Efficient oxidative biaryl coupling reaction of phenol ether derivatives using hypervalent iodine(III) reagents

Article abstract of DOI:10.1016/S0040-4020(00)00941-8

Oxidative biaryl coupling reaction of phenol ether derivatives with the hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA), in the presence of BF₃·Et₂O gave a variety of substituted biphenyl and binaphthyl compounds in high yields. Replacement of PIFA with a more practical polymer-supported hypervalent iodine reagent has also been achieved.

Full text of DOI:10.1016/S0040-4020(00)00941-8

TETRAHEDRON
Pergamon
Tetrahedron 57 (2001) 345±352
Ef®cient oxidative biaryl coupling reaction of phenol ether
derivatives using hypervalent iodine(III) reagents
*
Hirofumi Tohma, Hironori Morioka, Shinobu Takizawa, Mitsuhiro Arisawa and Yasuyuki Kita
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
Received 23 March 2000; revised 30 May 2000; accepted 10 July 2000
AbstractÐOxidative biaryl coupling reaction of phenol ether derivatives with the hypervalent iodine reagent, phenyliodine(III) bis(tri-
uoroacetate) (PIFA), in the presence of BF ´Et O gave a variety of substituted biphenyl and binaphthyl compounds in high yields.
Replacement of PIFA with a more practical polymer-supported hypervalent iodine reagent has also been achieved. q 2000 Elsevier Science
¯
3
2
Ltd. All rights reserved.
1
. Introduction
results obtained in the synthesis of highly functionalized
symmetrical or unsymmetrical biaryl compounds using
these reductive and oxidative methods have remained as
problems. Moreover, heavy metal oxidants are highly
toxic and must be handled very carefully. To solve these
problems, we planned to use hypervalent iodine(III) re-
agents.
The biaryl substructure is a central building block in a large
number of natural products, such as polyketides, terpenes,
lignanes, coumarins, ¯avonoids, tannins and many alka-
loids. Because of their interesting properties not only as
bioactive natural products but also as chiral ligands in asym-
1
2
metric reactions, natural and unnatural biaryls are con-
sidered attractive synthetic targets. The reported methods
for construction of these biaryl skeletons can be classi®ed
into two types: (1) the classical Ullmann reaction and other
reductive processes; and (2) the oxidative (biomimetic)
phenolic coupling reaction using a heavy metal oxidant.
Hypervalent iodine(III) reagents are now extensively used
1
1
in organic synthesis. In particular, phenyliodine(III)
diacetate (PIDA) and phenyliodine(III) bis(tri¯uoroacetate)
(PIFA) have received a great deal of attention due to low
toxicity, ready availability, easy handling, and reactivities
similar to that of heavy metal reagents or anodic oxidation.
Regarding the oxidation of phenol derivatives with PIDA or
PIFA, in most cases, the reaction proceeds via the inter-
mediate in which the phenolic oxygen reacts with the iodine
center of the hypervalent iodine reagent followed by the
The reductive processes include (1) the Ullmann coupling
reaction of aryl halides using copper bronze as a reducing
reagent, (2) Semmelhack's method using Ni(0) complexes
3
such as [Ni(cod) ] used in stoichiometric amounts to replace
2
4
copper, (3) a coupling reaction of aryl halides using a cata-
12
13
14
nucleophilic attack of 16 alcohol,
carboxylic acid, oxime, ¯uoride ion, water or elec-
a1lk7 ene,
amide,
1
5
18
lytic amount of low-valent nickel species which can be
regenerated either electrochemically or by coreductants
such as zinc or sodium hydride, (4) a reaction of aryl-
1
9
tron-rich aromatic ring to give the cross-conjugated cyclo-
hexadienone either by an inter- or intramolecular reaction
pathway (Eq. (1)).
5
Grignard or organozinc compounds with aryl halides (the
Kharash reaction') catalyzed by nickel or palladium
`
6
derivatives, (5) a palladium-catalyzed coupling reaction
of arylboronic acids (or aryl tin compounds) with aryl
halides (or tri¯ates), (6) the Meyers oxazoline method,
7
8
9
and (7) a cyanocuprate-mediated biaryl coupling reaction.
On the other hand, the biomimetic syntheses of aporphine
alkaloids, lignans and tannins were achieved using heavy
metal oxidants, such as thallium(III), vanadium(V), ruth-
1
0
enium(IV) and iron(III) salts. However, the unsatisfactory
Keywords: biaryls; hypervalent elements; phenolics; coupling reactions.
*
Corresponding author. Tel.: 181-6-6879-8225; fax: 181-6-6879-8229;
e-mail: kita@phs.osaka-u.ac.jp
ꢀ1†
0040±4020/01/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00941-8

3
46
H. Tohma et al. / Tetrahedron 57 (2001) 345±352
We have successfully applied this pathway to the total
syntheses of a variety of Amaryllidaceae alkaloid deriva-
2
tives (Eqs. (2) and (3)).
0
ꢀ4†
We have already found that the activated hypervalent iodine
reagents such as PIFA±BF ´Et O and PIFA±Me SiOTf are
effective for the intramolecular reactions on phenol ether
3
2
3
2
6
derivatives via SET (single electron transfer) process.
ꢀ2†
Although hypervalent iodine reagents have been used for
several phenolic coupling reactions of substrates possessing
free OH groups on the aromatic ring, biaryl coupling reac-
tion of non-phenolic type substrates has not been reported.
Thus, we developed a novel and ef®cient intramolecular
oxidative biaryl coupling reaction of 1,3-diarylpropanes,
N-benzyl-N-phenethylamines and N,N-dibenzylamines
leading to the dibenzoheterocyclic compounds using
PIFA±BF ´Et O. Similar methods gave high yields of
3
2
oxygen- and sulfur-containig dibenzoheterocyclic com-
pounds, which were easily cleaved by known methods to
give both symmetrical and unsymmetrical highly substi-
tuted biaryl compounds (Eq. 5).27
ꢀ3†
In contrast to the oxidation of phenol derivatives, reactions
of phenol ethers with hypervalent iodine reagents have been
limited and have yielded mostly iodonium salts. It is well-
2
1
known that iodonium salts are obtained by the reaction of
unsubstituted or meta-substituted phenol ethers with hyper-
valent iodine reagents. However, in the case of para-substi-
tuted phenol ethers with PIFA, no iodonium salts were
obtained. We found that the reaction of p-substituted phenol
ethers with some nucleophiles in the presence of PIFA in
polar and poorly nucleophilic solvents such as 2,2,2-tri-
ꢀ5†
¯
propanol ((CF ) CHOH) caused nucleophilic substitution
uoroethanol (CF CH OH) and 1,1,1,3,3,3-hexa¯uoro-2-
3 2
3
2
reactions. Thus, we explored a novel and straightforward
nucleophilic substitution reaction on p-substituted phenol
Furthermore, PIFA-induced oxidative phenolic coupling
was applied to the synthesis of chiral biaryls. That is, the
1,2-diaroyl derivatives of protected a-d-glucose under-
2
22,23
2 23
28
ethers with various nucleophiles (N ,
AcO , b-dicar-
and SCN225) using PIFA in
CF CH OH or (CF ) CHOH. This path involves an initial
3
2
3
2 24,25
bonyl compounds, ArS ,
went a smooth coupling reaction in the presence of PIFA±
BF ´Et O in a highly diastereoselective manner. The
coupling product was treated with LiAlH to yield the opti-
3
2
3 2
3
2
reaction of phenol ethers with the hypervalent iodine
reagent and generates a cation radical intermediate
4
cally active biphenyl compound (.99% ee) quantitatively
(Eq. 6).
1
ArH ] (Eq. 4).
z
23
29
[

H. Tohma et al. / Tetrahedron 57 (2001) 345±352
347
Table 1. Intermolecular biaryl coupling reaction using PIFA±BF
3
´Et
2
O
3
0
oxidation, and those using strong acids. However, these
methods still have drawbacks, such as (1) oxidants with high
toxicity, (2) low to moderate yields, (3) low generality, or
(
4) vigorous reaction conditions. Thus, we investigated the
use of PIFA±BF ´Et O for the oxidative intermolecular
3
2
biaryl coupling reaction.
2.1. Oxidative intermolecular biaryl coupling reaction
using PIFA±BF ´Et O
3
2
The intermolecular biaryl coupling reaction of 1,2,4-
trimethoxybenzene (1a) was examined by treatment with
PIFA±BF ´Et O in CH Cl at 2408C. The reaction
3
2
2
2
proceeded smoothly to give the hexa-methoxylated bi-
phenyl (2a) in 92% yield. Similarly, a variety of substituted
phenol ethers (1b,c,e±g) were converted to the correspond-
ing biaryls (2b,c,e±g) in excellent yields (Table 1).
However, no reaction proceeded when using 1d bearing a
ꢀ
6†
These intra- or intermolecular biaryl coupling reactions
were found to be effective for preparing highly substituted
biaryl compounds (hexa- to octa-substituted biaryls) though
they required a ®nal cleavage step (Eqs. (5) and (6)).
Although the PIFA-induced intermolecular biaryl coupling
reaction seems to be a direct route to multi-substituted (di-
to hexa-substituted) biaryls and binaphthyls from phenol
ethers and naphthol ethers, there is no report on the oxida-
tive intermolecular biaryl coupling reaction. In this paper,
we report our accomplishments on the intermolecular biaryl
coupling reaction that directly leads to substituted biaryls
and binaphthyls, which are useful precursors for a variety of
biologically active natural products. In addition, a more
practical preparation of biaryl compounds using a poly-
mer-supported (diacyloxyiodo)benzene is also described.
strong electron withdrawing NO group.
2
Binaphthyl compounds (2h±l) were also obtained in good
yields under these reaction conditions. Both the equivalency
of the reagents and the reaction temperature remarkably
affected the yields of biaryls. That is, in the oxidation of
1h, the best yield was obtained using 0.55 equiv. PIFA,
while the use of excess PIFA or higher reaction temperature
(.08C) gave oligomers or quinone derivatives as the by-
products due to overoxidation.
2.2. Facile and practical biaryl coupling reaction using
polymer-supported (diacyloxyiodo)benzene
Solid and polymer-supported reagents have applications in
combinatorial chemistry, and the use of such operationally
simple and environmentally benign reagents are becoming
more and more important in the pharmaceutical and
agrochemical industries. Several polymer-bound oxidants
2. Result and discussion
3
1
Compared to the abundant methods for biaryl coupling of
phenols, methods for oxidative intermolecular biaryl
coupling of phenol ether derivatives (non-phenolic
compounds) are limited to heavy metal oxidation, anodic
have been reported, and polymer-supported hypervalent
iodine reagents should be a welcome addition due to their
versatility, low toxicity, and high yields. Recently, Togo et
3
2
33
al. and Ley et al. demonstrated that polymer-supported

3
48
H. Tohma et al. / Tetrahedron 57 (2001) 345±352
Table 2. Biaryl coupling reaction using polymer-supported (diacyloxyiodo)benzene
3
diacetoxyiodo)benzene (PSDIB) shows similar reactivity
4
(
3. Conclusion
to (diacetoxyiodo)benzene and utilized it as a replacement
for previously reported iodine(III) reagents. We reported a
new and facile activation of PSDIB by the addition of KBr
and developed an environmentally benign oxidation of
alcohols in water. As an extention of our studies on the
practical utility of hypervalent iodine reagents, we
proceeded to investigate the use of polymer-supported
A facile and ef®cient preparation of biaryl compounds has
been developed by using the hypervalent iodine reagent,
PIFA, activated by BF ´Et O. This method was found to
3
2
3
5
be effective for the intermolecular biaryl coupling reaction
as well as for our previously reported intramolecular reac-
tion. Furthermore, we successfully improved this reaction to
a more practical and general method by utilizing the poly-
mer-supported hypervalent iodine reagent, PSBTI, under
mild reaction conditions. Hence, hypervalent iodine
reagents and their activated species show promise in
replacing highly toxic heavy metal oxidants and should
provide a useful tool for the syntheses of various bio-
logically active natural products containing a biaryl
structure.
(diacyloxyiodo)benzene in the presence of BF ´Et O for
3 2
the oxidative biaryl coupling reaction. First, we examined
the coupling reaction of 1a with PSDIB±BF ´Et O, and 2a
3
2
was obtained in 77% yield, while the reaction proceeded
slowly at 2408C due to the sparse solubility of PSDIB in
CH Cl . On the other hand, polymer-supported bis(tri-
2
2
¯
uoroacetoxyiodo)benzene (PSBTI), which is readily
prepared by heating PSDIB in CF CO H or oxidation of
3
2
polyiodostyrene with 30% H O ±(CF CO) O, showed
3
2
2
2
higher solubility in CH Cl than that of PSDIB and
2
2
demonstrated remarkable rate enhancement of the reaction.
Furthermore, the coupling reaction of naphthyl ether 1h also
proceeded smoothly to give 2h in 89% yield when using
PSBTI although the reaction of 1h with PSDIB gave a
complex mixture (entry 3, Table 2). In addition, the
overoxidation occurred in the reaction of 1n with PSDIB
to give 3 (86% yield) as the main product (entry 5, Table 2).
Table 2 shows that PSBTI is more effective for both inter-
and intramolecular biaryl coupling reactions than the use of
PSDIB.
4. Experimental
All melting points are uncorrected. Infrared (IR) absorption
spectra (cm ) were recorded as KBr pellets. H NMR (and
C NMR) spectra were recorded in CDCl
(67.8 MHz) and 300 MHz (75.3 MHz) spectrometers with
SiMe as an internal standard. E. Merck silica gel 60 for
2
1
1
1
3
at 270 MHz
3
4
column chromatography and E. Merck precoated TLC
plates, silica gel F254 for preparative thin-layer chroma-
tography were used. Organic layers were dried with anhy-
drous MgSO or Na SO . PIFA is commercially available.
4
2
4
The recovery and recycling of the resin (polyiodostyrene)
are easy. After quenching with saturated aqueous NaHCO3,
the resin was recovered nearly quantitatively by ®ltering
the resulting mixture. The recovered resin was easily
reoxidized to PSBTI via PSDIB by heating in CF CO H
BF ´Et O was obtained from commercial suppliers and was
3 2
used without further puri®cation. Compounds 1a±h, 1k, and
1l were purchased from Aldrich. Compounds 1j, 1m, and 1n
were prepared by known methods.2 Polymer-supported
(diacyloxyiodo)benzene, PSDIB and PSBTI, were prepared
7b
3
2
3
4
at 708C, followed by precipitation by Et O. Thus,
2
by literature's procedures.
PSBTI can be used repeatedly without loss of activity.
The reaction mechanism for the biaryl coupling reaction
with PSDIB or PSBTI in the presence of BF ´Et O possibly
4.1. General procedure for the intermolecular oxidative
biaryl coupling reaction of 1a±l using PIFA±BF ´Et O
3
2
3
2
involves a one-electron oxidation step similar to that of
PIFA.
To a stirred solution of 1a±l (0.2 mmol) in CH Cl (5.0 ml)
2
2

H. Tohma et al. / Tetrahedron 57 (2001) 345±352
349
1
126.6, 131.5, 133.4, 155.2. MS m/z 372 (M 12), 328, 139.
was added dropwise to a solution of PIFA (0.11 mmol) and
BF ´Et O (0.22 mmol) in CH Cl (5.0 ml) under nitrogen
Anal. Calcd for C H Br O : C, 45.20; H, 3.25; Br, 42.95.
14 12
3
2
2
2
2
2
atmosphere at 2408C. The reaction mixture was stirred at
408C for 1.5±3 h, then quenched with saturated aqueous
NaHCO and extracted with CH Cl . The organic layer was
washed with brine, dried, and evaporated. The residue was
puri®ed by column chromatography on silica gel (AcOEt±
n-hexane) to give 2a±l in yields shown in Table 1.
Found: C, 45.14; H, 3.30; Br, 42.61.
2
4.1.7. 2-Methoxy-1-(2-methoxynaphthyl)naphthalene (2h).
3
2
2
4
0
Colorless crystals, mp 199±2028C (hexane/toluene) (lit. mp
1
200±2048C (hexane/toluene)). IR (KBr) cm : 2838, 1507,
2
1
1246, 1069, 806. H NMR (300 MHz, CDCl
H), 7.03 (d, 2H, Jˆ7.9 Hz), 7.13 (t, 2H, Jˆ 7.9 Hz), 7.23
(t, 2H, Jˆ7.9 Hz), 7.38 (d, 2H, Jˆ8.9 Hz), 7.79 (d, 2H,
) d 3.69 (s,
3
6
4.1.1. 2,4,5-Trimethoxy-1-(2,4,5-trimethoxyphenyl)ben-
zene (2a). Colorless crystals, mp 2488C (decomp.) (hexane/
13
Jˆ7.9 Hz), 7.90 (d, 2H, Jˆ8.9 Hz). C NMR (75.3 MHz,
3
AcOEt) (lit. mp 2488C (decomp.)). IR (KBr) cm : 2928,
6
21
CDCl ) d 56.9, 114.2, 119.5, 123.5, 125.2, 126.3, 127.9,
3
1
507, 1464, 1032, 814. H NMR (300 MHz, CDCl ) d 3.69
1
129.2, 129.4, 134.0, 154.9. MS m/z 314 (M ), 269, 141.
1
3
(
s, 6H), 3.78 (s, 6H), 3.86 (s, 6H), 6.56 (s, 2H), 6.75 (s, 2H).
C NMR (67.8 MHz, CDCl ) d 56.1, 56.5, 56.9, 98.1,
1
3
4.1.8. 2,3-Dimethoxy-1-(2,3-dimethoxynaphthyl)naph-
thalene (2i). Colorless crystals, mp 153±1548C (hexane/
3
1
15.1, 118.7, 142.7, 148.6, 151.0. MS m/z 334 (M ), 288,
61, 167.
1
2
4
1
21
AcOEt) (lit. mp 152±1548C). IR (KBr) cm : 2938,
1
1
597, 1464, 1420, 1252, 1117, 1042, 864, 749. H NMR
(270 MHz, CDCl ) d 3.53 (s, 6H), 3.97 (s, 6H), 6.96±7.04
(m, 4H), 7.22±7.29 (m, 4H), 7.69 (d, 2H, Jˆ8.2 Hz).
NMR (67.8 MHz, CDCl ) d 55.6, 60.7, 107.1, 123.9, 125.0,
4.1.2. 2-Methyl-4,5-dimethoxy-1-(2-methyl-4,5-dimethoxy-
phenyl)benzene (2b). Colorless crystals, mp 1318C
3
1
3
37
C
2
hexane/AcOEt). IR (KBr) cm : 2851, 1674, 1651, 1609,
1
(
3
1
507, 1213, 910. H NMR (300 MHz, CDCl ) d 2.02 (s,
1
6
125.6, 125.8, 126.4, 128.8, 131.0, 147.1, 152.1. MS m/z 374
(M ), 328, 285, 107.
3
1
H), 3.84 (s, 6H), 3.92 (s, 6H), 6.65 (s, 2H), 6.77 (s, 2H).
C NMR (75.3 MHz, CDCl ) d 19.3, 55.8, 56.0, 112.7,
1
3
3
1
12.9, 128.2, 133.3, 146.5, 147.7. MS m/z 302 (M ), 257,
98, 158.
4.1.9. 6-Bromo-1-(6-bromo-2-methoxynaphthyl)-2-meth-
oxynaphthalene (2j). Colorless crystals, mp 243±2448C
1
1
2
hexane/AcOEt). IR (KBr) cm : 2938, 1586, 1495, 1266,
1
(
1
1
071, 905. H NMR (300 MHz, CDCl ) d 3.76 (s, 6H), 6.93
3
4.1.3. 2-Bromo-1-(2-bromo-4,5-dimethoxyphenyl)-4,5-
dimethoxybenzene (2c). Colorless crystals, mp 1608C
(
2
d, 2H, Jˆ8.9 Hz), 7.27 (dd, 2H, Jˆ8.9, 1.8 Hz), 7.46 (d,
3
8
H, Jˆ8.9 Hz), 7.88 (d, 2H, Jˆ8.9 Hz), 8.02 (d, 2H,
(
cm : 3002, 1603, 1505, 1173, 862. H NMR (300 MHz,
benzene). (lit. mp 157±1598C (benzene)). IR (KBr)
1 1
1
3
2
Jˆ1.8 Hz). C NMR (75.3 MHz, CDCl ) d 56.7, 114.9,
3
1
1
17.4, 119.0, 126.9, 128.7, 129.7, 129.9, 130.2, 132.4,
55.1. MS m/z 473 (M 13), 426, 361. Anal. Calcd for
CDCl ) d 3.79 (s, 6H), 3.85 (s, 6H), 6.69 (s, 2H), 7.04 (s,
3
1
1
3
2
1
2
3
H). C NMR (75.3 MHz, CDCl ) d 56.1£2, 113.8£2,
3
1
15.0, 133.9, 147.9, 149.0. MS m/z 432 (M 12), 257,
14. Anal. Calcd for C H Br O : C, 44.47; H, 3.73; Br,
4
C H Br O : C, 55.96; H, 3.42; Br, 33.85. Found: C,
22 16
5
2
2
5.80; H, 3.55; Br, 33.54.
1
6
16
2
6.98. Found: C, 44.57; H, 3.76; Br, 36.74.
4
.1.10. 4-Methoxy-1-(4-methoxynaphthyl)naphthalene
2k). Colorless crystals, mp 2658C (hexane/AcOEt) (lit.
3
0b
(
mp 264±2658C). IR (KBr) cm : 2959, 1590, 1266, 1086,
4.1.4. 4-Methyl-2,5-dimethoxy-1-(4-methyl-2,5-dimethoxy-
phenyl)benzene (2e). Colorless crystals, mp 1378C
2
1
1
64. H NMR (300 MHz, CDCl ) d 4.07 (s, 6H), 6.91 (d,
2
1
hexane/AcOEt). IR (KBr) cm : 2994, 1497, 1210, 1048,
7
6
7
2
(
3
1
H, Jˆ 7.9 Hz), 7.24±7.47 (m, 8H), 8.35 (d, 2H, Jˆ8.5 Hz).
77. H NMR (270 MHz, CDCl ) d 2.27 (s, 6H), 3.73 (s,
3
13
H), 3.79 (s, 6H), 6.77 (2H, s), 6.81 (s, 2H). C NMR
1
3
C NMR (75.3 MHz, CDCl ) d 55.6, 103.4, 122.0, 125.0,
3
1
(
25.5, 126.3, 126.4, 128.0, 130.7, 134.0, 155.0. MS m/z 314
M ), 268, 239, 119.
(
1
75.3 MHz, CDCl ) d 16.4, 56.0, 56.6, 113.8, 114.8,
3
1
1
25.5, 126.5, 150.6, 151.4. MS m/z 302 (M ), 273, 242,
151. Anal. Calcd for C H O : C, 71.50; H, 7.33. Found:
C, 71.30; H, 7.26.
1
8
22
4
4.1.11. 2,6-Dimethoxy-1-(2,6-dimethoxynaphthyl)naph-
thalene (2l). Colorless crystals, mp 2238C (hexane/
2
AcOEt). IR (KBr) cm : 2838, 1595, 1507, 1252, 1092,
1
4.1.5. 4-Bromo-1-(4-bromo-2,5-dimethoxyphenyl)-2,5-
dimethoxybenzene (2f). Colorless crystals, mp 1608C
1
9
11, 735. H NMR (270 MHz, CDCl ) d 3.65 (s, 6H),
3
3
9
21
3.81 (s, 6H), 6.82 (dd, 2H, Jˆ9.2, 2.6 Hz), 6.94 (d, 2H,
(
hexane/AcOEt) (lit. mp 159±1608C). IR (KBr) cm :
1
Jˆ9.2 Hz), 7.09 (d, 2H, Jˆ2.6 Hz), 7.34 (d, 2H,
2998, 1727, 1487, 1215, 1067, 762. H NMR (270 MHz,
CDCl ) d 3.67 (s, 6H), 3.79 (s, 6H), 6.74 (s, 2H), 7.10 (s,
1
3
Jˆ9.0 Hz), 7.77 (d, 2H, Jˆ9.0 Hz). C NMR (67.8 MHz,
3
1
H). C NMR (67.8 MHz, CDCl ) d 56.6, 56.9, 110.9,
3
CDCl ) d 55.3, 57.1, 105.7, 114.9, 119.1, 120.0, 126.8,
3
2
1
3
3
3
1
27.8, 129.3, 129.9, 153.3, 155.8. MS m/z 374 (M ), 328,
1
15.1, 116.7, 126.5, 149.7, 151.0. MS m/z 432 (M 12),
1
2
Found: C, 76.69; H, 5.97.
85, 164. Anal. Calcd for C H O : C, 76.99; H, 5.92.
24 22
38, 257, 209. Anal. Calcd for C H Br O : C, 44.47; H,
1
.73; Br, 36.98. Found: C, 44.56; H, 3.74; Br, 36.74.
4
6
16
2
4
4.1.6. 2-Bromo-4-(3-bromo-4-methoxyphenyl)-1-meth-
oxybenzene (2g). Colorless crystals, mp 1688C (hexane/
4.2. Iodination of polystyrene
2
AcOEt). IR (KBr) cm : 2840, 1601, 1482, 1250, 1059,
1
A mixture of polystyrene (5 g) (Mwˆ44,000, purchased
from Aldrich), iodine (5 g), diiodine pentaoxide (2 g),
carbon tetrachloride (10 ml), and 50% sulfuric acid
(10 ml) in nitrobenzene (30 ml) was stirred at 908C for
1
08. H NMR (270 MHz, CDCl ) d 3.86 (s, 6H), 6.87 (d,
8
2
3
H, Jˆ8.6 Hz), 7.35 (dd, 2H, Jˆ8.6, 2.3 Hz), 7.64 (d, 2H,
1
3
Jˆ2.3 Hz). C NMR (75.3 MHz, CDCl ) d 56.3, 112.1£2,
3

3
50
H. Tohma et al. / Tetrahedron 57 (2001) 345±352
1
50 h. The reaction mixture was precipitated by adding
C H F NO (M ) 441.1397, found 441.1397. Anal.
21 22 3 6
AcOEt (100 ml) and ®ltered. The residue was dissolved in
CH Cl (120 ml), precipitated again by the addition of
Calcd for C H F NO : C, 57.14; H, 5.02; N, 3.17.
21 22 3 6
Found: C, 57.18; H, 5.14; N, 3.14.
2
2
AcOEt, then ®ltered. The residue was washed with AcOEt
and methanol. The resulting solid was collected and dried in
vacuo to give poly iodostyrene (10.3 g). Elemental analysis
4.6.2. 2,3,9,10-Tetramethoxy-6,7-dihydro-5H-dibenzo[a,c]-
cycloheptene (2n). A colorless solid, mp 159±1608C
(hexane/AcOEt) (lit. mp 153±1558C). IR (KBr) cm :
1
2930, 1505, 1262, 1117, 752. H NMR (270 MHz, CDCl )
3
2
7b
21
(C, 43.87; H, 3.36; I, 51.65%) indicated that 87% of the
phenyl ring in polystyrene was iodinated.
d 2.20 (qui, 2H, Jˆ7.0 Hz), 2.44 (t, 4H, Jˆ7.0 Hz), 3.93 (s,
1
12H), 6.78 (s, 2H), 6.90 (s, 2H). C NMR (67.8 MHz,
3
4.3. Preparation of PSDIB
CDCl ) d 31.2, 34.0, 56.0, 56.2, 111.5, 111.8, 132.0,
3
1
(M )
Hydrogen peroxide (30%, 64.4 ml) was added dropwise to
an acetic anhydride solution (233.6 ml) at 08C. The solution
was slowly warmed to room temperature and stirred over-
night. To this solution, polystyrene (8.59 g) was added.
Then, the solution was kept stirring at 408C overnight.
132.8, 147.3, 147.7. HRMS (EI) Calcd for C19
314.1519, found 314.1519.
H
22
O
4
4.6.3. 9,10-Bis(methoxy)-6,7-dihydro-2H-dibenzo[a,c]cy-
cloheptene-2,3(5H)-dione (3). A red solid, mp 1208C
(hexane/AcOEt). IR (KBr) cm : 2936, 1657, 1510, 1279,
2
1
Et O was added and the mixture was ®ltered. The residue
2
was washed with Et O to give PSDIB (12.6 g). Elemental
2
1
1127, 1017, 855, 733. H NMR (270 MHz, CDCl ) d 1.90 (t,
3
analysis (C, 38.35; H, 3.57; I, 38.39%) indicated that 96% of
the iodophenyl ring in poly(4-iodostyrene) was converted to
a 4-(diacetoxyiodo)phenyl ring.
2H, Jˆ7.0 Hz), 2.32±2.37 (m, 2H), 2.67 (t, 2H, Jˆ 6.8 Hz),
3.84 (s, 3H), 3.87 (s, 3H), 6.22 (s, 1H), 6.28 (s, 1H), 6.65 (s,
1
3
1H), 6.80 (s, 1H). C NMR (67.8 MHz, CDCl
0.7, 32.2, 56.1, 56.2, 111.0, 112.2, 126.2, 126.9, 128.2,
) d 25.2,
3
3
4
.4. Preparation of PSBTI
131.5, 148.0, 151.2, 155.1, 156.3, 179.9, 180.3. Anal.
Calcd for C H O ´1/2H O: C, 69.61; H, 5.84. Found: C,
69.76; H, 5.73.
1
7
16
4
2
PSDIB was heated in CF CO H at 708C, then the mixture
2
3
was precipitated by adding Et O, ®ltered, washed with Et O,
2
2
and dried to give PSBTI.
Acknowledgements
4.5. General procedure for the biaryl coupling reaction
of 1a,b using PSDIB±BF ´Et O or PSBTI±BF ´Et O
3
2
3
2
This research was ®nancially supported in part by a Grant-
in-Aid for Scienti®c Research (B) (No. 10470469) from the
Ministry of Education, Science, Sports and Culture, Japan
and a Grant-in-Aid for Encouragement of Young Scientists
(No. 11771382) from Japan Society for the Promotion of
Science.
To a stirred suspension of 1a,b (0.1 mmol) and PSDIB or
PSBTI (0.15 mmol) in CH Cl (5.0 ml) was added dropwise
2
2
to BF ´Et O (0.3 mmol) under nitrogen atmosphere at
2
3
2
2
408C. The reaction mixture was stirred at 2408C for 3±
4 h and then Et O was added and the resulting precipitate
2
®
ltered off. The ®ltrate was washed with saturated aqueous
NaHCO and brine, dried, and evaporated. The residue was
3
puri®ed by column chromatography on silica gel (AcOEt±
n-hexane) to give 2a,b in yields shown in Table 2.
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1
2
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3
2
3
2
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2
2
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2
2
2
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27b
mp 142±1448C (hexane/AcOEt) (lit. mp 142±1448C). IR
2
KBr) cm : 2940, 1684, 1464, 1248, 1129, 756. H NMR
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3
1
1
(
(
3
(
1
.84±3.89 (m, 12H), 4.61 (dd, 1H, Jˆ11.9, 9.9 Hz), 5.06
dd, 1H, Jˆ13.9, 11.9 Hz), 6.68 (d, 1H, Jˆ47.6 Hz), 6.77 (d,
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