6.04 (1H, brs), 6.85 (1H, td, J=6.6,
was added to the reaction mixture. After 15min, the re- 15.2Hz). 13C-NMR (CDCl3, 100MHz) δ: 18.87, 27.34, 30.77,
action mixture was treated with triethylamine (16.6mL, 39.24, 50.40, 71.07, 78.76, 124.53, 142.45, 166.58. +ESI-MS
120.1mmol) and then allowed to warm to 0°C. Methyl m/z: 296 [M+Na]+. HR-ESI-MS m/z: 296.0260 (Calcd for
(triphenylphosphoranylidene)acetate (9.63g, 28.81mmol) was C11H16BrNO2Na, 296.0262). IR (KBr) cm−1: 3289, 1671, 1624,
then added to the reaction mixture, and stirred for 1h at 1548.
room temperature. The reaction was quenched with water
(100mL), and extracted with dichloromethane (100mL). The trien-6-ynamide (10)
(2E,8E,10E)-N-(2-Hydroxy-2-methylpropyl)dodeca-2,8,10-
mixture of Pd(OAc)2 (5mg,
A
organic extracts were dried over Na2SO4, and concentrated 0.0223mmol) and SPhos (18.3mg, 0.0446mmol) in THF
under reduced pressure. The crude product was purified by (1mL) was stirred for 1h at room temperature. To a solu-
flash chromatography on silica gel (hexane–EtOAc=15:1) to tion of 4 (61.2mg, 0.223mmol) and 3 (69.6mg, 0.312mmol)
give methyl (E)-hept-2-en-6-ynoate as a colorless oil (2.92g, in THF (2.2mL) was added the above catalyst solution and
1
88%). H-NMR (CDCl3, 200MHz) δ: 2.00 (1H, t, J=2.4Hz), a 1mol–L-NaOH solution (1.6mL). The reaction mixture was
2.30–2.50 (4H, m), 3.74 (3H, s), 5.90 (1H, td, J=1.5, 15.7Hz), stirred for 2h at 30°C. The mixture was diluted with water
6.99 (1H, td, J=6.6, 15.7Hz). +ESI-MS m/z: 161 [M+Na]+.
(10mL), and extracted with EtOAc (50mL). The organic
To a solution of methyl (E)-hept-2-en-6-ynoate (4.03g, extracts were dried over Na2SO4, and concentrated under
29.17mmol) in tetrahydrofuran (THF) (40mL) was added a reduced pressure. The crude product was purified by flash
1mol–L-NaOH solution (43.8mL) at room temperature. The chromatography on silica gel (hexane–EtOAc=1:2) to give the
reaction mixture was stirred for 1h at 50°C. The reaction was desired compound 10 as an unstable colorless solid (33.7mg,
1
quenched with 1mol–L-HCl solution (50mL), and extracted 58%). H-NMR (CDCl3, 400MHz) δ: 1.24 (6H, s), 1.78 (3H,
with EtOAc (100mL). The organic extracts were dried over dd, J=1.0, 6.8Hz), 2.39 – 2.51 (5H, m), 3.34 (2H, d, J=6.1Hz),
Na2SO4, and concentrated under reduced pressure to give the 5.44 (1H, d, J=15.6Hz), 5.76 (1H, qd, J=6.8, 15.0Hz), 5.89
1
desired compound 9 as a colorless solid (3.36g, 93%). H- (1H, td, J=1.5, 15.4Hz), 5.93 (1H, brs), 6.07 (1H, m), 6.48
NMR (CDCl3, 400MHz) δ: 2.01 (1H, t, J=2.6Hz), 2.35–2.40 (1H, dd, J=10.9, 15.4Hz), 6.88 (1H, td, J=6.7, 15.6Hz). 13C-
(2H, m), 2.44–2.50 (2H, m), 5.91 (1H, td, J=1.6, 15.7Hz), 7.10 NMR (CDCl3, 100MHz) δ: 18.28, 18.79, 27.37, 31.35, 50.42,
(1H, td, J=6.6, 15.7Hz). 13C-NMR (CDCl3, 100MHz) δ: 17.30, 71.09, 80.88, 90.19, 108.78, 124.26, 131.05, 131.89, 141.32,
31.08, 69.60, 82.45, 121.90, 149.25, 171.53. −ESI-MS m/z: 143.03, 166.72. +ESI-MS m/z: 284 [M+Na]+. HR-ESI-MS m/z:
123 [M−H]−. HR-ESI-MS m/z: 123.0448 (Calcd for C7H7O2, 284.1626 (Calcd for C16H23NO2Na, 284.1626). IR (KBr) cm−1:
123.0446).
3353, 1673, 1632, 1548.
(E)-7-Bromo-N-(2-hydroxy-2-methylpropyl)hept-2-en-6-
Hydroxyl-α-sanshool (1) A suspension of Zn dust
ylamide (4) To a solution of 9 (1.00g, 8.09mmol), 2-chloro- (250mg) in water (1.5mL) was stirred for 15min, and then
1-methylpyridium iodide (2.27g, 8.90mmol) and N,N-diiso- Cu(OAc)2 (25mg) were added to the suspension at room tem-
propylethylamine (4.23mL, 24.27mmol) in MeCN (20mL) perature. After 15min, AgNO3 (25mg) were added to the sus-
was added a solution of 6 (865mg, 9.71mmol) in MeCN pension, and the mixture was stirred for 30min at room tem-
(10mL). The reaction mixture was stirred for 1h at room perature. To the activated Zn suspension was added a solution
temperature. The reaction was quenched with water (50mL), of 10 (28.1mg, 0.108mmol) in MeOH (1.5mL). The reaction
and extracted with EtOAc (50mL). The organic extracts were mixture was stirred for 20h at room temperature. The mixture
dried over Na2SO4, and concentrated under reduced pressure. was then filtered through celite with MeOH, and concentrated
The crude product was purified by flash chromatography in vacuo. The residue was diluted with EtOAc (10mL) and sat-
on silica gel (hexane/EtOAc = 1/2 to 1/3) to give (E)-N-(2- urated NaCl aq. (20mL), and extracted with EtOAc (20mL).
hydroxy-2-methylpropyl) hept-2-en-6-ylamide as a colorless The organic extracts were dried over Na2SO4, and concen-
solid (1.15g, 73%). Recrystallization from EtOAc–hexane af- trated under reduced pressure. The crude product was purified
1
forded colorless crystals: mp 62.9–63.5°C. H-NMR (CDCl3, by flash chromatography on silica gel (hexane–EtOAc=1:2)