4
Y. Ohkubo et al. / Tetrahedron xxx (xxxx) xxx
4.1.3. Ethyl 2,10-dimethyldodecanoate (8)
(3H, d, J ¼ 6.4 Hz), 0.85 (3H, t, J ¼ 7.6 Hz), 1.06e1.15 (2H, m),
To
a
solution of LDA, prepared from (i-Pr)2NH (2.42 g,
1.21e1.36 (9H, m), 1.25 (3H, t, J ¼ 7.6 Hz), 1.62 (2H, quint, J ¼ 7.6 Hz),
24.0 mmol) and n-BuLi (1.57 M in hexane; 14.0 mL, 22.0 mmol) in
THF (20.0 mL), a solution of 6 (4.85 g, 20.0 mmol) in THF (10.0 mL)
was added dropwise at ꢀ78 ꢁC. After stirring for 30 min, a solution
of MeI (3.40 g, 24.0 mmol) and HMPA (1.08 g, 6.00 mmol) in THF
(5.0 mL) was added dropwise. After stirring for 1 h, the reaction
mixture was poured into 20% aq. NH4Cl and extracted with hexane.
The organic layer was washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by
silica-gel column chromatography (hexane/EtOAc ¼ 20:1) to give 8
(3.69 g, 72% yield). GC tR 23.67 min (98.2%); 1H NMR (CDCl3,
2.29 (2H, t, J ¼ 7.6 Hz), 4.12 (2H, q, J ¼ 7.6 Hz); 13C NMR (CDCl3,
100 MHz)
d 11.38, 14.25, 19.19, 25.00, 26.89, 29.18, 29.47, 29.60,
34.36, 34.40, 36.53, 60.13, 173.92; MS (70 eV, EI) m/z 187 (11), 186
(15), 169 (20), 151 (16), 139 (11), 129 (29), 95 (25), 83 (11), 71 (54),
70 (100), 69 (13), 57 (18), 55 (21), 43 (31), 41 (15); HRMS calcd for
C13H26O2: 214.1933, found: 214.1934.
4.1.7. Ethyl 2,8-dimethyldecanoate (9)
In the same manner as described for the synthesis of 8, 7 (4.85 g,
20.0 mmol) was converted to 9 (1.00 g, 47% yield). GC tR 19.18 min
(96.3%); 1H NMR (CDCl3, 400 MHz)
d
0.84 (3H, t, J ¼ 6.4 Hz), 0.85
400 MHz)
d
0.84 (3H, d, J ¼ 6.4 Hz), 0.85 (3H, t, J ¼ 7.6 Hz), 1.07e1.15
(2H, m), 1.13 (3H, d, J ¼ 7.2 Hz), 1.23e1.41 (14H, m), 1.25 (3H, t,
(3H, t, J ¼ 7.6 Hz), 1.06e1.15 (2H, m), 1.14 (3H, d, J ¼ 6.8 Hz),
1.23e1.43 (10H, m), 1.25 (3H, t, J ¼ 7.2 Hz), 1.64 (1H, m), 2.41 (1H,
sext, J ¼ 6.8 Hz), 4.13 (2H, q, J ¼ 7.2 Hz); 13C NMR (CDCl3, 100 MHz)
J ¼ 7.2 Hz), 1.66 (1H, m), 2.41 (1H, sext, J ¼ 7.2 Hz), 4.13 (2H, q,
J ¼ 7.2 Hz); 13C NMR (CDCl3, 100 MHz)
d 11.40, 14.27, 17.07, 19.21,
27.06, 27.22, 29.49, 29.53 (2C), 29.92, 33.82, 34.38, 36.61, 39.56,
60.04,176.99; MS (70 eV, EI) m/z 256 (13, Mþ), 213 (10),199 (21),171
(19), 157 (16), 115 (55), 103 (10), 102 (100), 87 (15), 83 (10), 74 (20),
69 (13), 57 (17), 55 (14), 43 (11), 41 (11); HRMS calcd for C16H32O2:
256.2402, found: 256.2397.
d
11.37, 14.25, 17.05, 19.17, 26.91, 27.25, 29.46, 29.85, 33.82, 34.35,
36.52, 39.55, 60.02, 176.94; MS (70 eV, EI) m/z 228 (5, Mþ), 183 (11),
171 (49), 157 (13), 129 (15), 115 (68), 103 (11), 102 (100), 97 (10), 87
(23), 83 (14), 74 (31), 71 (11), 69 (19), 57 (24), 55 (20), 43 (14), 41
(18), 29 (11); HRMS calcd for C14H28O2: 228.2089, found: 228.2108.
4.1.4. 2,10-Dimethyl-1-dodecanol (10)
4.1.8. 2,8-Dimethyl-1-decanol (11)
To an ice-cooled suspension of LiAlH4 (380 mg, 10.0 mmol) in
Et2O (10.0 mL), a solution of 8 (2.56 g, 10.0 mmol) in Et2O (10.0 mL)
was added dropwise at 0 ꢁC. After stirring for 1.5 h, water (0.38 g),
15% aq. NaOH (0.38 g) and water (1.14 g) were added dropwise with
vigorous stirring. After adding MgSO4, the resulting mixture was
filtered and the filtrate was concentrated under reduced pressure.
The residue was purified by silica-gel column chromatography
(hexane/EtOAc ¼ 10:1) to give 10 (2.00 g, 93% yield). GC tR
In the same manner as described for the synthesis of 10, 9
(0.80 g, 3.5 mmol) was converted to 11 (0.62 g, 95% yield). GC tR
17.39 min (99.0%); 1H NMR (CDCl3, 400 MHz)
d 0.84 (3H, d,
J ¼ 6.0 Hz), 0.86 (3H, t, J ¼ 7.6 Hz), 0.92 (3H, t, J ¼ 6.4 Hz), 1.07e1.17
(3H, m), 1.21e1.42 (10H, m), 1.48 (1H, br), 1.61 (1H, m), 3.42 (1H, dd,
J ¼ 10.8, 6.8 Hz), 3.50 (1H, dd, J ¼ 10.8, 6.0 Hz); 13C NMR (CDCl3,
100 MHz)
d 11.37, 16.56, 19.19, 27.01, 27.05, 29.46, 29.47, 30.27,
30.28, 33.15, 34.37, 35.75, 36.59, 68.38; MS (70 eV, EI) m/z 139 (22),
111 (12), 98 (15), 97 (48), 85 (24), 84 (20), 83 (82), 71 (62), 70 (100),
69 (58), 57 (91), 56 (37), 55 (54), 43 (40), 41 (32), 29 (11); HRMS
calcd for C12H26O: 186.1984, found: 186.1977.
22.12 min (98.9%); 1H NMR (CDCl3, 400 MHz)
d 0.84 (3H, d,
J ¼ 6.4 Hz), 0.85 (3H, t, J ¼ 7.6 Hz), 0.92 (3H, d, J ¼ 6.8 Hz), 1.06e1.16
(3H, m), 1.21e1.42 (15H, m), 1.60 (1H, m), 3.42 (1H, dd, J ¼ 10.4,
6.4 Hz), 3.51 (1H, dd, J ¼ 10.4, 6.0 Hz); 13C NMR (CDCl3, 100 MHz)
d
11.40, 16.58, 19.21, 26.98, 27.09, 29.49, 29.68, 29.95, 30.00, 33.15,
4.1.9. 2,8-Dimethyldecyl propanoate (2)
34.39, 35.77, 36.63, 68.44; MS (70 eV, EI) m/z 167 (14), 125 (22), 111
(54), 98 (13), 97 (69), 85 (37), 84 (20), 83 (62), 82 (13), 71 (77), 70
(100), 69 (70), 57 (88), 56 (39), 55 (52), 43 (39), 41 (31), 29 (10);
HRMS calcd for C14H30O: 214.2297, found: 214.2280.
In the same manner as described for the synthesis of 1, 11
(250 mg, 1.34 mmol) was converted to 2 (0.31 g, 95% yield). GC tR
22.17 min (98.8%); 1H NMR (CDCl3, 400 MHz)
d 0.84 (3H, d,
J ¼ 6.4 Hz), 0.86 (3H, t, J ¼ 7.6 Hz), 0.92 (3H, d, J ¼ 6.8 Hz), 1.07e1.14
(3H, m), 1.15 (3H, t, J ¼ 7.6 Hz), 1.21e1.38 (10H, m), 1.77 (1H, m), 2.33
(2H, q, J ¼ 7.6 Hz), 3.86 (1H, dd, J ¼ 10.8, 6.8 Hz), 3.95 (1H, dd,
4.1.5. 2,10-Dimethyldodecyl propanoate (1)
To an ice-cooled solution of 10 (643 mg, 3.00 mmol) and pyri-
dine (475 mg, 6.00 mmol) in CH2Cl2 (30.0 mL), propanoyl chloride
(416 mg, 4.50 mmol) was added. After stirring for 1 h, the reaction
mixture was poured into 5% aq. NaHCO3 and extracted with hexane.
The organic layer was washed with brine, dried over MgSO4, and
concentrated under reduced pressure. The residue was purified by
silica-gel column chromatography (hexane/EtOAc ¼ 20:1) and
Kugelrohr distillation to give ( )-1 (775 mg, 96% yield). GC tR
J ¼ 10.8, 6.0 Hz); 13C NMR (CDCl3, 100 MHz)
d 9.18, 11.38, 16.86,
19.19, 26.83, 27.00, 27.63, 29.46, 30.15, 30.16, 32.54, 33.36, 34.37,
36.56, 69.28, 174.61; MS (70 eV, EI) m/z 140 (11), 139 (36), 111 (13),
98 (11), 97 (33), 85 (10), 84 (15), 83 (56), 75 (27), 71 (30), 70 (64), 69
(32), 57 (100), 56 (31), 55 (25), 43 (14), 41 (14), 29 (12); HRMS calcd
for C15H30O2: 242.2246, found: 242.2231.
4.1.10. Ethyl (S)-10-methyldodecanoate [(S)-6]
26.52 min (99.0%); 1H NMR (CDCl3, 400 MHz)
d 0.84 (3H, d,
In the same manner as described for the synthesis of 6, (S)-3
(18.0 g, 119 mmol) was converted to (S)-6 (25.4 g). GC tR 23.30 min
J ¼ 6.4 Hz), 0.85 (3H, t, J ¼ 7.2 Hz), 0.92 (3H, d, J ¼ 6.8 Hz), 1.06e1.18
(3H, m), 1.15 (3H, t, J ¼ 7.6 Hz), 1.21e1.40 (14H, m), 1.77 (1H, m), 2.33
(2H, q, J ¼ 7.6 Hz), 3.86 (1H, dd, J ¼ 10.8, 6.8 Hz), 3.95 (1H, dd,
(96.8%); ½a 2D0
þ5.65 (c ¼ 1.75 in CHCl3); HRMS calcd for C15H30O2:
ꢂ
J ¼ 10.8, 6.0 Hz); 13C NMR (CDCl3, 100 MHz)
d 9.20, 11.39, 16.87,
242.2246, found: 242.2254.
19.21, 26.81, 27.08, 27.65, 29.49, 29.63, 29.83, 29.97, 32.55, 33.36,
34.39, 36.62, 69.30, 174.63; MS (70 eV, EI) m/z 167 (22), 125 (15), 111
(45), 97 (50), 86 (10), 85 (18), 84 (14), 83 (41), 75 (33), 71 (38), 70
(66), 69 (39), 57 (100), 56 (34), 55 (27), 43 (16), 41 (15), 29 (11);
HRMS calcd for C17H34O2: 270.2559, found: 270.2539.
4.1.11. (S)-10-Methyldodecanoic acid [(S)-12]
To a solution of (S)-6 (25.2 g) in THF (120 mL) was added 20% aq.
NaOH (120 g, 0.60 mol). The mixture was heated under reflux for
5 h. After the reaction mixture was cooled to room temperature, the
aqueous layer was separated and washed with Et2O. The aqueous
layer was acidified with 1 M aq. HCl and extracted with Et2O. The
extract was washed with water and brine, dried over MgSO4, and
concentrated under reduced pressure to give (S)-12 (20.8 g). GC tR
4.1.6. Ethyl 8-methyldecanoate (7)
In the same manner as described for the synthesis of 6, 3 (14.5 g,
96.0 mmol) was converted to 7 (16.7 g, 97% yield). bp 62e71 ꢁC/
0.1 kPa; GC tR 18.46 min (98.0%); 1H NMR (CDCl3, 400 MHz)
d
0.84
23.48 min (99.2%); ½a D20
ꢂ
þ6.13 (c ¼ 1.86 in CHCl3); 1H NMR (CDCl3,
Please cite this article as: Y. Ohkubo et al., Pheromone synthesis. Part 265: Synthesis and stereochemical composition of two pheromonal