K. Mori et al. / Tetrahedron 66 (2010) 7161e7168
7165
1.59e1.71 (2H, m), 2.08e2.14 (4H, m, C^CCH2ꢄ2), 2.45 (3H, s), 4.02
(2H, t, J 6.4, CH2OTs), 7.35 (2H, d, J 8.0), 7.79 (2H, d, J 8.4).
give 41.0 g (quant.) of crude 10. nmax (film): 2956 (s), 2937 (s), 2860
(m), 2175 (m), 1250 (s), 843 (s), 760 (s). This was employed in the
next step without further purification.
4.5. 7-Hexadecynyl iodide 6
4.9. 8-Trimethylsilyl-7-octynyl bromide 11 from 10
Powdered sodium iodide (3.8 g, 25 mmol) was added portion-
wise to a solution of 5 (3.9 g, 9.9 mmol) in DMF (20 mL) at room
temperature. After exothermic reaction, the mixture was stirred
and heated at 80 ꢂC for 4 h. After cooling, the mixture was diluted
with water, and extracted with Et2O. The combined Et2O solution
was successively washed with water, dil Na2S2O3 solution, NaHCO3
solution and brine, dried (MgSO4), and concentrated in vacuo. The
residue (3.3 g) was chromatographed over SiO2 (60 g). Elution with
hexane/EtOAc (100:1) gave 2.5 g (72%) of 6 as a colorless oil (this
solidified in a deep freezer). n1D9 1.4973; nmax (film): 2927 (s), 2854
(s), 1462 (m), 1198 (m), 723 (m), 598 (w); dH (CDCl3): 0.88 (3H, t, J
7.0, CH2CH3), 1.22e1.54 (18H, m), 1.79e1.88 (2H, m), 2.11e2.20 (4H,
m, C^CCH2ꢄ2), 3.19 (2H, t, J 7.0, CH2I); dC (CDCl3): 7.1, 14.1, 18.65,
18.74, 22.6, 27.7, 28.8, 28.9, 29.10, 29.12, 29.2, 30.0, 31.8, 33.4, 79.7,
80.4. HRMS calcd for C16H29I: 348.1314, found: 348.1325.
Lithium bromide (40 g, 460 mmol) was added to a solution of 10
(41.0 g, 148 mmol) in acetone (150 mL) and DMF (20 mL). The mix-
ture was stirred and heated under reflux for 1.5 h, and concentrated
in vacuo. The residue was diluted with water, and extracted with
hexane. The extract was washed with water and brine, dried
(MgSO4), andconcentratedinvacuo. Theresiduewas distilled togive
31.0 g (ca. 83%) of a mixture of 10,11 and the corresponding iodide as
a colorless oil. Bp 95e110 ꢂC/6 Torr, nD23 1.4732; nmax (film): 2956 (s),
2937 (s),2860 (m), 2173 (s),1250 (s), 843 (vs), 760 (s); dH (CDCl3): 0.14
(9H, s, SiMe3), 1.37e1.57 (6H, m), 1.75e1.92 (2H), 2.23 (2H, t, J 7.2,
C^CCH2), 3.19 (0.1H, t, J 7.2, CH2I), 3.41 (1.1H, t, J 6.8, CH2Br), 3.54
(0.8H, t, J 6.8, CH2Cl); GCeMS [same conditions as described for 9]: tR
11.00 min (33.6%, 10), 12.08 (48.6%, 11), 13.23 (7.8%, the corre-
sponding iodide). MS of 10 (70 eV, EI): m/z: 201 (4) [MþꢁCH3], 107
(44), 95 (28), 93 (100), 79 (11), 73 (20), 69 (5), 59 (4), 55 (5). MS of 11
(70 eV, EI): m/z: 247 (4) [MþꢁCH3], 245 (4) [MþꢁCH3], 165 (7), 139
(100), 137 (100), 107 (87), 73 (30). MS of the iodide (70 eV, EI): m/z:
308 (1.5) [Mþ],193 (32),185 (100),107 (31), 73 (55). HRMS of 11 calcd
for C10H18BrSi (MþꢁCH3): 245.0361, found: 245.0351.
4.6. 6-Chlorohexyl tosylate 8
Tosyl chloride (40.0 g, 210 mmol) was added portionwise to
a stirred and ice-cooled solution of 7 (25.1 g, 185 mmol) in dry
pyridine (80 mL) at 10e15 ꢂC. After the addition, the mixture was
stirred for 1.5 h at 0e5 ꢂC. It was then diluted with ice-water, and
extracted with Et2O. The extract was washed with water, dil HCl,
NaHCO3 solution and brine, dried (MgSO4), and concentrated in
vacuo to give 52.0 g (quant.) of 8 as an oil. nmax (film): 1599 (w),
1358 (s), 1188 (s), 1176 (s), 956 (m), 816 (m), 663 (m), 555 (m); dH
(CDCl3): 1.30e1.42 (4H, m), 1.62e1.78 (4H, m), 2.45 (3H, s, ArCH3),
3.49 (2H, t, J 6.4), 7.35 (2H, d, J 8.4), 7.79 (2H, d, J 8.4). This was
employed for the next step without further purification.
4.10. 8-Trimethylsilyl-7-octyn-1-ol tetrahydropyranyl ether 13
In the same manner as described above for 3, TMSC^CH (12,
11.8 g, 120 mmol) in dry THF (90 mL) and HMPA (20 mL) was treated
with n-BuLi in hexane (1.6 M, 75 mL, 0.12 mol) and 6-iodo-1-hexanol
THP ether (25.0 g, 80.1 mmol) in dry THF (20 mL) to give 23.6 g
(quant.) of crude 13 as an oil, n1D8 1.4609; nmax (film): 2175 (s, C^C),
1250 (m),1138(m, CeOeC),1120(m, CeOeC),1078(m, CeOeC),1036
(m, CeOeC), 843 (s), 760 (m), 640 (m); dH (CDCl3): 0.15 (9H, s, SiMe3),
1.33e1.47 (4H, m), 1.47e1.66 (8H, m), 1.68e1.76 (1H, m), 1.78e1.88
(1H, m), 2.22 (2H, t, J 7.2, C^CCH2), 3.36e3.41 (1H, m), 3.47e3.53 (1H,
m), 3.71e3.77 (1H, m), 3.83e3.91 (1H, m), 4.56e4.61 (1H, t-like). This
was employed for the next step without further purification.
4.7. 6-Chlorohexyl iodide 9
Sodium iodide (30.0 g, 200 mmol) was added to a solution of 8
(52.0 g, 185 mmol) in acetone (160 mL). The mixture was stirred
and heated under reflux for 30 min until solid sodium tosylate
precipitated. The mixture was cooled and diluted with water. The
lower layer was separated, and the upper aqueous layer was
extracted with hexane. The combined organic solution was washed
with water and brine, dried (MgSO4), and concentrated in vacuo.
The residue was distilled to give 36.7 g (82%) of 9 as a colorless oil.
Bp 90e92 ꢂC/4 Torr, nD24 1.5158; nmax (film): 2933 (s), 2858 (s), 727
(m), 650 (m); dH (CDCl3): 1.38e1.52 (4H, m), 1.74e1.90 (4H, m), 3.20
(2H, t, J 6.8, CH2I), 3.54 (2H, t, J 6.4, CH2Cl); GCeMS [column: HP-
5MS 5% phenylmethylsiloxane, 30 mꢄ0.25 mm i.d.; press:
60.7 kPa; temp: 70e230 ꢂC (þ10 ꢂC/min)]: tR 7.28 min [1.4%,
Cl(CH2)6Cl], 10.00 (97.4%, 9), 12.57 [1.2%, I(CH2)6I]. MS of 9 (70 eV,
EI): m/z: 246 (6) [Mþ, C6H12ICl], 155 (8), 119 (25), 83 (64), 55 (100),
43 (22) 41 (35). HRMS calcd for C6H12ICl: 245.9672, found:
245.9672.
4.11. 8-Trimethylsilyl-7-octyn-1-ol 14
p-Toluenesulfonic acid monohydrate (1.8 g, 9.5 mmol) was
added to a solution of crude 13 (21.6 g, 73.3 mmol) in methanol
(200 mL). The solution was stirred at room temperature for 1 h. It
was then diluted with water, and extracted with Et2O. The com-
bined Et2O solution was successively washed with water, NaHCO3
solution, and brine, dried (MgSO4), and concentrated in vacuo. The
residue (17.9 g) was chromatographed over SiO2 (200 g). Elution
with hexane/EtOAc (10:1e5:1) gave 13.2 g (91%, two steps) of 14 as
a colorless oil, n1D6 1.4593; nmax (film): 3342 (s, OeH), 2175 (s, C^C),
1250 (s), 1057 (m, CeO), 843 (s), 760 (m), 640 (m); dH (CDCl3): 0.15
(9H, s, SiMe3),1.33e1.47 (4H, m),1.50e1.62 (4H, m), 2.23 (2H, t, J 7.0,
C^CCH2), 3.65 (2H, t, J 6.6, CH2OH). HRMS calcd for C10H19OSi
(MþꢁCH3): 183.1205, found: 183.1196.
4.8. 8-Trimethylsilyl-7-octynyl chloride 10
4.12. 8-Trimethylsilyl-7-octynyl tosylate 15
A solution of n-BuLi in hexane (1.6 M, 95.6 mL, 153 mmol) was
added dropwise to a stirred and cooled solution of TMSC^CH
(15.0 g, 153 mmol) in dry THF (120 mL) and HMPA (12 mL) at ꢁ20
to ꢁ10 ꢂC under Ar. The stirred mixture was then cooled to ꢁ78 ꢂC.
A solution of 9 (36.6 g, 148 mmol) in dry THF (10 mL) was added
dropwise to the stirred mixture over 5 min, which was then left to
stand 3 days at room temperature. The mixture was diluted with
water, and extracted with hexane. The hexane solution was washed
with water and brine, dried (MgSO4), and concentrated in vacuo to
In the same manner as described above for 5, 14 (14.1 g,
71.1 mmol) in dry pyridine (90 mL) was treated with tosyl chloride
(20.3 g, 106 mmol) to give 23.9 g (95%) of crude 15 as a colorless oil,
n1D6 1.5028; nmax (film): 2173 (s, C^C), 1599 (m, arom, C]C), 1362 (s,
SO2), 1250 (m), 1178 (s, SO2), 1097 (m, CeO), 1020 (w), 964 (m), 918
(m), 843 (s), 760 (m), 663 (m), 555 (m); dH (CDCl3): 0.14 (9H, s,
SiMe3), 1.27e1.38 (4H, m), 1.42e1.52 (2H, m), 1.60e1.70 (2H, m),
2.18 (2H, t, J 7.0, C^CCH2), 2.45 (3H, s), 4.02 (2H, t, J 6.6, CH2OTs),