P. V. Murphy et al.
drop of anhydrous DMF, and the resulting mixture was stirred for 2 h at
room temperature. A mixture of the alcohol 12a (53 mg, 0.23 mmol) and
imidazole (22 mg, 0.32 mmol) in anhydrous CH2Cl2 was then added and
the reaction was stirred overnight at room temperature. HCl (1 mL of a
0.1m solution) was then added and stirring continued for a further 5 min
and then CH2Cl2 (5 mL) and water (2 mL) were added. The organic layer
was separated and the aqueous layer was extracted with CH2Cl2 (3
10 mL). The organic layers were combined, dried (MgSO4) and the sol-
vent removed under diminished pressure. Chromatography (EtOAc/cy-
clohexane 1:9 to 4:6) of the residue gave 17a (50 mg, 70%) as a colour-
less oil. 1H NMR (300 MHz, CDCl3, 258C, TMS): d=5.90–5.60 (m, 5H),
5.40 (dd, J=10.3, 5.1 Hz, 1H), 5.30 (dd, J=17.2, 6.5 Hz, 1H), 4.95 (m,
2H), 4.30 (dd, J=15.6, 7.7 Hz, 1H), 4.21 (dd, J=15.6, 7.7 Hz, 1H), 3.81
(m, 1H), 3.48 (q, J = 7.3 Hz, 1H), 3.26 (s, 3H), 2.31 (t, J=7.5 Hz, 1H),
2.29, (s, 3H), 2.30–2.25 (m, 2H), 1.65–1.55 (m, 2H), 1.45–1.30 ppm (m,
2H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=173.5, 169.6, 138.3,
134.4, 130.2, 126.9, 120.9, 114.6, 82.9, 73.6, 70.1, 56.3, 39.6, 34.0, 33.3, 28.3,
24.3, 21.0 ppm; HR-ESMS: m/z: calcd for C18H28O6Na: 363.1784; found:
363.1799 [M+Na]+.
1H), 5.22 (dd, J=17.3, 1.9 Hz, 1H), 4.55 (dd, J=8.4, 3.9 Hz, 1H), 4.12
(m, 2H), 3.66 (dd, J=5.9, 4.0 Hz, 1H), 3.48 (dd, J=8.0, 5.9 Hz, 1H), 3.23
(s, 3H), 0.90, 0.89, 0.87 (3s, 18H), 0.07, 0.06, 0.05, 0.02 ppm (4s, 12H);
13C NMR (100 MHz, CDCl3, 258C, TMS): d=135.6, 132.6, 129.6, 118.7,
84.1, 79.1, 69.0, 59.4, 56.3, 26.9, 26.1, 25.9, 18.4, 18.2, ꢀ4.0, ꢀ4.2, ꢀ4.3,
ꢀ4.7 ppm; IR (thin film): n˜ =3369, 3079, 2954, 2930, 2888, 2857, 1472,
1253, 1148, 1075, 836, 777 cmꢀ1
;
; HR-ESMS: m/z: calcd for
C21H44O4Si2Na: 439.2676; found: 439.2671 [M+Na]+.
[(2Z,4R,5R,6R)-6-Methoxy-4,5-bis-(tert-butyldimethylsilyloxy)-octa-2,7-
diene-1-yl] hept-6-enoate (19b): T o18b (70 mg, 0.168 mmol), 6-hepteno-
ic acid (45 mL, 0.33 mmol), and triphenylphosphine (120 mg, 0.458 mmol)
in toluene (4 mL), diisopropyl azodicarboxylate (105 mL, 0.533 mmol)
was added dropwise and the resulting mixture stirred at room tempera-
ture for 2 h. Satd. NH4Cl was added and the mixture extracted with
EtOAc (315 mL). The organic layers were combined, washed with
brine, dried (MgSO4) and the solvent removed under diminished pres-
sure. Chromatography (EtOAc/cyclohexane 0:100 to 2:98) gave 19b as a
yellow oil (74 mg, 84%). Rf =0.45 (EtOAc/cyclohexane 5:95); [a]D20
=
1
+15.88 (c=0.98 in CHCl3); H NMR (300 MHz, CDCl3, 258C, TMS): d=
5.79 (ddt, J=17.0, 10.3, 6.7 Hz, 1H), 5.75–5.65 (m, 2H), 5.54 (dt, J=11.3,
6.2 Hz, 1H), 5.28 (dd, J=10.6, 1.6 Hz, 1H), 5.21 (dd, J=17.2, 1.8 Hz,
1H), 5.00 (dq, J=17.2, 1.7 Hz, 1H), 4.95 (dq, J=10.2, 1.5 Hz, 1H), 4.65
(dd, J=12.9, 7.8 Hz, 1H), 4.53 (dd, J=12.9, 6.1 Hz, 1H), 4.45 (dd, J=9.3,
3.2 Hz, 1H), 3.67 (dd, J=6.5, 3.2 Hz, 1H), 3.38 (dd, J=8.0, 6.6 Hz, 1H),
3.22 (s, 3H), 2.31 (t, J=7.4 Hz, 2H), 2.06 (m, 2H), 1.64 (m, 2H), 1.42 (m,
2H), 0.90, 0.87 (2s, 18H), 0.07, 0.06, 0.04, 0.01 ppm (4s, 12H); 13C NMR
(100 MHz, CDCl3, 258C, TMS): d=173.4, 138.4, 135.3, 134.1, 124.4,
119.0, 114.7, 84.2, 79.5, 69.1, 60.9, 56.2, 34.1, 33.4, 28.3, 26.1, 25.9, 24.4,
18.4, 18.2, ꢀ4.2, ꢀ4.4, ꢀ4.8 ppm; IR (thin film): n˜ =3079, 2953, 2930,
2857, 1778, 1739, 1472, 1250, 1098, 836, 777 cmꢀ1; HR-ESMS: m/z: calcd
for C28H54O5Si2Na: 549.3408; found: 549.3392 [M+Na]+.
(7E,9S,10R,11R,11Z)-11-Acetoxy-10-hydroxy-9-methoxy-oxacyclotetra-
deca-7,12-dien-2-one (5): T o17a (17 mg, 0.05 mmol) in degassed and
dried toluene (90 mL) at 908C was added, via a cannula, Grubbs catalyst
2nd generation (9 mg, 0.011 mmol) in degassed and dried toluene (5 mL).
Heating was continued for 5 min at 908C and the solution was then fil-
tered through a short column of silica, washing with EtOAc. The organic
layer was removed under diminished pressure and 5 (6 mg, 38%) was ob-
tained as a colourless oil after chromatography (EtOAc/cyclohexane 9:1
to 7:3) of the residue. 1H NMR (500 MHz, CDCl3, 258C, TMS): d=5.81
(m, 2H), 5.61 (m, 2H), 5.51 (dd, J=16.1, 8.2 Hz, 1H), 4.78 (ddd, J=14.9,
4.7, 2.2 Hz, 1H), 4.59 (ddd, J=14.9, 5.3, 0.8 Hz, 1H), 3.95 (d, J=8.7 Hz,
1H), 3.69 (d, J=7.9 Hz, 1H), 3.32 (s, 3H), 2.43 (ddd, J=13.6, 8.7, 5.7 Hz,
1H), 2.25–2.15 (m, 2H), 2.15–2.05 (m, 1H), 2.06, (s, 3H), 1.85–1.70 (m,
2H), 1.55–1.45 ppm (m, 2H); 13C NMR (100 MHz, CDCl3, 258C, TMS):
d=171.6, 168.1, 134.6, 128.6, 127.7, 125.5, 81.8, 74.1, 69.7, 61.2, 56.6, 34.2,
30.8, 26.7, 23.8, 22.0 ppm; HR-ESMS: m/z: calcd for C16H24O6Na:
335.1471; found: 335.1487 [M+Na]+.
(7E,9R,10R,11R,12Z)-9-Methoxy-10,11-bis-(tert-butyldimethylsilyloxy)-
oxacyclotetradeca-7,12-dien-2-one (20b): Ester 19b (12 mg, 0.023 mmol)
was dissolved in dried and degassed toluene (40 mL) and the mixture
heated to 808C. Grubbs catalyst 2nd generation (6.0 mg 0.007 mmol) was
dissolved in toluene and added to the mixture via a cannula and heating
was continued for 30 min. The mixture was then filtered through a short
column of silica and the solvent removed under diminished pressure.
Chromatography (EtOAc/cyclohexane 0:100 to 2:98) gave 20b as a col-
ourless oil (11 mg, 97%). Rf =0.55 (EtOAc/cyclohexane 10:90); [a]D =
(2Z,4R,5R,6R)-6-Methoxy-4,5-bis-(tert-butyldimethylsilyloxy)-octa-2,7-
diene-1-ol (18b): T o12b (405 mg, 1.76 mmol) in anhydrous methanol
(10 mL) at 08C was added sodium (76 mg, 3.3 mmol) and the mixture
was then allowed to attain room temperature and after stirring for 2 h,
the solution was evaporated and the residue was taken up in CH2Cl2
(40 mL) and tert-butyldimethylsilyl triflate (2.0 mL, 8.7 mmol) and 2,6-lu-
tidine (2.0 mL, 17.2 mmol) were added. The mixture was stirred for 2 h
at room temperature, satd. NaHCO3 was added and the mixture was ex-
tracted with CH2Cl2 (350 mL). The organic layers were combined,
dried (MgSO4) and the solvent removed under diminished pressure.
Chromatography of the residue (EtOAc/cyclohexane 0:100 to 1:99) gave
fully silylated compound as a colourless oil (851 mg, 91% over two
steps). Rf =0.70 (EtOAc/cyclohexane 5:95); [a]2D0 =+22.48 (c=0.99 in
1
ꢀ20.28 (c=0.50 in CHCl3); H NMR (500 MHz, CDCl3, 258C, TMS): d=
5.96 (dd, J=11.5, 9.9 Hz, 1H), 5.65–5.60 (m, 2H), 5.31 (dd, J=15.6,
8.9 Hz, 1H), 4.65 (dd, J=9.8, 1.6 Hz, 1H), 4.60 (dd, J=13.1, 4.6 Hz, 1H),
4.49 (dd, J=13.1, 9.4 Hz, 1H), 3.78 (dd, J=7.4, 2.1 Hz, 1H), 3.19 (s and
m, 4H), 2.42–2.37 (m, 2H), 2.20–2.15 (m, 1H), 2.05–2.00 (m, 1H), 1.80–
1.75 (m, 2H), 1.50–1.45 (m, 1H), 1.45–1.40 (m, 1H), 0.90, 0.86 (2s, 18H),
0.09, 0.08, 0.04, 0.02 ppm (4s, 12H); 13C NMR (100 MHz, CDCl3): d=
173.5, 135.0, 134.4, 125.7, 122.7, 85.4, 79.2, 68.0, 61.3, 55.8, 34.7, 29.1, 26.6,
26.0, 25.9, 22.6, 18.4, 18.3, ꢀ4.2, ꢀ4.3, ꢀ4.4, ꢀ4.7 ppm; IR (thin film): n˜ =
2955, 2928, 2855, 1738, 1653, 1472, 1252, 1147, 1072, 835, 775 cmꢀ1; HR-
ESMS: m/z: calcd for C26H50O5Si2Na: 521.3095; found: 521.3094
[M+Na]+.
1
CHCl3); H NMR (300 MHz, CDCl3): d=5.68 (ddd, J=17.2, 10.4, 8.1 Hz,
1H), 5.51 (m, 2H), 5.26 (dd, J=10.5, 2.0 Hz, 1H), 5.21 (dd, J=17.2,
2.0 Hz, 1H), 4.40 (dd, J=7.0, 3.1 Hz, 1H), 4.22 (dd, J=12.9, 5.7 Hz, 1H),
4.06 (dd, J=12.9, 3.7 Hz, 1H), 3.62 (dd, J=6.6, 3.2 Hz, 1H), 3.41 (dd, J=
8.0, 6.7 Hz, 1H), 3.22 (s, 3H), 0.90, 0.89, 0.87 (3s, 27H), 0.07, 0.06, 0.05,
0.02 ppm (4s, 18H); 13C NMR (100 MHz, CDCl3, 258C, TMS): d=135.5,
130.5, 118.7, 84.2, 79.7, 69.5, 59.8, 56.2, 26.1, 26.0, 25.9 (3s), 18.4, 18.2
(2s), ꢀ4.2, ꢀ4.3, ꢀ4.7, ꢀ5.2 ppm; IR (thin film): n˜ =2955, 2930, 2858,
1640, 1473, 1253, 1149, 1080, 836, 776 cmꢀ1; HR-ESMS: m/z: calcd for
C27H58O4Si3Na: 553.3541; found: 553.3521 [M+Na]+.
(7E,9R,10S,11R,12Z)-10,11-Dihydroxy-9-methoxy-oxacyclotetradeca-
7,12-dien-2-one (6): T o20b (11.0 mg, 0.022 mmol) in THF (1.5 mL),
TBAF (120 mL of a 1.0m solution in THF, 0.12 mmol) was added, and the
resulting mixture was stirred at room temperature for 24 h. Solid NH4Cl
was added and the mixture extracted with EtOAc (315 mL). The or-
ganic layers were combined, washed with brine, dried (MgSO4) and the
solvent removed under diminished pressure. Chromatography (EtOAc/
cyclohexane 25:75 ! 40:60) gave 6 as a colourless oil (4.0 mg, 67%).
Rf =0.20 (EtOAc/cyclohexane 70:30); [a]2D0 =ꢀ348 (c=0.25 in CHCl3);
1H NMR (500 MHz, CDCl3, 258C, TMS): d=6.04 (t, J=10.3 Hz, 1H),
5.90–5.85 (m, 1H), 5.82 (dd, J=15.3, 7.8 Hz, 1H), 5.24 (dd, J=15.5,
8.7 Hz, 1H), 4.65 (dd, J=13.1, 8.7 Hz, 1H), 4.55–4.50 (m, 2H), 3.79 (dd,
J=8.6, 3.7 Hz, 1H), 3.40 (t, J = 8.6 Hz, 1H), 3.30 (s, 3H), 2.74 and 2.66
(2brs, 2H), 2.44 (ddd, J=15.0, 6.9, 4.5 Hz, 2H), 2.31 (ddd, J=14.7, 10.0,
4.3 Hz, 2H), 2.11 (m, 1H), 1.85–1.75 (m, 1H), 1.70–1.60 (m, 1H), 1.55–
1.50 (m, 1H), 1.35–1.25 ppm (m, 1H); 13C NMR (100 MHz, CDCl3, 258C,
This intermediate (373 mg, 0.702 mmol) was dissolved in AcOH/THF/
H2O 3:1:1 (50 mL) and the mixture was stirred at room temperature for
42 h. Solid Na2CO3 was then added and the mixture extracted with Et2O
(360 mL). The organic layers were combined, dried (MgSO4) and the
solvent removed under diminished pressure. Chromatography of the resi-
due (EtOAc/cyclohexane 0:100 to 5:95) gave 18b as colourless oil
(190 mg, 65%). Rf =0.40 (EtOAc/cyclohexane 30:70); [a]2D0 =+10.28 (c=
1.01 in CHCl3); 1H NMR (300 MHz, CDCl3, 258C, TMS): d=5.72 (ddd,
J=17.3, 10.4, 8.0 Hz, 1H), 5.68–5.60 (m, 2H), 5.27 (dd, J=10.4, 1.9 Hz,
1598
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 1592 – 1600