Anodic oxidation of monohalogenated phenols

Article abstract of DOI:10.1016/S0040-4020(01)00478-1

Anodic oxidation of simple o-halogenated phenol derivatives has been investigated. Among the oxidation products, tricyclic ketone 9 was obtained, along with both the corresponding diaryl ethers 3 and 4 and the diaryls 5-8. Additionally, the effect of the

Full text of DOI:10.1016/S0040-4020(01)00478-1

TETRAHEDRON
Pergamon
Tetrahedron 57 42001) 5527±5532
Anodic oxidation of monohalogenated phenols
Kazuki Mori, Masakatsu Takahashi, Shosuke Yamamura and Shigeru Nishiyamap
Department of Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi 3-14-1, Kohoku-ku, Yokohama 223-8522, Japan
Received 30 March 2001; accepted 1 May 2001
AbstractÐAnodic oxidation of simple o-halogenated phenol derivatives has been investigated. Among the oxidation products, tricyclic
ketone 9 was obtained, along with both the corresponding diaryl ethers 3 and 4 and the diaryls 5±8. Additionally, the effect of the alkyl
substituent on the oxidation mode was inspected: anodic oxidation of phenols carrying n-propyl or 3-hydroxylpropyl groups 10b and 10c
mainly provided the dienone compounds 11 and 15 through two-electron oxidation. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Upon comparison of the yields of the oxidation products,
entries using the bromo substituents 1b provided better
results than those of chloro and iodo derivatives 1a and
1c. Accordingly, the phenolic oxidation was extensively
inspected by using the bromo derivative 1b. As can be
seen in Table 1, all oxidation entries provided both the
diaryl ethers 3 and 4 and the diaryls 5±8. The reaction
looked to be independent of the kind of halogen atoms
in the present series, entirely different from the case of
dihalogenated derivatives.3 Additionally, the tricyclic
derivative 4Pummerer's ketone, 9) was obtained in the
monosubstituted halogen series.
Diverse biological activities of such isodityrosine-class
natural products as vancomycin, K-13 and OF-4949s
might be expressed by peptide chain-backbones rigidly
supported by the diaryl ether and diaryl moieties of the
molecules. In our extensive synthetic investigation of
these natural products, we have developed phenolic oxi-
dation methodology by employing anodic and thallium
4III) oxidations of o,o0-dihalogenated phenols.1,2 In addition
to an effect of lowering oxidation potentials, the halogen-
substituents were observed to control the reaction pathway
4Scheme 1): anodic oxidation of dibromo- and dichloro-
phenols speci®cally provide the corresponding diaryl ethers
4A), whereas diaryl derivatives 4B) are produced from
diiodo-phenols.3 In contrast to the synthetic availability of
dihalogenated phenol derivatives, no signi®cant information
on monohalogenated derivatives has been reported, to our
knowledge, with the exception of phenolic oxidation of
bastadins.4
To obtain further information on product distribution, the
effect of the alkyl chain at the p-position of bromophenol
derivatives was examined in the next stage. Thus, the
derivatives 10a±10c were submitted to the same anodic
oxidation conditions 4Fig. 2), and the results are summar-
ized in Table 2. In contrast to the case of the ethyl derivative
10a providing similar products distribution to that of 1b, an
obvious difference was observed in the propyl derivative
10b: the dienone compound 11, produced by the two-
electron oxidation, was obtained in a comparable yield to
This paper describes anodic oxidation of monohalogenated
phenol derivatives to understand the scope and limitation of
the oxidation reaction, as well as to probe the synthetic
availability of the oxidation products as building blocks
towards complicated naturally occurring molecules.
2. Results and discussion
To investigate the detailed pro®le of the oxidation of mono-
halogenated phenols, compounds 1a±1c5 were submitted to
anodic oxidation in the presence of LiClO4 as an electrolyte
in MeOH or CH3CN 4Table 1, Fig. 1).
Keywords: diaryl ethers; diaryls; electrochemical reaction; phenolic
oxidation.
p
Corresponding author. Tel./fax: 181-45-566-1717;
e-mail: nisiyama@chem.keio.ac.jp
Scheme 1.
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020401)00478-1

5528
K. Mori et al. / Tetrahedron 57 ,2001) 5527±5532
Table 1. Anodic oxidation of the halogenated cresols 41a, 1b, and 1c)
Entry
Educts
Conditions,a solvent
Products 4%)b
Diaryl ethers
Diaryls
2
3
4
5
6
7
8
9
1
2
3
4
5
6
7
1a 4XˆCl)
1b 4XˆBr)
a, MeOH
a, MeOH
ac, MeOH
n, MeOH
n, CH3CN
b, MeOH
a, MeOH
±
±
±
±
±
±
4
±
±
2
7
1
4
±
±
6
1
29
15
±
10
19
9
6
±
1
2
±
±
±
±
±
±
±
±
±
±
±
6
7
20
10
9
±
3
1
3
7
±
±
±
±
±
±
1c 4XˆI)
2
±
a
Substrate-concentration, 10 mM. a: acidic conditions. n: neutral conditions. b: basic conditions.
Conversion yields.
Substrate-concentration, 58 mM.
b
c
Figure 1. The oxidation products of the halogenated cresols 41a, 1b, and 1c).
that of 13. Additionally, upon using the 3-hydroxypropyl
derivative 10c, the spiro compound 15 was produced as a
main product, via intramolecular cycloadditions 4entries
3±6). Based on these ®ndings, it is deduced that intermolec-
ular couplings between the radical species electrochemi-
cally generated, might be hampered by steric hindrance of
the alkyl substituents at the p-position, and the following
oxidation gave rise to production of the dienone compounds.
can be depicted 4Scheme 2): abstraction of electron and
proton at the ®rst stage of the anodic oxidation provides
delocalization of the resultant radical, followed by inter-
molecular couplings at several positions on the phenol
4Path I). The reactive points are apparently the phenolic
oxygen and the o-position carrying no halogen substituent,
as well as the p-position. These radicals produced the same
diaryls as those obtained from iodo derivatives.3 Whereas
diaryl ether 3 4type A) and diaryl 5 4type B) undergo over-
oxidation to 4 and 12 4diaryl ether), and 6, 7, 8, and 13
4diaryl), the coupling between o- and p-positions 4type C)
effects the following Michael addition of a phenolic
hydroxyl group, yielding the tricyclic product 14.
With respect to these results, a plausible reaction process
Table 2. Anodic oxidation of the halogenated phenol derivatives 410a, 10b,
and 10c)
Entry
Educts
Conditions,a solvent
Products 4%)b
11 12 13 14 15
1
2
3
4
5
6
10a 4RˆEt)
a, 10 mM/MeOH
n, 10 mM/MeOH
±
13
5
±
±
16
3
6
±
±
±
±
15 12
±
±
16
38
56
76
10b 4RˆnPr)
12
±
±
±
±
±
±
10c 4RˆHOC3H5) n, 10 mM/MeOH
n, 1 mM/CH3CN
n, 1 mM/CH3CN
a, 1 mM/MeOH
±
±
±
a
Substrate concentration/solvent. a: acidic conditions. n: neutral con-
ditions.
Conversion yields.
Figure 2. The oxidation products of the halogenated phenol derivatives
410a, 10b, and 10c).
b

K. Mori et al. / Tetrahedron 57 ,2001) 5527±5532
5529
Scheme 2.
In contrast to substrates carrying methyl and ethyl groups 1b
and 10a leading to dimerization, the steric hindrance of
propyl or 3-hydroxypropyl substituents seems to restrain
the intermolecular radical coupling reactions 4Path II).
Since the radical species generated by the one-electron
oxidation possessed poor possibilities for intermolecular
reactions, they suffered the further abstraction of an elec-
tron. Attack of a nucleophile 4MeOH or the hydroxyl group
in the side chain) to the cation stabilized provides the
dienone compounds 11 and 15 as two-electron oxidation
products.
internal standard. High-resolution mass spectra were
obtained on a Hitachi M-80 B GC-MS spectrometer operat-
ing at the ionization energy of 70 eV. Preparative and ana-
lytical TLC were carried out on silica gel plates 4Kieselgel
60 F254, E. Merck AG., Germany) using UV light and/or 5%
molybdophosphoric acid in ethanol for detection. Katayama
silica gel 4K 070) was used for column chromatography.
3.1. General procedure for anodic oxidation of o-halo-
genated cresol
A solution of a phenol derivative 40.25 mmol) in a solvent
4MeOH 422.5 ml)± 60% HClO4 42.5 ml) for acidic con-
ditions; MeOH 425 ml) for neutral conditions; 0.05 M
NaOMe/MeOH for basic conditions) containing an electro-
lyte 4LiClO4) was electrolyzed 4C.C.E. at 0.13 mA/cm2:
1.4 F/mol), using a glassy carbon beaker as an anode and
a platinum wire as a cathode. The reaction mixture was
partitioned between an organic solvent and H2O. The
organic layer was dried over anhydrous Na2SO4, and
concentrated to give a crude product, which was puri®ed
by preparative TLC.
In conclusion, anodic oxidation of o-halogenated phenols
produced diaryl ethers, diaryls, and Pummerer's ketone or
dienone compounds. Whereas the oxidation mode seems to
be independent of the kind of halogen atoms, elongation of
the alkyl side chain at the p-position effected an increase of
steric hindrance leading to the corresponding two-electron
products such as 11 and 15. Since the 3-hydroxypropyl
derivative provided the corresponding spiro products 15 in
good yield, conversion into dihydrobenzopyrans will be
presented in the following paper,6 as an example of its
synthetic availability.
3.2. Anodic oxidation of 2-chloro-4-methylphenol *1a)
3. Experimental
Acidic condition: electrolysis of 1a 423 mg, 0.16 mmol)
[C.C.E.: 1914!1963 mV vs SCE] provided 4a 40.9 mg,
1.8%), 6a 44.9 mg, 9.7%), 7a 40.4 mg, 0.7%), 9a 43.3 mg,
7.3%) and recovered 1a 40.1 mg, 0.4%).
IR spectra were recorded on a JASCO Model A-202 spec-
trophotometer. 1H NMR and 13C NMR spectra were
obtained on a JEOL JNM EX-270, a JEOL JNM GX-400
or a JNM ALPHA-400 NMR spectrometers in a deuterio-
chloroform 4CDCl3) solution using tetramethylsilane as an
3.2.1. Compound 4a. IR 4®lm) 1692, 1653, and 1611 cm21
1H NMR: d 1.44 43H, s), 2.35 43H, s), 3.19 43H, s), 5.51 41H,
;

5530
K. Mori et al. / Tetrahedron 57 ,2001) 5527±5532
d, Jˆ2.8 Hz), 6.95 41H, d, Jˆ2.8 Hz), 6.98 41H, d, Jˆ
8.3 Hz), 7.09 41H, d, Jˆ8.2 Hz), and 7.27 41H, s). Found:
m/z 312.0287. Calcd for C15H1435Cl2O3: M, 312.0319.
41H, s). Found: m/z 399.9325. Calcd for C15H1479Br2O3: M,
399.9310.
3.3.3. Compound 5. IR 4®lm) 3409, 1720, 1572, and
1
1473 cm21; H NMR: d 2.31 46H, s), 5.79 42H, s), 7.01
3.2.2. Compound 6a. IR 4®lm) 1678, 1583, and 1480 cm21
;
1H NMR: d 1.55 43H, s), 2.28 43H, s), 3.32 43H, s), 5.71 41H,
s), 6.84 41H, d, Jˆ3.0 Hz), 6.85 41H, s), 7.01 41H, d, Jˆ
3.0 Hz), and 7.18 41H, s); 13C NMR: d 21.3, 25.2, 26.5, 29.8,
53.7, 120.3, 127.6, 129.7, 130.0, 142.7, 147.0, and 151.3.
Found: m/z 312.0281. Calcd for C15H1435Cl2O3: M,
312.0319.
42H, d, Jˆ1.8 Hz), and 7.35 42H, d, Jˆ1.8 Hz). Found:
m/z 371.9178. Calcd for C14H1279Br81BrO2: M, 371.9185.
3.3.4. Compound 6b. IR 4®lm) 3446, 1687, 1650, 1607, and
1487 cm21; 1H NMR: d 1.54 43H, s), 2.28 43H, s), 3.34 43H,
s), 5.70 41H, s), 6.84 41H, d, Jˆ2.8 Hz), 6.89 41H, s), 7.28
41H, d, Jˆ2.8 Hz), and 7.32 41H, s). Found: m/z 401.9292.
Calcd for C15H1479Br81BrO3: M, 401.9290.
3.2.3. Compound 7a. IR 4®lm) 1727, 1678, and 1463 cm21
;
1H NMR: d 1.56 43H, s), 3.32 43H, s), 3.38 43H, s), 4.37 42H,
s), 5.88 41H, s), 6.88 41H, d, Jˆ3.0 Hz), 7.02 41H, d, Jˆ
3.0 Hz), 7.05 41H, s), and 7.36 41H, s). Found: m/z
342.0450. Calcd for C16H1635Cl2O4: M, 342.0425.
3.3.5. Compound 7b. IR 4®lm) 3453, 1686, 1608, and
1
1487 cm21; H NMR: d 1.54 43H, s), 3.34 43H, s), 3.38
43H, s), 4.36 42H, s), 5.87 41H, s), 6.87 41H, d, Jˆ3.0 Hz),
7.07 41H, d, Jˆ2.2 Hz), 7.29 41H, d, Jˆ3.0 Hz), and 7.50
41H, d, Jˆ2.2 Hz). Found: m/z 429.9406. Calcd for
C16H1679Br2O4: M, 429.9415.
3.2.4. Compound 9a. IR 4®lm) 1702, 1610, and 1474 cm21
;
1H NMR: d 1.62 43H, s), 2.31 43H, s), 2.92 41H, dd, Jˆ3.8,
18 Hz), 3.35 41H, dd, Jˆ2.8, 18 Hz), 4.75 41H, complex),
6.60 41H, d, Jˆ2.0 Hz), 6.90 41H, s), and 7.04 41H, s).
Found: m/z 283.0301. Calcd for C14H1335Cl2O2: M1H,
283.0292.
3.3.6. Compound 9b. IR 4®lm) 1698, 1604, and 1470 cm21
;
1H NMR: d 1.57 43H, s), 2.31 43H, s), 2.93 41H, dd, Jˆ3.5,
17 Hz), 3.39 41H, dd, Jˆ2.8, 17 Hz), 4.77 41H, complex),
6.87 41H, d, Jˆ1.7 Hz), 6.93 41H, d, Jˆ0.7 Hz), and 6.93
41H, dd, Jˆ0.7, 1.7 Hz); 13C NMR: d 20.6, 21.4, 37.5, 49.3,
86.6, 103.3, 121.4, 122.2, 128.8, 132.3, 133.0, 133.3, 148.8,
and 186.5. Found: m/z 373.9176. Calcd for C14H1281Br2O2:
M, 373.9165.
3.3. Anodic oxidation of 2-bromo-4-methylphenol *1b)
4a) Acidic condition: electrolysis of 1b 446 mg, 0.25 mmol)
[C.C.E.: 1910!11056 mV vs SCE] provided 4b 46.1 mg,
6.1%), 6b 417 mg, 17%), 7b 41.7 mg, 1.6%), 9b 417 mg,
18%), and recovered 1b 45.0 mg, 11%).
3.4. Anodic oxidation of 2-iodo-4-methylphenol *1c)
Acidic condition: electrolysis of 1c 457 mg, 0.24 mmol)
[C.C.E.: 1906!11473 mV vs SCE] provided 2c 42.3 mg,
3.7%), 4c 42.5 mg, 2.1%), 8c 47.7 mg, 6.1%), and 9c
40.4 mg, 0.4%).
4b) Acidic condition: electrolysis of 1b 4270 mg, 1.5 mmol)
[C.C.E.: 1874!11008 mV vs SCE] provided 3b 42.7 mg,
0.5%), 4b 47.0 mg, 1.2%), 5 433 mg, 6.0%), 6b 451 mg,
8.6%), 9b 454 mg, 9.9%) and recovered 1b 43.6 mg, 1.3%).
3.4.1. Compound 2c. IR 4®lm) 1666 cm21; 1H NMR: d 1.45
43H, s), 3.24 43H, s), 6.44 41H, d, Jˆ10 Hz), 6.83 41H, dd,
Jˆ2.7, 10 Hz), and 7.56 41H, d, Jˆ2.7 Hz); 13C NMR: d
25.9, 53.8, 75.9, 105.1, 127.2, 151.9, 160.5, and 188.2.
Found: m/z 263.9619. Calcd for C8H9IO2: M, 263.9647.
4c) Neutral condition: electrolysis of 1b 450 mg, 0.27 mmol)
[C.C.E.: 1897!11046 mV vs SCE] provided 3b 42.8 mg,
2.8%), 4b 44.1 mg, 3.8%), 5 40.8 mg, 0.8%), 6b 46.1 mg,
5.6%), 9b 48.5 mg, 8.5%) and recovered 1b 41.9 mg, 3.8%).
4d) Neutral condition in CH3CN: electrolysis of 1b 447 mg,
0.25 mmol) [C.C.E.: 11077!11226 mV vs SCE] pro-
vided 3b 45.4 mg, 5.8%), 5 423 mg, 25%), and recovered
1b 47.0 mg, 15%).
3.4.2. Compound 4c. IR 4®lm) 1682, 1645, 1596, and
1
1480 cm21; H NMR: d 1.43 43H, s), 2.33 43H, s), 3.23
43H, s), 5.54 41H, d, Jˆ2.6 Hz), 6.89 41H, d, Jˆ8.3 Hz),
7.15 41H, dd, Jˆ1.7, 8.3 Hz), 7.53 41H, d, Jˆ2.6 Hz), and
7.68 41H, d, Jˆ1.7 Hz). Found: m/z 495.9009. Calcd for
C15H14I2O3: M, 495.9034.
4e) Basic condition: electrolysis of 1b 455 mg, 0.30 mmol)
[C.C.E.: 1298!11321 mV vs SCE] provided 5 417 mg,
15%), and 9b 43.7 mg, 3.3%).
3.4.3. Compound 8c. IR 4®lm) 1659, 1591, and 1456 cm21
;
1H NMR: d 1.49 43H, s), 1.51 43H, s), 3.32 43H, s), 3.36 43H,
s), 6.84 42H, d, Jˆ2.8 Hz), and 7.58 42H, d, Jˆ2.8 Hz).
Found: m/z 525.9123. Calcd for C16H16I2O4: M, 525.9139.
3.3.1. Compound 3b. IR 4®lm) 3507, 1724, 1584, and
1
1487 cm21; H NMR: d 2.19 43H, s), 2.27 43H, s), 5.79
41H, s), 6.46 41H, d, Jˆ1.7 Hz), 6.89 41H, d, Jˆ8.3 Hz),
7.06±7.11 42H, complex), and 7.46 41H, d, Jˆ1.7 Hz).
Found: m/z 369.9234. Calcd for C14H1279Br2O2: M,
369.9204.
1
3.4.4. Compound 9c. IR 4®lm) 1689 and 1466 cm21; H
NMR: d 1.58 43H, s), 2.30 43H, s), 2.29 41H, dd, Jˆ3.6,
17 Hz), 3.43 41H, dd, Jˆ3.0, 17 Hz), 4.79 41H, complex),
6.95 41H, d, Jˆ1.7 Hz), 7.19 41H, d, Jˆ1.7 Hz), and 7.40
41H, d, Jˆ1.7 Hz); 13C NMR: d 20.8, 21.5, 37.9, 48.0, 86.6,
121.4, 129.4, 129.7, 130.1, 130.5, 132.7, 132.9, 144.4, and
186.5. Found: m/z 465.8915. Calcd for C14H12I2O2: M,
465.8928.
3.3.2. Compound 4b. IR 4®lm) 1688, 1649, 1608, and
1
1487 cm21; H NMR: d 1.43 43H, s), 2.35 43H, s), 3.21
43H, s), 5.51 41H, d, Jˆ2.6 Hz), 6.96 41H, d, Jˆ8.1 Hz),
7.13 41H, d, Jˆ8.1 Hz), 7.21 41H, d, Jˆ2.6 Hz), and 7.45

K. Mori et al. / Tetrahedron 57 ,2001) 5527±5532
5531
3.5. Anodic oxidation of 2-bromo-4-ethylphenol *10a)
Jˆ2.0 Hz), 7.26 41H, d, Jˆ2.9 Hz), and 7.31 41H, d, Jˆ
2.0 Hz). Found: m/z 455.9942. Calcd for C19H2279Br2O3:
M, 455.9936.
Acidic condition: electrolysis of 10a 451 mg, 0.25 mmol)
[C.C.E.: 10.91!10.97 V vs SCE] provided 12a 41.3 mg,
2.4%), 13a 47.7 mg, 14%), 14a 45.5 mg, 11%), and
recovered 10a 43.7 mg, 7.3%).
3.7. Anodic oxidation of 2-bromo-4-*1-hydroxypropyl)-
phenol *10c)
4a) Neutral condition: electrolysis of 10c 498 mg, 0.42
mmol) in MeOH 430 ml) containing an electrolyte 40.25 g,
LiClO4) [C.C.E.: 11.95!11.30 V vs SCE] provided 11c
46 mg, 5%) and 15 415 mg, 16%).
3.5.1. Compound 12a. IR 4®lm) 1688, 1648, 1607, 1488,
1
1243, and 1096 cm21; H NMR: d 0.84 43H, t, Jˆ7.6 Hz),
1.26 43H, t, Jˆ7.6 Hz), 1.73±1.78 42H, complex), 2.65 42H,
q, Jˆ7.6 Hz), 3.23 43H, s), 5.44 41H, d, Jˆ2.6 Hz), 6.97
41H, d, Jˆ8.3 Hz), 7.15 41H, dd, Jˆ2.0, 8.3 Hz), 7.16
41H, d, Jˆ2.6 Hz), and 7.47 41H, d, Jˆ2.0 Hz). Found:
m/z 427.9604. Calcd for C19H2279Br2O3: M, 427.9623.
4b) Neutral condition in CH3CN: electrolysis of 10c 459 mg,
0.26 mmol) in CH3CN 425 ml) containing an electrolyte
40.25 g, LiClO4) [C.C.E.: 11.16!11.34 V vs SCE] pro-
vided 15 46.0 mg, 10%), and recovered 10c 443 mg, 73%).
3.5.2. Compound 13a. IR 4®lm) 3502, 1675, 1607, 1472,
1
and 1086 cm21; H NMR: d 0.94 43H, t, Jˆ7.6 Hz), 1.21
43H, t, Jˆ7.6 Hz), 1.88 42H, q, Jˆ7.6 Hz), 2.58 42H, q, Jˆ
7.6 Hz), 5.70 41H, s), 6.81 41H, d, Jˆ2.8 Hz), 6.90 41H, d,
Jˆ2.0 Hz), 7.24 41H, d, Jˆ2.8 Hz), and 7.33 41H, d, Jˆ
2.0 Hz). Found: m/z 427.9630. Calcd for C19H2279Br2O3:
M, 427.9623.
4c) Diluted neutral condition: electrolysis of 10c 49.3 mg,
0.04 mmol) in MeOH 430 ml) containing an electrolyte
40.25 g, LiClO4) [C.C.E.: 11.08!11.35 V vs SCE] pro-
vided 15 45.1 mg, 56%).
4d) Diluted acidic condition: electrolysis of 10c 49.9 mg,
0.043 mmol) in MeOH 427 ml) and aq. 60% HClO4 43 ml)
containing an electrolyte 40.25 g, LiClO4) [C.C.E.:
11.08!11.50 V vs SCE] provided 11c 41.4 mg, 12%),
15 45.7 mg, 58%), and recovered 10c 42.3 mg, 23%).
3.5.3. Compound 14a. IR 4®lm) 1697, 1604, 1469, and
1
1080 cm21; H NMR: d 1.05 43H, t, Jˆ7.6 Hz), 1.22 43H,
t, Jˆ7.6 Hz), 2.01 42H, q, Jˆ7.6 Hz), 2.60 42H, q, Jˆ
7.6 Hz), 2.90 41H, dd, Jˆ4.0, 18 Hz), 3.39 41H, dd, Jˆ
2.8, 18 Hz), 4.91 41H, m), 6.87 41H, d, Jˆ1.7 Hz), 6.91
41H, d, Jˆ1.7 Hz), and 7.21 41H, d, Jˆ1.7 Hz). Found:
m/z 401.9485. Calcd for C16H1681Br2O2: M, 401.9478.
3.7.1. Compound 11c. IR 4®lm) 3433, 1673, 1601, and
1
1455 cm21; H NMR: d 1.56±1.61 42H, multiplex), 1.84±
1.89 42H, multiplex), 3.26 43H, s), 3.66 42H, t, Jˆ6.3 Hz),
6.49 41H, d, Jˆ10 Hz), 6.81 41H, dd, Jˆ2.9, 10 Hz), and
7.23 41H, d, Jˆ2.9 Hz). Found: m/z 260.0039. Calcd for
C10H1379BrO3: M, 260.0048.
3.6. Anodic oxidation of 2-bromo-4-propylphenol *10b)
4a) Neutral condition: electrolysis of 10b 456 mg, 0.26
mmol) [C.C.E.: 10.93!11.15 V vs SCE] provided 11b
47.1 mg, 11%), 12b 42.0 mg, 3.3%), and 13b 45.4 mg,
9.1%).
3.7.2. Compound 15. IR 4®lm) 2875, 1672, 1636, and
1
1600 cm21; H NMR: d 2.10±2.22 44H, complex), 4.10
42H, t, Jˆ6.6 Hz), 6.27 41H, d, Jˆ10 Hz), 6.84 41H, dd,
Jˆ2.4, 10 Hz) and 7.26 41H, d, Jˆ2.4 Hz); 13C NMR: d
26.8, 36.8, 69.5, 79.9, 123.1, 125.7, 149.8, and 178.1.
Found: m/z 227.9802. Calcd for C9H979BrO2: M, 227.9786.
4b) Neutral condition: electrolysis of 10b 430 mg, 0.14
mmol) [C.C.E.: 11.02!11.21 V vs SCE] provided 11b
44.3 mg, 13%), 12b 42.0 mg, 6.2%), and 13b 43.8 mg, 12%).
3.6.1. Compound 11b. IR 4®lm) 1674, 1601, 1459, and
Acknowledgements
1
1084 cm21; H NMR: d 0.89 43H, t, Jˆ7.3 Hz) 1.22±1.30
42H, complex), 1.68±1.73 42H, complex), 3.22 43H, s), 6.45
41H, d, Jˆ10 Hz), 6.75 41H, dd, Jˆ2.5, 10 Hz), and 7.18
41H, d, Jˆ2.5 Hz). Found: m/z 244.0054. Calcd for
C10H1379BrO2: M, 244.0099.
The authors are ®nancially supported by a Grant-in-Aid for
Scienti®c Research 4C) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan 4No
10680574), as well as Keio Gijyuku Academic Develop-
ment Funds.
3.6.2. Compound 12b. IR 4®lm) 1689, 1648, 1607, 1487,
1
and 1240 cm21; H NMR: d 0.88 43H, t, Jˆ7.3 Hz), 0.96
References
43H, t, Jˆ7.3 Hz), 1.22±1.28 42H, complex), 1.61±1.71
44H, complex), 2.57 42H, t, Jˆ7.8 Hz), 3.22 43H, s), 5.46
41H, d, Jˆ2.7 Hz), 6.96 41H, d, Jˆ8.3 Hz), 7.13 41H, dd,
Jˆ2.0, 8.3 Hz), 7.19 41H, d, Jˆ2.7 Hz), and 7.44 41H, d,
Jˆ2.0 Hz). Found: m/z 455.9934. Calcd for C19H2279Br2O3:
M, 455.9936.
1. 4a) Yamamura, S.; Nishiyama, S. In Biomimetic Synthesis of
Macrocyclic Oligopeptides Having Isodityrosine and Related
Units; Atta-ur-Rahman, Ed.; Studies in Natural Products
Chemistry 10F, Elsevier: Amsterdam, 1992; pp 629±669.
4b) Yamamura, S.; Nishiyama, S. J. Syn. Org. Chem., Jpn
1997, 55, 1029±1039.
3.6.3. Compound 13b. IR 4®lm) 3503, 1674, and
1
1471 cm21; H NMR: d 0.93 43H, t, Jˆ7.3 Hz), 0.94 43H,
2. Related phenolic oxidations. For example: 4a) Fukuhara, T.;
Sawaguchi, M.; Yoneda, N. Electrochem. Commun. 2000, 2,
259±261. 4b) Eickhoff, H.; Jung, G.; Rieker, A. Tetrahedron
2001, 57, 353±364.
t, Jˆ7.3 Hz), 1.36±1.39 42H, complex), 1.61 42H, dt, Jˆ7.3,
7.8 Hz), 1.81 42H, t, Jˆ8.3 Hz), 2.50 42H, t, Jˆ7.8 Hz), 3.34
43H, s), 5.72 41H, s), 6.82 41H, d, Jˆ2.9 Hz), 6.87 41H, d,

5532
K. Mori et al. / Tetrahedron 57 ,2001) 5527±5532
3. Takahashi, M.; Konishi, H.; Iida, S.; Nakamura, K.; Yamamura,
S.; Nishiyama, S. Tetrahedron 1999, 55, 5295±5302.
4. Nishiyama, S.; Yamamura, S. Tetrahedron Lett. 1982, 23,
1281±1284.
synthesized from p-cresol under the following conditions: Cl2/
AcOH for 1a; Br2/THF for 1b; NIS/acetone for 1c.
6. Mori, K.; Yamamura, S.; Nishiyama, S. Tetrahedron, 2001, 57,
5533±5542.
5. Despite being commercially available, these compounds were