Total Synthesis of (ϩ) and (–) Enantiomers of the Oleander Scale Aspidiotus nerii Sex Pheromone
FULL PAPER
225 (6), 199 (100), 183 (28), 135 (30), 121 (27),105 (41), 91 (34), 77 time 6.77 min. Ϫ EI MS; m/z (%): 249 (1), 208 (2), 180 (2), 165 (1),
(49), 67 (44), 55 (30), 41 (39). Ϫ IR (neat): ν˜ ϭ 3450 cmϪ1, 3050, 140 (8), 126 (8), 125 (8), 111 (18), 82 (69), 81 (40), 67 (100), 55 (15),
2960, 2910, 2860, 1720, 1635.
41 (52). Ϫ IR (neat): ν˜ ϭ 3400 cmϪ1, 3040, 2940, 2900, 1710, 1630.
Ethyl 2-{2Ј-[(tert-Butyldiphenylsilyl)oxy]ethyl}-3-isopropenyl-5-(tos-
Ethyl 2-(3Ј,3Ј-Dimethylallyl)-3-isopropenyl-5-(tosyloxy)pentanoate
yloxy)pentanoate (26): Prepared from 25 by the same procedure as (30): Prepared from 29 by the same procedure as for 6 (70%).
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for 6 (93%). Colourless oil. Ϫ 1H NMR: δ ϭ 7.77 (d, 2 H, J ϭ
Colourless oil. Ϫ H NMR: δ ϭ 7.75 (d, 2 H, J ϭ 8 Hz), 7.32 (d,
8 Hz), 7.65 (m, 5 H), 7.40 (m, 7 H), 4.83 (br. s, 1 H), 4.69 (br. s, 1 2 H, J ϭ 8 Hz), 4.95 (t, 1 H, J ϭ 7 Hz), 4.82 (br. s, 1 H), 4.70 (br.
H), 4.08 (q, 2 H, J ϭ 7 Hz), 4.05Ϫ3.88 (m, 2 H), 3.59 (m, 2 H), s, 1 H), 4.17Ϫ3.80 (m, 4 H), 2.44 (s, 3 H), 2.40Ϫ2.14 (m, 2 H),
2.60 (m, 1 H), 2.45 (s, 3 H), 2.35 (m, 1 H), 1.71 (m, 3 H), 1.61 (s, 2.14Ϫ2.00 (m, 4 H), 1.63 (s, 3 H), 1.6Ϫ1.7 (m, 2 H), 1.53 (s, 6 H),
3 H), 1.21 (t, 3 H, J ϭ 7 Hz), 1.08 (m, 9 H). Ϫ 13C NMR: δ ϭ 1.22 (t, 3 H, J ϭ 7 Hz). Ϫ 13C NMR: δ ϭ 174.9 (s), 144.7 (s), 142.3
175.2 (s), 144.7 (s), 144.4 (s), 135.6 (d), 133.6 (s), 129.8 (d), 129.7
(s), 138.0 (s), 133.1 (s), 129.8 (d), 128.0 (d), 120.7 (d), 115.9 (t),
(d), 127.9 (d), 127.7 (d), 116.0 (t), 68.6 (t), 61.7 (t), 60.5 (t), 46.3 68.6 (t), 60.4 (t), 49.0 (d), 45.9 (d), 29.76 (t), 29.71 (t), 25.8 (q), 21.7
(d), 45.4 (d), 33.8 (t), 29.6 (t), 26.8 (q), 21.7 (q), 19.1 (s), 17.5 (q), (q), 17.77 (q), 17.63 (q), 14.4 (q).
14.5 (q).
Ethyl trans-1-(3Ј,3Ј-Dimethylallyl)-2-isopropenylcyclobutanecarbox-
Ethyl 2-{2Ј-[(tert-Butyldiphenylsilyl)oxy]ethyl}-5-chloro-3-isopropen-
ylpentanoate (27): A solution of LiHMDS (1 mL, 1 mmol, 1 solu-
tion in THF) was added dropwise under argon to a solution of the
ylate (31): A solution of LiHMDS (1.41 mL, 1.41 mmol, 1 solu-
tion in THF) was added dropwise under argon to a solution of
tosylate 30 (194 mg, 2.05 mmol, Ϫ20°C) in THF/HMPA (3.7
tosylate 26 (189 mg, 0.31 mmol, Ϫ20°C) in THF/HMPA (5:1, 6 mL:0.6 mL). The reaction mixture was stirred for 1 h at 0°C and
mL). The reaction mixture was stirred for 1 h at 0°C and for 1 h for 1 h at room temp., then quenched with satd. aqueous am-
at room temp., then quenched with satd. aqueous ammonium chlo-
monium chloride solution (10 mL) at 0°C. The aqueous phase was
ride solution (10 mL) at 0°C. The aqueous phase was extracted extracted with ether (3 ϫ 15 mL) and the combined organic layers
with ether (3 ϫ 15 mL) and the combined organic layers were were washed with water (10 mL), brine (10 mL), dried (MgSO4)
washed with water (10 mL), brine (10 mL), dried (MgSO4) and
concentrated under reduced pressure. The crude product was puri-
fied by flash chromatography (AcOEt/cyclohexane, 10:90) to give
and concentrated under reduced pressure. The crude product
{diastereoselectivity > 95:5; the ratio of stereomers was determined
by capillary GC analysis [DB5-MS, 0.32 mm i.d.
ϫ 30 m,
120 mg (80%) of the product 27 as a colourless oil. Ϫ Major iso-
mer: H NMR: δ ϭ 7.60 (m, 5 H), 7.39 (m, 5 H), 4.95 (br. s, 1 H), 95%)} was purified by flash chromatography (AcOEt/cyclohexane,
4.88 (br. s, 1 H), 4.13 (q, 2 H, J ϭ 7 Hz), 3.67Ϫ3.20 (m, 4 H), 2.66 5:95) to give 58 mg (50%) of the product 31 as a colourless oil. Ϫ
140Ϫ300°C, 10°C/min), retention time 4.40 min (< 5%), 4.51 (>
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(m, 1 H), 2.55 (dt, 1 H, J ϭ 11 Hz, J ϭ 3.5 Hz), 1.8Ϫ1.6 (m, 4 H),
1H NMR: δ ϭ 4.98 (t, 1 H, J ϭ 5 Hz), 4.95 (br. s, 1 H), 4.74 (br.
1.62 (s, 3 H), 1.22 (t, 3 H, J ϭ 7 Hz), 1.05 (s, 9 H). Ϫ 13C NMR: s, 1 H), 4.14 (m, 2 H), 3.06 (t, 1 H, J ϭ 9 Hz), 2.40Ϫ1.74 (m, 6 H),
δ ϭ 175.4 (s), 142.6 (s), 135.6 (d), 133,7 (s), 129.7 (d), 127.7 (d), 1.74 (s, 3 H), 1.65 (s, 3 H), 1.60 (s, 3 H), 1.25 (t, 3 H, J ϭ 7 Hz).
116.1 (t), 61.8 (t), 60.5 (t), 47.5 (d), 45.2 (d), 42.8 (t), 33.8 (t), 33.6
(t), 26.9 (q), 19.3 (s), 17.6 (q), 14.4 (q). Ϫ GC analysis (DB5-MS, 60.4 (t), 50.9 (s), 47.9 (d), 28.9 (t), 26.0 (q), 24.1 (t), 22.9 (q), 19.2
0.32 mm i.d. ϫ 30 m, 160Ϫ300°C, 10°C/min), retention time (t), 18.1 (q), 14.3 (q). Ϫ EI MS; m/z (%): 221 (1), 208 (1), 207 (1),
Ϫ
13C NMR: δ ϭ 176.5 (s), 144.2 (s), 133.9 (s), 119.6 (d), 111.6 (t),
16.20 min. Ϫ CI/NH3 MS; m/z (%): 489 (60), 488 (50), 487 (100), 191 (5), 190 (2), 180 (2), 175 (2), 153 (26), 139 (9), 125 (32), 111
429 (20), 409 (25), 371 (15). Ϫ IR (neat): ν˜ ϭ 3070 cmϪ1, 3020, (18), 107 (39), 95 (96), 94 (58), 93 (100), 81 (32), 79 (67), 77 (40),
2960, 2910, 2860, 1725, 1640.
67 (45), 55 (41), 55 (67), 53 (41), 43 (37), 41 (95).
Ethyl 2-(3Ј,3Ј-Dimethylallyl)-3-isopropenyl-5-oxopentanoate (28):
trans-1-(3Ј,3Ј-Dimethylallyl)-2-isopropenylcyclobutanemethanol
(32): A solution of ester 31 (195 mg, 0.82 mmol) in Et2O (6 mL)
Prepared from 20 by the same procedure as for 4 (60%). Colourless
1
oil. Ϫ H NMR: δ ϭ 9.54 (dd, 1 H, J ϭ 3 Hz, J ϭ 2 Hz), 4.99 (tt, was added under argon to a suspension of LiAlH4 (40 mg,
1 H, J ϭ 7.5 Hz, J ϭ 1.5 Hz), 4.87 (t, 1 H, J ϭ 1.5 Hz), 4.85 (br. 1.0 mmol, 0°C) in Et2O (6 mL). The reaction mixture was stirred
s, 1 H), 4.08 (m, 2 H), 2.92 (dt, 1 H, J ϭ 10 Hz, J ϭ 5 Hz),
for 1 h at 0°C, then quenched at 0°C with water (0.04 mL), 15%
2.50Ϫ2.13 (m, 4 H), 1.63 (s, 6 H), 1.54 (s, 3 H), 1.21 (t, 3 H, J ϭ NaOH (0.12 mL), water (0.04 mL) and stirred for 30 min at room
7 Hz). Ϫ 13C NMR: δ ϭ 201.3 (s), 174.6 (s), 143.3 (s), 133.9 (s), temp. The resultant mixture was filtered, the solid washed with
120.4 (d), 115.0 (t), 60.5 (t), 48.5 (d), 45.0 (t), 43.8 (d), 29.4 (t), 25.8 and the combined organic layers were concentrated under reduced
(q), 18.6 (q), 17.7 (2 C, q), 14.3 (q). Ϫ Capillary GC analysis (BPX-
5, 0.32 mm i.d. ϫ 30 m, 120Ϫ300°C, 10°C/min), retention time next step without further purification. Ϫ H NMR: δ ϭ 5.13 (td,
7.89 min. Ϫ EI MS; m/z (%): 237 (1), 234 (1), 209 (3), 208 (9), 206 1 H, J ϭ 7 Hz, J ϭ 1 Hz), 4.89 (br. s, 1 H), 4.71 (br. s, 1 H), 3.53
pressure to give the crude product 32 (150 mg, 94%) used in the
1
(8), 191 (1), 179 (5), 169 (9), 155 (9), 139 (17), 135 (14), 111 (15), (AB, 2 H, J ϭ 11 Hz), 2.81 (t, 1 H, J ϭ 7 Hz), 2.20Ϫ1.50 (m, 6
109 (40), 107 (11), 95 (16), 93 (34), 91 (12), 81 (79), 80 (22), 69 (52), H), 1.71 (s, 3 H), 1.69 (s, 3 H), 1.63 (s, 3 H). Ϫ 13C NMR: δ ϭ
67 (23), 55 (21), 53 (19), 43 (29), 41 (100). Ϫ IR (neat): ν˜ ϭ 3070 145.3 (s), 133.7 (s), 120.5 (d), 110.4 (t), 69.8 (t), 47.7 (s), 46.5 (d),
cmϪ1, 2970, 2920, 2720, 1725, 1640.
28.7 (t), 26.1 (q), 23.7 (q), 23.4 (t), 19.1 (t), 18.0 (q). Ϫ GC analysis
(DB5-MS, 0.32 mm i.d. ϫ 30 m, 120Ϫ300°C, 10°C/min), retention
time 5.92 min. Ϫ EI MS; m/z (%): 179 (1), 163 (6), 147 (1), 138 (1),
133 (4), 125 (4), 123 (4), 111 (5), 108 (26), 107 (20), 105 (10), 97
(6), 95 (29), 93 (98), 91 (21), 81 (16), 79 (24), 71 (16), 69 (53), 67
(37), 65 (8), 57 (19), 55 (41), 53 (27), 43 (39), 41 (100).
Ethyl
2-(3Ј,3Ј-Dimethylallyl)-5-hydroxy-3-isopropenylpentanoate
(29): Prepared from 28 by the same procedure as for 5 (80%).
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Colourless oil. Ϫ H NMR: δ ϭ 5.00 (t, 1 H, J ϭ 7 Hz), 4.88 (br.
s, 1 H), 4.86 (br. s, 1 H), 4.12 (m, 2 H), 3.52 (m, 2 H), 2.46 (dt, 1
H, J ϭ 11 Hz, J ϭ 4 Hz), 2.33 (ddd, 1 H, J ϭ 11 Hz, J ϭ 9 Hz,
J ϭ 5.5 Hz), 2.10 (m, 2 H), 1.64 (s, 3 H), 1.62 (s, 3 H), 1.54 (s, 3
trans-1-(3Ј,3Ј-Dimethylallyl)-2-isopropenylcyclobutanemethyl
p-
H), 1.23 (t, 3 H, J ϭ 7 Hz). Ϫ 13C NMR: δ ϭ 175.6 (s), 144.3 (s), Toluenesulfonate (33): 4-DMAP (117 mg, 0.96 mmol) and TsCl
140.9 (s), 133.5 (s), 120.9 (d), 115.0 (t), 61.2 (t), 60.3 (t), 49.2 (d), (95 mg, 0.66 mmol) were added to a solution of crude alcohol 32
46.8 (d), 33.8 (t), 29.8 (t), 25.8 (q), 17.7 (q), 14.4 (q). Ϫ GC analysis
(93 mg, 0.47 mmol, 0°C) in dichloromethane (1 mL) . The reaction
(DB5-MS, 0.32 mm i.d. ϫ 30 m, 140Ϫ300°C, 10°C/min), retention mixture was stirred for 36 h at 0°C under argon, poured into water
Eur. J. Org. Chem. 1999, 1201Ϫ1211
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