Juma’a. R. Al Dulayymi et al. / Tetrahedron 63 (2007) 2571–2592
2585
2.53 mmol) in acetone (30 mL) at room temperature. The re-
action mixture was stirred for 5 h at 40 ꢁC, at room temper-
ature for 16 h and then diluted with water (50 mL) and
dichloromethane (100 mL). The aqueous layer was re-
extracted with dichloromethane (2ꢂ25 mL). The combined
organic layers were washed with brine (2ꢂ50 mL), dried
and evaporated to give an oil, which solidified later. The
crude product was purified by chromatography on silica
eluting with petrol/ether (5:1) to give 5-{7-[(1S,2R)-2-
((17R,18R)-17-methoxy-18-methylhexatriacontyl)cyclopro-
pyl]heptylsulfanyl}-1-phenyl-1H-tetrazole (55) as a colour-
less viscous oil (0.5 g, 88%) [found [M+Na]+: 887.7434;
C55H100N4NaOS requires: 887.7510] {[a]2D5 +4.44 (c 1.07,
CHCl3)}, which showed dH (500 MHz, CDCl3): 7.61–7.54
(5H, m), 3.41 (2H, t, J 7.6 Hz), 3.35 (3H, s), 2.98–2.94
(1H, m), 1.83 (2H, pent, J 7.3 Hz), 1.65–1.61 (1H, m),
1.47–1.25 (72H, m), 1.17–1.08 (4H, m), 0.9 (3H, t, J
7.0 Hz), 0.87 (3H, d, J 7.0 Hz), 0.68–0.62 (2H, m),
0.57 (1H, dt, J 4.1, 8.2 Hz), ꢀ0.33 (1H, q, J 5.1 Hz); dC
(125 MHz, CDCl3): 154.0, 133.8, 130.0(ꢀ), 129.8(ꢀ),
123.9(ꢀ), 85.5(ꢀ), 57.7(ꢀ), 35.4(ꢀ), 33.4(+), 32.4(+),
31.9(+), 30.5(+), 30.2(+), 30.1(+), 30.0(+), 29.9(+),
29.8(+), 29.74(+), 29.7(+), 29.4(+), 29.3(+), 29.1(+),
29.07(+), 28.7(+), 28.6(+), 27.6(+), 26.2(+), 22.7(+),
15.8(ꢀ), 15.7(ꢀ), 14.9(ꢀ), 14.1(ꢀ), 10.9(+); nmax: 2926,
3.1.52. 5-{7-[(1R,2S)-2-((17S,18S)-17-Methoxy-18-
methylhexatriacontyl)cyclopropyl]heptane-1-sulfonyl}-
1-phenyl-1H-tetrazole (69). A solution of ammonium
heptamolybdate(VI) tetrahydrate (4.8 g, 3.88 mmol) in 35%
H2O2 (w/w) (13 mL) was added dropwise at 5 ꢁC to a stirred
solution of 5-{7-[1R,2S]-2-((17S,18S)-17-methoxy-18-meth-
ylhexatriacontyl)cyclopropyl]heptylsulfanyl}-1-phenyl-1H-
tetrazole (47) (7.5 g, 8.66 mmol) in methylated spirit
(120 mL) and tetrahydrofuran (120 mL). The resulting
yellow solution was stirred for 1 h then three more identical
solutions of ammonium heptamolybdate(VI) tetrahydrate in
35% H2O2 (w/w) were added over 1 h. The mixture was
stirred at room temperature for 16 h, then worked up and
purified as above to give 5-{7-[(1R,2S)-2-((17S,18S)-17-me-
thoxy-18-methylhexatriacontyl)cyclopropyl]heptane-1-sul-
fonyl}-1-phenyl-1H-tetrazole (69) as a white solid (6.53 g,
84%) {[a]2D2 ꢀ4.81 (c 1.391, CHCl3)}, which showed an
identical NMR spectrum to that above.
3.1.53. (R)-2-{(R)-1-Acetoxy-18-[(1R,2S)-2-((17R,18R)-
17-methoxy-18-methylhexatriacontyl)cyclopropyl]octa-
decyl}hexacosnoic acid methyl ester (58). Lithium hexa-
methyldisilazide (0.76 mL, 0.767 mmol, 1 M) was added
dropwise to a stirred solution of ((1R,2R)-1-acetoxy-11-
oxoundecyl)hexacosanoic acid methyl ester (57) (0.25 g,
0.393 mmol)31 and 5-{7-[1R,2S]-2-((17R,18R)-17-methoxy-
18-methylhexatriacontyl)cyclopropyl]heptane-1-sulfonyl}-
1-phenyl-1H-tetrazole (56) (0.52 g, 0.59 mmol) in dry THF
(15 mL) under nitrogen at ꢀ12 ꢁC. The reaction was exo-
thermic and the temperature rose to ꢀ5 ꢁC resulting in
a dark orange solution. The mixture was allowed to reach
room temperature and stirred for 2 h, cooled to 0 ꢁC and
quenched with satd aq ammonium chloride (5 mL). The
product was extracted with petrol/ether (2ꢂ50 mL), dried
and evaporated to give a thick oil, which was purified
by chromatography on silica eluting with petrol/ether
(5:0.5) to give (R)-2-{(E/Z)-(R)-1-acetoxy-18-[(1R,2S)-2-
((17R,18R)-17-methoxy-18-methylhexatriacontyl)cyclopro-
pyl]octadec-11-enyl}hexacosanoic acid methyl ester (2.5:1)
(0.35 g, 68%) as a thick colourless oil, which showed dH
(500 MHz, CDCl3) (major isomer): 5.40–5.38 (2H, br m),
5.09 (1H, br dt, J 4.0, 8.0 Hz), 3.68 (3H, s), 3.34 (3H, s),
2.98–2.94 (1H, m), 2.62 (1H, ddd, J 4.5, 7.0, 10.8 Hz),
2.03 (3H, s), 1.97 (3H, br s), 1.64–1.59 (2H, m), 1.55–1.52
(1H, m), 1.46–1.22 (133H, br m), 1.17–1.05 (4H, m), 0.88
(6H, t, J 7.0 Hz), 0.85 (3H, d, J 7.0 Hz), 0.68–0.64 (2H, br
m), 0.57 (1H, br dt, J 4.1, 8.2 Hz), ꢀ0.33 (1H, br q, J
5.1 Hz); minor isomer: 5.35 (2H, br m), the remaining sig-
nals were obscured by the major isomer; dC (125 MHz,
CDCl3) (for the mixture): 173.6, 170.3, 130.4, 130.3,
129.91, 129.9, 85.4, 74.1, 57.7, 51.5, 49.6, 35.6, 35.3,
32.6, 32.4, 31.9, 31.7, 30.5, 30.23, 30.2, 30.0, 29.9, 29.8,
29.7 (v br), 29.66, 29.63, 29.6, 29.52, 29.5, 29.44, 29.4,
29.36, 29.3, 29.23, 29.2, 28.72, 28.7, 28.1, 27.6, 27.5,
27.2, 26.2, 25.0, 22.7, 21.0, 15.8, 14.9, 14.1, 10.9. Dipotas-
sium azodicarboxylate (1.5 g, 8.04 mmol) was added with
stirring to the above methyl esters (0.35 g, 0.268 mmol) in
dry THF (10 mL) and methanol (5 mL) at 10 ꢁC under nitro-
gen, resulting in a yellow suspension. A solution of glacial
acetic acid (2 mL) in dry THF (4 mL) was added dropwise
over 16 h, after which a white precipitate had formed. The
mixture was cooled to 0 ꢁC and poured slowly into satd aq
ammonium chloride (5 mL). The product was extracted
2851, 1509, 1464, 1097 cmꢀ1
.
3.1.51. 5-{7-[(1R,2S)-2-((17R,18R)-17-Methoxy-18-
methyl-hexatriacontyl)cyclopropyl]heptane-1-sulfonyl}-
1-phenyl-1H-tetrazole (56). A solution of ammonium hep-
tamolybdate(VI) tetrahydrate (2.1 g, 1.7 mmol) in H2O2
(35% w/w, 6 mL) was added dropwise at 5 ꢁC to a stirred
solutionof5-{7-[1R,2S]-2-((17R,18R)-17-methoxy-18-meth-
ylhexatriacontyl)cyclopropyl]heptylsulfanyl}-1-phenyl-1H-
tetrazole (46) (2.9 g, 3.35 mmol) in methylated spirit
(40 mL) and tetrahydrofuran (40 mL). The resulting yellow
solution was stirred for 1 h then three more identical solu-
tions of heptamolybdate in H2O2 were added over 1 h. The
reaction mixture was stirred at room temperature for 16 h
and then diluted with water (100 mL) and dichloromethane
(50 mL). The aqueous layer was re-extracted with dichloro-
methane (2ꢂ50 mL). The combined organic layers were
washed with water, brine, dried and evaporated to give the
crude product. Chromatography on silica eluting with petrol/
ether (10:2) gave 5-{7-[(1R,2S)-2-((17R,18R)-17-methoxy-
18-methylhexatriacontyl)cyclopropyl]heptane-1-sulfonyl}-
1-phenyl-1H-tetrazole (56) as a white solid (2.19 g, 73%),
mp 37–39 ꢁC {[a]D22 +4.13 (c 1.92, CHCl3)} [found
[M+Na]+: 919.7435; C55H100N4O3SNa requires: 919.7408],
which showed dH (500 MHz, CDCl3): 7.71–7.69 (2H, br dd, J
1.3, 7.9 Hz), 7.63–7.57 (3H, m), 3.74 (2H, distorted t, J
8.2 Hz), 3.35 (3H, s), 2.98–2.95 (1H, br pent, J 4.1 Hz), 1.97
(2H, br pent, J 7.6 Hz), 1.65–1.62 (1H, m), 1.52 (2H, br
pent, J 7.6 Hz), 1.48–1.22 (70H, m), 1.17–1.05 (4H, m), 0.89
(3H, t, J 7.0 Hz), 0.86 (3H, d, J 7.0 Hz), 0.69–0.65 (2H, m),
0.58 (1H, dt, J 3.8, 8.0 Hz), ꢀ0.32 (1H, br q, J 5.1 Hz); dC
(125 MHz, CDCl3): 153.5, 133.1, 131.4(ꢀ), 129.7(ꢀ),
125.1(ꢀ), 85.4(ꢀ), 57.7(ꢀ), 56.1(+), 35.4(ꢀ), 32.4, 31.9(+),
30.5(+), 30.2(+), 30.0(+), 29.9(+), 29.74(+), 29.7(+), 29.6(+),
29.4(+), 29.1(+), 28.9(+), 28.7(+), 28.6(+), 28.1(+), 27.6(+),
26.2(+), 22.7(+), 21.9(+), 15.8(ꢀ), 15.7(ꢀ), 14.9(ꢀ),
14.1(ꢀ), 10.9(+); nmax: 2908, 1596, 1499, 1464, 1343, 1153,
1099, 760 cmꢀ1
.