Y.-J. Kim et al. / Tetrahedron 69 (2013) 7810e7816
7815
and the solution was washed with water (2 mL) and brine (2 mL).
The aqueous layer was extracted with dichloromethane (2 mLꢁ3).
Combined organic layers were dried over MgSO4, filtered, and
concentrated in vacuo. The crude mixture was purified by column
chromatography on silica gel (ethyl acetate/hexane¼1:20) to afford
were combined and dried over MgSO4. The filtrate was concentrated
in vacuo, and the residue was purified by flash column chromatog-
raphy on silica gel (ethyl acetate/hexane¼1:10) to afford aldehyde 24
(96 mg, 98%). 1H NMR (400 MHz, CDCl3):
d¼9.51e9.50 (d, J¼2.5 Hz,
1H), 5.41e5.31 (m, 2H), 4.67e4.65 (m, 2H), 2.16e2.15 (t, J¼3.0 Hz,
2H),1.95e1.89 (m, 2H),1.84e1.79 (m,1H),1.61e1.60 (d, J¼4.3 Hz, 3H),
1.50e1.41 (m, 1H), 1.29e1.20 (m, 1H), 1.07 (s, 6H) 0.96e0.95 ppm (d,
tosylate 22 (276 mg, 76%). 1H NMR (300 MHz, CDCl3):
d
¼7.79 (d,
J¼8.3 Hz, 2H), 7.31 (d, J¼8.3 Hz, 2H), 5.46e5.24 (m, 2H), 4.70 (d,
J¼2.1 Hz, 2H), 2.42 (s, 3H), 2.36e2.23 (m, 1H), 1.95 (ddt, J¼17.7, 13.9,
7.1 Hz, 2H), 1.65e1.54 (m, 3H), 1.32 (qd, J¼7.6, 3.3 Hz, 2H), 1.00 ppm
J¼6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 206.2, 206.0,131.2,124.8,
104.2, 78.2, 46.3, 38.8, 36.5, 35.3, 30.2, 22.1, 22.1,19.2,17.9 ppm; High
(dd, J¼6.9, 3.1 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d
144.8, 133.5,
resolution mass (ESI): Calculated for C15H24O [MþNa]þ: 243.1724,
130.3, 129.7, 128.1, 125.5, 94.5, 72.2, 58.8, 36.1, 30.1, 25.2, 21.6, 20.3,
found: 243.1713; [
a]
D
23 ꢂ30.3 (c 0.3, CHCl3).
33:0
17.9 ppm; ½a D
ꢃ
ꢂ32.8 (c 1.1, CHCl3).
4.1.15. Preparation of the compounds 26 and 260 from 24. To a stir-
red solution of aldehyde 24 (35 mg, 0.16 mmol) in MeOH (2 mL) was
added p-toluenesulfonhydrazide (H2NNHTs; 35 mg, 0.18 mmol) at
4.1.12. (R,E)-tert-Butyldimethyl (2,2,5-trimethyl-4-vinylidenedec-8-
enyloxy) silane (23). To Li wire (82.3 mg, 11.9 mmol) in dry
Et2O (4 mL) was added 3-(tert-butyldimethylsilyloxy)-2,2-
dimethylpropan-1-ol (474 mg, 1.7 mmol) in Et2O (2 mL). The re-
action mixture was stirred for 40 min. This solution of the lithiated
reagent was cooled to ꢂ78 ꢀC, and was added dropwise via syringe
pump to a suspension of copper(I) cyanide (CuCN; 121.4 mg,
1.4 mmol) in Et2O (3.4 mL). The mixture was stirred for 2 min,
warmed to 0 ꢀC for 15 min, and recooled to ꢂ78 ꢀC. Tosylate 22
(207.6 mg, 0.7 mmol) in Et2O (1 mL) was added dropwise via
cannula and resulting mixture was allowed to stir at ꢂ78 ꢀC for 1 h.
The reaction mixture was warmed to 0 ꢀC for 10 min then quenched
with saturated NH4Cl solution (3 mL) and extracted with Et2O
(3 mLꢁ3). The organic layers were combined and dried over MgSO4.
The filtrate was concentrated in vacuo, and the residue was purified
by flash column chromatography on silica gel (hexane) to afford
0
ꢀC. The reaction mixture was allowed to room temperature and
stirred for 2 h. The reaction mixture was concentrated in vacuo, and
the residue was purified by flash column chromatography on silica
gel (ethyl acetate/hexane¼1/4) to afford the N-tosyl hydrazone. To
a suspension of sodium hydride (7.6 mg, 60% dispersion in mineral
oil, 0.19 mmol) in benzene (10 mL) was added a solution of N-tosyl
hydrazone (61 mg, 0.16 mmol) in benzene (6 mL) at 0 ꢀC. The re-
action mixture was heated at 80 ꢀC for 12 h. The reaction mixture
was cooled to room temperature. The reaction was quenched with
saturated NH4Cl solution (5 mL) and extracted with Et2O (5 mLꢁ3).
The organic layers were combined and dried over MgSO4. The filtrate
was concentrated in vacuo, and the residue was purified by flash
column chromatography on silica gel (pentane) to produce a mixture
of the angularly triquinanes. A solution of the angular triquinanes,
allene 23 (245 mg, 94%). 1H NMR (300 MHz, CDCl3):
d
5.39 (dq,
pyridine (39 mL, 0.48 mmol), and selenium dioxide (SeO2; 27 mg,
J¼4.9, 2.2 Hz, 2H), 4.62 (dq, J¼4.4, 2.2 Hz, 2H), 3.25 (d, J¼2.1 Hz, 2H),
2.05e1.92 (m, 2H), 1.91e1.84 (m, 3H), 1.64e1.57 (m, 3H), 1.48 (ddt,
J¼13.6, 8.6, 6.8 Hz, 1H), 1.31e1.17 (m, 1H), 0.97 (dd, J¼8.5, 6.8 Hz,
3H), 0.87 (s, 9H), 0.86 (s, 6H), ꢂ0.00 ppm (s, 6H); 13C NMR
0.48 mmol) in benzene (2 mL) was refluxed for 3 h. The mixture was
diluted with Et2O and filtered through a Celite pad, and then the pad
was washed with Et2O. The filtrate and washings were concentrated
under reduced pressure. The residue was purified by flash column
chromatography on silica gel (diethyl ether/petroleum ether¼1:4) to
afford angularly fused triquinane 26 (12.3 mg, 35%) and 260 (1.8 mg,
(100 MHz, CDCl3):
d
¼207.1, 131.6, 124.6, 105.3, 75.9, 71.2, 39.4, 37.3,
36.6, 35.8, 30.5, 25.9, 24.4, 19.6, 18.3, 17.9, ꢂ5.5 ppm; High resolu-
tion mass (ESI): Calculated for C21H40OSi [MþNa]þ: 359.2746,
5%). 26; 1H NMR (400 MHz, CDCl3):
d¼5.26e5.25 (d, J¼2.1 Hz, 1H),
26:8
found: 359.2787; ½a D
ꢃ
ꢂ21.8 (c 0.5, CHCl3).
4.71e4.68 (dd, J¼8.4 Hz, J¼2.0 Hz, 1H), 2.04e2.01 (d, J¼13.2 Hz,1H),
2.00e1.94 (m, 1H), 1.92e1.82 (m, 2H), 1.76e1.71 (m, 1H), 1.61e1.58
(m,1H),1.48e1.41 (m, 2H),1.34e1.19 (m, 2H),1.11 (s, 3H),1.09 (s, 3H),
0.95e0.94 (d, J¼7.0 Hz, 3H) 0.86e0.84 ppm (d, J¼7.3 Hz, 3H); 13C
4.1.13. (R,E)-2,2,5-Trimethyl-4-vinylidenedec-8-en-1-ol. To a stirred
solution of allene 23 (235 mg, 0.7 mmol) in THF (2.5 mL) was added
1.0 M solution of tetrabutylammoniumfluoride in THF (TBAF;
2.1 mL, 2.1 mmol) at room temperature. After stirring for 5 h, the
reaction was quenched with saturated NH4Cl (2 mL). The aqueous
phase was extracted with Et2O (2 mLꢁ3) and the combined organic
phases were dried over MgSO4. The solvent was removed in vacuo,
and the residue was purified by column chromatography on silica
gel (ethyl acetate/hexane¼1:10) to afford the alcohol (144 mg, 93%).
NMR (100 MHz, CDCl3):
d
¼155.2, 129.1, 71.5, 64.1, 57.9, 49.3, 48.7,
47.1, 42.1, 36.0, 32.0, 31.7, 28.6, 17.3, 14.9; High resolution mass (ESI):
Calculated for C15H24NaO [MþNa]þ: 243.1724, found: 243.1709;
26:1
½
a D
ꢃ
ꢂ6.8 (c 0.1, CHCl3).; 260; 1H NMR (400 MHz, CDCl3):
¼5.30
d
(d, J¼2.1 Hz, 1H), 4.51 (dd, J¼8.5, 1.9 Hz, 1H), 1.92 (d, J¼13.0 Hz, 1H),
1.90e1.81 (m, 2H), 1.78e1.66 (m, 3H), 1.45e1.39 (m, 2H), 1.22e1.16
(m, 2H), 1.13 (s, 3H), 1.07 (s, 3H), 0.91 (d, J¼7.1 Hz, 3H), 0.84 (d,
1H NMR (400 MHz, CDCl3):
d
5.42e5.33 (m, 2H), 4.67e4.66 (m, 2H),
J¼7.3 Hz, 3H).13C NMR (100 MHz, CD2Cl2):
¼152.8,130.4, 72.8, 63.2,
d
3.33 (s, 2H), 1.97e1.81 (m, 5H), 1.68 (s, 1H), 1.61e1.60 (dd, J¼3.4 Hz,
58.6, 58.4, 48.3, 46.3, 45.4, 35.8, 33.1, 32.0, 28.7, 15.4, 15.2; High
J¼1.0 Hz, 3H), 1.53e1.44 (m, 1H), 1.30e1.20 (m, 1H), 0.98e0.96 (d,
resolution mass (ESI): Calculated for C15H24NaO [MþNa]þ: 243.1724,
27:2
J¼6.8 Hz, 3H), 0.89 ppm (s, 6H); 13C NMR (100 MHz, CDCl3):
d
206.8,
found: 243.1709; ½a D
ꢃ
ꢂ44.7 (c 0.03, CHCl3).
131.4, 124.7, 105.2, 76.3, 71.1, 39.4, 37.0, 36.8, 35.7, 30.3, 24.5, 19.5,
17.9 ppm; High resolution mass (ESI): Calculated for C15H26
O
4.1.16. (3aR,4S,5S,5aS,8R,81S)-2,2,5,8-Tetramethyl decahydro cyclo-
pentapentalen-4-ol. A solution of allylic alcohol 26 (6.7 mg,
0.03 mmol) in absolute ethanol (1 mL) with catalytic amount of
platinum oxide (PtO2; 0.7 mg, 10 mol %) was stirred under an at-
mosphere of hydrogen for 12 h. The catalyst was removed by fil-
tration and the solvent was evaporated to give the crude product,
which was purified using flash column chromatography on silica
gel (ethyl acetate/hexane¼1:10) to afford corresponding alcohol
30:6
[MþNa]þ: 245.1881, found: 245.1845; ½a D
ꢃ
ꢂ31.6 (c 0.4, CHCl3).
4.1.14. (E)-2,2,5-Trimethyl-4-vinylidenenedec-8-enal (24). To a solu-
tion of oxalyl chloride (79 mL, 0.90 mmol) in CH2Cl2 (2 mL) cooled at
ꢂ78 ꢀC was added dimethylsulfoxide (DMSO; 97
mL, 1.35 mmol)
dropwise. The reaction mixture was stirred for 10 min and a solution
of the alcohol from 4.1.7 (100 mg, 0.45 mmol) in CH2Cl2 (2 mL) was
added by cannula. After the solution was stirred for 15 min, trie-
(6.5 mg, 97%); 1H NMR (400 MHz, CDCl3):
d¼3.93e3.91 (t, J¼5.2 Hz,
thylamine (Et3N; 251
mL, 1.8 mmol) was added, and the reaction
1H) 2.29e2.24 (m, 1H), 1.84e1.63 (m, 7H), 1.49e1.45 (d, J¼13.3 Hz,
2H), 1.35e1.28 (m, 2H), 1.21e1.16 (m, 1H), 1.06 (s, 3H), 1.02e1.00 (d,
J¼7 Hz, 3H), 0.99 (3H, s), 0.87e0.85 ppm (d, J¼6.9 Hz, 3H); 13C NMR
mixture was stirred for 10 min and then allowed to warm to room
temperature. The reaction was quenched with saturated NH4Cl so-
lution (2 mL) and extracted with CH2Cl2 (2 mLꢁ3). The organic layer
(100 MHz, CDCl3): d 78.2, 65.8, 58.2, 57.2, 48.7, 48.4, 42.5, 41.2, 40.2,