Y. Mu et al. / Bioorg. Med. Chem. 10 (2002) 1207–1219
1215
solution was washed with 15 mL of water and dried
over MgSO4. Following concentration the residue was
purified by flash chromatography (hexanes/ethyl acetate
20:1, Rf 0.28), and ester 11 was obtained as a pale yel-
low oil (76 mg, 86%). The identity, and in particular the
stereochemistry, of this ester was confirmed by the
3-Cyclopropyl-7,11,15-trimethylhexadeca-2Z,6E,10E,14-
tetraen-1-ol 15. To a solution of 14 (0.12 mmol, 43 mg)
˚
in 1.0 mL of toluene (HPLC grade, dried over 4 A
sieves), at ꢀ78 ꢃC under argon, was added DIBALH
(1.0 M in toluene, 0.3 mmol, 0.3 mL). After 1 h at
ꢀ78 ꢃC, the reaction was quenched with Rochelle salt
solution (10 mL). The organic layer was separated and
the aqueous phase was extracted with ethyl acetate (3 ꢄ
15 mL). The combined organic layers were washed with
water (2 ꢄ 15 mL), dried over MgSO4 and concentrated.
The crude product was purified by flash chromatography
(hexanes/ethyl acetate, 4:1) and 23 mg (61%) of 15 was
obtained as a colorless oil. 1H NMR: d 0.50 (m, 2H), 0.67
(m, 2H), 1.60 (s, 9H), 1.68 (s, 3H), 1.76 (m, 1H), 1.9–2.1
(m, 12H), 4.33 (d, 2H), 5.12 (m, 3H), 5.48 (t, 1H); 13C
NMR: d 4.95, 11.58, 16.03, 17.69, 25.71, 26.60, 27.24,
27.76, 32.97, 39.71, 59.23, 123.32, 124.14, 124.36, 124.29,
131.29, 134.98, 135.40, 143.62. EI-MS: 316 (M+).
1
similarity of its H NMR spectrum to the previously
prepared ester 4b.23 1H NMR: d 1.07 (t, J=3.9 Hz, 3H),
1.53 (s, 3H), 1.60 (s, 6H), 1.68 (s, 3H), 2.00–2.07 (m,
10H), 2.47 (t, 2H), 4.00 (q, J=3.9 Hz, 2H), 5.09 (b, 3H),
5.88 (s, 1H), 7.15 (d, J=7.2 Hz, 2H), 7.34 (m, 3H); 13C
NMR d 13.94, 16.01, 16.07, 17.70, 25.72, 25.88, 26.53,
26.75, 39.66, 39.72, 40.46, 59.74, 117.31, 122.68, 124.08,
124.33, 127.11, 127.54, 127.79, 128.44, 128.64, 128.73,
131.29, 133.71, 135.04, 159.36, 166.05. MS-EI: 394
(M+).
3-Phenyl-7,11,15-trimethylhexadeca-2Z,6E,10E,14-tet-
raen-1-ol 12. A solution of ester 11 (70 mg, 0.18 mmol)
in 1mL of toluene was treated with DIBAL-H (1.0 M
solution in toluene, 0.44 mL, 0.44 mmol) under argon at
ꢀ78 ꢃC for 1h. The reaction was warmed to room tem-
perature and quenched with 20 mL of Rochelle salt
solution. The aqueous solution was extracted with ethyl
acetate (2 ꢄ 20 mL), and the combined organic layers
were washed with saturated NaCl (2 ꢄ 20 mL), and
then dried over MgSO4. The solvent was removed in
vacuo and the residue was purified by flash chromato-
graphy (hexanes/ethyl acetate, 4:1) to give 44 mg (67%)
Ethyl 3-tert-butyl-7,11,15-trimethylhexadeca-2Z,6E,10E,
14-tetraenoate 17. In a flame dried, argon flushed flask
were placed CuCN (0.40 mmol, 36 mg) and 1.0 mL of
ether (distilled from Na/benzophenone). The resulting
slurry was cooled to ꢀ78 ꢃC where tert-butyllithium
(1.7 M in pentane, 0.80 mmol, 0.47 mL) was added
dropwise. The mixture was warmed to 0 ꢃC and then
recooled to ꢀ78 ꢃC. A solution of triflate 8 (0.27 mmol,
124 mg) in 1.0 mL of ether was added dropwise and the
reaction was stirred for 1h at ꢀ78 ꢃC. The mixture was
warmed to 0 ꢃC and quenched with 2 mL of saturated
NH4Cl. The organic layer was separated, the aqueous
layer was extracted with ether (3 ꢄ 15 mL), and the
combined organic layers were dried over MgSO4. Con-
centration followed by flash chromatography (hexanes/
ethyl acetate, 20:1) gave 17 as a colorless oil (81mg,
82%). The identity, and in particular the stereo-
chemistry, of this ester was confirmed by the similarity
of its 1H NMR spectrum to the previously prepared
3-tert-butyl-3-desmethylfarnesyl ester.24 1H NMR: d 1.22
(s, 9H), 1.32 (t, 3H), 1.60 (s, 9H), 1.68 (s, 3H), 1.9–2.3
(m, 12H), 4.16 (q, 2H), 5.11 (m, 3H), 5.59 (s, 1H); 13C
NMR: d 14.14, 16.00, 17.69, 25.68, 26.58, 26.75, 27.94,
28.76, 29.37, 35.45, 39.24, 39.68, 60.16, 115.80, 123.31,
124.11, 124.25, 124.33, 135.00, 135.85, 161.41. MS-EI:
374 (M+).
1
of alcohol 12. H NMR: d 1.51 (s, 3H), 1.59 (s, 6H),
1.68 (s, 3H), 2.04 (m, 10H), 2.41 (t, 2H), 4.05 (t, 2H),
5.01 (m, 3H), 5.69 (t, 1H), 7.13 (d, J=6.9 Hz, 2H), 7.31
(m, 3H); 13C NMR: d 16.02, 17.69, 25.70, 26.49, 26.61,
26.75, 39.00, 39.66, 39.71, 60.29, 123.50, 124.17, 124.37,
125..59, 127.05, 128.06, 128.18, 131.29, 135.56, 139.92,
144.58. MS-EI: 352 (M+).
Ethyl 3-cyclopropyl-7,11,15-trimethylhexadeca-2Z,6E,
10E,14-tetraenoate 14. To a solution of cyclopropyl
bromide (0.36 mmol, 0.03 mL) in 1.0 mL ether was
added tert-butyllithium (1.7 M in pentane, 0.72 mmol,
0.42 mL) under argon at ꢀ78 ꢃC. The resulting solution
was stirred for 30 min, transferred to a slurry of CuCN
(0.36 mmol, 32 mg) in 1.0 mL of ether at ꢀ78 ꢃC and
then stirred for 15 min. Triflate 8 (0.24 mmol, 114 mg)
in 1.0 mL of ether was added to the mixture and the
reaction was stirred for 1.5 h at ꢀ78 ꢃC. The mixture
was warmed to 0 ꢃC and quenched with 2 mL of satu-
rated NH4Cl. The organic layer was separated, the
aqueous layer was extracted with ether (3 ꢄ 15 mL),
and the combined organic layers were dried over
MgSO4. Concentration followed by flash chromato-
graphy (hexanes/ethyl acetate, 20:1) gave 43 mg (51%)
of ester 14 as a colorless oil and 15 mg of triflate 16. The
identity, and in particular the stereochemistry, of 14 was
confirmed by the similarity of its 1H NMR spectrum to the
previously prepared 3-cyclopropyl-3-desmethylfarnesyl
ester.24 1H NMR: d 0.70 (m, 2H), 0.88 (m, 2H), 1.29 (t,
3H), 1.60 (s, 6H), 1.68 (s, 6H), 1.9–2.2 (m, 12H), 3.13
(m, 1H), 4.16 (q, 2H), 5.09 (m, 3H), 5.72 (s, 1H); 13C
NMR: d 6.75, 13.09, 14.37, 16.06, 17.67, 19.21, 31.02,
39.68, 59.42, 115.62, 121.58, 122.85, 124.04, 124.33,
131.29, 136.19, 164.02, 167.35.
3-tert-Butyl-7,11,15-trimethylhexadeca-2Z,6E,10E,14-
tetraene-1-ol 18. To a solution of 17 (0.21mmol, 79
˚
mg) in 1.0 mL of toluene (HPLC grade, dried over 4 A
sieves) at ꢀ78 ꢃC under argon, was added DIBALH
(1.0 M in toluene, 0.53 mmol, 0.53 mL). After 1 h at-
78 ꢃC, the reaction was quenched with Rochelle salt
solution (20 mL). The organic layer was separated and
the aqueous phase was extracted with ethyl acetate (3 ꢄ
15 mL). The combined organic layers were washed with
water (2 ꢄ 15 mL), dried over MgSO4 and con-
centrated. The crude product was purified by flash
chromatography (hexanes/ethyl acetate, 4:1) and 59 mg
1
(85%) of alcohol 18 was obtained as a colorless oil. H
NMR: d 1.14 (s, 9H), 1.60 (s, 9H), 1.68 (s, 3H),
2.0–2.2 (m, 12H), 4.37 (d, 2H), 5.12 (m, 3H), 5.25 (t,
1H). 13C NMR: d 16.00, 16.08, 17.68, 25.69, 26.59,