PdII-Catalyzed Reaction of Phenols with Propiolic Esters. A Single-Step Synthesis of Coumarins

Article abstract of DOI:10.1246/bcsj.76.1889

The intermolecular reaction of phenols with propiolic esters in TFA in the presence of a Pd(OAc)₂ catalyst, affording coumarin derivatives, is described. An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin was observed in the reaction of 3,4,5-trimethoxyphenol and ethyl phenylpropiolate with a catalytic amount of Pd(OAc)₂. The reaction in the absence of Pd(OAc)₂ did not give any coumarin at all. Coumarin derivatives were obtained in high yields in the cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-dimethoxyphenol. Furthermore, the reaction of some phenols with various 2-alkynoates or with diethyl acetylenedicarboxylate gave the corresponding coumarins in good-to-high yields.

Full text of DOI:10.1246/bcsj.76.1889

Ó 2003 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 76, 1889–1895 (2003) 1889
Headline Articles
b
Pd -Catalyzed Reaction of Phenols with Propiolic Esters.
A Single-Step Synthesis of Coumarins
ꢀ
Chengguo Jia, and Yuzo Fujiwara
y
Tsugio Kitamura, Kiyomi Yamamoto, Masashi Kotani, Juzo Oyamada,
y
y
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University,
Honjo-machi, Saga 840-8502
yDepartment of Applied Chemistry, Faculty of Engineering, Kyushu University, Hakozaki, Fukuoka 812-8581
Received May 9, 2003; E-mail: kitamura@cc.saga-u.ac.jp
The intermolecular reaction of phenols with propiolic esters in TFA in the presence of a Pd(OAc)2 catalyst, afford-
ing coumarin derivatives, is described. An exclusive formation of 5,6,7-trimethoxy-4-phenylcoumarin was observed in
the reaction of 3,4,5-trimethoxyphenol and ethyl phenylpropiolate with a catalytic amount of Pd(OAc)2. The reaction in
the absence of Pd(OAc)2 did not give any coumarin at all. Coumarin derivatives were obtained in high yields in the
cases of electron-rich phenols, such as 3,4-methylenedioxyphenol, 3-methoxyphenol, 2-naphthol, and 3,5-
dimethoxyphenol. Furthermore, the reaction of some phenols with various 2-alkynoates or with diethyl acetylenedicar-
boxylate gave the corresponding coumarins in good-to-high yields.
b
Coumarin 1 (Fig. 1) and its derivatives occur widely in na-
ture, particularly in plants; most of them show wide biological
Very recently, we reported on Pd -catalyzed hydroaryla-
tions of alkynes by simple arenes at room temperature in a
mixed solvent containing trifluoroacetic acid (TFA), as shown
1
activities. To date, many synthetic methods for coumarins
1
have been extensively reported, including the Perkin reaction,
7
in Scheme 1. Also, we have demonstrated that the intramolec-
ular hydroarylation of aryl propiolates provides coumarin de-
rivatives in high yields. This Pd -catalyzed intramolecular
reaction in Scheme 2 proceeds with high efficiency under mild
the Knoevenagel reaction and the Pechmann–Duisberg
reaction. The latter method has been widely used to synthesize
7
d
b
2
coumarin derivatives. However, there are still limitations,
such as severe reaction conditions, the need for a stoichiomet-
ric amount of a condensing agent, and a difficulty to obtain the
starting 2-hydroxybenzaldehyde derivatives.
Recently, several studies on coumarin synthesis concerning
palladium-catalyzed reactions of phenols have been reported.
These involve inter- and intramolecular reactions of 2-iodo-
3
phenol or its O-acyl derivatives in the presence of CO, intra-
4
molecular reactions of (2-hydroxyphenyl)alkenes or -alkynes,
5
reactions of phenols and ethyl propioloates, and reactions of
2
Scheme 1.
6
-iodophenol and alkynes in the presence of CO. In these re-
actions, however, a Pd(0) species acts as the actual catalyst.
To accomplish a catalytic cycle, these reactions need iodides
3,4,6
or triflates as substrates,
5
Pd(0) species.
or formic acid to re-oxidize the
Fig. 1.
Scheme 2.
Published on the web October 15, 2003; DOI 10.1246/bcsj.76.1889

1
890 Bull. Chem. Soc. Jpn., 76, No. 10 (2003)
HEADLINE ARTICLES
b
Table 1. Pd -Catalyzed Reaction of 2a with 3aa)
Entry
Pd(OAc)2/mmol
0.025
2a/mmol
3a/mmol
Time/h
Yield of 4a/%b)
1
1
2
1
1
1
1.5
6
1
2.5
2
1.2
1.2
1.2
6
6
6
66
76
76
2
3
4
5
6
7
8
9
0
0.025
0.025
0.025
1
2
87
0
2
2.5
1
1
1
6
6
18
18
6
0
60
93
91
78
80
c)
0.01
0.01
0.01
0.01
0.01
d)
e)
e)
f)
1
1
6
3
a) All reactions were carried out at room temperature using 2a, 3a, Pd(OAc)2, and TFA (1.5 cm ). b)
3
GC yield based on the least amount of the substrate. c) TFA (3.7 cm ) and Pd(OAc)2 (0.025 mmol)
3
3
3
were used. d) TFA (1.0 cm ) was used. e) TFA (0.6 cm ) was used. f) TFA (0.5 cm ) was used.
conditions. In this reaction, however, the starting aryl propio-
lates must be prepared by the condensation of propiolic acids
and phenols.
If we can synthesize coumarins directly from phenols and
propiolic esters without using aryl propiolates, the procedure
for coumarin synthesis becomes much simpler and more
convenient. We thus examined a direct synthesis of coumarin
derivatives from phenols and propiolic esters.
place to yield 8-(2-ethoxycarbonyl-1-phenylvinyl]-5,7-di-
methoxy-4-phenylcoumarin (5). This result shows that a
coumarin derivative also undergoes the hydroarylation of an
alkyne. It is considered to be due to a high concentration of
the substrates and an excess amount of alkyne 3a.
Moderately activated 3,4- and 3,5-dimethylphenols, 2f and
2g, were also useful for the hydroarylation of 3a to give the
corresponding coumarins, 4f and 4g, in moderate yields,
respectively. In the case of 3,5-dimethylphenol (2g), interest-
ingly, the hydroarylation of 3a occurred, even at the para po-
sition of 2g, to afford ethyl (Z)-3-(4-hydroxy-2,6-dimethyl-
phenyl)cinnamate (6a) in 37% yield.
Results and Discussion
Reaction of 3,4,5-Trimethoxyphenol (2a) with Ethyl
Phenylpropiolate (3a). We examined the reaction of 2a with
3
a in TFA to optimize the reaction conditions. A solution of
In the reaction of phenols 2, however, the hydroarylation of
3a occurred at the ortho position of the phenols with extremely
high selectivity. In addition, only the less-hindered ortho po-
sition took part in the hydroarylation during the reactions of
phenols 2a, 2c, 2d, and 2f, which have two possible ortho
positions. Such a high regioselectivity of phenols favors cou-
marin synthesis.
Reaction of 2 with Various 2-Alkynoates 3. Furthermore,
we examined the reaction of some phenols 2 with various 2-al-
kynoates 3, including ethyl propiolate (3b), 2-butynoate (3c),
2-octynoate (3d), and diethyl acetylenedicarboxylate (3e).
The results are given in Table 3. In the reaction of 3,5-dimeth-
oxyphenol (2e), all 2-alkynoates, including ethyl propiolate
(3b), 2-butynoate (3c), and 2-octynoate (3d) gave the corre-
sponding coumarins 4 in good-to-high yields (Entries 1–4).
3-Methoxyphenol (2c) and 4-methoxyphenol (2i) gave the cor-
responding coumarins 4, but the yields were low compared
with that of 2e (Entries 6 and 7). Although diethyl acetylene-
dicarboxylate (3e) also reacted with 3,5-dimethoxyphenol (2e)
to give coumarin 4k in 47% yield, it was found that coumarin
formation competed with hydroarylation at the para position
of 2e (Entry 5).
Pd(OAc)2, 2a, and 3a in TFA was stirred at room temperature
for 6 or 18 h and then neutralized with aqueous NaHCO3. The
product, 5,6,7-trimethoxy-4-phenylcoumarin (4a), was extract-
ed with CH2Cl2 and analyzed by GC. The results are given in
Table 1.
An exclusive formation of 4a was observed in the reaction
with a catalytic amount of Pd(OAc)2 (Entries 1–4and 6–10).
The reaction in the absence of Pd(OAc)2 did not give 4a at
all (Entry 5). The reaction using an excess amount of 3a, rath-
er than 2a, gave a better yield of 4a (Entries 2–4). The use of a
smaller amount of TFA as the solvent increased the yield of 4a
to 91%, even though the amount of 3a was reduced to 1.2
equivalent to that of 2a (Entry 8). This result suggests that
a higher concentration of the substrates promotes the reaction
effectively.
Reaction of 3a with Various Phenols 2. In order to inves-
tigate the scope and limitations of this coumarin synthesis, we
examined reactions with various phenols 2. The results are
summarized in Table 2.
Table 2 indicates that coumarins 4 were obtained in high
yields in the cases of electron-rich phenols 2, such as 3,4-
methylenedioxyphenol (2b), 3-methoxyphenol (2c), 2-naph-
thol (2d), and 3,5-dimethoxyphenol (2e). In the case of 3,5-di-
methoxylphenol (2e), a subsequent hydroarylation of 4e took
Mechanistic Consideration. We have already reported
and discussed the hydroarylation of arenes catalyzed by the
b
7
Pd species. In the coumarin synthesis from phenols and pro-

T. Kitamura et al.
Bull. Chem. Soc. Jpn., 76, No. 10 (2003) 1891
b
Table 2. Pd -Catalyzed Reaction of 3a with Various Phenols 2a)
3
Entry
Phenol 2
2/mmol 3a/mmol TFA/cm
Time/h
Product
Yield/%
60
1
2
3
1
1
1
2
1.5
0.5
1.0
6
18
20
b)
2b
1.2
2
4b
93
85
88
4
5
2
2
42.0
20
40.75
21
56
1
8
6
7
2
1
40.5
2
24
44c)
1.0
22
35
3
7
d)
8
2
41.0
24
—
a) All reactions were carried out at room temperature using 2, 3a, Pd(OAc)2 (0.025 mmol), and TFA. b)
Pd(OAc)2 (0.01 mmol) was used and the yield was determined by GC. c) Pd(OAc)2 (0.05 mmol) was used.
d) No coumarins were detected by GC.
piolates, Trost et al. reported a different catalytic system in for-
5
mic acid from our reaction. In their reaction, Pd(OAc)2 does
Lately, we have reported on coumarin formation by the in-
tramolecular hydroarylation of aryl 2-alkynoates, as shown in
Scheme 2. Because this intramolecular process is very effi-
cient, it is supposed that the present reaction involves the intra-
molecular hydroarylation of aryl 2-alkynoates generated in situ
by transesterification of 2-alkynoates with phenols.
We then examined whether aryl 2-alkynoates are formed or
not during coumarin formation. In the reaction of 3a with phe-
nols 2a and 2c, the formation of aryl 2-alkynoates 7a and 7b
not provide the coupling product between phenol 2e and ethyl
propiolate 3b in acetic acid, but Pd2(dba)3 affords coumarin 4h
in high yield in formic acid. Therefore, they have concluded
that a Pd(0) species acts as the actual catalyst, and that formic
acid plays an important role in the catalytic cycle. In our case,
a Pd (b ) species catalyzed the hydroarylation of 2-alkynoates in
TFA. Therefore, no additives were required for this reaction.

1
892 Bull. Chem. Soc. Jpn., 76, No. 10 (2003)
HEADLINE ARTICLES
b
Table 3. Pd -Catalyzed Reaction of 2 with Various 2-Alkynoates 3a)
2
2-Alkynoate 3
2
3
TFA Time
3
lsolated
Entry
1
Phenol 2
Product
3
mmol
R
R
mmol
cm
h
Yield/%
2
2
3b
3c
H
Et
Et
3
3
1.0
18
59
97
60
2
2e
Me
1.0
20
3
4
5
2e
2e
2e
2
2
2
3d
3d
3e
n-C5H11
n-C5H11
EtO2C
Me
Me
Et
3
3
3
1.0
1.0
1.0
21
77
66
b)
4j
96
47
2
0
6
7
2
2
3b
3b
H
H
Et
Et
41.5
41.5
37
34
24
37
a) All reactions were carried out at room temperature using 2, 3, Pd(OAc)2 (0.025 mmol), and TFA. b) GC yield.
Fig. 2.
(Fig. 2) was checked, respectively. However, no aryl 2-alky-
noates, 7a and 7b, were detected under the reaction conditions
employed in the coumarin synthesis. Even in the case of the
phenol blocked at the ortho position with a substituent, no aryl
Scheme 3.
ence of Pd(OAc) (0.025 mmol) in TFA did not give the cor-
2
2-alkynoates were formed. For example, the reaction of 2,4,6-
trimethylphenol (2j) with methyl 2-octynoate (3d) in the pres-
responding 2,4,6-trimethylphenyl 2-octynoate (7c) at all
(Scheme 3). Similarly, the ester exchange of 3-methoxyphenol

T. Kitamura et al.
Bull. Chem. Soc. Jpn., 76, No. 10 (2003) 1893
the present case, most phenols employed in this study showed
a high ortho selectivity for the hydroarylation, suggesting that
a Pd species may be stabilized by coordination with the oxy-
9
gen atom.
Conclusion
We have demonstrated a simple and direct synthesis of cou-
marins from phenols and propiolic esters by using Pd(OAc)2 as
an efficient catalyst. This process involves the hydroarylation
of propiolic esters and subsequent cyclization to coumarins.
This reaction proceeds at room temperature and does not need
any additives or special conditions, such as an inert
atmosphere. Because of its simplicity and convenience, the
present method will be widely utilized. This method is espe-
cially useful for alkoxy-substituted coumarin derivatives, most
of which show biological activities.
Scheme 4.
2c) and ethyl phenylpropiolate (3a) did not undergo in TFA
without Pd(OAc)2, and the starting materials were recovered
unchanged (Scheme 4).
(
We could not obtain any evidence for the intervention of ar-
yl 2-alkynoates 7 in coumarin formation. Therefore, at the
present time, we consider that a possible mechanism for cou-
marin formation from phenols and 2-alkynoates involves the
ortho palladation of a phenol by a Pd (b ) species, probably
Pd(OCOCF3)2, followed by the hydroarylation of an alky-
noate, and finally cyclization (intramolecular transesterifica-
tion) to afford a coumarin, as shown in Scheme 5.
Experimental
General. All of the reactions were performed in a Pyrex tube
with a glass cap under an ambient atmosphere. The regio- and
stereochemistry of the product were determined by differential
NOE experiments. Analytical GLC evaluations of the product
mixtures were performed with a Shimadzu GC-17A having a
flame ionization detector using a 30 m  0.25 mm capillary col-
umn (DB-1-30N-STD, J&W Scientific) under the conditions of
In a few cases, we observed the products produced by the
hydroarylation of 2-alkynoates 3 arising from the para pallada-
tion of phenols 2 (Table 2, Entry 7 and Table 3, Entry 5). A
ꢁ
the injection temperature (280 C) and the detector temperature
ꢁ
(
280 C). A GC/MS analysis was performed with a Shimadzu
GCMS-QP5050A. 1H and 13C NMR spectra were recorded on a
5
mechanism proposed by Trost et al. cannot explain the forma-
tion of these products. Furthermore, the reaction of an aryl
methyl ether and ethyl phenylpropiolate, giving a hydroaryla-
JEOL JNM-Al300 spectrometer, and the chemical shifts were ex-
pressed in parts per million downfield from tetramethylsilane. IR
spectra were obtained on a HORIBA FT-200 spectrometer. The
melting points were measured with a YANACO micro-melting
apparatus, and were not corrected. Elemental analyses were con-
ducted by the Service Center of the Elemental Analysis of Organic
Compounds, Faculty of Science, Kyushu University.
7
tion product, supports our mechanism.
In the sulfonation of phenol by 77.8 wt % H2SO4 at 25 C,
ortho and para partial rate factors are 3400 and 7300, respec-
ꢁ
8
tively. This means that the ortho/para selectivity is low. In
Scheme 5.

1
894 Bull. Chem. Soc. Jpn., 76, No. 10 (2003)
HEADLINE ARTICLES
Palladium(II) acetate was prepared from a palladium sponge
5.00%. Found: C, 72.21; H, 5.01%.
8-(2-Ethoxycarbonyl-1-phenylvinyl)-5,7-dimethoxy-4-phen-
11
and acetic acid according to a method of Wilkinson et al. All
chemicals were used as received without further purification.
ꢁ
1
ylcoumarin (5). Mp 185–187 C (CH2Cl2/hexane). H NMR
(CDCl3, 300 MHz) ꢀ 1.19 (t, J ¼ 7:2 Hz, 3H, Me), 3.49 (s, 3H,
OMe), 3.78 (s, 3H, OMe), 4.07 (q, J ¼ 7:2 Hz, 2H, OCH2),
5.94(s, 1H, =CH), 6.34(s, 1H, ArH), 6.64(s, 1H, =CH), 7.30–
b
Pd -Catalyzed Reaction of 3,4,5-Trimethoxyphenol (2a) and
Ethyl Phenylpropiolate (3a) in TFA. To a cold mixture of
Pd(OAc)2, 3,4,5-trimethoxyphenol (2a), and TFA in an ice/water
bath was added ethyl phenylpropiolate (3a). After stirring at the
same temperature for 5 min, the mixture was stirred at room tem-
perature for an appropriate time, described in Table 1. The reac-
tion mixture was then neutralized with an aqueous NaHCO3 solu-
tion, extracted with CH2Cl2, dried over anhydrous Na2SO4, and
concentrated. Flash column chromatography on silica gel with
hexane and ethyl acetate as an eluent gave 5,6,7-trimethoxy-4-
1
3
7.40 (m, 10H, Ph).
C NMR (CDCl3, 75.5 MHz) ꢀ 14.08,
55.28, 56.03, 59.82, 91.28, 103.13, 108.87, 112.79, 120.28,
126.81, 127.02, 127.25, 127.67, 128.39, 129.24, 139.11, 139.97,
147.24, 152.81, 155.43, 158.12, 159.72, 160.42, 165.33. IR
À1
(KBr, cm ) 1720 (C=O). Anal. Calcd for C28H24O6: C,
73.67; H, 5.30%. Found: C, 73.61; H, 5.31%. The stereochemistry
was determined by NOE experiment.
phenylcoumarin (4a) as colorless crystals. 1H NMR (CDCl3,
00 MHz) ꢀ 3.26 (s, 3H, OMe), 3.79 (s, 3H, OMe), 3.94(s, 3
H, OMe), 6.07 (s, 1H, =CH), 6.73 (s, 1H, ArH), 7.34(m, 2H,
7
d
6,7-Dimethyl-4-phenylcoumarin (4f). Mp 142.5–145.5 C
1
ꢁ
3
(CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 2.23 (s, 3H,
Me), 2.36 (s, 3H, Me), 6.29 (s, 1H, =CH), 7.19 (s, 1H, ArH),
1
3
13
Ph), 7.40 (m, 3H, Ph).
C NMR (CDCl3, 75.5 MHz) ꢀ 56.22,
0.88, 61.01, 96.23, 107.23, 114.02, 127.17, 127.46, 127.98,
7.20 (s, 1H, ArH), 7.45 (m, 2H, Ph), 7.53 (m, 3H, Ph). C NMR
(CDCl3, 75.5 MHz) ꢀ 19.32, 20.15, 114.06, 116.58, 117.80,
126.88, 128.37, 128.77, 129.48, 132.90, 135.54, 142.00, 152.56,
6
1
(
38.98, 139.41, 151.04, 151.64, 155.35, 156.86, 160.58. IR
À1
À1
KBr, cm ) 1726 (C=O).
General Procedure for Synthesis of Coumarins 4. To a cold
155.59, 161.24. IR (KBr, cm ) 1714(C=O). Anal. Calcd for
C17H14O2: C, 81.58; H, 5.64%. Found: C, 81.37; H, 5.67%.
7d
ꢁ
mixture of Pd(OAc)2, a phenol 2, and TFA in an ice/water bath
ꢁ
5,7-Dimethyl-4-phenylcoumarin (4g).
Mp 93.5–95 C
1
was added 2-alkynoate 3. After stirring at 0 C for 5 min, the mix-
(CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 1.79 (s, 3H,
Me), 2.39 (s, 3H, Me), 6.18 (s, 1H, =CH), 6.81 (s, 1H, ArH),
7.08 (s, 1H, ArH), 7.29 (m, 2H, Ph), 7.45 (m, 3H, Ph). 13C NMR
(CDCl3, 75.5 MHz) ꢀ 21.27, 23.29, 115.42, 115.75, 116.06,
127.29, 128.50, 128.66, 129.45, 137.00, 139.53, 142.31, 155.12,
ture was stirred at room temperature under the conditions describ-
ed in Tables 2 and 3. The reaction mixture was then neutralized
with an aqueous NaHCO3 solution, extracted with CH2Cl2, dried
over anhydrous Na2SO4, and concentrated. Flash column chroma-
tography on silica gel with hexane and ethyl acetate as an eluent
gave a coumarin 4.
À1
156.73, 160.49. IR (KBr, cm ) 1726 (C=O).
Ethyl (Z)-3-(4-Hydroxy-2,6-dimethylphenyl)-3-phenylpro-
ꢁ
1
6
,7-Methylenedioxy-4-phenylcoumarin (4b). Mp 144–146
1
penoate (6a).
Mp 170–171 C (CH2Cl2/hexane). H NMR
ꢁ
C (CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 6.05 (s, 2
H, OCH2O), 6.24(s, 1H, =CH), 6.83 (s, 1H, ArH), 6.90 (s, 1
(CDCl3, 300 MHz) ꢀ 1.15 (t, J ¼ 7:2 Hz, 3H, Me), 2.01 (s, 6
H, Me), 4.07 (q, J ¼ 7:2 Hz, 2H, OCH2), 4.81 (s, 1H, OH),
6.53 (s, 2H, ArH), 6.64(s, 1H, =CH), 7.34(m, 5H, Ph).
1
3
H, ArH), 7.43 (m, 2H, Ph), 7.52 (m, 3H, Ph). C NMR (CDCl3,
7
1
3
5.5 MHz) ꢀ 98.56, 102.34, 104.35, 112.21, 112.84, 128.22,
C NMR (CDCl3, 75.5 MHz) ꢀ 14.01, 19.90, 60.19, 114.24,
117.68, 126.98, 128.66, 129.59, 130.29, 136.37, 138.52, 154.81,
1
28.87, 129.58, 135.66, 144.81, 151.13, 151.33, 155.87, 161.17.
À1
À1
IR (KBr, cm ) 1708 (C=O). Anal. Calcd for C16H10O4: C,
155.40, 166.27. IR (KBr, cm ) 3293 (OH), 1672 (C=O). Anal.
Calcd for C19H20O3: C, 77.00; H, 6.80%. Found: C, 76.93; H,
6.80%. The stereochemistry was determined by NOE experiment.
7
2.18; H, 3.79%. Found: C, 72.38; H, 3.81%.
-Methoxy-4-phenylcoumarin (4c).
CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 3.89 (s, 3H,
ꢁ
7
Mp 110–111
C
1
ꢁ
(
5,7-Dimethoxycouamrin (4h). Mp 140.5–142 C (CH2Cl2/
1
OMe), 6.23 (s, 1H, =CH), 6.80 (dd, J ¼ 2:7, 9.0 Hz, 1H,
ArH), 6.90 (d, J ¼ 2:7 Hz, 1H, ArH), 7.40 (d, J ¼ 9:0 Hz, 1
hexane). H NMR (CDCl3, 300 MHz) ꢀ 3.86 (s, 3H, OMe),
3.89 (s, 3H, OMe), 6.16 (d, J ¼ 9:9 Hz, 1H, =CH), 6.29 (d, J ¼
1
3
H, ArH), 7.45 (m, 2H, Ph), 7.51 (m, 3H, Ph). C NMR (CDCl3,
7
2:1 Hz, 1H, ArH), 6.42 (d, J ¼ 2:1 Hz, 1H, ArH), 7.97 (d, J ¼ 9:9
1
3
5.5 MHz) ꢀ 55.79, 101.05, 111.85, 112.33, 112.50, 127.97,
Hz, 1H, =CH). C NMR (CDCl3, 75.5 MHz) ꢀ 55.77, 55.91,
92.76, 94.79, 103.97, 110.91, 138.71, 156.78, 156.94, 161.51,
1
28.36, 128.81, 129.57, 135.55, 155.82, 156.00, 161.24, 162.78.
À1
À1
IR (KBr, cm ) 1733 (C=O). Anal. Calcd for C16H12O3: C,
163.67. IR (KBr, cm ) 1726 (C=O). Anal. Calcd for C11H10O4:
C, 64.07; H, 4.89%. Found: C, 63.88; H, 4.98%.
7
6.18; H, 4.79%. Found: C, 76.02; H, 4.88%.
-Phenyl-3H-naphtho[2,1-b]pyran-3-one (4d). Mp 159–161
ꢁ
1
5,7-Dimethoxy-4-methylcoumarin (4i). Mp 170.5–172
C
ꢁ
1
1
C (MeOH). H NMR (CDCl3, 300 MHz) ꢀ 6.39 (s, 1H, =CH),
.13–7.54(m, 9H, ArH), 7.85 (d, J ¼ 8:1 Hz, 1H, ArH), 8.01 (d,
(CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 2.53 (d, J ¼
1:2 Hz, 3H, Me), 3.85 (s, 3H, OMe), 3.86 (s, 3H, OMe), 5.95
(d, J ¼ 1:2 Hz, 1H, =CH), 6.29 (d, J ¼ 2:4 Hz, 1H, ArH), 6.44
7
1
3
J ¼ 9 Hz, 1H, ArH).
C NMR (CDCl3, 75.5 MHz) ꢀ 112.99,
16.77, 117.45, 125.35, 125.87, 126.68, 127.41, 128.98, 129.12,
1
3
1
1
(d, J ¼ 2:4 Hz, 1H, ArH).
C NMR (CDCl3, 75.5 MHz) ꢀ
29.20, 129.28, 131.26, 133.94, 139.51, 154.71, 156.46, 160.36.
À1
24.18, 55.67, 55.71, 93.35, 95.42, 104.87, 111.36, 154.46,
À1
IR (KBr, cm ) 1726 (C=O). Anal. Calcd for C19H12O2: C,
156.98, 159.10, 161.07, 162.75. IR (KBr, cm ) 1729 (C=O).
Anal. Calcd for C12H12O4: C, 65.45; H, 5.49%. Found: C,
65.28; H, 5.48%.
8
3.81; H, 4.44%. Found: C, 83.56; H, 4.46%.
,7-Dimethoxy-4-phenylcoumarin (4e).
CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 3.43 (s, 3H,
ꢁ
5
Mp 168–170
C
1
ꢁ
(
5,7-Dimethoxy-4-pentylcoumarin (4j).
Mp 102–103
C
1
OMe), 3.87 (s, 3H, OMe), 6.01 (s, 1H, =CH), 6.23 (d, J ¼ 2:1
Hz, 1H, ArH), 6.53 (d, J ¼ 2:1 Hz, 1H, ArH), 7.27 (m, 2H,
(CH2Cl2/hexane). H NMR (CDCl3, 300 MHz) ꢀ 0.91 (m, 3H,
Me), 1.37 (m, 4H, 2CH2), 2.38 (m, 2H, CH2), 2.86 (m, 2H,
CH2), 3.84(s, 3H, OMe), 3.87 (s, 3H, OMe), 5.96 (s, 1H,
=CH), 6.30 (s, 1H, ArH), 6.45 (s, 1H, ArH). 13C NMR (CDCl3,
75.5 MHz) ꢀ 14.00, 22.44, 29.31, 31.80, 36.48, 55.63, 55.72,
93.55, 95.49, 104.23, 110.56, 157.27, 158.53, 158.59, 161.25,
1
3
Ph), 7.38 (m, 3H, Ph). C NMR (CDCl3, 75.5 MHz) ꢀ 55.37,
5.76, 93.50, 95.73, 103.51, 112.66, 127.08, 127.33, 127.88,
5
1
39.73, 155.67, 157.14, 158.18, 160.88, 163.32. IR (KBr,
À1
cm ) 1716 (C=O). Anal. Calcd for C17H14O4: C, 72.33; H,

T. Kitamura et al.
Bull. Chem. Soc. Jpn., 76, No. 10 (2003) 1895
À1
1
62.56. IR (KBr, cm ) 1718 (C=O). Anal. Calcd for C16H20O4:
C, 69.54; H, 7.30%. Found: C, 69.56; H, 7.34%.
-Ethoxycarbonyl-5,7-dimethoxycoumarin (4k).
CDCl3, 300 MHz) ꢀ 1.40 (t, J ¼ 7:2 Hz, 3H, Me), 3.85 (s, 3
C. D. Gabbutt, and B. M. Heron, ‘‘Comprehensive Heterocyclic
Chemistry b,’’ ed by A. McKillop, Pergamon Press, Oxford
(1996), Vol. 5, Chap. 5.08, pp. 351–468.
1
4
H NMR
(
2
a) S. Sethna and R. Phadke, Org. React., 7, 1 (1953). b) S.
M. Sethna and N. M. Shah, Chem. Rev., 36, 10 (1945).
a) Z. An, M. Catellani, and G. P. Chiusoli, J. Organomet.
H, OMe), 3.87 (s, 3H, OMe), 4.40 (q, J ¼ 7:2 Hz, 2H, OCH2),
6
.09 (s, 1H, =CH), 6.31 (s, 1H, ArH), 6.48 (s, 1H, ArH).
C NMR (CDCl3, 75.5 MHz) ꢀ 14.15, 55.89, 56.33, 62.15,
3.62, 95.66, 100.57, 109.37, 145.33, 156.63, 157.01, 160.26,
3
1
3
Chem., 371, C51 (1989). b) M. Catellani, G. P. Chiusoli, M. C.
Fagnola, and G. Solari, Tetrahedron Lett., 35, 5919 (1994). c)
M. Catellani, G. P. Chiusoli, M. C. Fagnola, and G. Solari, Tetra-
hedron Lett., 35, 5923 (1994).
4a) A. Arcadi, S. Cacchi, G. Fabrizi, F. Marinelli, and P.
Pace, Synlett, 1996, 568. b) S. Cacchi, G. Fabrizi, L. Moro, and
P. Pace, Synlett, 1997, 1367.
9
1
À1
64.13, 166.46. IR (KBr, cm ) 1733 (C=O). Anal. Calcd for
C14H14O6: C, 60.43; H, 5.07%. Found: C, 60.40; H, 5.14%.
Ethyl (Z)-3-Ethoxycarbonyl-3-(4-hydroxy-2,6-dimethoxy-
1
phenyl)propenoate (6b).
H NMR (CDCl3, 300 MHz) ꢀ 1.19
(
(
t, J ¼ 7:2 Hz, 3H, Me), 1.27 (t, J ¼ 7:2 Hz, 3H, Me), 3.66
s, 6H, OMe), 4.12 (q, J ¼ 7:2 Hz, 2H, OCH2), 4.24 (q, J ¼ 7:2
5
a) B. M. Trost and F. D. Toste, J. Am. Chem. Soc., 118,
Hz, 2H, OCH2), 5.94(s, 2H, ArH), 6.27 (bs, 1H, OH),
6305 (1996). b) B. M. Trost and F. D. Toste, J. Am. Chem.
Soc., 120, 9074(1998). c) B. M. Trost, F. D. Toste, and K.
Greenman, J. Am. Chem. Soc., 125, 4518 (2003).
1
3
6
1
1
1
.87 (s, 1H, =CH). C NMR (CDCl3, 75.5 MHz) ꢀ 13.97,
4.07, 55.43, 60.62, 61.61, 92.23, 104.02, 128.25, 138.21,
58.10, 159.00, 166.27, 168.17. IR (KBr, cm ) 3405 (OH),
720 (C=O). This sample did not give a satisfactory analysis be-
À1
6
(2000).
7
D. V. Kadnikov and R. C. Larock, Org. Lett., 2, 3643
cause of the presence of inseparable impurities.
1
a) C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, and Y.
7
-Methoxycoumarin (4l).
H NMR (CDCl3, 300 MHz) ꢀ
Fujiwara, Science, 287, 1992 (2000). b) C. Jia, W. Lu, J.
Oyamada, T. Kitamura, K. Matsuda, M. Irie, and Y. Fujiwara,
J. Am. Chem. Soc., 122, 7252 (2000). c) W. Lu, C. Jia, T.
Kitamura, and Y. Fujiwara, Org. Lett., 2, 2927 (2000). d) C. Jia,
D. Piao, T. Kitamura, and Y. Fujiwara, J. Org. Chem., 65, 7516
(2000).
3
2
.88 (s, 3H, OMe), 6.26 (d, J ¼ 9:6 Hz, 1H, =CH), 6.92 (d, J ¼
:7 Hz, 1H, ArH), 7.11 (dd, J ¼ 2:7, 8.9 Hz, 1H, ArH), 7.38 (d,
J ¼ 8:9 Hz, 1H, ArH), 7.65 (d, J ¼ 9:6 Hz, 1H, =CH).
1
3
C NMR (CDCl3, 75.5 MHz) ꢀ 55.75, 100.77, 112.47, 112.58,
13.04, 128.72, 143.43, 155.86, 161.21, 162.78. IR (KBr,
1
À1
cm ) 1712 (C=O). Anal. Calcd for C10H8O3: C, 68.18; H,
8
R. Tayler, ‘‘Electrophilic Aromatic Substitution,’’ John
Wiley & Sons, Chichester (1990).
A referee has suggested the intermediacy of an ArO–Pd
4
.58%. Found: C, 68.08; H, 4.69%.
1
6
-Methoxycoumarin (4m).
H NMR (CDCl3, 300 MHz) ꢀ
9
3
.86 (s, 3H, OMe), 6.43 (d, J ¼ 9:3 Hz, 1H, =CH), 6.92 (d, J ¼
species. Although Trost et al. favor a mechanism involving a pal-
ladium(0) and a hydridopalladium phenoxide, we cannot abandon
a mechanism depicted in Scheme 5 for the following reasons. (ffi )
Coumarin formation readily takes place in case of electron-rich
phenols. According to Trost’s mechanism, the coumarin formation
should be independent or weakly dependent upon the substituent
of phenols. (ffl ) A phenoxide complex suggested by Trost et al.
is supposed to be difficult to form easily under our reaction system
(in a strong acid, TFA). (ꢀ) Although there is a possibility that a
2
:7 Hz, 1H, ArH), 7.11 (dd, J ¼ 2:7, 9.3 Hz, 1H, ArH), 7.27 (d,
J ¼ 2:7 Hz, 1H, ArH), 7.67 (d, J ¼ 9:3 Hz, 1H, =CH).
1
3
C NMR (CDCl3, 75.5 MHz) ꢀ 55.77, 109.91, 117.02, 117.84,
19.11, 119.43, 143.21, 148.38, 156.00, 160.99. IR (KBr,
1
À1
cm ) 1700 (C=O). Anal. Calcd for C10H8O3: C, 68.18; H,
4
.58%. Found: C, 68.06; H, 4.59%.
This work was supported by a Grant-in-Aid for Scientific
Research on Priority Areas (No. 14044080) from the Ministry
of Education, Culture, Sports, Science and Technology.
11
phenoxide complex undergoes O-alkenylation of phenols, we
have not observed any products derived from O-alkenylation of
phenols.
1
0
T. A. Stephenson, S. M. Morehouse, A. R. Powel, J. P.
References
Heffer, and G. Wilkinson, J. Chem. Soc., 1965, 3632.
11 a) B. M. Trost and F. D. Toste, J. Am. Chem. Soc., 120, 815
(1998). b) J. Ruiz, J. M. Marti, F. Florenciano, and G. Lopez, Pol-
yhedron, 18, 2281 (1999). c) B. M. Trost and F. D. Toste, J. Am.
Chem. Soc., 121, 4545 (1999). d) O. Roy, A. Riahi, F. Henin, and
J. Muzart, Tetrahedron, 56, 8133 (2000).
1
a) J. D. Hepworth, ‘‘Comprehensive Heterocyclic Chemis-
try,’’ ed by A. R. Katritzky and C. W. Rees, Pergamon Press, Ox-
ford (1984), Vol. 3, pp. 737–883. b) T. Ishikawa, Yuki Gosei Ka-
gaku Kyokaishi, 56, 116 (1998). c) J. Stannton, ‘‘Comprehensive
Organic Chemistry,’’ ed by P. G. Sammes, Pergamon Press, Ox-
ford (1979), Vol. 4, Part 18.2, pp. 629–658. d) J. D. Hepworth,