Oxidative biaryl coupling reaction of phenol ether derivatives using a hypervalent lodine(III) reagent

Article abstract of DOI:10.1021/jo980704f

The hypervalent iodine(III)-induced intramolecular biaryl coupling reaction of phenol ether derivatives (nonphenolic derivatives) was investigated with the aim of preparing various dibenzo heterocyclic compounds. 1,3-Diarylpropanes (la-e), AT-benzyl-W-phenethylamines (2a-c) and N,Ndibenzylamines (3a-e) react with a hypervalent iodine reagent, phenyliodine(III) bis(trifluoroacetate) (PIFA), containing BF₃·Et₂O in CH₂Cl₂ to give the biaryl coupling products (4-6) in good yield. As an application of the reaction, we examined the synthesis of oxygen- and sulfur-containing dibenzoheterocyclic compounds (12-15), whose side chain moiety could be easily cleaved by the known method to give 2,2'-substituted biphenyl compounds (16-18).

Full text of DOI:10.1021/jo980704f

7698
J . Org. Chem. 1998, 63, 7698-7706
Oxid a tive Bia r yl Cou p lin g Rea ction of P h en ol Eth er Der iva tives
Usin g a Hyp er va len t Iod in e(III) Rea gen t
Takeshi Takada, Mitsuhiro Arisawa, Michiyo Gyoten, Ryuji Hamada, Hirofumi Tohma, and
Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamada-oka,
Suita, Osaka 565-0871, J apan
Received April 15, 1998
The hypervalent iodine(III)-induced intramolecular biaryl coupling reaction of phenol ether
derivatives (nonphenolic derivatives) was investigated with the aim of preparing various dibenzo
heterocyclic compounds. 1,3-Diarylpropanes (1a -e), N-benzyl-N-phenethylamines (2a -c) and N,N-
dibenzylamines (3a -e) react with a hypervalent iodine reagent, phenyliodine(III) bis(trifluoroace-
tate) (PIFA), containing BF3‚Et2O in CH2Cl2 to give the biaryl coupling products (4-6) in good
yield. As an application of the reaction, we examined the synthesis of oxygen- and sulfur-containing
dibenzoheterocyclic compounds (12-15), whose side chain moiety could be easily cleaved by the
known method to give 2,2′-substituted biphenyl compounds (16-18).
In tr od u ction
On the other hand, intramolecular oxidative biaryl
coupling reactions of phenol ether derivatives are also
convenient for the synthesis of cross-coupled products.
The biomimetic syntheses of aporphine alkaloids, lignans,
and tannins were achieved using heavy metal oxidants,
such as thallium(III), vanadium(V), ruthenium(IV), and
iron(III) salts.10
The biaryl substructure is a central building block in
a very large number of natural products, such as
polyketides, terpenes, lignanes, coumarins, flavonoids,
tannins, and many alkaloids.1 Because of their interest-
ing properties not only as bioactive natural products but
also as chiral ligands in asymmetric reactions,2 natural
and unnatural biaryls are considered attractive synthetic
targets. The reported methods for construction of these
biaryl skeletons can be classified 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.
However, the unsatisfactory results obtained in the
synthesis of highly functionalized symmetrical or unsym-
metrical biaryl compounds using these reductive and
oxidative methods have remained a problem. Moreover,
heavy metal oxidants are highly toxic and must be
handled very carefully. To solve these problems, we
examined the oxidative biaryl coupling reaction using
hypervalent iodine(III) reagents, which are safe and
useful synthetic reagents.
The reductive processes include (1) the Ullmann cou-
pling reaction of aryl halides using copper bronze as a
reducing reagent,3 (2) Semmelhack’s method using Ni-
(0) complexes such as [Ni(cod)2] used in stoichiometric
amounts to replace copper,4 (3) a coupling reaction of aryl
halides using a catalytic amount of low-valent nickel
species which can be regenerated either electrochemically
or by coreductants such as zinc or sodium hydride,5 (4) a
reaction of aryl-Grignard or organozinc compounds with
aryl halides (the “Kharash reaction”) catalyzed by nickel
or palladium derivatives,6 (5) a palladium-catalyzed
coupling reaction of arylboronic acids (or aryl tin com-
pounds) with aryl halides (or triflates),7 (6) the Meyers
oxazoline method,8 (7) a cyanocuprate-mediated biaryl
coupling reaction,9 etc. Cross-coupled products can be
obtained in moderate yields by methods 4-7.
Recently, we reported the novel and direct nucleophilic
substitution of phenol ethers by nitrogen, carbon, oxygen
and sulfur nucleophiles using a hypervalent iodine(III)
reagent, phenyliodine bis(trifluoroacetate) (PIFA), in
1,1,1,3,3,3-hexafluoropropane-2-ol ((CF3)2CHOH) or 2,2,2-
(6) (a) Kumada, M. Pure. Appl. Chem. 1980, 52, 669. (b) Trost, B.
M.; Verhoeven, T. R Comprehensive Organometallic Chemistry; Wilkin-
son, G., Ed.; Pergamon: Oxford, U.K., 1982; Vol. 8, p 799. (c) Negishi,
E. Acc. Chem. Res. 1982, 15, 340. (d) Negishi, E.; Hayashi, T.; King,
A. O. Org. Synth. 1987, 66, 57. (e) Tamao, K. Comprehensive Organic
Synthesis; Trost, B. M., Fleming, I., Pattenden, G., Eds.; Pergamon:
New York, 1991; Vol. 3, p 435. (f) Farina, V. Comprehensive Organo-
metallic Chemistry II; Abel, E. W., Stone, F. G. A., Wilkinson, G.,
Hegedus, L. S., Eds.; Pergamon: New York, 1995; Vol. 12, p 161.
(7) (a) Stille, J . K. Angew. Chem., Int. Ed. Engl. 1986, 25, 505. (b)
Suzuki, A. Pure Appl. Chem. 1991, 63, 419. (c) Percec. V.; Bae, J .-Y.;
Hill, D. H. J . Org. Chem. 1995, 60, 1060. (d) Saito, S.; Sakai, M.;
Miyaura, N. Tetrahedron Lett. 1996, 37, 2993.
(8) Reviews: (a) Reuman, M.; Meyers, A. I. Tetrahedron 1985, 41,
837. (b) Gant, T. G.; Meyers, A. I. Tetrahedron 1994, 50, 2297.
(9) (a) Lipshutz, B. H.; Kayser, F.; Liu, Z.-P. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1842. (b) Lin. G.-Q.; Zhong, M. Tetrahedron Lett. 1997,
38, 1087.
(10) (a) Taylor, E. C.; Andrade, J . G.; Rall, G. J . H.; McKillop, A. J .
Am. Chem. Soc. 1980, 102, 6513. (b) Tomioka, K.; Ishiguro, T.; Itaka,
Y.; Koga, K. Tetrahedron 1984, 40, 1303. (c) Buckleton, J . S.; Cambie,
R. C.; Clark, G. R.; Craw, P. A.; Rickard, C. E. F.; Rutledge, P. S.;
Woodgate, P. D. Aust. J . Chem. 1988, 41, 305. (d) Tanaka, M.;
Mukaiyama, C.; Mitsuhashi, H.; Maruno, M.; Wakamatsu, T. J . Org.
Chem. 1995, 60, 4339. (e) Quideau, S.; Feldman, K. S. Chem. Rev. 1996,
96, 475.
(1) For leading references on both the synthesis and natural
occurrence of biaryls, see: Bringmann, G.; Walter, R.; Weirich, R.
Angew. Chem., Int. Ed. Engl. 1990, 29, 977.
(2) (a) Noyori, R. Chem. Soc. Rev. 1989, 18, 187. (b) Narasaka, K.
Synthesis 1991, 1.
(3) (a) Ullmann, F.; Bielecki, J . Chem. Ber. 1901, 34, 2174. (b) Fanta,
P. E. Synthesis 1974, 9.
(4) Semmelhack, M. F.; Helquist, P.; Lones, L. D.; Keller, L.;
Mendelson, L.; Ryono, L. S.; Smith, J . G.; Stauffer, R. D. J . Am. Chem.
Soc. 1981, 103, 6460.
(5) (a) Takagi, K.; Hayama, N.; Sasaki, K. Bull Chem. Soc. J pn.
1984, 57, 1887. (b) Colon, I.; Kelsey, D. R. J . Org. Chem. 1986, 51,
2627. (c) Vanderesse, R.; Brunet, J .-J .; Caubere. P. J . Organomet.
Chem. 1984, 264, 263.
10.1021/jo980704f CCC: $15.00 © 1998 American Chemical Society
Published on Web 10/03/1998

A Coupling Reaction of Phenol Ether Derivatives
J . Org. Chem., Vol. 63, No. 22, 1998 7699
Ta ble 1. In tr a m olecu la r Cycliza tion of 1a in Va r iou s
Solven ts
Sch em e 1. Nu cleop h ilic Su bstitu tion of P h en ol
Eth er s Usin g P IF A
yield of 4a (%)
solvent
temp (°C)
none
containing BF3‚Et2O
(CF3)2CHOH
CF3CH2OH
CH3CN
0
-40
-40
-40
63
65
46
25
63
84
73
91
CH2Cl2
Sch em e 2
Ta ble 2. Bia r yl Cou p lin g Rea ction of 1-3 w ith P IF A
yield
4-6 (%)
1-3 R1
1a OMe
1b -OCH2O- -OCH2O-
1c OMe OMe OMe OMe
R2
R3
R4
R5
n
X
H
OMe OMe
H
H
H
1
1
1
1
1
2
2
2
1
1
1
1
1
CH2
4a
4b
4c
4d
4e
91
91
99
92
75
89
68
52
94
85
85
64
60
CH2
CH2
CH2
CH2
1d OMe OMe OMe OMe OMe
1e OMe OMe OMe OTBS
2a OMe OMe OMe
2b OMe OMe OMe OMe
H
H
H
H
NCOCF3 5a
NCOCF3 5b
NCOCF3 5c
NCOCF3 6a
NCOCF3 6b
NCOCF3 6c
NCOCF3 6d
NCOCF3 6e
trifluoroethanol (CF3CH2OH) (Scheme 1).11 As part of
our continued studies concerning PIFA-induced nucleo-
philic substitution of phenol ethers, we have briefly
communicated the intramolecular oxidative biaryl cou-
pling reactions of phenol ether derivatives using PIFA
activated by BF3‚Et2O.12 In this paper, we describe a full
account of our studies on the intramolecular nonphenolic
oxidative coupling reactions leading to the dibenzohet-
erocyclic compounds, which could be easily converted into
the 2,2′-substituted biaryl compounds possessing formyl,
methyl, and hydroxy groups (Scheme 2).
2c OMe OMe OMe OMe OMe
3a
-OCH2O- -OCH2O-
H
H
3b OMe OMe OMe OMe
3c OMe OMe OMe OMe OMe
3d OMe OMe OMe OTBS
3e OMe OMe OMe OAc
H
H
dichloromethane, also gave 4a in 65, 46, and 25% yields,
respectively.12 When the reaction was carried out in the
presence of BF3‚Et2O, which could coordinate with the
trifluoroacetoxy ligands to activate it, the yield of 4a was
dramatically improved. Thus, the biaryl coupling reac-
tion proceeded smoothly at low temperature (-40 °C) to
give 4a in good yield. In dichloromethane, the yield of
4a from 1a increased to 91% (Table 1).
Other 1,3-diarylpropanes (1b-e), N-benzyl-N-phen-
ethylamine derivatives (2a -c), and N,N-dibenzylamine
derivatives (3a -e) were similarly converted into the
biaryl compounds (4b-e, 5a -c, 6a -e) in good yields
under the same condition. These results are summarized
in Table 2.
As an application of the PIFA-induced biaryl coupling
reaction, we next examined the synthesis of various
dibenzo heterocyclic compounds, whose side chain moiety
could be easily cleaved by the known methods to give
various 2,2′-substituted biaryl compounds. We investi-
gated the intramolecular coupling reaction of five types
of compounds, silaketal derivatives (7a -f), dibenzyl
sulfide (8), dibenzyl sulfoxides (9a -d ), dibenzyl sulfones
(10a ,b), and dibenzyl ethers (11a -f) using the combined
reagent PIFA-BF3‚Et2O. These phenol ether derivatives
(7-11) were prepared from the corresponding benzyl
alcohols, benzyl bromides, or alkoxyphenols (Scheme 3).
Treatment of silaketal derivatives (7a -f) with PIFA
activated by BF3‚Et2O afforded the corresponding cou-
Resu lts a n d Discu ssion
At first, we examined the biaryl coupling reaction of
1,3-diarylpropanes (1a -e), N-benzyl-N-phenethylamine
derivatives (2a -c), and N,N-dibenzylamine derivatives
(3a -e) under the same conditions as an intermolecular
nucleophilic substitution of phenol ethers using PIFA.
The starting compounds (1a -e, 2a -c, 3a -e) were
prepared by the reaction of a corresponding benzaldehyde
with an acetophenone, a tyramine, or a benzylamine
derivative according to the reported method.13 Treat-
ment of 1-(3,4-dimethoxyphenyl)-3-(4-methoxyphenyl)-
propane (1a ) with PIFA in (CF3)2CHOH gave a biaryl
coupling compound (4a ) in 63% yield. The reaction in
other solvents, such as CF3CH2OH, acetonitrile, and
(11) (a) Kita, Y.; Tohma, H.; Hatanaka, K.; Takada, T.; Fujita, S.;
Mitoh, S.; Sakurai, H.; Oka, S. J . Am. Chem. Soc. 1994, 116, 3684. (b)
Kita, Y.; Takada, T.; Tohma, H. Pure Appl. Chem. 1996, 68, 627.
(12) For a preliminary communication of a portion of the studies
described herein, see: Kita, Y.; Gyoten, M.; Otsubo, M.; Tohma, H.;
Takada, T. Chem. Commun. 1996, 1481.
(13) (a) Palmquist, U.; Nilsson, A.; Parker, V. D.; Ronla´n, A. J . Am.
Chem. Soc. 1976, 98, 2571-2580. (b) Kita, Y.; Takada, T.; Gyoten, M.;
Tohma, H.; Zenk, M. H.; Eichho¨rn, J . J . Org. Chem. 1996, 61, 5857.

7700 J . Org. Chem., Vol. 63, No. 22, 1998
Ta ble 3. Bia r yl Cou p lin g Rea ction of Com p ou n d s 7-11 w ith P IF A
Takada et al.
7-11
R1
R2
R3
R4
R5
R6
X
Y
12-15
yield (%)
7a
7b
7c
7d
7e
7f
8
9a
9b
OMe
OMe
H
H
H
H
H
H
H
H
H
H
OMe
H
H
H
H
H
OMe
OMe
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
OMe
OMe
O
O
O
O
O
O
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
CH2
SiiPr2
SiiPr2
SiiPr2
SitBu2
SitBu2
SitBu2
S
SO
SO
SO
SO
SO2
SO2
O
O
O
12a
12b
12c
12d
12e
12f
56
69
46
81
89
83
-OCH2O-
OMe
OMe
-OCH2O-
-OCH2O-
OMe OMe
-OCH2O-
-OCH2O-
OMe
OMe
-OCH2O-
-OCH2O-
OMe
OMe
-OCH2O-
OMe
OMe
OMe
-OCH2O-
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
13a
13b
13c
13d
14a
14b
15a
15b
15c
15d
15e
73
71
-OCH2O-
9c
9d
OMe
OMe
OMe
OMe
OMe
OMe
59 (73)a
42 (73)a
78
OMe
OMe
10a
10b
11a
11b
11c
11d
11e
-OCH2O-
OMe
72
85
80
51
50
38
OMe
OMe
-OCH2O-
-OCH2O-
-OCH2O-
OMe
OMe
OMe
OMe
OMe
OMe
OMe
OMe
H
OMe
OMe
OMe
O
O
a
Yields based on the reacted substrates are given in parentheses.
Sch em e 3. P r ep a r a tion of P h en ol Eth er s 7-11
pling products (12a -f). Di-tert-butyl silaketals (7d -f)
caused a favorable biaryl coupling reaction to give 12d -f
in good yields. The silaketal moiety of 12a -f was not
cleaved during the reaction. Silaketals are used for a
silicon tether to link two alcohol compounds. For ex-
ample, silicon-tethered Diels-Alder reactions have been
reported.14 We found that the silaketals could also be
applicable as a tether to link two phenol derivatives, and
the silaketal moiety was stable under the PIFA oxidation
conditions.
Next, we investigated the biaryl coupling reaction of
sulfur-containing phenol ether derivatives (8-10). Al-
though the sulfoxide (9a -d ) and sulfone (10a ,b) deriva-
tives caused a favorable biaryl coupling reaction upon
treatment with PIFA, no coupling products were obtained
from the sulfide (8) derivative. Due to the high reactivity
of the sulfide moiety of 8 toward PIFA, many oxidized
products were generated.
The dibenzyl ethers (11a -e) were also converted into
the coupled biaryl compounds (15a -e) under the same
conditions. The oxidation of the benzyl position of 11 did
not appreciably take place. Highly functionalized biaryl
compounds (15d -e) were also obtained (Table 3).
The methods of the selective cleavage of the tether
moiety of the coupling product are as follows. Treatment
of the silylene derivatives (12d -f) with tetrabutylam-
monium fluoride afforded the corresponding 2,2′-dihy-
droxybiphenyl compounds (16d -f) in good yields. Hy-
drogenolysis of the sulfoxide (13b) in EtOH containing
Raney Ni as a catalyst gave a 2,2′-dimethylbiphenyl
compound (17b) in good yield. Because of poor solubility,
hydrogenolysis of other sulfoxides (13) did not proceed
well. Oxidative cleavage of the dibenzyl ether derivatives
(15a ,b,d ) took place with DDQ15 to give the 2,2′-diformyl-
biphenyl compounds (18a ,b,d ) in moderate yields. These
results are summarized in Table 4.
The reaction mechanism for the biaryl coupling reac-
tion of phenol ether derivatives with PIFA possibly
involves a one-electron oxidation step.12 It is assumed
that the reaction of an electron-rich aromatic ring with
the reagent PIFA-BF3‚Et2O results in the formation of
a cation radical intermediate. The nucleophilic attack
by the other aromatic ring on the cation radical then
occurs to give the corresponding biaryl product.
In our continuing effort to develop hypervalent iodine
chemistry, a novel biaryl coupling reaction of phenol
ether derivatives has been developed using a hypervalent
iodine reagent. By using these reactions, we can obtain
the dibenzo heterocyclic compounds, which can be easily
converted into the 2,2′-substituted biaryl compounds
possessing hydroxy, methyl, and formyl groups. The
(14) Bols, M. Chem. Rev. 1995, 95, 1253.
(15) Oikawa, Y.; Yoshida, T.; Yonemitsu, O. Tetrahedron Lett. 1982,
23, 885.

A Coupling Reaction of Phenol Ether Derivatives
J . Org. Chem., Vol. 63, No. 22, 1998 7701
Ta ble 4. Clea va ge of th e Sid e Ch a in a
sub.
R1
R2
R3
R4
R5
R6
X
Y
method
prod
Z
yield (%)
12d
12e
13b
15a
15b
15d
OMe
OMe
H
H
H
H
H
OMe
H
H
H
H
H
H
OMe
OMe
O
O
CH2
CH2
CH2
CH2
SitBu2
SitBu2
SO
O
O
A
A
B
C
C
C
16d
16e
17b
18a
18b
18d
OH
OH
CH3
CHO
CHO
CHO
98
96
97
66
56
46
-OCH2O-
-OCH2O-
OMe OMe
-OCH2O-
OMe OMe
-OCH2O-
-OCH2O-
OMe OMe
-OCH2O-
OMe OMe
O
a
Method: (A) TBAF/THF, rt, 2 h; (B) Raney Ni (w-1)/EtOH, reflux, 6 h; (C) DDQ/S CH2Cl2-H2O (18:1), reflux, 24 h.
111.2, 111.8, 112.5, 120.2, 120.5, 120.6, 135.0, 135.8, 142.9,
147.1, 148.7, 150.6; HRMS calcd for C24H36O4Si (M+) m/e
416.2383, found m/e 416.2387.
chemistry of 2,2′-disubstituted symmetrical or unsym-
metrical biphenyls has attracted considerable interest
because of the presence of these moieties in a number of
natural products, such as vancomycin, elladitannins, and
dibenzocyclooctalignans.
Further application of this reaction to the synthesis of
natural products and development of the atropisomer-
selective biaryl coupling reaction are currently in progress.
Gen er a l P r oced u r e of P r ep a r in g N-Ben zyl-N-p h en -
eth yla m in e Der iva tives (2) a n d N,N-Diben zyla m in e De-
r iva tives (3). N-Benzyl-N-phenethylamine derivatives (2)
and N,N-dibenzylamine derivatives (3) were prepared from
corresponding to the benzaldehyde and the tyramine or the
benzylamine derivative according to the reported method.13b
N-(3,4-Dim eth oxyben zyl)-N-(3,4-dim eth oxyp h en eth yl)-
2,2,2-tr iflu or oa ceta m id e (2b): colorless solid; mp 68-69 °C;
IR 1690; 1H NMR (270 MHz, CDCl3) δ 2.75-2.86 (m, 2H),
3.46-3.54 (m, 2H), 3.85, 3.86, 3.87, 3.88 (s, 12H), 4.31, 4.59
(s, 2H), 6.61-6.68 (m, 3H), 6.76-6.85 (m, 3H); 13C NMR (75.5
MHz, CDCl3) δ 32.5, 34.9, 48.3, 48.5, 49.8, 51.7, 55.8, 56.1,
60.8, 104.2, 105.0, 111.3, 111.5, 111.7, 111.9, 116.5 (J ) 287
Hz), 116.7 (J ) 287 Hz), 120.6, 120.7, 129.8, 130.3, 130.7,
130.9, 147.8, 148.1, 149.0, 149.2, 153.6, 156.9 (J ) 36 Hz);
HRMS calcd for C21H24F3NO5 (M+) m/e 427.1606, found m/e
427.1608. Anal. Calcd for C21H24F3NO5: C, 59.01; H, 5.66;
N, 3.28. Found: C, 59.08; H, 5.69; N, 3.30.
Exp er im en ta l Section
All melting points are uncorrected. Infrared (IR) absorption
spectra (cm-1) were recorded as KBr pellets. 1H NMR (and
13C NMR) spectra were recorded, with TMS or CHCl3 as an
internal standard. Most of the 1H (and 13C) NMR spectra of
amido compounds exhibited the presence of two rotamers. E.
Merck silica gel 60 for column chromatography and E. Merck
precoated TLC plates, silica gel F254 for preparative thin-layer
chromatography were used. Organic layers were dried with
anhydrous MgSO4 or Na2SO4. PIFA is commercially available.
BF3‚Et2O was obtained from commercial suppliers and was
used without further purification. Compounds 1a ,c, 2a , 10b,
and 11a were prepared by known methods.13b,16
N-(3,4-Dim eth oxyp h en eth yl)-N-(3,4,5-tr im eth oxyben -
zyl)-2,2,2-tr iflu or oa ceta m id e (2c): colorless solid; mp 100-
1
101 °C; IR 1690; H NMR (270 MHz, CDCl3) δ 2.78-2.88 (m,
2H), 3.49-3.57 (m, 2H), 3.83, 3.84, 3.86 (s, 15H), 4.30, 4.58 (s,
2H), 6.30, 6.42 (s, 2H), 6.62-6.83 (m, 3H); 13C NMR (50.3 MHz,
CDCl3) δ 32.1, 34.5, 48.1, 49.4, 51.3, 55.5, 55.7, 60.4, 104.0,
104.6, 111.0, 111.2, 111.4, 111.6, 116.2 (J ) 288 Hz), 116.4 (J
) 288 Hz), 120.3, 129.6, 130.0, 130.4, 130.7, 137.4, 137.5, 147.5,
147.7, 148.7, 148.8, 153.3, 156.4 (J ) 35 Hz), 156.9 (J ) 36
Hz). Anal. Calcd for C22H26F3NO6: C, 57.76; H, 5.73; N, 3.06.
Found: C, 57.88; H, 5.73; N, 3.10.
N,N-Bis(3,4-(m et h ylen ed ioxy)b en zyl)-2,2,2-t r iflu or o-
a ceta m id e (3a ): white solid; mp 109-110 °C; IR 1692; 1H
NMR (270 MHz, CD3OD) δ 4.43, 4.50 (s, 4H), 5.93, 5.96 (s,
4H), 6.62-6.84 (m, 6H); 13C NMR (50.3 MHz, CDCl3) δ 47.4,
48.9, 101.1, 101.3, 107.6, 108.2, 108.4, 108.7, 116.7 (J ) 288
Hz), 121.1, 122.0, 127.9, 128.7, 147.4, 147.6, 148.0, 148.3, 157.1
(J ) 36 Hz). Anal. Calcd for C18H14F3NO5: C, 56.70; H, 3.70;
N, 3.67. Found: C, 56.62; H, 3.83; N, 3.69.
N ,N -Bis(3,4-d im e t h oxyb e n zyl)-2,2,2-t r iflu or oa ce t -
a m id e (3b): colorless solid; mp 91-92 °C; IR 1690; 1H NMR
(270 MHz, CDCl3) δ 3.84, 3.86 (s, 6H), 3.88, 3.90 (s, 6H), 4.46,
4.47 (s, 4H), 6.66-6.76 (m, 4H), 6.82, 6.87 (d, 2H, J ) 8.3, 7.9
Hz); 13C NMR (50.3 MHz, CDCl3) δ 47.7, 49.0, 55.9, 110.3,
111.0, 111.2, 111.5, 116.8 (J ) 288 Hz), 120.0, 121.0, 126.7,
127.5, 148.8, 149.0, 149.2, 149.4, 157.3 (J ) 35 Hz). Anal.
Calcd for C20H22F3NO5: C, 58.11; H, 5.36; N, 3.39. Found: C,
58.17; H, 5.29; N, 3.45.
N-(3,4-Dim eth oxyben zyl)-N-(3,4,5-tr im eth oxyben zyl)-
2,2,2-tr iflu or oa ceta m id e (3c): colorless solid; mp 126-128
°C; IR 1692; 1H NMR (270 MHz, CDCl3) δ 3.82, 3.84, 3.85,
3.87, 3.89, 3.91 (s, 15H), 4.45-4.50 (m, 4H), 6.37 (s, 2H), 6.68,
6.75 (dd, 1H, J ) 7.6, 2.0 Hz), 6.73 (s, 1H), 6.82, 6.87 (d, 1H,
J ) 8.3, 7.9 Hz); 13C NMR (67.9 MHz, CDCl3) δ 47.7, 47.9,
49.0, 55.1, 55.3, 60.0, 103.8, 104.8, 109.9, 110.5, 110.7, 111.0,
Gen er a l P r oced u r e for P r ep a r in g 1,3-Dia r ylp r op a n es
(1). 1,3-Diarylpropanes (1) were prepared by the reaction of
a corresponding benzaldehyde with an acetophenone derivative
according to the reported method.13a
1,3-Bis(3,4-(m eth ylen ed ioxy)p h en yl)p r op a n e (1b): col-
1
orless solid; mp 70-72 °C; H NMR (200 MHz, CDCl3) δ 1.85
(qui, 2H, J ) 7.6 Hz), 2.55 (t, 4H, J ) 7.6 Hz), 5.92 (s, 4H),
6.61 (dd, 2H, J ) 7.8, 1.6 Hz), 6.67 (d, 2H, J ) 1.6 Hz), 6.72
(d, 2H, J ) 7.8 Hz); 13C NMR (67.9 MHz, CDCl3) δ 33.4, 35.0,
100.7, 108.1, 108.8, 121.1, 136.1, 145.5, 147.5; HRMS calcd
for C17H16O4 (M+) m/e 284.1048, m/e found 284.1049.
1-(3,4-Dim et h oxyp h en yl)-3-(3,4,5-t r im et h oxyp h en yl)-
p r op a n e (1d ): colorless amorphous; 1H NMR (270 MHz,
CDCl3) δ 1.94 (qui, 2H, J ) 7.6 Hz), 2.59 (t, 2H, J ) 7.6 Hz),
2.62 (t, 2H, J ) 7.6 Hz), 3.82 (s, 3H), 3.85 (s, 6H), 3.87 (s, 3H),
3.88 (s, 3H), 6.40 (s, 2H), 6.71-6.75 (m, 2H), 6.81 (d, 1H, J )
7.9 Hz); 13C NMR (67.9 MHz, CDCl3) δ 33.0, 35.0, 35.7, 55.7,
55.8, 55.9, 60.7, 105.2, 111.1, 111.7, 120.1, 134.7, 138.0, 147.1,
148.7, 153.0; HRMS calcd for C20H26O5 (M+) m/e 346.1780,
found m/e 346.1784.
1-(4-((ter t-Bu tyld im eth ylsilyl)oxy)-3-m eth oxyp h en yl)-
3-(3,4-d im eth oxyp h en yl)p r op a n e (1e): colorless oil; 1H
NMR (200 MHz, CDCl3) δ 0.14 (s, 6H), 0.99 (s, 9H), 1.91 (qui,
2H, J ) 7.8 Hz), 2.59 (t, 4H, J ) 7.8 Hz), 3.79 (s, 3H), 3.86 (s,
3H), 3.87 (s, 3H), 6.62-6.81 (m, 6H); 13C NMR (75.5 MHz,
CDCl3) δ -4.7, 18.4, 25.7, 33.3, 35.0, 35.1, 55.5, 55.8, 55.9,
(16) (a) Parker V. D.; Ronla´n A. J . Am. Chem. Soc. 1975, 97, 4714
(1a ). (b) Tamura, S.; Okuma, K.; Hayashi, T. J . Agric. Chem. Soc. J pn.
1953, 27, 491 (1c). (c) Rosowsky, A.; Lin, M.; Modest, E. J . J . Med.
Chem. 1973, 16, 869 (10b). (d) Kametani, T.; Yamaki, K.; Ogasawara,
K. Yakugaku Zasshi 1969, 89, 638 (11a ).

7702 J . Org. Chem., Vol. 63, No. 22, 1998
Takada et al.
116.2 (J ) 288 Hz), 119.5, 120.4, 126.1, 127.1, 127.6, 129.5,
130.3, 137.0, 137.1, 148.3, 148.4, 148.6, 148.8, 152.8, 153.1,
156.6 (J ) 36 Hz). Anal. Calcd for C21H24F3NO6: C, 56.88;
H, 5.46; N, 3.16. Found: C, 56.98; H, 5.45; N, 3.20.
mL) at room temperature. The mixture was stirred for 0.5 h
at 60 °C and then added the solution of sesamol (0.2 mmol)
and Et3N (0.2 mmol) in DMF (1.5 mL). The mixture was
stirred for 4 h at 60 °C and then cooled. The solution was
extracted by Et2O. The extracts were washed with water and
brine and concentrated in vacuo. The residue was purified
by chromatography on silica gel (AcOEt-n-hexane) to give the
corresponding to the silaketal (7c or 7f).
N-(4-((ter t-Bu tyld im eth ylsilyl)oxy)-3-m eth oxyben zyl)-
N-(3,4-d im et h oxyb en zyl)-2,2,2-t r iflu or oa cet a m id e (3d ):
colorless oil; IR 1692; 1H NMR (500 MHz, CDCl3) δ 0.16, 0.17
(s, 6H), 0.99, 1.00 (s, 9H), 3.76, 3.78 (s, 3H), 3.83, 3.85 (s, 3H),
3.88, 3.90 (s, 3H), 4.43-4.45 (m, 4H), 6.59-6.73 (m, 4H), 6.78-
(3,4-Dim et h oxyp h en oxy)(3,4-(m et h ylen ed ioxy)p h en -
oxy)d iisop r op ylsila n e (7c). Reactants: diisopropyldichlo-
rosilane (0.050 mL, 0.28 mmol); 3,4-dimethoxyphenol (42.0 mg,
0.28 mmol); Et3N (0.038 mL, 0.28 mmol); DMF (1.0 mL);
sesamol (37.0 mg, 0.28 mmol); Et3N (0.038 mL, 0.28 mmol);
6.87 (m, 2H); HRMS calcd for
C
25H34F3NO5Si (M+) m/e
513.2158, found m/e 513.2158.
N-(4-Acetoxy-3-m eth oxyben zyl)-N-(3,4-d im eth oxyben -
zyl)-2,2,2-tr iflu or oa ceta m id e (3e): colorless solid; mp 86-
87 °C; IR 1692; 1H NMR (300 MHz, CDCl3) δ 0.16, 0.17 (s,
6H), 0.99, 1.00 (s, 9H), 3.76, 3.78 (s, 3H), 3.83, 3.85 (s, 3H),
3.88, 3.90 (s, 3H), 4.43-4.45 (m, 4H), 6.59-6.73 (m, 4H), 6.78-
6.87 (m, 2H); 13C NMR (75.5 MHz, CDCl3) δ 20.6, 47.6, 48.1,
49.0, 49.1, 49.3, 49.4, 55.8, 55.9, 110.3, 111.0, 111.3, 111.5,
112.4, 116.7 (J ) 288 Hz), 119.5, 120.0, 120.6, 121.0, 122.9,
123.1, 126.5, 127.3, 133.4, 134.0, 139.5, 139.6, 148.9, 149.0,
149.3, 149.5, 151.4, 151.6, 157.4 (J ) 35 Hz). Anal. Calcd for
1
DMF (1.5 mL). 7c (52 mg, 48%): colorless oil; H NMR (200
MHz, CDCl3) δ 1.09 (d, 12H, J ) 5.2 Hz), 1.20 (m, 2H), 3.78
(s, 3H), 3.83 (s, 3H), 5.91 (s, 2H), 6.38-6.50 (m, 2H), 6.53 (d,
1H, J ) 2.2 Hz), 6.54 (d, 1H, J ) 2.2 Hz), 6.65 (d, 1H, J ) 8.4
Hz), 6.71 (d, 1H, J ) 8.4 Hz); 13C NMR (67.9 MHz, CDCl3) δ
12.4, 17.1, 55.7, 56.2, 101.2, 102.1, 104.4, 108.0, 110.2, 111.3,
111.7, 142.0, 143.9, 148.0, 148.8, 149.5, 149.6. Anal. Calcd
for C21H28O6Si: C, 62.35; H, 6.98. Found: C, 62.34; H, 6.89.
C
21H22F3NO6: C, 57.14; H, 5.02; N, 3.17. Found: C, 57.05; H,
Di-ter t-bu tyl(3,4-d im eth oxyp h en oxy)(3,4-(m eth ylen e-
d ioxy)p h en oxy)sila n e (7f). Reactants: di-tert-butylsilyl bis-
(trifluoromethanesulfonate) (0.21 mL, 0.57 mmol); 3,4-dimethox-
yphenol (88.0 mg, 0.57 mmol); Et3N (0.080 mL, 0.57 mmol);
DMF (3.0 mL); sesamol (79.0 mg, 0.57 mmol); Et3N (0.080 mL,
0.57 mmol); DMF (3.0 mL). 7f (117 mg, 48%): colorless solid;
mp 72-73 °C; 1H NMR (250 MHz, CDCl3) δ 1.08 (s, 18H), 3.75
(s, 3H), 3.83 (s, 3H), 5.91 (s, 2H), 6.45 (dd, 1H, J ) 8.5, 2.5
Hz), 6.50-6.56 (m, 3H), 6.65 (d, 1H, J ) 8.5 Hz), 6.72 (d, 1H,
J ) 8.5 Hz); 13C NMR (67.9 MHz, CDCl3) δ 21.7, 27.8, 55.7,
56.3, 101.2, 102.4, 104.7, 107.9, 110.6, 111.6, 141.9, 143.7,
148.0, 149.3, 150.1. Anal. Calcd for C23H32O6Si: C, 63.86; H,
7.46. Found: C, 63.95; H, 7.45.
Bis(3,4-d im eth oxyben zyl) Su lfid e (8). A solution of
Na2S‚9H2O (659 mg, 2.74 mmol) in EtOH (10 mL) was added
to 3,4-dimethoxybenzyl bromide (792 mg, 3.43 mmol) at room
temperature. The suspension was refluxed for 1.5 h and then
cooled. The mixture was concentrated, and then the residue
was dissolved in AcOEt. The solution was washed with water
and brine and then evaporated. The residue was purified by
chromatography on silica gel (AcOEt-n-hexane) to give 8 (518
mg, 90%) as a colorless solid; mp 94-96 °C; 1H NMR (200 MHz,
CDCl3) δ 3.58 (s, 4H), 3.88 (s, 12H), 6.80 (s, 4H), 6.85 (s, 2H);
13C NMR (67.9 MHz, CDCl3) δ 35.2, 55.6, 55.7, 110.6, 111.8,
120.9, 130.4, 147.8, 148.8; HRMS calcd for C18H22O4S (M+) m/e
334.1238, found m/e 334.1243.
5.05; N, 3.22.
Gen er a l P r oced u r e for th e P r ep a r a tion of Sila k eta ls
(7a ,b,d ,e). Dialkyldichlorosilane or dialkylsilyl bis(trifluo-
romethanesulfonate) (0.1 mmol) was added to the solution of
the alkoxyphenol (0.05 mmol) and Et3N (0.15 mmol) in DMF
at room temperature. The mixture was stirred for 3 h at 60
°C and then cooled. The solution was extracted with Et2O.
The extracts were washed with water and brine and concen-
trated in vacuo. The residue was purified by chromatography
on silica gel (AcOEt-n-hexane) to give the corresponding to
the silaketal (7).
Bis(3,4-d im eth oxyp h en oxy)d iisop r op ylsila n e (7a ). Re-
actants: diisopropyldichlorosilane (0.050 mL, 0.28 mmol); 3,4-
dimethoxyphenol (167 mg, 1.08 mmol); Et3N (0.150 mL, 1.08
mmol); DMF (2.5 mL). 7a (66 mg, 58%): colorless oil; 1H NMR
(200 MHz, CDCl3) δ 1.10 (d, 12H, J ) 5.8 Hz), 1.19 (m, 2H),
3.77 (s, 6H), 3.82 (s, 6H), 6.48-6.53 (m, 4H), 6.71 (d, 2H, J )
8.4 Hz); 13C NMR (67.9 MHz, CDCl3) δ 12.5, 17.1, 55.7, 56.2,
104.4, 110.3, 111.6, 143.9, 148.8, 149.5. Anal. Calcd for
C
22H32O6Si: C, 62.83; H, 7.67. Found: C, 62.83; H, 7.63.
B is (3,4-(d im e t h y le n e d io x y )p h e n o x y )d iis o p r o p y l-
sila n e (7b). Reactants: diisopropyldichlorosilane (0.050 mL,
0.27 mmol); sesamol (149 mg, 1.08 mmol); Et3N (0.15 mL, 1.08
mmol); DMF (2.5 mL). 7b (62 mg, 59%): colorless solid; mp
90-91 °C; 1H NMR (200 MHz, CDCl3) δ 1.07 (d, 12H, J ) 6.2
Hz), 1.20 (m, 2H), 5.91 (s, 4H), 6.42 (d, 2H, J ) 8.2, 2.4 Hz),
6.52 (d, 2H, J ) 2.4 Hz), 6.65 (d, 2H, J ) 8.2 Hz); 13C NMR
(67.9 MHz, CDCl3) δ 12.4, 17.0, 101.2, 102.0, 108.0, 111.2,
142.2, 148.0, 149.5. Anal. Calcd for C20H24O6Si: C, 61.83; H,
6.23. Found: C, 61.96; H, 6.18.
Di-ter t-bu tylbis(3,4-dim eth oxyph en oxy)silan e (7d). Re-
actants: di-tert-butylsilyl bis(trifluoromethanesulfonate) (0.066
mL, 0.18 mmol); 3,4-dimethoxyphenol (111 mg, 0.72 mmol);
Et3N (0.10 mL, 0.72 mmol); DMF (3.0 mL). 7d (66 mg, 81%):
colorless solid; mp 76-77 °C; 1H NMR (250 MHz, CDCl3) δ
1.10 (s, 18H), 3.73 (s, 6H), 3.83 (s, 6H), 6.52-6.54 (m, 4H),
6.71 (d, 2H, J ) 9.3 Hz); 13C NMR (75.5 MHz, CDCl3) δ 21.6,
27.8, 55.7, 56.2, 104.7, 110.7, 111.6, 143.7, 149.3. Anal. Calcd
for C24H36O6Si: C, 64.25; H, 8.09. Found: C, 64.30; H, 8.02.
Di-ter t-b u t ylb is(3,4-(d im et h ylen ed ioxy)p h en oxy)si-
la n e (7e). Reactants: di-tert-butylsilyl bis(trifluoromethne-
sulfonate) (0.083 mL, 0.23 mmol); sesamol (127 mg, 0.92
mmol); Et3N (0.13 mL, 0.92 mmol); DMF (4.0 mL). 7e (74 mg,
78%): colorless solid; mp 75-77 °C; 1H NMR (250 MHz, CDCl3)
δ 1.07 (s, 18H), 5.91 (s, 4H), 6.42 (dd, 2H, J ) 8.5, 2.5 Hz),
6.53 (d, 2H, J ) 2.5 Hz), 6.65 (d, 2H, J ) 8.5 Hz); 13C NMR
(67.9 MHz, CDCl3) δ 21.7, 27.8, 101.2, 102.4, 107.9, 111.6,
141.9, 147.9, 150.0. Anal. Calcd for C22H26O6Si: C, 63.44; H,
6.78. Found: C, 63.59; H, 6.82.
Bis(3,4-d im eth oxyben zyl) Su lfoxid e (9a ). m-Chloro-
perbenzoic acid (80 mg, 0.37 mmol) was added to the solution
of 8 (62 mg, 0.37 mmol) in CH2Cl2 (2 mL) at 0 °C. The mixture
was stirred for 24 h at room temperature and then quenched
with aqueous potassium carbonate. The organic layer was
washed with water and brine and concentrated in vacuo. The
residue was purified by chromatography on silica gel (CH2-
Cl2-MeOH) to give 9a (52 mg, 80%) as a colorless solid: mp
1
146-148 °C; H NMR (200 MHz, CDCl3) δ 3.86 (m, 4H), 3.89
(s, 12H), 6.82-6.87 (m, 6H); 13C NMR (67.9 MHz, CDCl3) δ
55.9, 55.9, 57.1, 111.3, 112.9, 122.5, 149.1; HRMS calcd for
C
18H22O5S (M+) m/e 350.1188, found m/e 350.1188. Anal.
Calcd for C18H22O5S: C, 61.70; H, 6.33; S, 9.15. Found: C,
61.57; H, 6.30; S, 8.97.
Bis(3,4-(m eth ylen ed ioxy)ben zyl) Su lfoxid e (9b). m-
Chloroperbenzoic acid (124 mg, 0.58 mmol) was added to the
solution of bis(3,4-methylenedioxybenzyl) sulfide16c (183 mg,
0.58 mmol) in CH2Cl2 (3 mL) at 0 °C. The mixture was stirred
for 48 h at room temperature and then quenched with aqueous
potassium carbonate. The organic layer was washed with
water and brine and concentrated in vacuo. The residue was
purified by chromatography on silica gel (CH2Cl2-MeOH) to
give 9b (93 mg, 48%) as a colorless solid: mp 128-130 °C; 1H
NMR (270 MHz, CDCl3) δ 3.77 (d, 2H, J ) 12.9 Hz), 3.84 (d,
2H, J ) 12.9 Hz), 5.97 (s, 4H), 6.72-6.82 (m, 6H); 13C NMR
(67.9 MHz, CDCl3) δ 57.0, 101.3, 108.6, 110.2, 123.5, 123.6,
147.8, 148.1; HRMS calcd for C16H14O5S (M+) m/e 318.0570,
P r oced u r e for th e P r ep a r a tion of Sila k eta ls (7c,f).
Diisopropyldichlorosilane or di-tert-butylsilyl bis(trifluoro-
methanesulfonate) (0.2 mmol) was added to the solution of 3,4-
dimethoxyphenol (0.2 mmol) and Et3N (0.2 mmol) in DMF (1.0

A Coupling Reaction of Phenol Ether Derivatives
J . Org. Chem., Vol. 63, No. 22, 1998 7703
found m/e 318.0562. Anal. Calcd for C16H14O5S: C, 60.37; H,
4.43; S, 10.07. Found: C, 60.38; H, 4.51; S, 10.05.
Gen er a l P r oced u r e for P r ep a r in g Dib en zyl E t h er s
(11). Dibenzyl ethers (11) were prepared by the reaction of
the corresponding alkoxybenzyl alcohol with an alkoxybenzyl
bromide according to the reported method.17
1,3-Bis(3,4-(m eth ylen ed ioxy)ben zyl) Eth er (11b): color-
less solid; mp 41-43 °C; 1H NMR (200 MHz, CDCl3) δ 4.42 (s,
4H), 5.95 (s, 4H), 6.78 (s, 4H), 6.86 (s, 2H); 13C NMR (75.5
MHz, CDCl3) δ 71.6, 100.9, 108.0, 108.5, 121.3, 132.0, 147.1,
147.7; HRMS calcd for C16H14O5 (M+) m/e 286.0841, found m/e
286.0826. Anal. Calcd for C16H14O5: C, 67.13; H, 4.93.
Found: C, 67.06; H, 5.00.
3,4-Dim eth oxyben zyl 3,4-(Meth ylen ed ioxy)ben zyl Su l-
foxid e (9c). Sodium hydroxide (44 mg, 1.1 mmol) was added
to the solution of 3,4-dimethoxybenzyl mercaptan (203 mg, 1.1
mmol) in EtOH (5 mL). The mixture was stirred for a few
minutes at room temperature, and then 3,4-(methylenedioxy)-
benzyl bromide (237 mg, 1.0 mmol) was added to the solution.
After the solution was stirred for 1.5 h at room temperature,
the solvent was evaporated and then the residue was dissolved
in AcOEt. The solution was washed with water and brine and
concentrated in vacuo. The residue was purified by chroma-
tography on silica gel (AcOEt-n-hexane) to give 3,4-dimethox-
ybenzyl 3,4-(methylenedioxy)benzyl sulfide (183 mg, 52%).
m-Chloroperbenzoic acid (124 mg, 0.58 mmol) was added
to a solution of 3,4-dimethoxybenzyl 3,4-(methylenedioxy)-
benzyl sulfide (183 mg, 0.58 mmol) in CH2Cl2 (3 mL) at 0 °C.
The mixture was stirred for 48 h at room temperature and
then quenched with aqueous potassium carbonate. The
organic layer was washed with water and brine and concen-
trated in vacuo. The residue was purified by chromatography
on silica gel (CH2Cl2-MeOH) to give 9c (93 mg, 48%) as a
colorless solid: mp 148-150 °C; 1H NMR (200 MHz, CDCl3) δ
3.80-3.86 (m, 4H), 3.89 (s, 6H), 5.98 (s, 2H), 6.78-6.86 (m,
6H); 13C NMR (67.9 MHz, CDCl3) δ 55.9, 56.0, 57.0, 101.3,
108.6, 110.3, 111.4, 112.9, 122.4, 122.5, 123.6, 123.6, 147.8,
148.1, 149.2; HRMS calcd for C17H18O5S (M+) m/e 334.0875,
found m/e 334.0880. Anal. Calcd for C17H18O5S: C, 61.06; H,
5.43. Found: C, 60.62; H, 5.34.
3,4-Dim eth oxyben zyl-3,4,5-tr im eth oxyben zyl Su lfox-
id e (9d ). Sodium hydroxide (28 mg, 0.71 mmol) was added
to a solution of 3,4,5-trimethoxybenzyl mercaptan (152 mg,
0.71 mmol) in EtOH (10 mL). The mixture was stirred for a
few minutes at room temperature, and then 3,4-(methylene-
dioxy)benzyl bromide (164 mg, 0.71 mmol) was added to the
solution. After the solution was stirred for 3 h at room
temperature, the mixture was evaporated and then the residue
was dissolved in AcOEt. The solution was washed with water
and brine and concentrated in vacuo. The residue was purified
by chromatography on silica gel (AcOEt-n-hexane) to give 3,4-
dimethoxybenzyl-3,4,5-tetramethoxybenzyl sulfide (181 mg,
70%).
3,4-Dim eth oxyben zyl 3,4-(Meth ylen edioxy)ben zyl Eth er
(11c): colorless oil; 1H NMR (250 MHz, CDCl3) δ 3.88 (s, 3H),
3.89 (s, 3H), 4.43 (s, 2H), 4.46 (s, 2H), 5.95 (s, 2H), 6.78-6.91
(m, 6H); 13C NMR (50.3 MHz, CDCl3) δ 55.7, 55.8, 71.7, 100.9,
108.0, 108.5, 110.8, 111.0, 120.3, 121.3, 130.7, 132.1, 147.0,
147.7, 148.5, 148.9; HRMS calcd for
C
17H18O5 (M+) m/e
302.1154, found m/e 302.1147. Anal. Calcd for C17H18O5: C,
67.54; H, 6.00. Found: C, 67.64; H, 6.04.
3,4-Dim eth oxyben zyl 3,4,5-Tr im eth oxyben zyl Eth er
(11d ): colorless solid; mp 58-59 °C; 1H NMR (200 MHz,
CDCl3) δ 3.85 (s, 3H), 3.87 (s, 6H), 3.89 (s, 6H), 4.47 (s, 2H),
4.51 (s, 2H), 6.59 (s, 2H), 6.87-6.93 (m, 3H); 13C NMR (75.5
MHz, CDCl3) δ 55.6, 55.7, 55.9, 60.6, 71.8, 71.9, 104.5, 110.7,
111.0, 120.3, 130.5, 133.8, 137.2, 148.5, 148.9, 153.1; HRMS
calcd for C19H24O6 (M+) m/e 348.1573, found m/e 348.1581.
Anal. Calcd for C19H24O6: C, 65.50; H, 6.94. Found: C, 65.36;
H, 6.85.
1,3-Bis(3,4,5-tr im eth oxyben zyl) Eth er (11e): colorless
solid; mp 86-87 °C; 1H NMR (250 MHz, CDCl3) δ 3.83 (s, 6H),
3.85 (s, 12H), 4.48 (s, 4H), 6.59 (s, 4H); 13C NMR (67.9 MHz,
CDCl3) δ 55.7, 60.4, 72.0, 104.3, 133.5, 137.0, 152.9. Anal.
Calcd for C20H26O7: C, 63.48; H, 6.92. Found: C, 63.42; H,
6.88.
Gen er a l P r oced u r e for th e Bia r yl Cou p lin g Rea ction
of P h en ol Eth er Der iva tives Usin g P IF A-BF 3‚Et2O.22 To
a stirred -40 °C solution of the phenol ether derivatives (0.05
mmol) in CH2Cl2 (1.0 mL) was added a solution of PIFA (0.05
mmol) and BF3‚Et2O (0.10 mmol) in CH2Cl2 (1.0 mL) dropwise
under a nitrogen atmosphere. The reaction mixture was then
stirred at -40 °C for 1.5 h and then evaporated in vacuo.
Purification of the residue on silica gel gave the biaryl coupling
products.
2,3,10-T r i m e t h o x y -6,7-d i h y d r o -5H -d i b e n z o [a ,c ]-
cycloh ep ten e16a (4a ). Reactants: 1a (14.2 mg, 0.0498 mmol);
PIFA (21.4 mg, 0.0498 mmol); BF3‚Et2O (6.0 mg, 0.0423 mmol);
CH2Cl2 (1 + 1 mL). 4a (12.8 mg, 91%): colorless solid; mp
70-71 °C (lit.16a mp 79-80 °C); 1H NMR (250 MHz, CDCl3) δ
2.13 (qui, 2H, J ) 6.8 Hz), 2.44 (t, 4H, J ) 6.8 Hz), 3.85 (s,
3H), 3.92 (s, 3H), 3.93 (s, 3H), 6.77 (s, 1H), 6.94 (d, 1H, J )
2.6 Hz), 7.15 (d, 1H, J ) 8.2 Hz); 13C NMR (75.5 MHz, CDCl3)
δ 30.5, 31.0, 33.6, 55.4, 56.0, 56.1, 111.8, 111.9, 114.0, 129.3,
132.0, 132.1, 132.9, 142.2, 147.4, 148.1, 158.3; HRMS calcd
for C18H20O3 (M+) m/e 284.1409, found m/e 284.1403.
2,3,9,10-Bis(m eth ylen ed ioxy)-6,7-d ih yd r o-5H-d iben zo-
[a ,c]cycloh ep ten e (4b). Reactants: 1b (21.6 mg, 0.0760
mmol); PIFA (32.7 mg, 0.0760 mmol); BF3‚Et2O (11.6 mg,
0.0817 mmol); CH2Cl2 (1.5 + 1.5 mL). 4b (19.6 mg, 91%):
colorless solid; mp 149-151 °C; 1H NMR (250 MHz, CDCl3) δ
2.10 (qui, 2H, J ) 6.5 Hz), 2.38 (t, 4H, J ) 6.5 Hz), 5.96 (s,
4H), 6.72 (s, 2H), 6.81 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ
m-Chloroperbenzoic acid (107 mg, 0.50 mmol) was added
to a solution of 3,4-dimethoxybenzyl-3,4,5-tetramethoxybenzyl
sulfide (181 mg, 0.50 mmol) in CH2Cl2 (3 mL) at 0 °C. The
mixture was stirred for 30 h at room temperature and then
quenched with aqueous potassium carbonate. The organic
layer was washed with water and brine and concentrated in
vacuo. The residue was purified by chromatography on silica
gel (CH2Cl2-MeOH) to give 9d (98 mg, 52%) as a colorless
1
solid: mp 127-128 °C; H NMR (250 MHz, CDCl3) δ 3.82-
3.91 (m, 4H), 3.85 (s, 3H), 3.86 (s, 6H), 3.89 (s, 6H), 6.50 (s,
2H), 6.83 (s, 1H), 6.84 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ
55.8, 55.9, 56.0, 57.5, 57.8, 60.7, 106.9, 111.3, 112.8, 122.3,
122.4, 125.8, 137.9, 149.1, 153.3; HRMS calcd for C19H24O6S
(M+) m/e 380.1293, found m/e 380.1285. Anal. Calcd for
C
19H24O6S: C, 59.98; H, 6.36; S, 8.43. Found: C, 59.83; H,
6.28; S, 8.48.
Bis(3,4-d im eth oxyben zyl) Su lfon e (10a ). A 30% solution
of H2O2 (237 mg, 1.12 mmol) was added to a solution of 8 (208
mg, 0.62 mmol) in AcOH (10 mL) at room temperature. After
the solution was stirred for 0.5 h at room temperature,
additional 30% H2O2 (392 mg, 1.87 mmol) was added to the
reaction mixture. The mixture was stirred for 0.5 h at 100 °C
and then cooled. The mixture was quenched with aqueous
NaOH. The solution was extracted with AcOEt, and then the
organic layer was washed with water and brine and concen-
trated in vacuo. The residue was purified by chromatography
on silica gel (n-hexane-AcOEt) to give 10a (71 mg, 31%) as a
colorless solid: mp 164-166 °C; 1H NMR (250 MHz, CDCl3) δ
3.90 (s, 12H), 4.08 (s, 4H), 6.88-6.93 (m, 6H); 13C NMR (67.9
MHz, CDCl3) δ 53.4, 55.9, 56.0, 57.6, 111.1, 113.5, 119.7, 123.4,
149.2, 149.5; HRMS calcd for C18H22O6S (M+) m/e 366.1138,
found m/e 366.1139.
(17) Hart, D. J .; Hong, W.-P.; Hsu, L.-Y. J . Org. Chem. 1987, 52,
4665.
(18) Adderley C. J . R.; Hewgill, F. R. J . Chem. Soc. C 1968, 1434.
(19) Hewgill, F. R. Tetrahedron 1978, 34, 1595.
(20) Semmelhack, M. F.; Helquist, P.; J ones, L. D.; Keller, L.;
Mendelson, L.; Ryono, L. S.; Smith, J . G.; Stauffer, R. D. J . Am. Chem.
Soc. 1981, 103, 6460.
(21) Ziegler, F. E.; Chliwner I.; Fowler, K. W.; Kanfer, S. J .; Kuo, S.
J .; Sinha, N. D. J . Am. Chem. Soc. 1980, 102, 790.
(22) We adopted the ratio, substrate-PIFA-BF3‚Et2O of 1:1:2, from
experimental optimization, though for some substrates without het-
eroatoms only 1 equiv of BF3‚Et2O was enough and for some substrates
having some functional groups that could react with BF3‚Et2O a little
excess of BF3‚Et2O was required.

7704 J . Org. Chem., Vol. 63, No. 22, 1998
Takada et al.
31.2, 33.9, 100.8, 108.6, 108.8, 133.2, 134.1, 146.2, 146.3;
HRMS calcd for C17H14O4 (M+) m/e 282.0893, found m/e
282.0900.
NMR (75.5 MHz, CDCl3) δ 34.3, 48.5, 48.6, 55.9, 56.0, 60.9,
61.1, 110.2, 111.6, 114.1, 116.7 (J ) 287 Hz), 126.7, 127.3,
131.0, 131.4, 142.1, 147.1, 149.0, 151.0, 153.0, 156.3 (J ) 38
Hz); HRMS calcd for C22H24F3NO6 (M+) m/e 455.1555, found
m/e 455.1558. Anal. Calcd for C22H24F3NO6: C, 57.76; H, 5.73;
N, 3.06. Found: C, 57.86; H, 5.38; N, 3.05.
6-(Tr iflu or oa cet yl)-2,3,9,10-b is(m et h ylen ed ioxy)-6,7-
d ih yd r o-5H-d iben z[c,e]a zep in e (6a ). Reactants: 3a (24.7
mg, 0.0648 mmol); PIFA (30.6 mg, 0.0713 mmol); BF3‚Et2O
(18.5 mg, 0.130 mmol); CH2Cl2 (1 + 2 mL). 6a (23.2 mg,
94%): colorless solid; mp 282-285 °C; IR 1686; 1H NMR (270
MHz, CDCl3) δ 4.23 (br, 4H), 6.04 (s, 4H), 6.83, 6.89 (s, 2H),
6.92, 6.94 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ 47.6, 47.9,
48.0, 101.6, 108.2, 108.3, 109.2, 110.5, 116.7 (J ) 288 Hz),
125.5, 125.7, 134.4, 134.6, 147.5, 148.5, 154.7 (J ) 37 Hz);
HRMS calcd for C18H12F3NO5 (M+) m/e 379.0665, found m/e
379.0659. Anal. Calcd for C18H12F3NO5‚1/2H2O: C, 55.68; H,
3.37; N, 3.60. Found: C, 56.02; H, 3.30; N, 3.64.
2,3,9,10-Tet r a m et h oxy-6,7-d ih yd r o-5H -d ib en zo[a ,c]-
cycloh ep ten e10a (4c). Reactants: 1c (22.1 mg, 0.0698 mmol);
PIFA (30.0 mg, 0.0698 mmol); BF3‚Et2O (5.8 mg, 0.0409 mmol);
CH2Cl2 (1.5 + 1.5 mL). 4c (21.7 mg, 99%): colorless solid; mp
159-160 °C (lit10a mp 153-155 °C); 1H NMR (200 MHz,
CDCl3) δ 2.20 (qui, 2H, J ) 7.0 Hz), 2.44 (t, 4H, J ) 7.0 Hz),
3.93 (s, 12H), 6.78 (s, 2H), 6.90 (s, 2H); 13C NMR (67.9 MHz,
CDCl3) δ 31.1, 33.9, 56.0, 56.2, 111.7, 112.0, 132.2, 133.0, 147.5,
147.9; HRMS calcd for C19H22O4 (M+) m/e 314.1519, found m/e
314.1519.
1,2,3,9,10-P en ta m eth oxy-6,7-d ih yd r o-5H-d iben zo[a ,c]-
cycloh ep ten e (4d ). Reactants: 1d (24.7 mg, 0.0713 mmol);
PIFA (30.7 mg, 0.0713 mmol); BF3‚Et2O (20.2 mg, 0.143 mmol);
CH2Cl2 (1.5 + 1.5 mL). 4d (22.5 mg, 92%): colorless solid;
1
mp 110-111 °C; H NMR (250 MHz, CDCl3) δ 2.04-2.14 (m,
2H), 2.29-2.48 (m, 4H), 3.57 (s, 3H), 3.89 (s, 3H), 3.91 (s, 3H),
3.92 (s, 3H), 3.93 (s, 3H), 6.59 (s, 1H), 6.76 (s, 1H), 7.08 (s,
1H); 13C NMR (67.9 MHz, CDCl3) δ 30.9, 31.7, 33.3, 55.8, 56.0,
60.6, 61.2, 107.7, 111.3, 113.5, 126.0, 128.2, 132.3, 136.0, 140.8,
146.7, 147.7, 150.7, 152.1; HRMS calcd for C20H24O5 (M+) m/e
344.1624, found m/e 344.1626.
2-((ter t-Bu tyld im eth ylsilyl)oxy)-3,9,10-tr im eth oxy-6,7-
d ih yd r o-5H-d iben zo[a ,c]cycloh ep ten e (4e). Reactants: 1e
(27.6 mg, 0.0662 mmol); PIFA (28.5 mg, 0.0662 mmol);
BF3‚Et2O (18.8 mg, 0.132 mmol); CH2Cl2 (1.5 + 1.5 mL). 4e
(20.7 mg, 75%): colorless solid; mp 113-115 °C; 1H NMR (200
MHz, CDCl3) δ 0.18 (s, 6H), 1.01 (s, 9H), 2.17 (m, 2H), 2.42
(m, 4H), 3.85 (s, 3H), 3.91 (s, 3H), 3.92 (s, 3H), 6.73 (s, 1H),
6.76 (s, 1H), 6.85 (s, 1H), 6.86 (s, 1H); 13C NMR (75.5 MHz,
CDCl3) δ -4.5, 18.5, 25.8, 31.1, 31.2, 33.8, 55.7, 56.0, 56.1,
111.8, 111.9, 112.7, 120.7, 132.0, 133.0, 133.3, 143.4, 147.4,
147.7, 149.7; HRMS calcd for C24H34O4Si (M+) m/e 414.2227,
found m/e 414.2232.
6-(Tr iflu or oa cetyl)-2,3,9,10-tetr a m eth oxy-6,7-d ih yd r o-
5H-d iben z[c,e]a zep in e (6b). Reactants: 3b (23.3 mg, 0.0564
mmol); PIFA (26.7 mg, 0.0620 mmol); BF3‚Et2O (16.0 mg, 0.113
mmol); CH2Cl2 (1 + 2 mL). 6b (19.6 mg, 85%): colorless solid;
1
mp 166-167 °C; IR 1686; H NMR (500 MHz, CDCl3) δ 3.94
(s, 6H), 3.98 (s, 6H), 4.30, 4.41 (br., 4H), 6.86, 6.94 (s, 2H),
7.00, 7.02 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ 47.7, 48.2,
56.1, 56.2, 110.8, 110.9, 112.1, 113.3, 116.7 (J ) 288 Hz), 124.5,
124.6, 133.1, 148.7, 149.5, 149.7, 154.6 (J ) 35 Hz); HRMS
calcd for C20H20F3NO5 (M+) m/e 411.1293, found m/e 411.1303.
Anal. Calcd for C20H20F3NO5: C, 58.39; H, 4.90; N, 3.40.
Found: C, 58.31; H, 4.96; N, 3.39.
6-(Tr iflu or oa cet yl)-1,2,3,9,10-p en t a m et h oxy-6,7-d ih y-
d r o-5H-d iben z[c,e]a zep in e (6c). Reactants: 3c (23.1 mg,
0.0521 mmol); PIFA (24.6 mg, 0.0573 mmol); BF3‚Et2O (14.8
mg, 0.104 mmol); CH2Cl2 (1 + 2 mL). 6c (19.6 mg, 85%):
1
colorless solid; mp 142-144 °C; IR 1686; H NMR (270 MHz,
CDCl3) δ 3.67, 3.92, 3.93, 3.94, 3.95, 3.96 (s, 15H), 3.51-3.98
(m, 2H), 4.61 (dd, 1H, J ) 11.9, 9.9 Hz), 5.06 (dd, 1H, J )
13.9, 11.6 Hz), 6.68, 6.77, 6.84, 6.93 (s, 2H), 7.24-7.27 (m, 1H);
13C NMR (50.3 MHz, CDCl3) δ 47.8, 48.2, 48.3, 48.4, 48.5, 56.0,
56.1, 60.9, 61.0, 61.2, 108.2, 109.4, 111.5, 112.7, 113.0, 116.7
(J ) 288 Hz), 124.5, 124.7, 126.0, 128.2, 128.3, 142.8, 143.0,
148.5, 148.6, 148.8, 150.8, 150.9, 153.1, 154.6 (J ) 36 Hz);
HRMS calcd for C21H22F3NO6 (M+) m/e 441.1397, found m/e
441.1397. Anal. Calcd for C21H22F3NO6: C, 57.14; H, 5.02;
N, 3.17. Found: C, 57.18; H, 5.14; N, 3.14.
6-(Tr iflu or oa ce t yl)-2,3,11-t r im e t h oxy-5,6,7,8-t e t r a -
h yd r od iben z[c,e]a zocin e13b (5a ). Reactants: 2a (31.1 mg,
0.0783 mmol); PIFA (37.0 mg, 0.0861 mmol); BF3‚Et2O (12.2
mg, 0.0861 mmol); CH2Cl2 (0.5 + 2 mL). 5a (27.7 mg, 89%):
1
colorless solid; mp 134-136 °C; IR 1686; H NMR (270 MHz,
CDCl3) δ 2.41 (dd, 1H, J ) 14.7, 9.7 Hz), 2.99 (dd, 1H, J )
14.7, 7.1 Hz), 3.19 (dd, 1H, J ) 14.2, 10.6 Hz), 3.31 (d, 1H, J
) 13.9 Hz), 3.85 (s, 3H), 3.90 (s, 3H), 3.94 (s, 3H), 4.26 (dd,
1H, J ) 12.7, 6.4 Hz), 5.19 (d, 1H, J ) 13.9 Hz), 6.82 (s, 1H),
6.86 (d, 1H, J ) 2.6 Hz), 6.93 (dd, 1H, J ) 8.6, 2.6 Hz), 7.18
(d, 1H, J ) 8.6 Hz), 7.40 (s, 1H); HRMS calcd for C20H20F3-
NO4 (M+) m/e 395.1341, found m/e 395.1338. Anal. Calcd for
6-(Tr iflu or oa cet yl)-2-((ter t-b u t yld im et h ylsilyl)oxy)-
3,9,10-tr im eth oxy-6,7-dih ydr o-5H-diben z[c,e]azepin e (6d).
Reactants: 3d (28.4 mg, 0.0553 mmol); PIFA (26.2 mg, 0.0608
mmol); BF3‚Et2O (15.7 mg, 0.111 mmol); CH2Cl2 (1 + 2 mL).
6d (18.0 mg, 64%): colorless solid; mp 172-173 °C; IR 1688;
1H NMR (250 MHz, CDCl3) δ 0.19, 0.20 (s, 6H), 0.97, 0.98 (s,
9H), 3.86 (s, 3H), 3.93 (s, 3H), 3.96 (s, 3H), 4.28, 4.36 (br, 4H),
6.81, 6.83, 6.90, 6.92, 6.94, 6.95, 6.98, 7.00 (s, 4H); 13C NMR
(75.5 MHz, CDCl3) δ -3.9, 19.1, 26.3, 48.4, 48.5, 48.8, 48.9,
56.2, 56.7, 111.5, 111.6, 112.6, 113.4, 113.9, 114.6, 117.4 (J )
287 Hz), 120.8, 120.9, 124.8, 125.0, 125.9, 126.1, 133.6, 133.8,
146.2, 146.4, 149.2, 150.1, 150.2, 151.2, 155.3 (J ) 36 Hz);
HRMS calcd for C25H32F3NO5Si (M+) m/e 511.2002, found m/e
551.1972. Anal. Calcd for C25H32F3NO5Si: C, 58.69; H, 6.30;
N, 2.74. Found: C, 58.39; H, 6.24; N, 2.80.
C
20H20F3NO4: C, 60.76; H, 5.10; N, 3.54. Found C, 60.56; H,
5.07; N, 3.55.
6-(Tr iflu or oa cetyl)-2,3,10,11-tetr a m eth oxy-5,6,7,8-tet-
r a h yd r od iben z[c,e]a zocin e (5b). Reactants: 2b (19.7 mg,
0.0461 mmol); PIFA (21.8 mg, 0.0507 mmol); BF3‚Et2O (13.1
mg, 0.0922 mmol); CH2Cl2 (1 + 2 mL). 5b (13.3 mg, 68%):
1
colorless solid; mp 157-158 °C; IR 1686; H NMR (250 MHz,
CDCl3) δ 2.42 (dd, 1H, J ) 15.0, 10.0 Hz), 2.96 (dd, 1H, J )
14.5, 6.8 Hz), 3.22 (dd, 1H, J ) 14.0, 10.3 Hz), 3.31 (d, 1H, J
) 13.5 Hz), 3.92 (s, 6H), 3.95 (s, 6H), 4.26 (dd, 1H, J ) 13.5,
6.8 Hz), 5.20 (d, 1H, J ) 13.5 Hz), 6.75 (s, 1H), 6.82 (s, 2H),
7.40 (s, 1H); 13C NMR (75.5 MHz, CDCl3) δ 34.5, 48.3, 48.5,
56.0, 56.1, 111.9, 112.1, 112.9, 114.0, 116.7 (J ) 287 Hz), 127.2,
131.0, 132.0, 132.9, 147.7, 148.5, 148.6, 148.9, 156.3 (J ) 35
Hz); HRMS calcd for C21H22F3NO5 (M+) m/e 425.1443, found
m/e 425.1445. Anal. Calcd for C21H22F3NO5: C, 59.21; H, 5.21;
N, 3.29. Found: C, 59.33; H, 5.26; N, 3.30.
6-(Tr iflu or oa cetyl)-2-a cetoxy-3,9,10-tr im eth oxy-6,7-d i-
h yd r o-5H-d iben z[c,e]a zep in e (6e). Reactants: 3e (28.0 mg,
0.0634 mmol); PIFA (30.0 mg, 0.0698 mmol); BF3‚Et2O (18.0
mg, 0.127 mmol); CH2Cl2 (1 + 2 mL). 6e (16.7 mg, 60%):
1
colorless solid; mp 174-176 °C; IR 1767, 1684; H NMR (500
6-(Tr iflu or oa cet yl)-1,2,3,10,11-p en t a m et h oxy-5,6,7,8-
tetr a h yd r od iben z[c,e]a zocin e (5c). Reactants: 2c (30.6
mg, 0.0669 mmol); PIFA (31.6 mg, 0.0736 mmol); BF3‚Et2O
(19.0 mg, 0.134 mmol); CH2Cl2 (1.5 + 2 mL). 5c (15.9 mg,
52%): colorless solid; mp 135-136 °C; IR 1685; 1H NMR (250
MHz, CDCl3) δ 2.43 (dd, 1H, J ) 14.5, 10.5 Hz), 2.94 (dd, 1H,
J ) 14.5, 6.8 Hz), 3.18 (dd, 1H, J ) 14.3, 10.5 Hz), 3.26 (d,
1H, J ) 14.0 Hz), 3.55 (s, 3H), 3.87 (s, 3H), 3.90 (s, 3H), 3.92
(s, 3H), 3.93 (s, 3H), 4.23 (dd, 1H, J ) 14.3, 6.3 Hz), 5.13 (d,
1H, J ) 13.5 Hz), 6.74 (s, 1H), 6.84 (s, 1H), 6.93 (s, 1H); 13C
MHz, CDCl3) δ 2.36 (s, 3H), 3.90 (s, 3H), 3.94 (s, 3H), 3.95 (s,
3H), 4.33 (s, 2H), 4.40 (brs, 2H), 6.84, 6.93, 6.95, 6.97, 7.05 (s,
3H), 7.21, 7.23 (s, 1H); 13C NMR (67.9 MHz, CDCl3) δ 20.7,
47.9, 48.3, 110.9, 111.0, 112.1, 113.3, 114.5, 116.7 (J ) 287
Hz), 122.3, 124.2, 124.3, 130.6, 132.2, 133.2, 140.2, 140.4,
148.9, 149.6, 149.8, 154.8 (J ) 36 Hz), 168.9; HRMS calcd for
C
21H20NO6F3 (M+) m/e 439.1283, found m/e 439.1264.
6,6-Diisop r op yl-2,3,9,10-tetr a m eth oxy-6,7-d ih yd r o-5H-
6-sila d iben zo[a ,c]cycloh ep ten e (12a ). Reactants: 7a (19.1
mg, 0.0454 mmol); PIFA (19.5 mg, 0.0454 mmol); BF3‚Et2O

A Coupling Reaction of Phenol Ether Derivatives
J . Org. Chem., Vol. 63, No. 22, 1998 7705
(12.9 mg, 0.0908 mmol); CH2Cl2 (1 + 1 mL). 12a (13.3 mg,
56%): colorless solid; mp 132-133 °C; 1H NMR (200 MHz,
CDCl3) δ 1.09 (d, 12H, J ) 5.4 Hz), 1.18 (m, 2H), 3.90 (s, 12H),
6.62 (s, 2H), 6.81 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ 12.4,
17.0, 56.0, 56.5, 105.0, 113.3, 120.3, 144.7, 146.4, 149.3; HRMS
calcd for C22H30O6Si (M+) m/e 418.1811, found m/e 418.1813.
6,6-Diisop r op yl-2,3,9,10-bis(m eth ylen ed ioxy)-6,7-d ih y-
) 14.8 Hz), 3.37 (d, 1H, J ) 17.8 Hz), 3.66 (d, 1H, J ) 17.8
Hz), 4.07 (d, 1H, J ) 14.8 Hz), 6.03 (dd, 4H, J ) 6.0, 2.4 Hz),
6.82 (s, 1H), 6.83 (s, 1H), 6.88 (s, 2H); 13C NMR (67.9 MHz,
CDCl3) δ 53.2, 55.6, 101.5, 101.6, 109.0, 109.5, 109.7, 111.6,
122.1, 123.3, 134.2, 134.3, 147.0, 147.3, 148.3, 148.5; HRMS
calcd for C16H12O5S (M+) m/e 316.0405, found m/e 316.0441.
Anal. Calcd for C16H12O5S: C, 60.75; H, 3.82. Found: C,
60.33; H, 3.91.
d r o-5H-6-sila d iben zo[a ,c]cycloh ep ten e (12b).
Reac-
tants: 7b (12.5 mg, 0.0322 mmol); PIFA (13.8 mg, 0.0454
mmol); BF3‚Et2O (9.1 mg, 0.0644 mmol); CH2Cl2 (1 + 1 mL).
12b (13.3 mg, 56%): colorless solid; mp 148-149 °C; 1H NMR
(200 MHz, CDCl3) δ 1.09 (d, 12H, J ) 5.4 Hz), 1.18 (m, 2H),
3.90 (s, 12H), 6.62 (s, 2H), 6.81 (s, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 12.2, 17.0, 101.4, 102.5, 109.4, 121.6, 143.3, 147.0,
2,3-Dim et h oxy-9,10-(m et h ylen ed ioxy)-5,7-d ih yd r od i-
ben zo[c,e]th iep in e 6-Oxid e (13c). Reactants: 9c (12.0 mg,
0.0359 mmol); PIFA (19.3 mg, 0.108 mmol); BF3‚Et2O (15.3
mg, 0.108 mmol); CH2Cl2 (1 + 1 mL). 13c (7.1 mg, 59%):
colorless solid; mp 247-248 °C; 1H NMR (270 MHz, CDCl3) δ
3.19, 3.23 (d, 1H, J ) 12.5 Hz), 3.37, 3.45 (d, 1H, J ) 14.5
Hz), 3.65, 3.71 (d, 1H, J ) 8.3 Hz), 3.92, 3.93 (s, 3H), 3.94,
3.95 (s, 3H), 4,03-4.14 (m, 1H), 6.02-6.06 (m, 2H), 6.83-6.93
(m, 4H); 13C NMR (67.9 MHz, CDCl3) δ 53.2, 53.3, 55.6, 56.1,
56.2, 101.5, 101.6, 109.0, 109.4, 109.8, 111.6, 111.8, 112.1,
112.5, 114.1, 121.1, 122.2, 123.1, 132.8, 132.8, 134.3, 134.4,
146.9, 147.2, 148.2, 148.5, 149.3, 149.6; HRMS calcd for
147.5. Anal. Calcd for
Found: C, 62.13; H, 5.73.
C20H22O6Si: C, 62.16; H, 5.74.
6,6-Diisop r op yl-2,3-d im eth oxy-9,10-(m eth ylen ed ioxy)-
6,7-d ih yd r o-5H-6-sila d iben zo[a ,c]cycloh ep ten e (12c). Re-
actants: 7c (15.4 mg, 0.0381 mmol); PIFA (16.3 mg, 0.0381
mmol); BF3‚Et2O (16.2 mg, 0.144 mmol); CH2Cl2 (1 + 1 mL).
12c (7.0 mg, 46%): colorless solid; mp 129-130 °C; H NMR
C
17H16O5S (M+) m/e 332.0718, found m/e 333.0711.
1
(250 MHz, CDCl3) δ 1.08 (d, 12H, J ) 6.8 Hz), 1.16 (m, 2H),
3.88 (s, 6H), 5.97 (s, 2H), 6.58 (s, 1H), 6.60 (s, 1H), 6.76 (s,
1H), 6.78 (s, 1H); 13C NMR (67.9 MHz, CDCl3) δ 12.3, 17.0,
56.0, 56.3, 101.4, 102.5, 104.9, 109.3, 113.2, 120.3, 121.5, 143.2,
144.7, 146.2, 147.1, 147.5, 149.1. Anal. Calcd for C21H26O6-
Si: C, 62.66; H, 6.51. Found: C, 62.52; H, 6.53.
1,2,3,9,10-P en t a m et h oxy-5,7-d ih yd r od ib en zo[c,e]t h i-
ep in e 6-Oxid e (13d ). Reactants: 9d (13.2 mg, 0.0347 mmol);
PIFA (14.9 mg, 0.0347 mmol); BF3‚Et2O (9.8 mg, 0.0694 mmol);
CH2Cl2 (1 + 1 mL). 13d (5.6 mg, 42%): colorless solid; mp
193-194 °C; 1H NMR (270 MHz, CDCl3) δ 3.15, 3.25 (d, 1H, J
) 11.7 Hz), 3.36, 3.47 (d, 1H, J ) 13.8 Hz), 3.63, 3.75 (s, 3H),
3.68 (m, 1H), 3.91, 3.92 (s, 3H), 3.94 (s, 6H), 3.95, 3.96 (s, 3H),
4.05-4.17 (m, 1H), 6.69, 6.75 (s, 1H), 6.85, 6.92 (s, 1H), 7.03,
7.09 (s, 1H); 13C NMR (75.5 MHz, CDCl3) δ 53.4, 53.6, 55.6,
55.8, 56.0, 56.1, 56.2, 60.9, 61.0, 61.1, 109.0, 110.6, 112.1, 113.6,
113.8, 114.1, 121.2, 122.3, 124.4, 125.7, 125.8, 125.9, 128.2,
128.5, 142.6, 143.1, 148.1, 148.4, 148.7, 149.0, 151.0, 151.4,
152.7, 152.9; HRMS calcd for C19H22O6S (M+) m/e 378.1137,
found m/e 378.1145.
2,3,9,10-Te t r a m e t h oxy-5,7-d ih yd r od ib e n zo[c,e]t h i-
ep in e 6,6-Dioxid e (14a ). Reactants: 10a (39.4 mg, 0.107
mmol); PIFA (48.1 mg, 0.112 mmol); BF3‚Et2O (31.8 mg, 0.223
mmol); CH2Cl2 (1 + 1 mL). 14a (32.3 mg, 83%): colorless solid;
mp >300 °C; 1H NMR (250 MHz, CDCl3) δ 3.90-4.05 (m, 4H),
3.96 (s, 6H), 3.97 (s, 6H), 6.94 (s, 2H), 6.96 (s, 2H); 13C NMR
(75.5 MHz, CDCl3) δ 56.2, 56.2, 57.3, 111.9, 113.2, 120.6, 132.6,
149.3, 149.6; HRMS calcd for C18H20O6S (M+) m/e 364.0980,
found m/e 364.0979.
2,3,9,10-Bis(m eth ylen ed ioxy)-5,7-d ih yd r od iben zo[c,e]-
th iep in e 6,6-Dioxid e (14b). Reactants: 10b (22.8 mg, 0.0682
mmol); PIFA (29.3 mg, 0.0682 mmol); BF3‚Et2O (19.4 mg, 0.136
mmol); CH2Cl2 (3 + 1 mL). 14b (16.3 mg, 72%): colorless solid;
mp >300 °C; 1H NMR (250 MHz, CDCl3) δ 3.90 (m, 4H), 6.06
(dd, 4H, J ) 8.0, 1.3 Hz), 6.89 (s, 2H), 6.91 (s, 2H); 13C NMR
(75.5 MHz, CDCl3) δ 57.0, 57.7, 101.5, 101.9, 108.6, 109.3,
110.5, 110.9, 121.7, 124.6, 133.9, 148.1, 148.2, 148.4, 148.6;
HRMS calcd for C16H12O6S (M+) m/e 332.0354, found m/e
332.0353.
2 ,3 ,9 ,1 0 -T e t r a m e t h o x y -5 ,7 -d i h y d r o d i b e n z [c ,e ]-
oxep in e10a (15a ). Reactants: 11a (14.3 mg, 0.0449 mmol);
PIFA (19.3 mg, 0.0449 mmol); BF3‚Et2O (12.7 mg, 0.0898
mmol); CH2Cl2 (1 + 1 mL). 15a (12.0 mg, 85%): colorless solid;
mp 243-244 °C (lit.10a mp 247.1 °C); 1H NMR (200 MHz,
CDCl3) δ 3.96 (s, 6H), 3.99 (s, 6H), 4.28 (s, 4H) 6.96 (s, 2H),
7.03 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ 56.0, 56.2, 67.3,
110.2, 112.7, 127.9, 133.8, 148.5, 149.3.
6,6-Di-ter t-bu tyl-2,3,9,10-tetr a m eth oxy-6,7-d ih yd r o-5H-
6-sila d iben zo[a ,c]cycloh ep ten e (12d ). Reactants: 7d (30.7
mg, 0.0684 mmol); PIFA (29.4 mg, 0.0684 mmol); BF3‚Et2O
(29.1 mg, 0.205 mmol); CH2Cl2 (1 + 1 mL). 12d (23.9 mg,
78%): colorless solid; mp 193-194 °C; 1H NMR (200 MHz,
CDCl3) δ 1.06 (s, 18H), 3.89 (s, 6H), 3.90 (s, 6H), 6.61 (s, 2H),
6.80 (s, 2H); 13C NMR (67.9 MHz, CDCl3) δ 21.4, 27.7, 56.1,
56.6, 105.2, 113.7, 119.9, 144.5, 147.3, 149.3; HRMS calcd for
C
24H34O6Si (M+) m/e 446.2124, found m/e 446.2124. Anal.
Calcd for C24H34O6Si: C, 64.54; H, 7.67. Found: C, 64.70; H,
7.69.
6,6-Di-ter t-bu tyl-2,3,9,10-bis(m eth ylen ed ioxy)-6,7-d ih y-
d r o-5H -6-sila d ib en zo[a ,c]cycloh ep t en e (12e).
Reac-
tants: 7e (20.8 mg, 0.0499 mmol); PIFA (21.5 mg, 0.0499
mmol); BF3‚Et2O (14.2 mg, 0.0998 mmol); CH2Cl2 (1 + 1 mL).
12e (16.6 mg, 80%): colorless solid; mp 253-254 °C; 1H NMR
(250 MHz, CDCl3) δ 1.04 (s, 18H), 5.96 (s, 4H), 6.57 (s, 2H),
6.71 (s, 2H); 13C NMR (75.5 MHz, CDCl3) δ 21.3, 27.7, 101.4,
102.6, 109.7, 121.1, 143.0, 147.5, 147.9. Anal. Calcd for
C
22H26O6Si: C, 63.74; H, 6.32. Found: C, 63.79; H, 6.33.
6,6-Di-ter t-bu tyl-2,3-d im eth oxy-9,10-m eth ylen ed ioxy-
6,7-d ih yd r o-5H-6-sila d iben zo[a ,c]cycloh ep ten e (12f). Re-
actants: 7f (14.3 mg, 0.0331 mmol); PIFA (14.2 mg, 0.0331
mmol); BF3‚Et2O (14.0 mg, 0.0993 mmol); CH2Cl2 (1 + 1 mL).
12f (11.9 mg, 83%): colorless solid; mp 140-142 °C; 1H NMR
(250 MHz, CDCl3) δ 1.05 (s, 18H), 3.88 (s, 6H), 3.89 (s, 6H),
5.97 (s, 2H), 6.59 (s, 1H), 6.60 (s, 1H), 6.74 (s, 1H), 6.77 (s,
1H); 13C NMR (75.5 MHz, CDCl3) δ 21.3, 27.7, 56.0, 56.3, 101.4,
102.6, 104.2, 109.5, 113.5, 119.9, 121.1, 143.0, 144.5, 147.0,
147.4, 148.0, 149.1; HRMS calcd for C23H30O6Si (M+) m/e
430.1811, found m/e 430.1811.
2,3,9,10-Te t r a m e t h oxy-5,7-d ih yd r od ib e n zo[c,e]t h i-
ep in e 6-Oxid e (13a ). Reactants: 9a (13.8 mg, 0.0394 mmol);
PIFA (16.9 mg, 0.0394 mmol); BF3‚Et2O (11.2 mg, 0.0788
mmol); CH2Cl2 (1 + 1 mL). 13a (10.0 mg, 73%): colorless solid;
1
mp >300 °C; H NMR (250 MHz, CDCl3) δ 3.25 (d, 1H, J )
2,3,9,10-Bis(m et h ylen ed ioxy)-5,7-d ih yd r od ib en z[c,e]-
oxep in e (15b). Reactants: 11b (59.3 mg, 0.207 mmol); PIFA
(89.0 mg, 0.207 mmol); BF3‚Et2O (58.8 mg, 0.414 mmol); CH2-
Cl2 (1 + 1 mL). 15b (47.6 mg, 81%): colorless solid; mp 226-
228 °C; 1H NMR (200 MHz, CDCl3) δ 4.21 (s, 4H), 6.03 (s, 4H),
6.89 (s, 2H), 6.94 (s, 2H); 13C NMR (75.5 MHz, CDCl3) δ 67.0,
101.3, 107.5, 109.8, 128.9, 135.2, 147.1, 148.1; HRMS calcd
for C16H12O5 (M+) m/e 284.0685, found m/e 284.0678.
2,3-Dim et h oxy-9,10-(m et h ylen ed ioxy)-5,7-d ih yd r od i-
ben z[c,e]oxep in e (15c). Reactants: 11c (20.6 mg, 0.0681
mmol); PIFA (29.3 mg, 0.0681 mmol); BF3‚Et2O (19.3 mg, 0.136
mmol); CH2Cl2 (1 + 1 mL). 15c (11.0 mg, 54%): colorless solid;
mp 221-222 °C; 1H NMR (200 MHz, CDCl3) δ 3.95 (s, 3H),
12.3 Hz), 3.45 (d, 1H, J ) 14.0 Hz), 3.71 (d, 1H, J ) 14.8 Hz),
4.12 (d, 1H, J ) 12.3 Hz), 3.94 (s, 3H), 3.96 (s, 6H), 6.86 (s,
1H), 6.91 (s, 1H), 6.93 (s, 1H), 6.96 (s, 1H); 13C NMR (75.5
MHz, CDCl3) δ 53.3, 55.6, 56.1, 56.2, 56.3, 111.9, 112.1, 112.6,
114.2, 121.2, 122.1, 132.9, 133.0, 148.2, 148.5, 149.3, 149.7;
HRMS calcd for C18H20O5S (M+) m/e 348.1030, found m/e
348.1028.
2,3,9,10-Bis(m eth ylen ed ioxy)-5,7-d ih yd r od iben zo[c,e]-
th iep in e 6-Oxid e (13b). Reactants: 9b (14.3 mg, 0.0449
mmol); PIFA (19.3 mg, 0.0449 mmol); BF3‚Et2O (19.1 mg, 0.135
mmol); CH2Cl2 (1 + 1 mL). 13b (10.1 mg, 71%): colorless solid;
1
mp 269-270 °C; H NMR (200 MHz, CDCl3) δ 3.17 (d, 1H, J

7706 J . Org. Chem., Vol. 63, No. 22, 1998
Takada et al.
3.96 (s, 3H), 4.21 (s, 2H), 4.28 (s, 2H), 6.03 (s, 2H), 6.91 (s,
1H), 6.94 (s, 1H), 6.98 (s, 1H), 7.01 (s, 1H); 13C NMR (75.5
MHz, CDCl3) δ 56.1, 67.2, 101.3, 107.4, 109.9, 110.2, 112.6,
127.7, 129.1, 133.7, 135.4, 147.0, 148.1, 148.5, 149.3. Anal.
Calcd for C17H16O5: C, 67.99; H, 5.37. Found: C, 68.02; H,
5.34.
1,2,3,9,10-P e n t a m e t h oxy-5,7-d ih yd r od ib e n z[c,e]ox-
ep in e (15d ). Reactants: 11e (45.2 mg, 0.130 mmol); PIFA
(55.9 mg, 0.130 mmol); BF3‚Et2O (36.9 mg, 0.260 mmol); CH2-
Cl2 (1 + 1 mL). 15d (31.4 mg, 70%): colorless solid; mp 124-
125 °C; 1H NMR (250 MHz, CDCl3) δ 3.66 (s, 3H), 3.93 (s, 3H),
3.94 (s, 3H), 3.95 (s, 3H), 3.96 (s, 3H), 4.10-4.50 (m, 4H), 6.77
(s, 1H), 6.94 (s, 1H), 7.30 (s, 2H); 13C NMR (67.9 MHz, CDCl3)
δ 55.9, 56.1, 60.8, 61.2, 67.3, 67.6, 108.9, 112.1, 112.5, 126.5,
127.9, 129.7, 131.4, 142.6, 148.3, 148.5, 150.4, 152.8. Anal.
Calcd for C19H22O6: C, 65.88; H, 6.40. Found: C, 65.81; H,
6.36.
1,2,3,9,10,11-H exa m et h oxy-5,7-d ih yd r od ib en z[c,e]ox-
ep in e (15e). Reactants: 11d (20.6 mg, 0.0544 mmol); PIFA
(23.4 mg, 0.0544 mmol); BF3‚Et2O (15.5 mg, 0.109 mmol); CH2-
Cl2 (1 + 1 mL). 15d (7.8 mg, 38%): colorless solid; mp 111-
113 °C; 1H NMR (200 MHz, CDCl3) δ 3.70 (s, 3H), 3.75 (d, 1H,
J ) 11.4 Hz), 3.91 (s, 3H), 3.93 (s, 3H), 3.95 (s, 6H), 3.96 (s,
3H), 3.99 (d, 1H), 4.39 (d, 1H, J ) 11.2 Hz), 4.98 (d, 1H, J )
11.2 Hz), 6.77 (s, 1H), 7.07 (s, 1H); 13C NMR (67.9 MHz, CDCl3)
δ 56.0, 59.7, 60.9, 61.0, 61.1, 62.1, 67.5, 108.7, 121.6, 126.3,
128.2, 131.4, 133.1, 141.3, 142.5, 150.4, 151.6, 152.7, 153.0;
HRMS calcd for C20H24O7 (M+) m/e 376.1522, found m/e
376.1521. Anal. Calcd for C20H24O7: C, 63.82; H, 6.43.
Found: C, 63.73; H, 6.37.
2H), 6.65 (s, 2H); HRMS calcd for C14H10O6 (M+) m/e 274.0477,
found m/e 274.0469.
2,2′-Dim eth yl-4,5,4′,5′-bis(m eth ylen ed ioxy)bip h en yl20
(17b). To a solution of 13b (8.9 mg, 0.028 mmol) in EtOH
(5.0 mL) was added excess Raney Ni (w-1) as a catalyst. The
suspension was refluxed for 7 h and then cooled. The catalyst
was filtered, and then the filtrate was evaporated in vacuo.
Purification of the residue on a preparative TLC gave 17b (7.3
mg, 97%): colorless solid; mp 120-121 °C; 1H NMR (200 MHz,
CDCl3) δ 1.96 (s, 6H), 5.95 (s, 4H), 6.56 (s, 2H), 6.73 (s, 2H);
13C NMR (67.9 MHz, CDCl3) δ 19.6, 100.8, 109.8, 109.8, 129.3,
134.2, 145.3, 146.5; HRMS calcd for C16H14O4 (M+) m/e
270.0892, found m/e 270.0890.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2,2′-Di-
for m yl Der iva tives (18). To a stirred solution of 15 (0.05
mmol) in CH2Cl2 (2.0 mL) containing H2O (0.11-0.15 mL) was
added DDQ (0.14-0.15 mmol) at room temperature. The
reaction mixture was refluxed for 24 h and then cooled. The
mixture was quenched with saturated sodium bicarbonate
solution and then washed with water and brine. The organic
layer was evaporated in vacuo and then purified by column
chromatography on silica gel to give the 2,2′-diformylbiphenyl
derivatives (18).
2,2′-Difor m yl-4,4′,5,5′-tetr am eth oxybiph en yl21 (18a). Re-
actants: 15a (14.6 mg, 0.046 mmol); DDQ (29.4 mg, 0.123
mmol); CH2Cl2 (2.0 mL); H2O (0.15 mL). 18a (10.0 mg, 66%):
colorless solid; mp 213-215 °C (lit.21 mp 213-215 °C); IR 1682;
1H NMR (250 MHz, CDCl3) δ 3.96 (s, 3H), 4.01 (s, 3H), 6.80
(s, 2H), 7.56 (s, 2H), 9.67 (s, 2H); HRMS calcd for C18H18O6
(M+) m/e 330.1103, found m/e 330.1105.
P r ep a r a tion of 2,2′-Su bstitu ted Bip h en yl Der iva tives.
Gen er a l P r oced u r e for th e P r ep a r a tion of 2,2′-Dih y-
d r oxy Der iva t ives (16). To a stirred solution of 12 (0.05
mmol) in THF (1.0 mL) was added 1.0 M solution of TBAF in
THF (0.05 mL) at room temperature. The reaction mixture
was then stirred at room temperature for 2 h and then
evaporated in vacuo. Purification of the residue on preparative
TLC gave the 2,2′-dihydroxybiphenyl derivatives (16).
4,4′,5,5′-Tetr a m eth oxybip h en yl-2,2′-d iol18 (16a ). Reac-
tants: 12a (23.9 mg, 0.054 mmol); 1.0 M TBAF solution in
THF (0.054 mL, 0.054 mmol); THF (1.0 mL). 16a (15.8 mg,
96%): colorless solid; mp 182-184 °C (lit.18 mp 181.5-182.5
2,2′-Difor m yl-4,4′,5,5′-b is(m et h ylen ed ioxy)b ip h en yl21
(18b). Reactants: 15b (12.6 mg, 0.044 mmol); DDQ (27.1 mg,
0.119 mmol); CH2Cl2 (2.0 mL); H2O (0.11 mL). 18b (7.3 mg,
56%): colorless solid; mp 245-248 °C (lit.21 mp 213-215 °C);
1
IR 1682; H NMR (200 MHz, CDCl3) δ 6.15 (s, 4H), 6.77 (s,
2H), 7.48 (s, 2H), 9.61 (s, 2H); HRMS calcd for C16H10O6 (M+)
m/e 298.0477, found m/e 298.0479.
2,2′-Difor m yl-3,4,4′,5,5′-p en ta m eth oxybip h en yl (18d ).
Reactants: 15d (13.2 mg, 0.038 mmol); DDQ (25.9 mg, 0.114
mmol); CH2Cl2 (2.0 mL); H2O (0.11 mL). 18d (6.0 mg, 46%):
1
colorless solid; mp 152-153 °C; IR 1688, 1682; H NMR (200
1
°C); IR 3319; H NMR (250 MHz, CDCl3) δ 3.84 (s, 6H), 3.87
MHz, CDCl3) δ 3.61 (s, 3H), 3.94 (s, 3H), 3.99 (s, 3H), 4.01 (s,
3H), 4.02 (s, 3H), 6.73 (s, 1H), 7.40 (s, 1H), 7.57 (s, 1H), 9.62
(s, 1H), 9.65 (s, 1H); 13C NMR (75.5 MHz, CDCl3) δ 56.1, 56.2,
56.3, 61.0, 61.2, 105.6, 108.8, 114.3, 128.7, 130.4, 131.2, 149.3,
151.3, 153.2, 153.9, 190.0, 190.1; HRMS calcd for C19H20O7
(M+) m/e 360.1209, found m/e 360.1211.
(s, 6H), 6.62 (s, 2H), 6.72 (s, 2H); HRMS calcd for C16H18O6
(M+) m/e 306.1103, found m/e 306.1101.
4,5,4′,5′-Bis(m eth ylen ed ioxy)bip h en yl-2,2′-d iol19 (16b).
Reactants: 12b (16.6 mg, 0.040 mmol); 1.0 M TBAF solution
in THF (0.040 mL, 0.040 mmol); THF (2.0 mL). 16b (10.6 mg,
97%): colorless solid; mp 201-202 °C (lit.19 mp 207-207.5 °C);
1
IR 3264; H NMR (250 MHz, CD3OD) δ 5.88 (s, 4H), 6.46 (s,
J O980704F