K. Tanabe et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 8 (2007) 1603
concentrated. The residue was purified by column chromatogra-
phy (silica gel, hexane/EtOAc = 10:1 v/v) to afford 5 (4.5 mg,
0.016 mmol, 32%) as a pale yellow oil and an intramolecular
Diels–Alder product 31 (5.4 mg, 0.019 mmol, 38%) as a pale
yellow oil. Compound 5: Rf ¼ 0:56 (silica gel, hexane/EtOAc =
3:1 v/v); IR (neat) 3463, 3316, 3077, 2946, 2850, 1735, 1662
dropwise n-BuLi (0.580 mL, 0.911 mmol; 1.56 M in hexane). The
mixture was stirred at this temperature for 20 min and then cooled
to ꢂ78 ꢁC. A solution of compound 33 (73.0 mg, 0.434 mmol) in
THF (1.0 mL) was added to the reaction mixture, and the solution
was stirred at ꢂ78 ꢁC for 30 min. On the other hand, to a solution
of compound 27 (83.4 mg, 0.651 mmol) in THF (3.5 mL) were
added triethylamine (0.12 mL, 0.86 mmol) and pivaloyl chloride
(0.10 mL, 0.81 mmol) at 0 ꢁC. The mixture was stirred for 40
min and cooled to ꢂ78 ꢁC. The solution containing compound
33 was transferred at ꢂ78 ꢁC into the solution containing com-
pound 28, and the reaction mixture was allowed to gradually
warm to room temperature. After 7 h, the mixture was quenched
with sat. NH4Cl, and the aqueous layer was extracted with ether.
The organic extracts were combined, washed with brine, dried
over anhydrous MgSO4, and concentrated. The residue was puri-
fied by column chromatography (silica gel, hexane/EtOAc = 10:1
v/v) to afford 34 (41.8 mg, 0.150 mmol, 35%) as a pale yellow oil.
Rf ¼ 0:38 (silica gel, hexane/EtOAc = 10:1 v/v); IR (neat) 3074,
2965, 2933, 1719, 1641, 1607; 1H NMR (500 MHz, CDCl3): ꢀ
13.88 (s, 1H), 5.80 (tdd, J ¼ 6:7, 10.4, 17.1 Hz, 1H), 5.02 (dd, J ¼
1:8, 17.1 Hz, 1H), 4.98 (d, J ¼ 10:4 Hz, 1H), 4.75 (s, 1H), 4.70 (s,
1H), 3.98 (dd, J ¼ 1:2, 11.0 Hz, 1H), 3.92 (dd, J ¼ 1:2, 11.0 Hz,
1H), 2.27 (t, J ¼ 7:6 Hz, 2H), 2.24 (d, J ¼ 14:3 Hz, 1H), 2.18 (d,
J ¼ 14:3 Hz, 1H), 2.11–2.03 (m, 4H), 1.79–1.74 (m, 2H), 1.73 (s,
3H), 1.48–1.36 (m, 2H), 1.00 (s, 3H); 13C NMR (125 MHz,
CDCl3): ꢀ 216.7, 179.3, 172.7, 144.8, 138.1, 114.9, 110.6, 91.4,
76.1, 37.2, 36.0, 34.8, 32.0, 31.3, 27.8, 23.8, 22.2, 21.4. HRMS
(EI): Calcd for C17H26O3: 278.1882. Found: 278.1880.
Attempted RCM Reaction of 34. To a solution of compound
34 (28.37 mg, 0.102 mmol) in CH2Cl2 (10.0 mL) was added the
2nd generation Grubbs catalyst (8.65 mg, 0.0102 mmol), and the
mixture was refluxed for 8 h. The reaction mixture was then
evaporated, and the residue was purified by column chromato-
graphy (silica gel, hexane/EtOAc = 5:1 v/v) to afford dimeric
compound 36 (4.30 mg, 0.0078 mmol) as a pale yellow oil instead
of the desired product 35. Rf ¼ 0:26 (silica gel, hexane/EtOAc =
3:1 v/v); 1H NMR (500 MHz, CDCl3): ꢀ 13.87 (s, 2H), 5.42–5.39
(br, 2H), 4.75 (s, 2H), 4.70 (s, 2H), 3.98 (dd, J ¼ 1:2, 11.0 Hz,
2H), 3.91 (dd, J ¼ 1:2, 11.0 Hz, 2H), 2.29–2.23 (m, 4H), 2.22–
2.15 (m, 4H), 2.11–1.97 (m, 8H), 1.79–1.73 (m, 4H), 1.73 (s, 6H),
1.44–1.30 (m, 4H), 0.99 (s, 6H); 13C NMR (125 MHz, CDCl3):
ꢀ 216.7, 179.6, 172.5, 148.2, 144.8, 110.6 h110:6i, 91.4, 75.7,
37.2, 36.6, 34.8, 32.0, 31.3, 26.4, 23.8, 22.2, 21.4. HRMS (EI):
Calcd for C32H48O6: 528.3451. Found: 528.3454.
cmꢂ1
;
1H NMR (500 MHz, CDCl3): ꢀ 5.79 (tdd, J ¼ 6:7, 10.4,
17.1 Hz, 1H), 5.75 (s, 1H), 4.99 (dd, J ¼ 1:5, 17.1 Hz, 1H), 4.92
(d, J ¼ 10:4 Hz, 1H), 4.76 (s, 1H), 4.70 (s, 1H), 3.70 (s, 3H), 2.38
(d, J ¼ 15:2 Hz, 1H), 2.31–2.26 (m, 2H), 2.23 (d, J ¼ 15:2 Hz,
1H), 2.19–2.14 (m, 2H), 2.05–1.99 (m, 2H), 1.75 (s, 3H), 1.50–
1.43 (m, 1H), 1.39–1.32 (m, 1H), 0.98 (s, 3H); 13C NMR (125
MHz, CDCl3): ꢀ 171.1, 152.5, 144.7, 143.0, 139.3, 130.9, 114.0,
110.6, 50.5, 39.6, 36.8, 34.4, 33.4, 29.2, 28.9, 27.2, 25.2, 22.6.
HRMS (EI): Calcd for C18H27NO2: 289.2042. Found: 289.2030.
Compound 31: Rf ¼ 0:31 (silica gel, hexane/EtOAc = 3:1
v/v); IR (neat) 3471, 3073, 2950, 2869, 1731, 1627 cmꢂ1; 1H NMR
(500 MHz, CDCl3): ꢀ 4.70 (s, 1H), 4.66 (s, 1H), 3.88 (d, J ¼ 4:6
Hz, 1H), 3.76 (s, 3H), 2.37 (dd, J ¼ 7:0, 9.1 Hz, 2H), 2.11–2.06
(m, 1H), 2.03 (t, J ¼ 7:6 Hz, 2H), 1.99–1.92 (m, 1H), 1.92–1.85
(m, 1H), 1.73–1.66 (m, 2H), 1.70 (s, 3H), 1.62–1.53 (m, 4H),
1.42–1.35 (m, 2H), 0.97 (s, 3H); 13C NMR (125 MHz, CDCl3):
ꢀ 176.7, 174.7, 145.2, 110.3, 69.2, 51.9, 48.9, 44.0, 40.9, 38.1,
38.0, 37.5, 34.4, 34.1, 29.4, 26.4, 23.7, 22.2. HRMS (EI): Calcd
for C18H27NO2: 289.2042. Found: 289.2029.
Attempted RCM Reaction of 5. To a solution of compound 5
(12.7 mg, 0.0439 mmol) in CH2Cl2 (5.0 mL) was added the 2nd
generation Grubbs catalyst (5.1 mg, 0.0060 mmol), and the mix-
ture was refluxed for 1 day. Then, the solvent was evaporated,
and the residue was purified by column chromatography (silica
gel, hexane/EtOAc = 10:1 v/v) to afford dimeric compound 32
(4.30 mg, 0.0078 mmol) as a pale yellow oil instead of the desired
product 4. Rf ¼ 0:16 (silica gel, hexane/EtOAc = 5:1 v/v);
1H NMR (500 MHz, CDCl3): ꢀ 5.77–5.73 (br, 2H), 5.35 (d, J ¼
4:0 Hz, 2H), 4.76 (s, 2H), 4.70 (s, 2H), 3.70 h3:69i (s, 6H), 2.40–
2.34 (m, 2H), 2.31–2.26 (m, 4H), 2.25–2.19 (m, 2H), 2.19–2.14
(m, 4H), 2.00–1.90 (m, 4H), 1.74 (s, 6H), 1.45–1.38 (m, 2H),
1.34–1.27 (m, 2H), 0.97 h0:96i (s, 6H); 13C NMR (125 MHz,
CDCl3): ꢀ 171.1, 152.5, 144.7, 143.2, 136.9, 131.2, 110.6, 50.5,
39.9, 36.8, 34.4, 33.7, 29.2, 28.8, 27.2, 25.2, 22.6. HRMS (EI):
Calcd for C34H50N2O4: 550.3771. Found: 550.3745.
5-(But-3-enyl)-5-methyltetrahydropyran-2-one (33). A solu-
tion consisting of compound 22 (615.8 mg, 1.96 mmol), 1 M HCl
(5.0 mL), water (15 mL), and THF (20 mL) was refluxed for 40 h.
After cooling, the reaction mixture was quenched with sat.
NaHCO3, and the aqueous layer was extracted with ether. The or-
ganic extracts were combined, dried over anhydrous Na2SO4, and
concentrated. The residue was purified by column chromato-
graphy (silica gel, hexane/EtOAc = 5:1 v/v) to afford 33 (265.6
mg, 1.58 mmol, 81%) as a colorless oil. Rf ¼ 0:32 (silica gel, hex-
ane/EtOAc = 3:1 v/v); IR (neat) 3077, 2962, 2931, 1739, 1639
Methyl 10-(t-Butyldimethylsilanyloxymethyl)-6,10-dimeth-
yl-2-oxocycloundec-6-ene-1-carboxylate (37). To a solution
of compound 29 (47.4 mg, 0.111 mmol) in CH2Cl2 (200 mL) was
added the 2nd generation Grubbs catalyst (14.1 mg, 0.0167 mmol)
in CH2Cl2 (5.0 mL), and the mixture was refluxed for 2 days. The
reaction mixture was then evaporated and the residue was purified
by column chromatography (silica gel, hexane/EtOAc = 10:1
v/v) to afford 37 (15.9 mg, 0.040 mmol, 36%) as a pale yellow
oil. Rf ¼ 0:66 (silica gel, hexane/EtOAc = 10:1 v/v); IR (neat)
cmꢂ1
;
1H NMR (500 MHz, CDCl3): ꢀ 5.80 (tdd, J ¼ 6:7, 10.4,
17.1 Hz, 1H), 5.02 (dd, J ¼ 1:5, 17.1 Hz, 1H), 4.98 (dd, J ¼ 1:5,
10.4 Hz, 1H), 4.04 (d, J ¼ 11:3 Hz, 1H), 3.96 (d, J ¼ 11:3 Hz,
1H), 2.54 (t, J ¼ 7:3 Hz, 2H), 2.11–2.02 (m, 2H), 1.80–1.72 (m,
1H), 1.71–1.64 (m, 1H), 1.44 (t, J ¼ 8:5 Hz, 2H), 1.03 (s, 3H);
13C NMR (125 MHz, CDCl3): ꢀ 171.6, 138.0, 114.9, 77.3, 36.8,
32.1, 31.1, 27.8, 27.1, 22.0. HRMS (EI): Calcd for C10H16O2:
168.1150. Found: 168.1148.
2954, 2931, 2861, 1751, 1712, 1257 cmꢂ1 1H NMR (500 MHz,
;
CDCl3): ꢀ 5.26 (t, J ¼ 9:2 Hz, 1H), 3.68 h3:65i (s, 3H), 3.33–
3.20 (m, 2H), 2.90–2.79 (m, 1H), 2.68–2.59 (m, 1H), 2.52 (td,
J ¼ 3:4, 13.1 Hz, 1H), 2.12–1.87 (m, 3H), 1.75–1.52 (m, 5H),
1.66 h1:65i (s, 3H), 1.29–1.18 (m, 2H), 0.90 h0:89i (s, 9H), 0.87
h0:81i (s, 3H), 0.03 h0:01i (s, 6H); 13C NMR (125 MHz, CDCl3):
ꢀ 209.3 h208:8i, 170.4 h170:3i, 132.7 h132:5i, 127.2 h127:1i, 73.1,
69.3, 53.4, 52.6 h52:5i, 41.3 h41:2i, 38.7, 37.7, 35.8, 35.4, 34.6,
28.3 h28:3i, 25.8 h25:8i, 24.5, 23.4 h23:3i, 23.1, 22.3, 18.8 h18:8i,
5-(But-3-enyl)-3-(5-methyl-1-oxo-5-hexenylidene)-5-methyl-
tetrahydropyran-2-one (34). To a solution of the (i-Pr)2NH
(0.125 mL, 0.954 mmol) in THF (3.5 mL) at ꢂ78 ꢁC was added