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T. Okitsu et al. / Bioorg. Med. Chem. 19 (2011) 2939–2949
J = 15.9 Hz, 1H), 6.22 (d, J = 14.7 Hz, 1H), 6.05 (d, J = 11.4 Hz, 1H),
5.77 (s, 1H), 5.73 (s, 1H), 4.17 (q, J = 7.2 Hz, 2H), 2.67 (br t,
J = 4.2 Hz, 1H), 2.51 (dt, J = 8.7, 5.7 Hz, 1H), 2.42-2.39 (m, 2H),
2.38 (d, J = 1.2 Hz, 3H), 2.17-2.15 (m, 1H), 1.99 (s, 3H), 1.38 (s,
3H), 1.29 (t, J = 7.2 Hz, 3H), 1.18 (d, J = 8.7 Hz, 1H), 0.83 (s, 3H).
The 1H NMR spectral data of this compound was identical with that
of literature.9
4.3.17. Ethyl (2E,4E,6Z)-3-methyl-7-((2S,4aR)-1,2,3,4,4a,5-
hexahydro-1,1,5,5-tetramethyl-2,4a-methanonaphthalen-7-yl)-
2,4,6-octatrienoate (12m)
According to Method A (GP-B-1), 12m (42.3 mg, 75%) was ob-
tained as a yellow oil from vinyl triflate 8m (56.9 mg, 0.162 mmol),
stannanyl ester 10 (69.3 mg, 0.148 mmol), Pd2(dba)3ꢁCHCl3
(6.1 mg, 5.91
l
mol), AsPh3 (7.2 mg, 23.6
l
mol), and CsF (44.9 mg,
ꢀ164 (c 1.04,
;
1H NMR (300 MHz, CDCl3) d 6.90
0.295 mmol). Eluent: hexane/Et2O = 40:1.
½ ꢂ
a 2D7
4.3.14. Ethyl (2E,4E,6Z,8E)-3,7-dimethyl-9-((1S,4R,5R)-1-
isopropyl-4-methylbicyclo[3.1.0]hex-2-en-3-ly)-2,4,6,8-
nonatetraenoate (11l)
According to Method A (GP-B-1), 11l (130 mg, 66%) was ob-
tained as a yellow oil from vinyl triflate 8l (180 mg, 0.633 mmol),
MeOH); IR 1698, 1603 cmꢀ1
(dd, J = 15.3, 11.1 Hz, 1H), 6.14 (d, J = 15.3 Hz, 1H), 6.00 (d,
J = 11.1 Hz, 1H), 5.72 (s, 1H), 5.42 (d, J = 0.6 Hz, 1H), 5.11 (d,
J = 1.2 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 2.24 (d, J = 0.9 Hz, 3H),
1.95-1.89 (m, 1H), 1.93 (s, 3H), 1.79-1.75 (m, 1H), 1.70-1.62 (m,
2H), 1.54-1.46 (m, 1H), 1.30-1.25 (m, 4H), 1.16-1.06 (m, 1H), 1.13
(s, 3H), 1.09 (s, 3H), 1.04 (s, 3H), 0.97 (s, 3H); 13C NMR (75 MHz,
CDCl3) d 167.3, 159.0, 153.2, 144.7, 134.0, 133.44, 133.40, 132.6,
126.0, 117.8, 111.1, 59.5, 56.0, 46.6, 43.2, 35.8, 33.7, 28.9, 27.5,
24.9, 24.8, 24.3, 24.2, 24.0, 14.3, 13.6. Anal. Calcd for C26H36O2:
C, 82.06; H, 9.53. Found: C, 81.80; H, 9.70; HR-EIMS calcd for
stannanyl ester
9
(285 mg, 0.576 mmol), Pd2(dba)3ꢁCHCl3
(23.8 mg, 23.0 lmol), AsPh3 (28.2 mg, 922 lmol), and CsF
(175 mg, 1.15 mmol). Eluent: hexane/Et2O = 40:1. ½a D25
ꢂ
+27.7 (c
1.30, MeOH); IR 2960, 1698, 1608 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 7.05 (dd, J = 15.0, 11.7 Hz, 1H), 6.68 (d, J = 15.9 Hz, 1H), 6.34 (d,
J = 15.9 Hz, 1H), 6.20 (d, J = 15.0 Hz, 1H), 6.02 (d, J = 11.7 Hz, 1H),
5.96 (s, 1H), 5.75 (s, 1H), 4.16 (q, J = 7.2 Hz, 2H), 2.89 (q,
J = 7.2 Hz, 1H), 2.35 (s, 3H), 1.93 (s, 3H), 1.44 (quint, J = 6.6 Hz
1H), 1.27 (t, J = 7.2 Hz, 3H) 1.20 (d, J = 6.9 Hz, 3H), 1.17-1,13 (m,
1H), 1.03 (d, J = 6.9 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H), 0.80 (dd,
J = 8.1, 3.9 Hz, 1H), 0.13-0.11 (m, 1H); 13C NMR (75 MHz, CDCl3) d
167.0, 152.5, 144.5, 138.1, 136.7, 134.5, 129.4, 128.4, 127.6,
123.7, 118.6, 59.5, 41.2, 41.1, 30.6, 27.8, 22.3, 21.8, 21.0, 20.8,
20.6, 14.3, 13.7; HR-EIMS calcd for C23H32O2 (M+) 340.2402, found
340.2424.
C
26H36O2 (M+) 380.2715, found 380.2727.
4.3.18. Ethyl (2E,4E,6Z)-7-((4R,4aS,6R)-4,4a,5,6,7,8-hexahydro-
4,4a-dimethyl-6-(1-methyl)ethenylnaphthalen-2-yl)-3-methyl-
2,4,6-octatrienoate (12n)
According to Method B (GP-B-2), 12n (72.3 mg, 84%) was obtained
as a yellow oil from vinyl triflate 8n(79.0 mg, 0.225 mmol), stannanyl
ester 10(138 mg, 0.293 mmol), CsF (68.5 mg, 0.451 mmol), Pd(PPh3)4
(26.1 mg, 22.6
l
ꢂ
mol), and CuI (8.6 mg, 45.1
l
mol). Eluent: hexane/
Et2O = 40:1. ½a 2D5
+81.9 (c 1.44, MeOH); IR 1698, 1601 cmꢀ1
;
1H
NMR (500 MHz, CDCl3) d 6.89 (dd, J = 15.5, 11.0 Hz, 1H), 6.13 (d,
J = 15.5 Hz, 1H), 5.99 (d, J = 11.0 Hz, 1H), 5.70 (s, 1H), 5.58 (s, 1H),
5.23 (s, 1H), 4.71 (s, 2H), 4.13 (q, J = 7.0 Hz, 2H), 2.37 (td, J = 7.5,
2.5 Hz, 1H), 2.32 (t, J = 2.5 Hz, 2H), 2.22 (d, J = 1.0 Hz, 3H), 2.16 (tt,
J = 12.5, 2.5 Hz, 1H), 1.93-1.90 (m, 1H), 1.91 (s, 3H), 1.80 (dq,
J = 12.5, 2.5 Hz, 1H), 1.73 (s, 3H), 1.29-1.24 (m, 1H), 1.26 (t,
J = 7.0 Hz, 3H), 1.15 (t, J = 12.5 Hz, 1H), 1.03 (d, J = 7.5 Hz, 3H), 0.87
(s, 3H); 13C NMR (125 MHz, CDCl3) d 167.2, 153.1, 150.2, 146.1,
143.4, 135.3, 133.1, 132.9, 129.7, 126.2, 119.8, 118.0, 108.6, 59.5,
45.7, 42.2, 41.4, 38.4, 31.6, 31.4, 23.8, 20.9, 14.3 (2C), 13.64, 13.60;
HR-EIMS calcd for C26H36O2 (M+) 380.2715, found 380.2707.
4.3.15. Ethyl (2E,4E,6Z)-3-methyl-7-((3R,6S)-6-(1-methylethyl)-
3-methyl-1-cyclohexen-1-yl)- 2,4,6-octatrienoate (12d)
According to Method A (GP-B-1), 12d (243 mg, 77%) was ob-
tained as a yellow oil from vinyl triflate 8d (310 mg, 1.08 mmol),
stannanyl ester 10 (465 mg, 0.991 mmol), Pd2(dba)3ꢁCHCl3
(41.0 mg, 39.6 lmol), AsPh3 (48.5 mg, 0.158 mmol), and CsF
(300 mg, 1.97 mmol). Eluent: hexane/Et2O = 30:1. ½a D26
ꢂ
+215 (c
0.858, MeOH); IR 1698, 1600 cmꢀ1 1H NMR (300 MHz, CDCl3) d
;
6.98 (dd, J = 15.3, 11.1 Hz, 1H), 6.15 (d, J = 15.3 Hz, 1H), 5.97 (d,
J = 10.8 Hz, 1H), 5.72 (s, 1H), 5.42 (s, 1H), 4.15 (q, J = 7.2 Hz, 2H),
2.34-2.18 (m, 2H), 2.27 (d, J = 1.2 Hz, 3H), 1.88 (s, 3H), 1.88-1.69
(m, 3H), 1.47-1.34 (m, 1H), 1.27 (t, J = 7.2 Hz, 3H), 1.12-0.99 (m,
1H), 0.96 (d, J = 7.2 Hz, 3H), 0.90 (d, J = 7.2 Hz, 3H), 0.67 (d,
J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3) d 167.3, 153.3, 146.8,
141.1, 135.1, 133.1, 132.7, 126.3, 117.6, 59.5, 41.7, 31.2, 30.8,
28.9, 23.9, 22.0, 21.20, 21.16, 16.6, 14.3, 13.8; HR-EIMS calcd for
4.4. General procedure for the hydrolysis of ester compounds
4.4.1. Standard conditions for hydrolysis (GP-C-1)
A mixture of an ester (1.0 equiv) and 10% KOH (0.133 M) aque-
ous solution in EtOH (0.08 M) was heated at 50 °C overnight. After
cooling, the reaction mixture was made acidic or neutral by addi-
tion of 5% HCl aqueous solution at 0 °C. The mixture was extracted
with AcOEt, and the organic layer was washed with brine, dried
over Na2SO4, filtered, and evaporated in vacuo. The residue was
purified by flash column chromatography on silica gel to give the
carboxylic acid.
C
21H32O2 (M+) 316.2402, found 316.2420.
4.3.16. Ethyl (2E,4E,6Z)-3-methyl-7-((1R,4R)-1,7,7-
trimethylbicyclo[2.2.1]hept-2-en-2-yl)-2,4,6-octatrienoate
(12h)
According to Method B (GP-B-2), 12h (81.6 mg, 76%) was ob-
tained as a yellow oil from vinyl triflate 8h (98.0 mg, 0.345 mmol),
stannanyl ester 10 (210 mg, 0.448 mmol), CsF (300 mg,
4.4.2. Microwave conditions for hydrolysis (GP-C-2)
1.97 mmol), Pd(PPh3)4 (39.9 mg, 34.5 lmol), and CuI (13.1 mg,
A mixture of an ester (1.0 equiv) and 10% KOH (0.133 M) aque-
ous solution in EtOH (0.08 M) was microwave-irradiated at 130 °C
for 3 min. After cooling, the reaction mixture was made acidic or
neutral by addition of 5% HCl aqueous solution at 0 °C. The mixture
was extracted with AcOEt, and the organic layer was washed with
brine, dried over Na2SO4, filtered, and evaporated in vacuo. The res-
idue was purified by flash column chromatography on silica gel to
give the carboxylic acid.
68.9
l
mol). Eluent: hexane/Et2O = 40:1. ½a D26
ꢀ185 (c 1.63, MeOH);
ꢂ
IR 1698, 1600 cmꢀ1; 1H NMR (500 MHz, CDCl3) d 6.91 (dd, J = 15.0,
11.0 Hz, 1H), 6.16 (d, J = 15.0 Hz, 1H), 6.07 (d, J = 11.0 Hz, 1H), 5.76
(d, J = 3.5 Hz, 1H), 5.71 (s, 1H), 4.15 (q, J = 7.0 Hz, 2H), 2.38 (t,
J = 3.5 Hz, 1H), 2.24 (d, J = 1.0 Hz, 3H), 1.94-1.89 (m, 1H), 1.91 (s,
3H), 1.60 (ddd, J = 12.0, 8.5, 3.5 Hz, 1H), 1.28 (t, J = 7.0 Hz, 3H),
1.20 (ddd, J = 12.5, 9.0, 3.5 Hz, 1H), 1.07 (ddd, J = 12.0, 9.0, 3.5 Hz,
1H), 1.01 (s, 3H), 0.93 (s, 3H), 0.80 (s, 3H); 13C NMR (125 MHz,
CDCl3) d 167.3, 153.3, 148.8, 141.9, 133.3, 133.03, 132.97, 128.0,
117.8, 59.5, 56.9, 55.8, 51.9, 31.5, 25.5, 23.9, 19.78, 19.76, 14.3,
13.7, 12.2; HR-EIMS calcd for C21H30O2 (M+) 314.2246, found
314.2242.
4.4.3. (2E,4E,6Z,8E)-3,7-Dimethyl-9-((3S,6R)-3-methyl-6-(1-
propen-2-yl)-1-cyclohexen-1-yl)-2,4,6,8-nonatetraenoic acid (5a)
According to general procedure (GP-C-1), 5a (151 mg, 92%) was
obtained as yellow crystals from ester 11a (179 mg, 0.525 mmol),