Intramolecular Anodic Carbon-Carbon Bond Formation
J . Org. Chem., Vol. 61, No. 4, 1996 1273
the THF in vacuo, Et2O (60 mL) was added, and the resultant
slurry was filtered through Celite. Extractive workup with
Et2O (3 × 80 mL) gave a dark orange oil (6.05 g). The oil was
chromatographed on base-washed silica gel11 [5 × 1 in. column,
20% Et2O/PE (300 mL), 50% Et2O/PE (400 mL) as eluants] to
yield a white crystalline alcohol (2.70 g, 42%): mp 88-89 °C;
IR (KBr) 3467 (s), 2962 (m), 2888 (m), 1412 (s), 1379 (m), 1207
(m), 1138 (s), 1115 (s), 1080 (m), 1069 (m), 1015 (s), 992 (m),
956 (s), 911 (m) cm-1; 1H NMR δ 5.90 (s, 4 H), 5.32 (br s, 1 H),
5.0 (br s, 1 H), 4.09 (s, 4 H), 1.70 (br s, 3 H); HRMS calcd for
C11H14O3 m/ z 194.0943, obsd 194.0920.
workup with Et2O (3 × 60 mL) and silica gel chromatography
[5 in. × 0.25 in. column, 100% CH2Cl2 as eluant] gave 9c as a
slightly yellow oil (376 mg, 97%): IR (NaCl) 3390 (m, br), 1610
(s), 1518 (s), 1490 (m), 1467 (m), 1442 (m), 1371 (m), 1317 (m),
1295 (m), 1254 (m), 1220 (s), 1210 (s), 1173 (s), 1039 (m), 892
(m), 833 (s), 811 (m), 785 (m), 758 (m), 610 (m), cm-1; 1H NMR
δ 7.4-7.2 (complex m, 3 H), 6.9-6.8 (m, 4 H), 5.10 (s, 1 H),
5.03 (s, 1 H), 4.96 (s, 1 H), 3.84 (s, 3 H), 1.64 (s, 3 H); HRMS
calcd for C16H16O2 m/ z 240.1151, obsd 240.1166.
An od ic Oxid a tion of 9d . A solution of 9d (0.25 g, 0.92
mmol) in 4:1 CH3CN/CH3OH (150 mL) containing HOAc (0.28
mL) and 1% by weight LiClO4 as the electrolyte was anodically
oxidized at 0 °C in a single cell with perforated cylindrical
platinum sheet anode and copper wire cathode at a constant
current of 0.05 A for 60 min (92% current efficiency) until no
starting material remained by TLC (2:1 Et2O/PE). After
addition of a saturated NaHCO3 solution (50 mL), extractive
workup gave 17d (0.255 g, 92%) as a light yellow powder, mp
143-146 °C. Recrystallization of a portion of this material
from Et2O/PE gave the analytical sample: mp 145.5-147 °C;
IR (KBr) 1660 (s), 1501 (s), 1460 (m), 1445 (m), 1290 (m), 1280
4-Meth oxy-4-(2-p r op en yl)-2,5-cycloh exa d ien on e (11).
To a slurry of NaH (0.272 g, 11.3 mmol) in THF (50 mL) was
added (2.00 g, 10.3 mmol) of the above alcohol dissolved in
THF (30 mL). The reaction mixture was heated at reflux for
1 h and then cooled to rt. Methyl iodide (1.93 mL) was added,
and the system was stirred for an additional 1 h after which
time TLC (50% Et2O/PE) indicated that no starting material
remained. The reaction was quenched by addition of H2O (25
mL), and extractive workup with Et2O (3 × 40 mL) gave 2.50
g of the ether which was carried on crude to the next step.
To the crude product dissolved in THF (50 mL) was added
5% HCl (15 mL), and the reaction mixture was stirred for 24
h at rt. The reaction was quenched by addition of saturated
NaHCO3 (15 mL), and extractive workup with Et2O (3 × 30
mL) gave a yellow solid which was recrystallized form cold
hexane to afford white crystals of 11 (0.696 g, 41% yield): mp
47-48 °C; IR (KBr) 3270 (m), 2995 (m), 2945 (m), 1675 (s),
1637 (m), 1604 (s), 1454 (m), 1390 (m), 1085 (s), 912 (m), 855
1
(m), 1219 (m), 1065 (m), 850 (m) cm-1; H NMR (80 MHz) δ
7.15-6.13 (highly str m, 4 H), 6.83 (s, 1 H), 6.37 (s, 1 H), 3.90
(s, 3 H), 3.78 (s, 3 H), 3.18 (s, 3 H), 2.42 (AB q, ∆ν ) 28 Hz, J
) 14 Hz, 2 H), 1.64 (s, 3 H); HRMS calcd for C18H20O4 m/ z
300.1361, obsd 300.1344. Anal. Calcd for C18H20O4: C, 71.98;
H, 6.66. Found: C, 71.89; H, 6.76.
Gen er a l P r oced u r e for Iod oben zen e Dia ceta te Oxid a -
tion . A general procedure for iodobenzene diacetate oxidation
can be described as follows. To a solution of the 4-(2′-
alkenylphenyl)phenol (0.5 mmol) in CH3OH (40 mL) at 0 °C
were added iodobenzene diacetate (209 mg, 0.65 mmol) and
NaOAc (100 mg, 2.4 equiv). The resulting suspension was
stirred for 5-10 min, poured into H2O (30 mL), and concen-
trated in vacuo. The residue was extracted with EtOAc (3 ×
20 mL), and the combined organic layer was washed with brine
(50 mL) and dried through CaSO4. The crude product was
purified via silica gel chromatography (0.2 × 12 in., 3-15%
EtOAc/PE as eluants) to afford the pure products. The spectral
data for the products not reported in the anodic oxidations
section are given in the supporting information.
4-(2-Acetylp h en yl)p h en ol. To a solution of 3′-methoxy-
3′-methyl-3′H-spirocyclohexa-2,5-diene-1-isobenzofuran-4-
one17a (0.5 g, 2.0 mmol) in THF (2.5 mL) was added zinc-copper
couple (0.24 g), and the resulting mixture was heated at reflux
for 30 min and then cooled to rt. After addition of cold 5%
HCl (25 mL) extractive workup with Et2O (2 × 25 mL)) gave
a light yellow oil which crystallized to give 4-(2-acetylphenyl)-
phenol (0.41 g, 96%, mp 115-118 °C). Recrystallization from
Et2O/PE gave analytically pure material: mp 118-119 °C; IR
(KBr) 1685 cm-1; 1H NMR (200 MHz) δ 7.6-7.45 (str m, 2 H),
7.45-7.3 (str m, 2 H), 7.04 (AB q, ∆ν ) 62 Hz, J ) 9 Hz, 4 H),
2.08 (s, 3 H), OH absorption not detected; HRMS calcd for
C14H12O2 m/ z 212.0837, obsd 212.0819.
1
(s) cm-1; H NMR δ 6.69 (d, J ) 10.4 Hz, 2 H), 6.38 (d, J )
10.4 Hz, 2 H), 5.36 (s, 1 H), 5.08 (s, 1 H), 3.30 (s, 3 H), 1.69 (br
s, 3 H); HRMS calcd for C10H12O2 m/ z 164.0837, obsd 164.0860.
4-Met h oxy-4-(2-p r op en yl)-5-(p -(ter t-b u t yld im et h ylsi-
loxy)p h en yl)-2-cycloh exen on e (14). Trimethylaluminum
(10 mL, 2.0 M) was added slowly, accompanied by evolution
of a large volume of methane gas, to a solution of BHT (8.8 g,
40 mmol) and CH2Cl2 (115 mL). After methane gas evolution
ceased, the MAD solution was cooled to -78 °C, and (0.690 g,
4.2 mmol) of 11 dissolved in CH2Cl2 (5 mL) was added,
resulting in a dark red/brown complex solution. After 15 min,
(4-(tert-butyldimethylsiloxy)phenyl)magnesium bromide (10.5
mL, 1.2 M in CH2Cl2) was added to the MAD complex solution,
resulting in a lightening of the intensely colored solution. The
reaction mixture was stirred for 0.5 h, the reaction was
quenched by addition of CH3OH (5 mL) and H2O (15 mL), and
then the reaction mixture was allowed to warm to rt. The
resultant slurry of aluminum and magnesium salts was
filtered through Celite. After concentration of the filtrate in
vacuo, extractive workup with CH2Cl2 (3 × 30 mL) and
chromatography of the residue on silica gel [6 in. × 0.5 in.
column, 100% PE (150 mL); 5% Et2O/PE (100 mL); 10% Et2O/
PE (100 mL); 15% Et2O/PE (100 mL) as eluant] gave two
fractions as slightly yellow oils: 0.469 g of pure product and
0.977 g with a slight impurity. The 0.977 g fraction was
rechromatographed on silica gel (3 in. × 0.5 in. column, 5%
Et2O/PE) as eluant) to give pure 14 (0.857 g), overall yield
(84%), mp 73-74 °C: IR (KBr) 2956 (s), 2930 (s), 2892 (m),
2860 (m), 1691 (s), 1609 (m), 1514 (s), 1472 (m), 1465 (m), 1390
(m), 1258 (s), 1172 (m), 1093 (s), 1062 (m), 909 (s), 848 (s),
4-[2-(1-(P h en ylth io)vin yl)p h en yl]p h en ol (25). To a 0°
solution of the 4-(2-acetylphenyl)phenol (1.07 g, 5.05 mmol)
under Ar in THF (90 mL) was added TiCl4 (10.1 mmol, as a 1
M solution in CH2Cl2) dropwise with rapid stirring.22 The
resulting red solution was allowed to warm to rt followed by
dropwise addition of a THF solution (20 mL) of thiophenol
(0.725 mL, 7.07 mmol) and triethylamine (2.11 mL, 15.2
mmol). The reaction mixture was stirred for 15 min followed
by addition of 5% HCl (30 mL). Extractive workup with Et2O
(2 × 20 mL) gave a yellow oil which was purified by silica gel
chromatography [2 × 20 cm column, PE (200 mL), 8% EtOAc/
PE (500 mL) as eluants] to give the vinyl sulfide 25 as a clear
colorless oil (1.21 g, 79%): IR (neat) 3396 (br), 1516, 1476,
1
840 (s), 823 (m), 799 (m), 779 (s) cm-1; H NMR (80 MHz) δ
7.07 (d, J ) 8 Hz, 2H), 7.02 (d, J ) 10.2 Hz, 1 H), 6.72 (d, J )
8 Hz, 2 H), 6.24 (d, J ) 10.2 Hz, 1 H), 5.00 (d, J ) 1 Hz, 1 H),
4.73 (s, 1 H), 3.21 (3 line m, 5 H), 2.50 (m, 1 H), 1.42 (s, 3 H),
0.97 (s, 9 H), 0.18 (s, 6 H); HRMS calcd for C22H32O3Si m/ z
372.2122, obsd 372.2124.
4-[5-Meth oxy-2-(2-p r op en yl)p h en yl]p h en ol (9c). The
above ketone (600 mg, 1.63 mmol), CH3OH (120 mL), trimethyl
orthoformate (30 mL), and p-TsOH (60 mg) were heated at
reflux for 12 h, after which time no starting ketone remained.
The reaction was quenched by addition of NaHCO3 (30 mL),
and the CH3OH was removed in vacuo. Extractive workup
with Et2O (3 × 60 mL) gave an oil. This residue was then
dissolved in CH3OH (10 mL) and added to a solution formed
from Na (35 mg) and CH3OH (95 mL). The reaction mixture
was heated at reflux for 1.25 h, and then the reaction was
quenched by adding saturated NH4Cl (30 mL). Extractive
1
1256, 748 cm-1; H NMR (C6D6) δ 7.5-7.4 (m, 1 H), 7.4-7.25
(m, 2 H), 7.38 (d, J ) 4 Hz, overlapping with m at ca. 7.3, 2
H), 7.25-7.18 (m, 1 H), 7.10-7.0 (m, 2 H), 6.85-6.45 (m, 3
H), 6.63 (d, J ) 7 Hz, 2 H), 5.11 (s, 1 H), 4.48 (s, 1 H), 4.39 (s,
1 H); HRMS calcd for C20H16OS m/ z 304.0922, obsd 304.0924.
An od ic Oxid a tion of 25. A 0 °C solution of the vinyl
sulfide 25 (0.2 g, 0.65 mmol) in CH3CN/HOAc/CH3O (8:1:1)
(22) Mukaiyama, T.; Saigo, K. Tetrahedron Lett. 1973, 479.