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R. J. Armstrong-Chong et al. / Tetrahedron 60 (2004) 10239–10244
and the reaction mixture was stirred at K78 8C for 5 min then
at 0 8C for 1 h. Standard aqueous work-up using ether and satd
aqueous NH4Cl provided crude material which was purified
by flash chromatography on silica gel (15 g) using hexanes as
eluent to provide 250 mg (91%) of the known16 alkyne 3 as a
procedure B (Section 4.3) from bromoalcohol 1b in 55%
yield after purification. 1H NMR (300 MHz, CDCl3) d 4.78
(1H, t, JZ3 Hz), 4.21 (2H, AB of ABX2, DnZ25.9 Hz,
JABZ15.2 Hz, JAXZJBXZ2 Hz), 3.87–3.77 (1H, m), 3.53–
3.46 (1H, m), 2.23–2.10 (6H, m), 1.85–1.20 (22H, m), 0.87
(3H, t, JZ7 Hz); 13C NMR (75 MHz, CDCl3) d 96.50,
86.62, 80.09, 80.04, 75,64, 61.86, 54.54, 31.18, 30.21,
29.05, 28.95 (2C), 28.74, 28.71, 28.51, 25.32, 21.85, 19.03,
1
colorless liquid. H NMR (300 MHz, CDCl3) d 3.39 (2H, t,
JZ7 Hz), 2.12 (4H, m), 1.83 (2H, quintet, JZ7 Hz), 1.5–1.2
(14H, m), 0.88(3H, t, JZ7 Hz);13C NMR (75 MHz, CDCl3) d
80.07, 79.90, 33.77, 32.71, 31.17, 28.98, 28.85, 28.59, 28.58,
28.02, 21.83, 18.61, 18.33, 13.54; MS (EI) m/z 272 (MC, 79Br,
0.1), 215 (3), 95 (59), 81 (100), 67 (84).
18.73, 18.65, 18.36, 13.56; IR (neat) 1132, 1118, 1025 cmK1
;
MS (EI) m/z 247 (MCKTHP, 1), 85 (100), 67 (59), 55 (72).
Anal. Calcd for C22H36O2: C, 79.46; H, 10.91. Found: C,
79.60; H, 10.85.
4.3. General procedure B: sequential dialkynylation of
bromotriflates
4.3.4. 1-Tetrahydropyranyloxy-3,13-octadecadiyne (4d).
This compound was prepared following General procedure
B (Section 4.3) from bromoalcohol 1b in 58% yield after
purification. 1H NMR (300 MHz, CDCl3) d 4.61 (1H, t, JZ
3 Hz), 3.91–3.72 (2H, m), 3.51–3.42 (2H, m), 2.12–2.05
(6H, m), 1.81–1.23 (22H, m), 0.87 (3H, t, JZ7 Hz); 13C
NMR (75 MHz, CDCl3) d 98.54. 81.17, 80.03, 80.00, 76.61,
66.11, 61.97, 31.16, 30.47, 29.03, 28.96, 28.93, 28.87,
28.70, 28.68, 25.38, 21.81, 20.12, 19.30, 18.62 (2C), 18.32,
13.52; IR (neat) 1130, 1110, 1070, 1040 cmK1; MS (EI) m/z
85 (100), 67 (20), 55 (20). Anal. Calcd for C23H38O2: C,
79.71; H, 11.05. Found: C, 79.90; H, 10.86.
To a cold (K78 8C), stirred solution of propargyl alcohol
THP ether or 3-butyn-1-ol THP ether in THF (3 mL/mmol)
was added n-BuLi (1.6 M in hexanes, 1.0 equiv). The
solution was stirred at 0 8C for 15 min then cooled to
K78 8C and a THF solution (2 mL/mmol) of bromotriflate 2
(1.0 equiv, crude material prepared according to General
procedure A (Section 4.2)) was slowly added. The mixture
was stirred at 0 8C for 1 h to generate the intermediate
bromoalkyne. A THF solution (2 mL/mmol) of an alkynyl-
lithium (freshly prepared from a terminal alkyne and
n-BuLi, K78 8C/0 8C, 15 min, 2.0 equiv) and NaI (10–
20 mol%) were then added and the mixture was heated at
reflux for 16–30 h (monitor by TLC). After cooling to rt,
standard extractive workup (ether/aq NH4Cl then brine)
afforded crude materials which were purified by flash
chromatography on silica gel using 3–5% ether in hexanes
as eluent to yield the desired diynes as colorless oils.
4.3.5. 1-Tetrahydropyranyloxy-3,13-icosadiyne (4e).
This compound was prepared following General procedure
B (Section 4.3) from bromoalcohol 1b in 75% yield after
purification. 1H NMR (300 MHz, CDCl3) d 4.61 (1H, t, JZ
3 Hz), 3.90–3.69 (2H, m), 3.51–3.42 (2H, m), 2.46–2.36
(2H, m), 2.10 (6H, br t, JZ7 Hz), 1.82–1.22 (26H, m), 0.85
(3H, t, JZ7 Hz); 13C NMR (75 MHz, CDCl3) d 98.54,
81.18, 80.11, 80.02, 76.61, 66.12, 61.98, 31.29, 30.48,
29.04, 28.98, 28.96, 28.88, 28.72, 28.70, 28.44, 25.37,
22.49, 20.13, 19.31, 18.65, 18.64, 13.96; IR (neat) 1130,
1110, 1060, 1030 cmK1; MS (EI) m/z 289 (MCKTHP, 0.3),
85 (100), 67 (20), 55 (23). Anal. Calcd for C25H42O2: C,
80.16; H, 11.30. Found: C, 80.18; H, 11.05.
4.3.1. 1-Tetrahydropyranyloxy-2,10-heptadecadiyne
(4a). This compound was prepared following General
procedure B (Section 4.3) from bromoalcohol 1a in 62%
yield after purification. 1H NMR (300 MHz, CDCl3) d 4.77
(1H, t, JZ3 Hz), 4.20 (2H, AB of ABX2, DnZ25.6 Hz,
JABZ15.2 Hz, JAXZJBXZ2 Hz), 3.86–3.74 (1H, m), 3.51–
3.41 (1H, m), 2.20–2.07 (6H, m), 1.88–1.25 (22H, m), 0.85
(3H, t, JZ7 Hz); 13C NMR (75 MHz, CDCl3) d 96.44,
86.43, 80.19, 79.85, 75.68, 61.79, 54.47, 31.27, 30.18,
29.01, 28.88, 28.42, 28.38, 28.27, 28.19, 25.29, 22.47,
19.01, 18.66, 18.63, 18.58, 13.94; IR (neat) 1480, 1110,
1040, 1020 cmK1; MS (EI) m/z 247 (MCKTHP, 11), 85
(100), 67 (40), 55 (38). Anal. Calcd for C22H36O2: C, 79.46;
H, 10.91. Found: C, 79.61; H, 10.97.
4.3.6. 1-Tetrahydropyranyloxy-3,13-docosadiyne (4f).
This compound was prepared following General procedure
B (Section 4.3) from bromoalcohol 1b in 78% yield after
purification. 1H NMR (300 MHz, CDCl3) d 4.61 (1H, t, JZ
3 Hz), 3.90–3.70 (2H, m), 3.52–3.42 (2H, m), 2.40 (2H, br t,
JZ7 Hz), 2.09 (6H, br t, JZ7 Hz), 1.82–1.23 (30H, m),
0.84 (3H, t, JZ7 Hz); 13C NMR (75 MHz, CDCl3) d 98.57,
81.20, 80.14, 80.05, 76.63, 66.14, 62.01, 31.78, 30.50,
29.16, 29.09, 29.07, 29.00, 28.98, 28.90, 28.80, 28.75,
28.73, 25.39, 22.60, 20.15, 19.33, 18.67, 18.65, 14.03; IR
(neat) 1130, 1110, 1070, 1030 cmK1; MS (EI) m/z 85 (100),
67 (24), 55 (20). Anal. Calcd for C27H46O2: C, 80.54; H,
11.51. Found: C, 80.22; H, 11.13.
4.3.2. 1-Tetrahydropyranyloxy-3,11-octadecadiyne (4b).
This compound was prepared following General procedure
B (Section 4.3) from bromoalcohol 1a in 70% yield after
purification. 1H NMR (300 MHz, CDCl3) d 4.62 (1H, t, JZ
3 Hz), 3.90–3.73 (2H, m), 3.54–3.44 (2H, m), 2.45 (2H, tt,
JZ7, 3 Hz), 2.12 (6H, br t, JZ7 Hz), 1.88–1.36 (18H, m),
0.88 (3H, t, JZ7 Hz); 13C NMR (75 MHz, CDCl3) d 98.52,
81.05, 80.07, 79.87, 76.66, 66.08, 61.95, 31.13, 30.45,
28.90, 28.75, 28.22, 25.35, 21.80, 20.10, 19.28, 18.59,
4.3.7. 1-Tetrahydropyranyloxy-2,13-octadecadiyne (4g).
This compound was prepared following General procedure
B (Section 4.3) from bromoalcohol 1c in 67% yield after
purification. 1H NMR (300 MHz, CDCl3) d 4.76 (1H, t, JZ
3 Hz), 4.18 (2H, AB of ABX2, DnZ24.2 Hz, JABZ15.2 Hz,
JAXZJBXZ2 Hz), 3.82–3.73 (1H, m), 3.49–3.41 (1H, m),
2.18–2.07 (6H, m), 1.82–1.22 (24H, m), 0.84 (3H, t, JZ
7 Hz); 13C NMR (75 MHz, CDCl3) d 96.39, 86.51, 79.97
(2C), 75.60, 61.76, 54.45, 31.14, 30.16, 29.27, 29.01, 28.97,
18.57, 18.30, 13.50; IR (neat) 1137, 1122, 1070, 1034 cmK1
;
MS (EI) m/z 85 (100), 67 (15), 55 (13). Anal. Calcd for
C21H34O2: C, 79.19; H, 10.76. Found: C, 79.36; H, 10.67.
4.3.3. 1-Tetrahydropyranyloxy-2,12-heptadecadiyne
(4c). This compound was prepared following General