20
oil; [α] Ϫ0.9 (c 2.58 in CHCl3); (Found C, 61.0; H, 9.2;
(4R)-N-(tert-Butoxycarbonyl)-2,2-dimethyl-4-
C16H28SO4 requires C, 60.7; H, 8.9%); νmax (film) 2933, 1356,
1175 and 1095 cmϪ1; δH (360 MHz; CDCl3) 6.28 (1H, dd, J 15.0,
10.8 Hz, CHCH:CH), 5.86–5.75 (2H, m, 2 × CH), 5.51 (1H, dt,
J 15.0, 7.1 Hz, CH:CHCH2), 5.11–5.04 (2H, m, CH2:CH), 4.23
[2H, t, J 6.5 Hz, CH2(OSO2CH3)], 3.34 (3H, s, OCH3), 3.19 [1H,
tt, J 5.8, 5.8 Hz, CH(OCH3)], 3.00 (3H, s, OSO2CH3), 2.31–2.03
(6H, m, 3 × CH2), 1.85 (2H, tt, J 6.5, 6.5 Hz, CH2CH2CH2),
1.73 (3H, s, CH3), 1.62–1.56 (2H, m, CHCH2CH2); δC (90.6
MHz; CDCl3) 137.34 (s), 134.66 (d), 129.35 (d), 128.18 (d),
124.28 (d), 116.92 (t), 79.81 (d), 69.36 (t), 56.48 (q), 37.58 (t),
37.28 (q), 35.29 (t), 31.51 (t), 28.84 (t), 28.56 (t), 16.52 (q); m/z
(FAB) 317.1783 (MHϩ, 52%, C16H29SO4 requires 317.1787), 307
(21), 284 (48), 275 (19), 243 (23), 154 (100), 149 (32), 136 (74),
121 (34), 107 (49), 91 (51).
[(1Z,5E,7E,11R)-11-methoxy-8-methyltetradeca-1,5,7,13-
tetraen-1-yl]oxazolidine 19
A solution of sodium hexamethyldisilazide (1.0 M) in THF (1.6
ml, 1.6 mmol) was added dropwise over 30 min to a stirred
solution of the phosphonium salt 17c (1.0 g, 1.6 mmol) in dry
THF (10 ml) at Ϫ78 ЊC under an atmosphere of argon. The
orange mixture was stirred at Ϫ78 ЊC for 1 h and a solution of
the aldehyde 18 (0.45 g, 2.0 mmol) in dry THF (10 ml) was
added dropwise over 1 h. The mixture was stirred at Ϫ78 ЊC for
a further 1 h and then allowed to warm to 0 ЊC over 1 h. Water
(30 ml) was added and the mixture was then extracted with
ether (3 × 100 ml). The combined organic extracts were dried
(Na2SO4) and evaporated in vacuo to leave an oil. The oil was
purified by column chromatography on silica gel using 15%
ether–light petroleum as eluant to give the tetraene (0.58 g,
82%) as a colourless viscous oil; [α]20 ϩ 73.6 (c 1.10 in CHCl3);
(Found C, 72.0; H, 10.2; N, 3.2; C26H43O4N requires C, 72.0; H,
10.0; N, 3.2%); λmax (EtOH) 205 (10 761), 236 (19 958) nm; νmax
(film) 2978, 2931, 1698, 1384 and 1095 cmϪ1; δH (360 MHz;
CDCl3) 6.24 (1H, dd, J 15.0, 10.8 Hz, CHCH:CH), 5.87–5.76
(2H, m, 2 × CH), 5.56–5.40 (3H, m, 3 × CH), 5.12–5.05 (2H, m,
CH2:CH), 4.72–4.53 (1H, m, NCH), 4.04 (1H, dd, J 8.7, 6.2 Hz,
OCHHCH), 3.63 (1H, dd, J 8.7, 3.2 Hz, OCHHCH), 3.35 (3H,
s, OCH3), 3.20 [1H, tt, J 5.9, 5.9 Hz, CH(OCH3)], 2.30–2.07
(8H, m, 4 × CH2), 1.74 (3H, s, CH3), 1.63–1.52 (8H, m, 2 ×
CH3, CH2), 1.45 [9H, s, (CH3)3CO]; δC (90.6 MHz; CDCl3)
151.93 (s), 136.58 (s), 134.69 (d), 130.94 (d), 130.82 (d), 129.61
(d), 127.31 (d), 124.57 (d), 116.90 (t), 93.61 (s), 79.83 (d), 79.61
(s), 68.93 (t), 56.50 (q), 54.47 (d), 37.60 (t), 35.33 (t), 32.83 (t),
31.56 (t), 28.45 (q), 27.42 (t), 26.39 (q), 24.05 (q), 16.50 (q); m/z
(EI) 433.3191 (Mϩ, 1%, C26H43O4N requires 433.3192), 333
(19), 286 (7), 234 (6), 144 (19), 107 (14), 85 (28).
[(4E,6E,10R)-10-Methoxy-7-methyltrideca-4,6,12-trienyl]-
triphenylphosphonium iodide 17c
Sodium iodide (1. 9 g, 12.6 mmol) was added in one portion to
a stirred solution of the mesylate 17b (0.8 g, 2.5 mmol) in dry
acetone (10 ml) under an atmosphere of nitrogen. The mixture
was stirred for 24 h in the dark and the solvents were then
removed in vacuo to leave a residue. The residue was diluted
with ether–hexane (1:1, 25 ml) and filtered through a short pad
of silica gel. The solvents were removed in vacuo to leave a pale
yellow oil which was purified by column chromatography on
silica gel using 5% ether–light petroleum as eluant to give the
20
corresponding iodide (0.85 g, 98%) as a colourless oil; [α]
Ϫ1.6 (c 4.28 in CHCl3); (Found C, 52.0; H, 7.5; C15H25IO
requires C, 51.7; H, 7.2%); λmax (EtOH) 237 (6812) nm; νmax
(film) 2926, 1440, 1096, 963 and 911 cmϪ1; δH (360 MHz;
CDCl3) 6.30 (1H, dd, J 15.0, 10.8 Hz, CHCH:CH), 5.87–5.76
(2H, m, 2 × CH), 5.50 (1H, dt, J 15.0, 7.1 Hz, CH:CHCH2),
5.12–5.05 (2H, m, CH2:CH), 3.35 (3H, s, OCH3), 3.24–3.17 [1H,
m, CH(OCH3)], 3.20 (2H, t, J 7.0 Hz, CH2I), 2.31–2.02 (6H, m,
3 × CH2), 1.92 (2H, tt, J 7.0, 7.0 Hz, CH2CH2CH2), 1.75 (3H, s,
CH3), 1.60 (2H, td, J 7.9, 5.9 Hz, CHCH2CH2); δC (90.6 MHz;
CDCl3) 137.14 (s), 134.73 (d), 129.51 (d), 128.11 (d), 124.46 (d),
116.97 (t), 79.88 (d), 56.55 (q), 37.64 (t), 35.35 (t), 33.44 (t),
33.06 (t), 31.56 (t), 16.59 (q), 6.58 (t); m/z (FAB) 349.1018
(MHϩ, 47%, C15H25IO requires 349.1028), 348 (71), 316 (44),
307 (51), 275 (45), 249 (35), 154 (100), 136 (62), 119 (35), 107
(53), 93 (54).
(2R,3Z,7E,9E,13R)-13-Methoxy-10-methyl-2-aminohexadeca-
3,7,9,15-tetraen-1-ol 10
10% Aqueous HCl solution (16 ml) was added dropwise over 5
min to a stirred solution of the oxazolidine 19 (325 mg, 0.7
mmol) in methanol (32 ml). The mixture was heated at 40 ЊC
(bath temperature) for 3 h and then neutralised with saturated
NaHCO3 solution. The mixture was extracted with dichloro-
methane (3 × 50 ml) and the combined organic extracts were
then dried (Na2SO4) and evaporated in vacuo to leave the crude
amino-alcohol (200 mg, 91%) as a colourless viscous oil; νmax
(film) 3356, 2922, 1443, 1097, 963 and 913 cmϪ1; δH (360 MHz;
CDCl3) 6.25 (1H, dd, J 15.0, 10.8 Hz, CHCH:CH), 5.87–5.76
(2H, m, 2 × CH), 5.59–5.55 (2H, m, 2 × CH), 5.27 [1H, dd,
J 9.9, 9.9 Hz, CH:CHCH(NH2)], 5.12–5.05 (2H, m, CH2:CH),
3.74–3.73 [1H, m, CH(NH2)], 3.50 [1H, dd, J 10.4, 4.5 Hz,
CHH(OH)], 3.37–3.29 [1H, m, CHH(OH)], 3.35 (3H, s, OCH3),
3.20 [1H, tt, J 5.9, 5.9 Hz, CH(OCH3)], 2.30–2.08 (9H, m, 4 ×
CH2, OH), 1.74 (3H, s, CH3), 1.74–1.68 (2H, br m, NH2), 1.60
[2H, td, J 7.9, 6.0 Hz, CH(OCH3)CH2CH2];δC (90.6 MHz;
CDCl3) 136.88 (s), 134.74 (d), 131.60 (d), 130.95 (d), 127.44 (d),
124.53 (d), 116.95 (t), 79.88 (d), 77.20 (d), 66.43 (t), 56.53 (q),
50.11 (d), 37.64 (t), 35.36 (t), 32.88 (t), 31.58 (t), 27.83 (t), 16.56
(q); m/z (EI) 293.2343 (Mϩ, 9%, C18H31O2N requires 293.2355),
262 (35), 220 (13), 185 (5), 145 (15), 119 (42), 107 (40), 93 (52),
85 (100), which was used without further purification.
Triphenylphosphine (0.6 g, 2.4 mmol) was added in one
portion to a stirred solution of the iodide (0.74 g, 2.1 mmol) in
dry acetonitrile (10 ml) under an atmosphere of argon. The
mixture was heated under reflux for 16 h and then concentrated
in vacuo to leave a residue. The residue was purified by column
chromatography on silica gel using dichloromethane to 10%
methanol–dichloromethane as eluant to give the phosphonium
20
salt (1.2 g, 92%) as a colourless foam; [α] ϩ0.4 (c 11.30 in
CHCl3); (Found C, 65.0; H, 6.7; C33H40IPO requires C, 64.9; H,
6.6%); λmax (EtOH) 229 (32 283) nm; νmax (film) 2926, 1438,
1112, 996, 968, 914, 734, 723 and 690 cmϪ1; δH (500 MHz;
CDCl3) 7.78–7.72 (9H, m, 9 × ArCH), 7.68–7.64 (6H, m, 6 ×
ArCH), 6.25 (1H, dd, J 15.0, 10.8 Hz, CHCH:CH), 5.77–5.68
(2H, m, 2 × CH), 5.36 (1H, dt, J 15.0, 7.2 Hz, CH:CHCH2),
5.03–4.97 (2H, m, CH2:CH), 3.60–3.54 (2H, m, CH2P), 3.26
(3H, s, OCH3), 3.13 [1H, tt, J 5.9, 5.9 Hz, CH(OCH3)], 2.41
(2H, dt, J 7.2, 7.2 Hz, :CHCH2CH2), 2.23–2.16 (2H, m,
CH2CH2C), 2.08–1.93 (2H, m, CHCH2CH), 1.73–1.65 (2H,
m, CH2CH2CH2), 1.65 (3H, s, CH3), 1.53–1.48 (2H, m,
CHCH2CH2); δC (125.8 MHz; CDCl3) 137.65 (s), 134.94 (d),
134.41 (d), 133.38 (d, J 10 Hz, d), 130.36 (d, J 13 Hz, d), 128.80
(d, J 24 Hz, d), 123.98 (d), 118.05 (d), 117.37 (s), 116.71 (t),
79.55 (d), 56.27 (q), 37.32 (t), 35.08 (t), 32.88 (d, J 16 Hz, t),
31.29 (t), 22.35 (d, J 12 Hz, t), 21.90 (t), 16.49 (q); m/z (FAB)
483.2819 (Mϩ Ϫ I, 100%, C33H40PO requires 483.2817), 289
(12), 262 (20), 154 (17), 136 (12), 97 (18).
(1R,2S )-2-Methylcyclopropanecarboxylic acid (2-aminophenyl)-
amide 26
Benzotriazol-1-yloxy(tripyrrolidino)phosphonium hexafluoro-
phosphate (2.40 g, 4.6 mmol) was added in one portion to a
stirred mixture of cis-2-methylcyclopropane carboxylic acid 22
(420 mg, 4.2 mmol), phenylene-1,2-diamine (454 mg, 4.2 mmol)
and triethylamine (1.2 ml, 8.4 mmol) in dry dichloromethane
(30 ml) at 0 ЊC and under an atmosphere of nitrogen. The
mixture was stirred at 0 ЊC for 3 h and then at room temperature
2248
J. Chem. Soc., Perkin Trans. 1, 2002, 2243–2250