980
K. MORI
ZnCl2 (1.10 g, 8 mmol) in dry Et2O (20 mL) at 0–5 ꢂC. The mixture
was stirred for 1 h at 0–5 ꢂC, poured into an ice-water solution, and left
until the organic layer had separated. The aqueous layer was extracted
with a small amount of Et2O. The combined Et2O solution was washed
with brine, dried (MgSO4), and concentrated by fractional distillation
through a Vigreux column under atmospheric pressure. The residue
was distilled to give 1.84 g (48%) of (ꢀ)-2 as a colorless oil with a
(m), 820 (m), 793 (m). 1H-NMR ꢀH (CDCl3): 1.08 (3H, t, J ¼ 7:6 Hz),
1.44 (3H, d, J ¼ 6:4 Hz), 1.49–1.66 (2H, m), 2.02 (1H, d, J ¼ 4:8 Hz),
2.28–2.37 (1H, m), 2.56–2.64 (1H, m), 2.92–2.98 (1H, m), 3.12–3.18
(1H, m), 4.53 (1H, m). GC-MS (same conditions as those for 7a)
tR: 9.38 min [99.2%, (ꢀ)-14]. MS of (ꢀ)-14 (70 eV, EI) m=z: 153 (4)
(<1) (Mþ ꢁ 1), 136 (3), 125 (4), 121 (10), 109 (37), 95 (54), 91 (21), 81
(87), 79 (37), 77 (33), 67 (49), 55 (29), 53 (34), 45 (29), 43 (100), 41
(57), 39 (40). HRMS: calcd. for C9H13O2 (Mþ ꢁ H), 153.0921; found,
153.0915.
21
camphor-like odour, bp 92–96 ꢂC at 45 Torr, nD ¼ 1:4462. IRꢁmax
(film) cmꢁ1: 2960 (s), 2877 (m), 1463 (m), 1379 (s), 1348 (w), 1307
(w), 1257 (m), 1238 (s), 1198 (m), 1173 (s), 1108 (s), 1032 (s), 1001
(s), 968 (m), 903 (m), 870 (w), 852 (s). 1H-NMR ꢀH (CDCl3): 0.99
(3H, dt, J ¼ 2, 7.6 Hz), 1.43 (3H, d, J ¼ 2 Hz), 1.53–1.70 (6H, m),
1.75–1.90 (2H, m), 3.95–4.03 (1H, m), 4.19–4.25 (1H, m). 13C-NMR
ꢀC (CDCl3): 11.0, 17.6, 21.9, 23.6, 25.0, 34.4, 76.5, 81.6, 106.9. GC-
MS (same conditions as those for 7a) tR: 11.9 min [3.1%, (ꢀ)-3],
12.6 min (8.1%, Mþ ¼ 142, unidentified), 12.8 min [88.8%, (ꢀ)-2].
MS of (ꢀ)-2 (70 eV, EI) m=z: 156 (4) (Mþ), 114 (63), 98 (59), 86 (32),
81 (23), 71 (29), 68 (29), 67 (17), 57 (15), 55 (15), 43 (100), 41 (15), 39
(10). HMRS: calcd. for C9H16O2 (Mþ), 156.1150; found, 156.1148.
(ꢀ)-cis-6,7-Epoxy-3-nonyn-2-one (9c).
A
solution of (ꢀ)-14
(1.65 g, 10.7 mmol) in dry CH2Cl2 (10 mL) was added dropwise to a
vigorously stirred and ice-cooled suspension of PCC (6.45 g, 40 mmol),
NaOAc (1.90 g, 23 mmol) and SiO2 (6.0 g) in dry CH2Cl2 (80 mL). The
mixture was stirred at 0–5 ꢂC for 2 h, diluted with Et2O, and filtered.
The filtrate was concentrated in vacuo, and the residue (ca. 1.6 g) was
chromatographed over SiO2 (20 g). Elution with hexane/EtOAc (20:1)
20
gave 1.12 g (69%) of (ꢀ)-9c as a yellowish oil, nD ¼ 1:4702. IRꢁmax
(film) cmꢁ1: 2972 (s), 2937 (m), 2879 (m), 2214 (s), 1678 (vs), 1360
(m), 1230 (s). 1H-NMR ꢀH (CDCl3): 1.09 (3H, t, J ¼ 7:6 Hz), 1.49–
1.67 (2H, m), 2.34 (3H, s), 2.49 (1H, dd, J ¼ 6:8, 17.6 Hz), 2.75 (1H,
dd, J ¼ 5:6, 17.6 Hz), 2.94–2.98 (1H, m), 3.12–3.22 (1H, m). GC-MS
(same conditions as those for 7a) tR: 9.25 min [90.0%, (ꢀ)-9c],
9.32 min (3.8%, trans-isomer), 11.41 min (6.2%, unidentified). MS of
(ꢀ)-9c (70 eV, EI) m=z: 152 (4) (Mþ), 137 (13), 123 (8), 109 (29), 95
(54), 81 (38), 79 (56), 67 (13), 53 (18), 43 (100), 41 (21), 39 (23).
HRMS: calcd. for C9H11O2 (Mþ ꢁ H), 151.0765; found, 151.0760.
(ꢀ)-cis-2,3-Epoxy-1-pentanol (13a). MCPBA (65% purity, 41.3 g,
156 mmol) was added portionwise over 30 min to a stirred and ice-
cooled solution of 12 (13.4 g, 156 mmol) in CH2Cl2 (250 mL) at
5–10 ꢂC. Stirring was continued for 2 h at 0–5 ꢂC, and the mixture was
then filtered and the filter cake washed with hexane. The filtrate and
washings were washed with a solution of Na2CO3 containing a small
amount of Na2S2O3, dried (MgSO4), and concentrated in vacuo. The
resulting residue was distilled to give 8.36 g (53%) of (ꢀ)-13a as a
20
colorless oil, bp 77–78 ꢂC at 8 Torr or 68–69 ꢂC at 5 Torr, nD
¼
(ꢀ)-cis-6,7-Epoxy-2-nonanone (10c). 10% Pd–C (0.25 g) and Et3N
(0.3 mL) were added to a solution of (ꢀ)-9c (1.02 g, 6.7 mmol) in
EtOAc (20 mL). The suspension was stirred under an H2 atmosphere
(balloon) for 1 h at room temperature and then filtered through Celite.
The Celite layer was washed with Et2O, and the filtrate and washings
were combined and concentrated in vacuo to give 1.10 g (quant.) of
1:4359. IRꢁmax (film) cmꢁ1: 3419 (s), 2972 (s), 2937 (m), 2879 (m),
1460 (m), 1043 (s), 895 (m), 818 (m), 800 (m). 1H-NMR ꢀH (CDCl3):
1.05 (3H, dt, J ¼ 2, 7.6 Hz), 1.49–1.68 (2H, m), 2.52–2.85 (1H, br.),
2.99–3.05 (1H, m), 3.14–3.22 (1H, m). 3.62–3.70 (1H, m), 3.81–3.90
(1H, m). GC-MS (same conditions as those for 7a) tR: 6.85 min
[0.98%, trans-isomer], 8.07 min [99.02%, (ꢀ)-13a]. MS of (ꢀ)-13a
(70 eV, EI) m=z: 102 (<1) (Mþ), 59 (100), 57 (20), 55 (11), 44 (29), 43
(39), 41 (46), 39 (18), 31 (38). HRMS: calcd. for C5H8O (Mþ ꢁ H2O),
84.0575; found, 84.0576.
21
(ꢀ)-10c as a colorless oil, nD ¼ 1:4442. IRꢁmax (film) cmꢁ1: 2970
(s), 2937 (s), 2877 (m), 1714 (vs), 1367 (m), 1242 (m), 906 (m).
1H-NMR ꢀH (CDCl3): 1.04 (3H, t, J ¼ 7:6 Hz), 1.40–1.65 (4H, m),
1.77 (2H, m), 2.15 (3H, s), 2.50–2.61 (1H, m), 2.84–2.94 (1H, m). Oily
(ꢀ)-10c was immediately employed in the next step.
(ꢀ)-cis-2,3-Epoxypentyl triflate (13b). A solution of Tf2O (7.6 mL,
12.7 g, 45 mmol) in dry CH2Cl2 (45 mL) was added dropwise over
20 min to a stirred and cooled solution of (ꢀ)-13a (3.06 g, 30 mmol)
and Et3N (13.6 mL, 100 mmol) in dry CH2Cl2 (70 mL) at ꢁ70 ꢂC
under Ar. The mixture was stirred for 20 min at ꢁ70 ꢂC, before being
transferred to a separatory funnel, successively washed with water and
an aqueous NaHCO3 solution, dried (MgSO4), and filtered through a
short column of SiO2 (30 g) in CH2Cl2. The column was washed with a
small amount of CH2Cl2, and the combined filtrate and washings were
concentrated in vacuo to give crude (ꢀ)-13b as an oil (5.52 g, 79%).
IRꢁmax (film) cmꢁ1: 2979 (m), 2945 (w), 2885 (w), 1415 (s), 1248 (s),
1209 (s), 1144 (s), 941 (s), 615 (m). 1H-NMR ꢀH (CDCl3): 1.09 (3H, t,
J ¼ 7:6 Hz), 1.50–1.67 (2H, m), 3.00–3.10 (1H, m), 3.30–3.34 (1H,
m), 4.47–4.56 (1H, m), 4.64–4.71 (1H, m). Triflate (ꢀ)-13b was
extremely unstable and spontaneously polymerized by an exothermic
reaction in the presence of air to give a dark-colored and viscous oil.
Crude (ꢀ)-13b was immediately employed in the next step.
(ꢀ)-exo-Brevicomin (exo-7-ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]-
octane, 3). A solution of (ꢀ)-10c (1.00 g, 6.4 mmol) in dry Et2O
(10 mL) was added dropwise to a stirred and ice-cooled suspension of
ZnCl2 (1.00 g, 3.7 mmol) in dry Et2O (30 mL) at 0–5 ꢂC. After stirring
for 30 min at 0–5 ꢂC, the mixture was quenched with an NH4Cl
solution and extracted with Et2O. The extract was washed with brine,
dried (MgSO4), and concentrated under atmospheric pressure by
fractional distillation through a Vigreux column. The residue was
distilled to give 310 mg (31%) of (ꢀ)-3 as a colorless oil with a
21
camphor-like odour, bp 81–82 ꢂC at 29 Torr, nD ¼ 1:4408. IRꢁmax
(film) cmꢁ1: 2939 (s), 2877 (m), 2848 (m), 1462 (m), 1381 (s), 1346
(w), 1333 (w), 1238 (s), 1174 (s), 1107 (m), 1032 (m), 1007 (m), 970
(m), 926 (m), 879 (m), 847 (s), 615 (w). 1H-NMR ꢀH (CDCl3): 0.92
(3H, t, J ¼ 7:6 Hz), 1.42 (3H, s), 1.45–1.61 (1H, m), 1.61–1.65 (2H,
m), 1.75–1.85 (2H, m), 1.85–1.95 (1H, m), 3.94 (1H, t, J ¼ 7:6 Hz),
4.14 (1H, br. s). 13C-NMR ꢀC (CDCl3): 9.8, 17.2, 25.1, 28.0, 28.6,
34.9, 78.3, 81.2, 107.7. GC-MS (same conditions as those for 7a)
tR: 11.96 min [97.2%, (ꢀ)-3], 12.83 min [1.4%, (ꢀ)-2]. MS of (ꢀ)-3
(70 eV, EI) m=z: 156 (12) (Mþ), 127 (11), 114 (100), 99 (15), 98 (36),
86 (31), 85 (81), 81 (17), 68 (27), 43 (100). HRMS: calcd. for C9H16O2
(Mþ), 156.1150; found, 156.1142.
(ꢀ)-cis-6,7-Epoxy-3-nonyn-2-ol (14). A solution of n-BuLi in
hexane (1.6 M, 50 mL, 80 mmol) was added dropwise to a stirred and
cooled solution of (ꢀ)-6 (2.80 g, 40 mmol) in dry THF (200 mL) at
ꢁ70 ꢂC to ꢁ50 ꢂC under Ar. The resulting sticky suspension was stirred
without cooling to warm the mixture to ꢁ10 ꢂC. It was then cooled
again to ꢁ30 ꢂC to ꢁ20 ꢂC, and a solution of (ꢀ)-13b (5.52 g,
23.6 mmol) in dry C6H6 (40 mL) was added dropwise over 10 min to the
vigorously stirred mixture to make it homogeneous. Stirring was
continued for 1 h without cooling, before the mixture was poured into a
solution of ice and NH4Cl, and extracted with Et2O. The extract was
successively washed with water and brine, dried (MgSO4), and
concentrated in vacuo. The resulting residue (3.69 g) was chromato-
graphed over SiO2 (80 g), elution with hexane/EtOAc (8:1 to 5:1)
(ꢀ)-(Z)-cis-6,7-Epoxy-3-nonen-2-one (15). Lindlar’s Pd catalyst on
CaCO3 with Pb2þ (Aldrich, 100 mg) and quinoline (1 drop) were added
to a solution of (ꢀ)-9c (381 mg, 2.5 mmol) in cyclohexane (15 mL).
The mixture was stirred under an H2 atmosphere (balloon) at 0–5 ꢂC
for 1 h and was then filtered through SiO2 (3.0 g). The SiO2 column
was washed with hexane/EtOAc (20:1), and the combined filtrate and
washings were concentrated in vacuo to give 344 mg (89%) of crude
21
(ꢀ)-15, nD ¼ 1:4662. IRꢁmax (film) cmꢁ1: 2972 (s), 1693 (s), 1616
20
giving 1.71 g (41%) of (ꢀ)-14 as a colorless oil, nD ¼ 1:4694. IRꢁmax
(m), 1415 (m), 1358 (m), 1180 (s), 968 (m), 928 (m), 808 (m). 1H-
NMR ꢀH (CDCl3): 1.02 (3H, t, J ¼ 7:6 Hz), 1.42–1.65 (2H, m), 2.23
(3H, s), 2.69–2.73 (1H, m), 2.85–2.94 (1H, m), 3.01–3.10 (2H, m),
(film) cmꢁ1: 3417 (vs), 2976 (s), 2937 (m), 2879 (m), 2249 (w), 1454
(m), 1371 (m), 1290 (m), 1153 (s), 1078 (vs), 1003 (s), 935 (m), 893