S.-ichi Takekuma et al. / Tetrahedron 68 (2012) 8318e8329
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to the mixture and then, was stirred at 25 ꢀC for 20 min and further,
was treated using 10%H2SO4 aqueous solution. The resulting
products were extracted with diethyl ether (10 mLꢃ3). The extract
was washed with water, dried (MgSO4), and evaporated in vacuo.
The residue thus obtained was carefully separated by silica gel
column chromatography with hexane/ethyl acetate (8:2, vol/vol) as
an eluant. The crude product thus obtained was recrystallized from
hexane to provide pure 11 (38 mg, 0.15 mol, 76% yield) as crystals.
Compound 11: Dark-green plates [Rf¼0.23 on silica gel TLC (solv.
hexane:ethyl acetate¼8:2, vol/vol)]; mp 124 ꢀC; exact FABMS (3-
nitrobenzyl alcohol matrix), found: m/z 252.1536; calcd for
C18H20O: Mþ, m/z 252.1514; 500 MHz 1H NMR (acetonitrile-d3),
z 84 (Mþ); IR nmax (NaCl, neat) cmꢁ1, 2920, 2851 (CeH), 1717 (CHO),
and 1543 (C]C).
4.1.5. Preparation of (E)-ethylene-1,2-bis(3-guaiazulenylmethylium)
bis(hexafluorophosphate) (14). To
a solution of 13 (6 mg,
0.07 mmol) in acetonitrile (2 mL) was added a solution of hexa-
fluorophosphoric acid (i.e., 65% HPF6 aqueous solution, 0.2 mL,
0.83 mmol) and then, was stirred at 25 ꢀC for 30 min. The mixture
was added to a solution of guaiazulene (6) (33 mg, 0.17 mmol) in
diethyl ether (2 mL) and then, was stirred at 25 ꢀC for 1 h. After the
reaction, the mixture was poured into diethyl ether (10 mL), and
was centrifuged at 2.6 krpm for 1 min. The thus obtained crude
product was carefully washed with diethyl ether to provide pure 14
(10 mg, 0.01 mmol, 13% yield) as crystals.
signals from a 3-guaiazulenyl group:
d
1.34 (6H, d, J¼6.8 Hz,
(CH3)2CH-70), 2.56 (3H, d, J¼0.8 Hz, Me-10), 3.07 (3H, s, Me-40), 3.11
(1H, sept, J¼6.8 Hz, (CH3)2CH-70), 7.33 (1H, d, J¼10.6 Hz, H-50), 7.54
(1H, dd, J¼10.6, 2.2 Hz, H-60), 7.98 (1H, br s, H-20), and 8.21 (1H, d,
Compound 14: Dark-green needles [from acetonitrile/diethyl
ether (1:5, vol/vol)]; Found: C, 51.32; H, 4.42%. Calcd for
C34H38O4F12P2 (i.e., C34H38þ2PF6þ2O2): C, 51.01; H, 4.78%; UVevis
J¼2.2 Hz, H-80); signals from an (E)-ethylene unit:
d 6.57 (1H, dd,
J¼15.1, 7.8 Hz, H-1) and 8.48 (1H, d, J¼15.1 Hz, H-2); and a signal
lmax/nm (log ) in CF3COOH, 265 (4.62), 334 (4.37), 430 sh (4.40),
3
from a formyl group:
d
9.62 (1H, d, J¼7.8 Hz, CHO).
490 sh (4.66), 530 sh (4.89), and 561 (4.94); IR nmax (KBr) cmꢁ1, 841,
559 (PF6ꢁ); exact FABMS (3-nitrobenzyl alcohol matrix), found: m/z
446.3000; calcd for C34H38: [Mꢁ2PF6]2þ, m/z 446.2974; 500 MHz
1H NMR (trifluoroacetic acid-d1), signals based on an equivalent of
4.1.3. Preparation of (2E,4E)-1,4-di(3-guaiazulenyl)-1,3-butadiene
(4). To a solution of 11 (76 mg, 0.30 mmol) in ethanol (3 mL) was
added a solution of (3-guaiazulenylmethyl)triphenylphosphonium
bromide25,26 (9) (165 mg, 0.30 mmol) in ethanol (3 mL) with so-
dium ethoxide (50 mg, 1.3 mmol) under argon. The mixture was
stirred at 25 ꢀC for 24 h under argon. After the reaction, distilled
water was added to the mixture and then, the resulting products
were extracted with dichloromethane (20 mLꢃ3). The extract was
washed with distilled water, dried (MgSO4), and evaporated in
vacuo. The residue thus obtained was carefully separated by alu-
mina column chromatography with hexane/benzene/ethyl acetate
(90:5:5, vol/vol/vol) as an eluant. The crude product 4 was recrys-
tallized from hexane/dichloromethane (5:1, vol/vol) (several times)
to provide pure 4 (45 mg, 0.10 mmol, 33% yield) as crystals.
two 3-guaiazulenylmethylium moieties with a delocalized p-elec-
tron system at
d
1.55 (12H, d, J¼6.8 Hz, (CH3)2CH-70,700), 2.60 (6H, br
s, Me-10,100), 3.41 (6H, s, Me-40,400), 3.50 (2H, sept, J¼6.8 Hz,
(CH3)2CH-70,700), 8.03 (2H, br s, H-20,200), 8.40 (2H, dd, J¼11.4, 1.2 Hz,
H-60,600), 8.64 (2H, d, J¼1.2 Hz, H-80,800), 8.54 (2H, d, J¼11.4 Hz, H-
50,500), and 8.49 (2H, br ddd, J¼3.7, 0.6, 0.3 Hz, HCþ-a0
,a
00); and
signals based on an (E)-ethylene unit:
d
8.07 (2H, br ddd, J¼15.3, 3.7,
0.6 Hz0,0 H-1,2); 125 MHz 13C NMR (trifluoroacetic acid-d1):
d 176.0
(C-70,7 ), 165.1 (C-8a0,8a00), 159.5 (C-40,400), 154.3 (C-3a0,3a00), 152.5
(C-50,500), 148.9 (C-10,100), 147.2 (C-30,300), 146.4 (C-60,600), 145.6 (C-
a,a
0), 144.8 (C-1,2), 140.3 (C-80,800), 139.7 (C-20,200), 42,4 ((CH3)2CH-
70,700), 29.7 (Me-40,400), 24.4 ((CH3)2CH-70,700), and 14.2 (Me-10,100).
Compound 4: Dark-green needles [Rf¼0.50 on silica gel TLC
(solv. hexane: benzene: ethyl acetate¼90: 5: 5, vol/vol/vol)]; mp
4.1.6. Zinc reduction of 14. To a solution of 14 (10 mg, 13.7 mol) in
m
242 ꢀC; UVevis lmax/nm (log
3 ) in CH2Cl2, 236 (4.49), 276 (4.55),
trifluoroacetic acid (1 mL) was added a zinc powder (58 mg,
0.89 mmol). The mixture was stirred at 0 ꢀC for 1 h under argon.
After the reaction, the used zinc powder was removed using
a centrifugal separator. The reaction solution was carefully neu-
tralized with aq NaHCO3 and then, the resulting products were
extracted with diethyl ether (20 mLꢃ3). The extract was washed
with water, dried (MgSO4), and evaporated in vacuo. The residue
thus obtained was carefully separated by alumina column chro-
matography with hexane/benzene/ethyl acetate (90:5:5, vol/vol/
vol) as an eluant. The crude product 4 was recrystallized from
hexane/dichloromethane (5:1, vol/vol) (several times) to provide
339 (4.45), 473 (4.77), 500 sh (4.68), 647 (3.20), and 780 sh (2.91);
exact FABMS (3-nitrobenzyl alcohol matrix), found: m/z 446.2971;
calcd for C34H38: Mþ, m/z 446.2974; 700 MHz 1H NMR (benzane-
d6), signals from an equivalent of two 3-guaiazulenyl groups: d 1.19
(12H, d, J¼6.9 Hz, (CH3)2CH-70,700), 2.53 (6H, s, Me-10,100), 2.71 (2H,
sept, J¼6.9 Hz, (CH3)2CH-70,700), 2.87 (6H, s, Me-40,400), 6.55 (2H, d,
J¼10.4 Hz, H-50,500), 6.97 (2H, dd, J¼10.4, 2.0 Hz, H-60,600), 7.92 (2H,
d, J¼2.0 Hz, H-80,800), and 7.99 (2H, s, H-20,200); and signals from
a (2E,4E)-1,3-butadiene unit:
d
7.20 (2H, ddd, J¼15.3, 3.7, 1.3 Hz, H-
2,3) and 7.74 (2H, ddd, J¼15.3, 3.7, 1.3 Hz, H-1,4); 176 MHz 13C NMR
(benzene-d6):
d
146.4 (C-40,400), 141.8 (C-8a0,8a00), 140.6 (C-70,700),
pure 4 (6 mg, 13.4 mmol, 98% yield) as dark green needles.
136.3 (C-20,200), 134.7 (C-60,600), 133.4 (C-80,800), 132.7 (C-3a0,3a00),
130.0 (C-2,3), 127.8 (C-1,4), 128.0 (C-30,300), 127.3 (C-50,500), 126.6 (C-
10,100), 37.8 ((CH3)2CH-70,700), 28.4 (Me-40,400), 24.4 ((CH3)2CH-70,700),
and 13.0 (Me-10,100).
The structure of the product 4 was identified by 1H NMR spectral
datum (see Section 4.1.3).
4.1.7. Treatment of 4 in THF containing HPF6 under aerobic con-
ditions. To a solution of 4 (10 mg, 22
a solution of haxafluorophosphoric acid (i.e., 65% HPF6 aqueous
solution, 0.02 mL, 83
mol). The mixture was stirred at 25 ꢀC for 1 h
under aerobic conditions, precipitating a dark-purple solid of 14
and then, was centrifuged at 2.6 krpm for 1 min. The crude product
thus obtained was carefully washed with diethyl ether, and was
recrystallized from acetonitrile/diethyl ether (1:5, vol/vol) to pro-
mmol) in THF (3 mL) was added
4.1.4. Preparation of ethylene-1,2-dicarbaldehyde47 (13). To a sus-
pension of manganese dioxide (2.57 g, 30 mmol) in chloroform
(7 mL) was added a solution of a commercially available (2Z)-2-
butene-1,4-diol (12) (536 mg, 6.1 mmol) in chloroform. The mix-
ture was stirred at 25 ꢀC for 24 h. After the reaction, the used
manganese dioxide was removed using a centrifugal separator. The
reaction solution was evaporated in vacuo. The residue thus
obtained was carefully separated by silica gel column chromatog-
raphy with ethyl acetate as an eluant, the solution, of which was
evaporated in vacuo to provide 13 (264 mg, 3.1 mmol, 51% yield) as
a yellow paste.
m
vide pure 14 as crystals (16 mg, 22 mmol, 100% yield).
The structure of the product 14 was identified by 1H NMR
spectral datum (see Section 4.1.5).
4.1.8. X-ray crystal structure of (2E,4E)-1,4-di(3-guaiazulenyl)-1,3-
butadiene (4). The X-ray measurement of the single crystal 4 was
made on a Rigaku Saturn CCD area detector with graphite
Compound 13: Yellow paste [a mixture of E and Z forms;
Rf¼0.34, 0.53 on silica gel TLC (solv. ethyl acetate)]; EIMS (70 eV), m/