Pt(II)-catalyzed hydroarylation reaction of alkynes with pyrroles and furans

Article abstract of DOI:10.1016/j.tet.2009.03.022

A Pt(II) catalyst showed a drastic effect on hydroarylation of alkynes with pyrroles and furans compared with Pd(OAc)₂ catalyst. The hydroarylation reactions proceeded smoothly under mild conditions to give double-hydroarylation products in goo

Full text of DOI:10.1016/j.tet.2009.03.022

Tetrahedron 65 (2009) 3842–3847
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Pt(II)-catalyzed hydroarylation reaction of alkynes with pyrroles and furans
*
Juzo Oyamada, Tsugio Kitamura
Department of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi, Saga 840-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A Pt(II) catalyst showed a drastic effect on hydroarylation of alkynes with pyrroles and furans compared
with Pd(OAc)2 catalyst. The hydroarylation reactions proceeded smoothly under mild conditions to give
double-hydroarylation products in good yields. Mono-adducts were formed only when the second
hydroarylation was inhibited by steric hindrance of substrates or low reactivity of the mono-adducts.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 20 December 2008
Received in revised form 9 March 2009
Accepted 10 March 2009
Available online 14 March 2009
Keywords:
Hydroarylation
Platinum catalyst
Pyrrole
Furan
1. Introduction
Recently, we found that Pt(II) catalysts such as K2PtCl4/AgOTf
and PtCl2/AgOTf were more effective than Pd(OAc)2 in the hydro-
Heteroarenes are an important class of compounds in organic
chemistry because they are incorporated in a wide range of useful
organic compounds such as fluorescent dyes, natural products, and
pharmaceuticals. Development of their functionalization methods
for synthesis of such useful compounds has attracted much atten-
tion of many chemists.
Direct C–H bond functionalization is one of the most effective
methods in terms of atom-economic and environmentally be-
nign processes because it dose not require pre-functionalization
like halogenation.1 Addition of aromatic C–H bonds to un-
saturated C–C bonds is a useful C–H functionalization method
for introducing carbon framework onto arenes. To date, it has
been reported that some transition metals catalyze addition of
heteroarenes to alkynes, affording heteroarylalkenes and bis-
(heteroaryl)alkanes.2–9
We have reported that hydroarylation of alkynes proceeded
under mild conditions by using a catalytic amount of Pd(OAc)2 and
trifluoroacetic acid (TFA) as solvent to give cis-aryl substituted al-
kenes.10 The hydroarylation was applied to the reaction of hetero-
arenes such as pyrroles, indoles, and furans.4 In the case of
heteroarenes, the hydroarylation did not occur in TFA but pro-
ceeded in acetic acid or a neutral solvent like CH2Cl2 to give het-
eroarylalkenes in most cases.
arylation of propiolic acids with arenes.11 Thus, we examined the
effect of a more cationic Pt(II) catalyst on the hydroarylation with
heteroarenes and found that two molecules of heteroarenes added
to the triple bonds. Furthermore, recently published papers12 let us
recognize that this methodology is useful for direct synthesis of
meso-substituted dipyrromethanes, which are the key building
blocks of porphyrinoid macrocycles. Here, we report the Pt(II)-
catalyzed double hydroarylation of alkynes with pyrroles and
furans.
2. Results and discussion
First of all, we examined the reaction of pyrrole (1a, R¼H) with
ethyl phenylpropiolate (2a, R0¼Ph) (Eq. 1). The reaction of 1a
(4 mmol) with 2a (2 mmol) in AcOH (1 mL) was carried out in the
presence of K2PtCl4 (0.02 mmol) and AgOTf (0.08 mmol) at 30 ꢀC
for 9 h to afford ethyl (2Z)-3-(pyrrol-2-yl)cinnamate (3a) and ethyl
3-phenyl-3,3-di(pyrrol-2-yl)propionate (4a) in 4 and 46% yields,
respectively (Table 1, entry 1). Double addition of 1a to the triple
bond of 2a occurred predominantly. This result is in contrast to
our previous Pd(II)-catalyzed reaction in which 3a was obtained
exclusively.4a It may be attributed to the fact that K2PtCl4/AgOTf is
a more cationic and active catalyst than Pd(OAc)2.11b This in-
teresting result encouraged us to investigate the reaction condi-
tions. The results are listed in Table 1. When the reaction was
carried out with 3 equiv of 1a in the presence of 2% K2PtCl4 and 8%
AgOTf, 4a was obtained in 59% yield (entry 2). Use of AgOAc in-
stead of AgOTf retarded the reaction, resulting in the major
* Corresponding author. Tel.: þ81 952 28 8550; fax: þ81 952 28 8548.
E-mail address: kitamura@cc.saga-u.ac.jp (T. Kitamura).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.03.022

J. Oyamada, T. Kitamura / Tetrahedron 65 (2009) 3842–3847
3843
Table 1
Pt(II)-catalyzed hydroarylation of ethyl phenylpropiolate with pyrrolea
Table 2
Pt(II)-catalyzed hydroarylation of alkynes with pyrrolesa
Entry
Catalyst (%)
Solvent
Time/h
Yieldb
Entry
1
R
2
R0
Time/h
Product and yieldb/%
4a/%
3a/%
1
2
3
4
5
6
7
8
9
10
K2PtCl4/AgOTf (1/4)
K2PtCl4/AgOTf (2/8)
K2PtCl4/AgOAc (2/8)
K2PtCl4/AgOTf (2/8)
K2PtCl4/AgOTf (2/8)
AgOTf (8)
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
DCE
AcOH
DCE
DCE
9
11
50
10
20
10
12
15
15
50
46c
59d
16d
68
4c
0d
43d
0
Me
2a
Ph
2
3b
71
50c
43
67e
0e
No reaction
2
3
H
H
2b
2c
nC5H11
24
2
4b
3c
K2PtCl4/AgOTf (2/8)
(nBu4N)2PtCl4 (2)
67
60
66
0
0
0
(nBu4N)2PtCl4/AgOTf (2/8)
(nBu4N)2PtCl4/AgOAc (2/8)
No reaction
a
EtO2C
Reaction conditions: pyrrole (1a) (6 mmol), ethyl phenylpropiolate (2a)
(1 mmol), Pt salt (0.02 mmol), Ag compound (0.08 mmol), and solvent (1 mL) at
30 ꢀC.
b
Isolated yield based on 2a.
Compounds 1a (4 mmol) and 2a (2 mmol) were used.
Compound 1a (3 mmol) was used.
AcOH (2 mL) was used.
c
3d
3e
46d
22d
d
e
4
H
2d
H
2
formation of 3a (Entry 3). The yield of 4a was improved to be 68%
when 6 equiv of 1a was used (entry 4). The increase of the amount
of acetic acid only retarded the reaction rate (entry 5). The re-
action did not proceed in the absence of K2PtCl4, revealing clearly
that a Pt species is an active catalyst in this reaction (entry 6). A
neutral solvent, 1,2-dichloroethane (DCE), can be used instead of
AcOH, affording 4a in a similar yield to that in AcOH (entry 7). In
order to increase the solubility of catalyst precursor, we examined
a soluble Pt(II) salt, (nNBu4)2PtCl4, which was prepared from
K2PtCl4 and nBu4NCl. Interestingly, the hydroarylation using
(nNBu4)2PtCl4 in AcOH proceeded even in the absence of AgOTf (entry
8). This result reveals that Pt catalyst itself plays an important role in
the catalytic cycle and AgOTf is not necessarily required for the re-
action. Moreover, (nNBu4)2PtCl4 also catalyzed the reaction in DCE
when AgOTf was added (entry 9). These results suggest that Pt pre-
catalyst is activated by AgOTf or by AcOH in the absence of AgOTf. The
role of AgOTf is considered to dissolve K2PtCl4, which is hardly soluble
in organic solvent and to form a more active, cationic Pt species by
anion exchange. No reaction took place when AgOAc was added in-
stead of AgOTf (entry 10).
a
Reaction conditions:
a pyrrole (6 mmol), an alkyne (1 mmol), K2PtCl4
(0.02 mmol), AgOTf (0.08 mmol), and AcOH (1 mL) at 30 ꢀC.
b
Isolated yield based on an alkyne.
Cl(CH2)2Cl (1 mL) was used instead of AcOH.
NMR yields. Compound 1a (2 mmol) was used.
c
d
(entry 4 and Eq. 2). The low selectivity may be attributed to the
higher reactivity of 2d compared to the other substituted pro-
piolates or the reaction environment.13 In this reaction, NMR
experiments indicated that the elongation of reaction gave an
inseparable mixture of double-adducts. For a substituted pyr-
role, 2,5-dimethylpyrrole (1c), the reaction with 2a was con-
ducted for 24 h under the conditions of entry 1 in Table 2, but
only mono-adduct 3f was obtained in 48% yield as a mixture of E-
and Z-isomers (3:1).
ð1Þ
Next, we examined the reaction of other pyrroles and al-
kynes (Table 2). Interestingly, the reaction of 1-methylpyrrole
(1b, R¼Me) with 2a gave mono-adduct 3b exclusively in 71%
yield (entry 1). The result is in contrast with the reaction of 1a
that gives 4a as a main product. This is probably because the
steric hindrance of the methyl group in pyrrole 1b inhibits the
second hydroarylation. The reaction of 1a with ethyl 2-octy-
noate (2b, R0¼nC5H11) gave double-adduct 4b in 50% yield (entry
2). The reaction with diethyl acetylenedicarboxylate (2c,
R0¼CO2Et) gave mono-adduct 3c in 43% yield (entry 3). The
reaction with ethyl propiolate (2d, R0¼H) gave the regio-iso-
meric products 3d and 3e in 46 and 22% yields, respectively
ð2Þ
ð3Þ

3844
J. Oyamada, T. Kitamura / Tetrahedron 65 (2009) 3842–3847
Table 3
Table 5
Pt(II)-catalyzed hydroarylation of phenylacetylene with pyrrolesa
Pt(II)-catalyzed hydroarylation of alkynes with 2,5-dimethylfuransa
Entry
R
1/mmol
Time/h
Product
Yieldb/%
Entry 5b/mmol
2
R
Time/h
Product and yieldb/%
1
2
3
4
H
10
10
6
20
20
20
21
4c
4d
4d
4d
65
65
45
0c
Me
Me
Me
1
2
6
2a Ph 48
7a 80 (Z/E¼1.3/1)
6
a
Reaction conditions:
a pyrrole 1, phenylacetylene (2e) (1 mmol), K2PtCl4
(0.02 mmol), AgOTf (0.08 mmol), and AcOH (1 mL) at 30 ꢀC.
b
12
2d
2d
H
H
40
40
7b 62c
Isolated yield based on 2e.
Without K2PtCl4/AgOTf.
c
Phenylacetylene (2e) also participated in the reaction as well as
propiolates (Eq. 4 and Table 3). The reactions of 1a and 1b gave the
corresponding double-adducts 4c and 4d in good yields, re-
spectively, although a large amount of a pyrrole was required
(entries 1 and 2). Use of 6 equiv of 1b resulted in an inferior yield
(entry 3). Again, no products were formed in the absence of
K2PtCl4/AgOTf (entry 4).
3
10
6b 51d,e
a
Reaction Conditions: 2,5-dimethylfuran (5b), an alkyne 2 (1 mmol), K2PtCl4
(0.02 mmol), AgOTf (0.08 mmol), and AcOH (1 mL) at 30 ꢀC.
b
Isolated yield based on 2.
Ethyl propiolate (2 mmol) was used.
Temperature 50 ꢀC.
c
d
e
Compound 7b was formed in 10% yield.
a main product when the reaction was carried out at 50 ꢀC (entry 3).
In the reaction of 2b with 5a, hydroarylation did not take place,
resulting in the formation of ethyl 2-oxooctanoate by hydration of
2b. The reactions of 2c did not afford any hydroarylation products
although a small amount of Diels–Alder adducts 8a and 8b was
isolated (Eq. 7). These results are explained by low reactivity of
furans for hydroarylation compared with pyrroles.
ð4Þ
The reaction was applied to furans like 2-methylfuran (5a) and
2,5-dimethylfuran (5b). The reaction of 5a with 2a proceeded under
the same reaction conditions to give a double-adduct, ethyl 3,3-
bis(4-methylfur-2-yl)-3-phenylpropionate (6a) in 78% yield (Eq. 5
and entry 1, Table 4). This result is completely different from that of
the corresponding Pd(OAc)2 catalyzed reaction where mono-
adduct is formed.4a (nBu4N)2PtCl4 did not catalyze the reaction of
furan effectively, resulting in almost no reaction (entry 2) because
of lower reactivity of a furan. Again, AgOTf does not catalyze the
reaction, suggesting that an active species in the reaction is a Pt
species (entry 3).
ð6Þ
ð7Þ
ð5Þ
The hydroarylation is considered to proceed via electrophilic
aromatic substitution mechanism. The mechanism is illustrated in
Scheme 1. An alkyne is activated by the coordination of an active
Pt(II) catalyst derived from a Pt precursor, followed by attack to
a heteroarene electrophilically to form a Wheland intermediate.
Proton release followed by protonation of the resulting in-
termediate affords a heteroarylalkene. The second hydroarylation
of the forming heteroarylalkene leading to a bis(heteroaryl)alkane
is also considered to proceed in the same way. In some cases, the
reactions gave mono-adducts exclusively. This is explained by the
steric and electronic reasons. In the case of the reaction of 2a with
The reactions of 5b with alkynes 2 were also examined (Eq. 6
and Table 5). The reaction of 2a with 5b gave mono-addition
product 7a in 80% yield (entry 1). In this case, the product was
obtained as a mixture of the stereoisomers (E/Z¼1.3:1). No double-
adduct was observed probably due to the steric reason. In the case
of 2d, the reaction of 5b in the presence of 1% K2PtCl4 and 4% AgOTf
gave mono-adduct 7b selectively (entry 2). The second addition
reaction of 5b to mono-adduct 7b is slow under the reaction con-
ditions and requires a higher reaction temperature. Actually, the
second addition of 5b occurred to afford double-adduct 6b as
1b or 5b, steric hindrance at the b-position of the resulting cinna-
mate probably inhibits the second hydroarylation because methyl
group is present at the 2-position of the heteroaryl group. In the
case of 2c, the second hydroarylation is considered to be prevented
because mono-adduct 3c is an electron-deficient alkene, which is
less reactive for the hydroarylation. The heteroarylalkenes obtained
from the hydroarylation are usually electron-rich alkenes and
reactive enough to undergo the second hydroarylation. This is
consistent with the fact that the reaction of pyrrole with less
electron-rich alkenes, ethyl cinnamates, did not take place.
Table 4
Pt(II)-catalyzed hydroarylation of ethyl phenylpropiolate with 2-methylfurana
Entry
Catalyst (%)
Solvent
5a/mmol
Time/h
Yield of 6ab/%
1
2
3
K2PtCl4/AgOTf (2/8)
(nBu4N)2PtCl4 (2)
AgOTf (8)
AcOH
AcOH
AcOH
6
6
6
12
120
45
90
8
0
a
Reaction conditions: 2-methylfuran (5a), ethyl phenylpropiolate (2a) (1 mmol),
catalyst, and solvent (1 mL) at 30 ꢀC.
b
Isolated yield based on 2a.

J. Oyamada, T. Kitamura / Tetrahedron 65 (2009) 3842–3847
3845
reduced pressure. The residue was purified by silica-gel column
chromatography with a mixture of AcOEt/hexane as eluent to give
4a in 68% yield.
4.2.1. Ethyl (2Z)-3-(1H-pyrrol-2-yl)cinnamate (3a)4a
Light yellow liquid. 1H NMR (300 MHz, CDCl3):
d 1.32 (t,
J¼7.1 Hz, 3H, CH3), 4.23 (q, J¼7.1 Hz, 2H, OCH2), 5.58 (s, 1H, vinyl),
6.09 (m, 1H, pyrrolyl), 6.21 (m, 1H, pyrrolyl), 7.07 (m, 1H, pyrrolyl),
7.35–7.42 (m, 5H, Ph), 12.96 (br s, 1H, NH). 13C NMR (75.5 MHz,
CDCl3):
d 14.26, 60.60, 109.71, 109.74, 118.97, 122.82, 127.78, 128.16,
128.86, 130.31, 142.50, 149.18, 168.89.
4.2.2. Ethyl (2Z)-3-(1-methyl-1H-pyrrol-2-yl)cinnamate (3b)4a
Light yellow liquid. 1H NMR (300 MHz, CDCl3):
d
1.19 (t, J¼7.1 Hz,
3H, CH3), 3.32 (s, 3H, Me), 4.11 (q, J¼7.1 Hz, 2H, OCH2), 6.12 (dd,
J¼1.8, 3.7 Hz,1H, pyrrolyl), 6.19 (dd, J¼2.6, 3.7 Hz,1H, pyrrolyl), 6.37
(s, 1H, vinyl), 6.73 (dd, J¼1.8, 2.6 Hz, 1H, pyrrolyl), 7.31–7.35 (m, 5H,
Ph). 13C NMR (75.5 MHz, CDCl3):
d 14.14, 34.34, 60.04, 107.74, 111.60,
118.83, 123.69, 127.98, 128.42, 129.51, 129.85, 140.36, 147.03, 165.95.
4.2.3. Diethyl (2Z)-2-(1H-pyrrol-2-yl)fumarate (3c)15
Yellow liquid. 1H NMR (300 MHz, CDCl3):
CH3), 1.38 (t, J¼7.1 Hz, 3H, CH3), 4.24 (q, J¼7.1 Hz, 2H, OCH2), 4.36 (q,
J¼7.1 Hz, 2H, OCH2), 5.94 (s, 1H, vinyl), 6.29 (m, 1H, pyrrolyl), 6.73
(m, 1H, pyrrolyl), 7.04 (m, 1H, pyrrolyl), 12.60 (br s, 1H, NH). 13C
d
1.33 (t, J¼7.1 Hz, 3H,
Scheme 1. The plausible reaction mechanism.
NMR (75.5 MHz, CDCl3):
d 14.09, 14.11, 61.13, 61.99, 110.08, 110.47,
117.84, 123.59, 125.94, 139.04, 167.80, 168.58. MS (EI, m/z (relative
intensity)): 237 (Mþ, 98), 192 (18), 191 (17), 165 (58), 136 (20), 119
(30), 91 (100).
3. Conclusion
We have demonstrated that Pt(II) catalysts showed a drastic
effect on the hydroarylation of alkynes with pyrroles and furans.
The Pt(II) catalysts like K2PtCl4/AgOTf is revealed to catalyze the
hydroarylation effectively to give double-hydroarylation products
in good yields. Mono-adducts were obtained predominantly when
second hydroarylation was inhibited by steric hindrance of sub-
strates or low reactivity of forming mono-adducts.
4.2.4. Ethyl (2Z)-3-(1H-pyrrol-2-yl)acrylate (3d)4a
Light yellow liquid. 1H NMR (300 MHz, CDCl3):
d 1.32 (t,
J¼7.1 Hz, 3H, CH3), 4.21 (q, J¼7.1 Hz, 2H, OCH2), 5.52 (d, J¼12.6 Hz,
1H, vinyl), 6.26 (m, 1H, pyrrolyl), 6.50 (m, 1H, pyrrolyl), 6.76 (d,
J¼12.6 Hz, 1H, vinyl), 6.99 (m, 1H, pyrrolyl), 12.24 (br s, 1H, NH). 13C
NMR (75.5 MHz, CDCl3):
d 14.24, 60.39, 107.67, 110.09, 118.54,
122.87, 129.09, 134.66, 169.18.
4. Experimental
4.1. General
4.2.5. Ethyl (2Z)-3-(1H-pyrrol-3-yl)acrylate (3e)
Yellow liquid. 1H NMR (300 MHz, CDCl3):
CH3), 4.20 (q, J¼7.1 Hz, 2H, OCH2), 5.62 (d, J¼12.6 Hz,1H, vinyl), 6.70
(m, 1H, pyrrolyl), 6.74 (m, 1H, pyrrolyl), 6.82 (d, J¼12.6 Hz, 1H, vi-
nyl), 7.75 (m, 1H, pyrrolyl), 8.57 (br s, 1H, NH). 13C NMR (75.5 MHz,
d
1.31 (t, J¼7.1 Hz, 3H,
All solvents and reagents were commercially available and used
as received without further purification. (nNBu4)2PtCl4 was pre-
pared from K2PtCl4 and nBu4NCl according to the reported
method.14 All reactions were conducted in a dry Pyrex tube with
a rubber septum. In the cases of furans, the reactions were con-
ducted in the tube with screw cap. 1H and 13C NMR spectra were
recorded on a JEOL JNM-AL 300 FT-NMR using tetramethylsilane
(TMS) as internal standard. Melting points were measured with
YANACO micro melting apparatus and are uncorrected. Mass
spectra were measured on a Shimadzu GC/MS 5020A. Elemental
analyses were performed by the Service Center of the Elementary
Analysis of Organic Compounds, Faculty of Science, Kyushu
University.
CDCl3):
d 14.33, 59.64, 111.80, 112.27, 118.15, 119.65, 123.99, 138.33,
167.07. Anal. Calcd for C9H11NO2: C, 65.44; H, 6.71; N, 8.48. Found:
C, 65.20; H, 6.75; N, 8.36.
4.2.6. Ethyl 3-(2,5-1H-pyrrol-3-yl)cinnamate (E/Z¼3:1) (3f)
Yellow crystals. Mp 84–85 ꢀC (CH2Cl2/hexane). 1H NMR
(300 MHz, CDCl3):
d
1.08 (t, J¼7 Hz, CH3), 1.26 (t, J¼7 Hz, CH3), 1.78
(s, CH3), 1.93 (s, CH3), 2.15 (s, CH3), 2.19 (s, CH3), 3.99 (q, J¼7 Hz,
CH3), 4.15 (q, J¼7 Hz, CH3), 5.68 (s, ]CH), 5.77 (s, ]CH), 6.03 (s,
ArH), 6.07 (s, ArH), 7.21–7.25 (m, ArH), 7.30–7.40 (m, ArH), 7.74 (br
s, NH), 7.79 (br s, NH). 13C NMR (75.5 MHz, CDCl3):
d 12.35, 12.54,
12.78, 13.17, 13.98, 14.28, 59.30, 59.60, 106.8, 108.52, 111.56, 114.87,
117.56, 120.76, 125.08, 125.98, 127.18, 127.36, 127.57, 127.92, 128.31,
128.44, 128.61, 128.75, 140.51, 142.72, 152.71, 153.99, 166.54, 167.04.
Anal. Calcd for C17H19NO2: C, 75.81; H, 7.11; N, 5.20. Found: C, 75.64;
H, 7.16; N, 5.20.
4.2. General procedure for the K2PtCl4/AgOTf-catalyzed
hydroarylation of alkynes with pyrroles or furans. Typical
example: the reaction of pyrrole with ethyl phenylpropiolate
(Table 1, entry 3)
After a mixture of K2PtCl4 and AgOTf in acetic acid was stirred
for 1 h, pyrrole (6 mmol) and ethyl phenylpropiolate (1 mmol)
were added to the mixture. The reaction was monitored by TLC.
After the reaction, the reaction mixture was poured into water,
neutralized by NaHCO3, and extracted with CH2Cl2 (10 mLꢁ4). The
organic layer was dried over Na2SO4 and concentrated under
4.2.7. Ethyl 3-phenyl-3,3-di(1H-pyrrol-2-yl)propionate (4a)
Colorless crystals. Mp 123–125 ꢀC (CH2Cl2/hexane). 1H NMR
(300 MHz, CDCl3):
d
1.17 (t, J¼7.1 Hz, 3H, CH3), 3.59 (s, 2H, CH2CO),
4.06 (q, J¼7.1 Hz, 2H, OCH2), 5.69 (m, 2H, pyrrolyl), 6.11 (m, 2H,
pyrrolyl), 6.70 (m, 2H, pyrrolyl), 6.98–7.01 (m, 2H, Ph), 7.21–7.29 (m,
3H, Ph), 9.05 (br s, 2H, NH). 13C NMR (75.5 MHz, CDCl3):
d 13.95,

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J. Oyamada, T. Kitamura / Tetrahedron 65 (2009) 3842–3847
46.14, 46.89, 61.10, 107.50, 107.59, 117.27, 126.86, 127.32, 128.07,
135.57, 145.97, 173.31. MS (EI, m/z (relative intensity)): 308 (Mþ, 21),
221 (100), 154 (15), 110 (9). Anal. Calcd for C19H20N2O2: C, 74.00; H,
6.54; N, 9.08. Found: C, 74.16; H, 6.55; N, 9.15.
(61), 152 (52), 128 (26), 115 (26), 91 (20), 77 (29). Anal. Calcd for
17H18O3: C, 75.53; H, 6.71. Found: C, 75.20; H, 6.73. Compound 7a
was obtained as a mixture of Z- and E-stereoisomers. The Z-isomer
of 7a was partially isolated from the mixture of the stereoisomers
by column chromatography. The stereochemistry of 7a was de-
termined by NOE experiments.
C
4.2.8. Ethyl 3,3-bis(1H-pyrrol-2-yl)octanoate (4b)
Yellow oil. 1H NMR (300 MHz, CDCl3):
d
0.84 (t, J¼6.6 Hz, 3H,
CH3), 1.16 (t, J¼7.1 Hz, 3H, CH3), 1.25 (m, 6H, CH2), 2.05 (m, 2H, CH2),
3.01 (s, 2H, CH2CO), 4.03 (q, J¼7.1 Hz, 2H, OCH2), 6.00 (m, 2H,
pyrrolyl), 6.12 (m, 2H, pyrrolyl), 6.64 (m, 2H, pyrrolyl), 8.55 (br s, 2H,
4.2.14. Ethyl (2E)-3-(2,5-dimethylfur-3-yl)cinnamate (7a-E)
Colorless liquid. 1H NMR (300 MHz, CDCl3):
d
1.09 (t, J¼7.1 Hz,
3H, CH3), 1.76 (s, 3H, CH3), 2.21 (s, 3H, CH3), 4.01 (q, J¼7.1 Hz, 2H,
OCH2), 5.92 (s, 1H, furyl), 6.05 (s, 1H, vinyl), 7.19–7.22 (m, 2H, Ph),
7.34–7.36 (m, 2H, Ph). MS (EI, m/z (relative intensity)): 270 (Mþ, 97),
253 (66), 227 (100), 225 (74), 199 (58), 195 (63), 182 (57), 181 (62),
153 (63), 152 (51), 128 (25), 115 (26), 91 (20), 77 (31). The E-isomer
of 7a could not be separated from a mixture of the Z- and E-
stereoisomers.
NH). 13C NMR (75.5 MHz, CDCl3):
d 13.98, 14.01, 22.47, 24.07, 32.12,
40.86, 41.77, 43.54, 60.63, 105.29, 107.64, 116.92, 135.45, 172.73. MS
(EI, m/z (relative intensity)): 302 (Mþ, 24), 231 (100), 215 (41), 185
(20), 157 (8), 143 (7), 94 (9), 92 (14). Anal. Calcd for C18H26N2O2: C,
71.49; H, 8.67; N, 9.26. Found: C, 71.39; H, 8.64; N, 9.23.
4.2.9. 1,1-Bis(1H-pyrrol-2-yl)-1-phenylethane (4c).16
Light orange crystals. Mp 114–117 ꢀC (CH2Cl2/hexane). 1H NMR
4.2.15. Ethyl (2Z)-3-(2,5-dimethylfur-3-yl)acrylate (7b)17
(300 MHz, CDCl3):
1H, pyrrolyl), 6.65 (m, 1H, pyrrolyl), 7.09–7.13 (m, 2H, Ph), 7.19–7.30
(m, 3H, Ph), 7.76 (br s, 2H, NH). 13C NMR (75.5 MHz, CDCl3):
28.84,
d
2.05 (s, 3H, CH3), 5.97 (m, 2H, pyrrolyl), 6.17 (m,
Light yellow liquid. 1H NMR (300 MHz, CDCl3):
d
1.31 (t, J¼7.1 Hz,
3H, CH3), 2.24 (s, 3H, CH3), 2.31 (s, 3H, CH3), 4.20 (q, J¼7.1 Hz, 2H,
d
OCH2), 5.65 (d, J¼12.6 Hz, 1H, vinyl), 6.63 (d, J¼12.6 Hz, 1H, vinyl),
44.76, 106.30, 108.26, 116.87, 126.66, 127.41, 128.16, 137.46, 147.28.
MS (EI, m/z (relative intensity)): 236 (Mþ, 36), 221 (100), 154 (31),
110 (17), 92 (12).
6.82 (s, 1H, furyl). 13C NMR (75.5 MHz, CDCl3):
d 11.79, 13.16, 14.23,
59.82, 107.30, 114.15, 117.63, 133.79, 149.84, 154.36, 166.46. MS (EI,
m/z (relative intensity)): 194 (Mþ, 100), 165 (61), 149 (77), 123 (42),
119 (42), 91 (55), 77 (57). IR (neat, cmꢂ1) 2983, 1718 (C]O), 1627,
1176, 1444, 1399, 1030.
4.2.10. 1,1-Bis(1-methyl-1H-pyrrol-2-yl)-1-phenylethane (4d)
Yellow viscous oil. 1H NMR (300 MHz, CDCl3):
d 2.08 (s, 3H, CH3),
3.09 (s, 6H, CH3), 5.86 (dd, J¼2.1, 3.6 Hz, 1H, pyrrolyl), 6.02 (dd,
J¼3.0, 3.6 Hz, 1H, pyrrolyl), 6.55 (dd, J¼2.1, 3.0 Hz, 1H, pyrrolyl),
7.11–7.14 (m, 2H, Ph), 7.21–7.31 (m, 3H, Ph). 13C NMR (75.5 MHz,
4.2.16. Diethyl 1,4-dimethyl-7-oxabicyclo[2,2,1]hepta-2,5-diene-
2,3-dicarboxylate (8a)18
1H NMR (300 MHz, CDCl3):
d
1.31 (t, J¼7.1 Hz, 6H, CH3), 1.80 (s,
CDCl3):
d
29.76, 35.24, 45.00, 105.90, 109.23, 123.57, 126.34, 127.81,
6H, CH3), 4.25 (q, J¼7.1 Hz, 4H, OCH2), 6.95 (s, 2H, vinyl). 13C NMR
127.88, 136.96, 146.99. MS (EI, m/z (relative intensity)): 264 (Mþ,
49), 249 (100). The regiochemistry of the compound was de-
termined by NOE experiments. Anal. Calcd for C18H20N2: C, 81.78;
H, 7.63; N, 10.60. Found: C, 81.94; H, 7.55; N, 10.32.
(75.5 MHz, CDCl3):
164.04.
d 14.08, 15.36, 61.14, 92.00, 147.22, 154.49,
4.2.17. Diethyl 7-oxabicyclo[2,2,1]hepta-2,5-diene-2,3-
dicarboxylate (8b)18
4.2.11. Ethyl 3,3-bis(5-methylfur-2-yl)-3-phenylpropionate (6a)
1H NMR (300 MHz, CDCl3):
d
1.32 (t, J¼7.1 Hz, 6H, CH3), 4.27 (q,
Light yellow liquid. 1H NMR (300 MHz, CDCl3):
d
1.09 (t,
J¼7.1 Hz, 4H, OCH2), 5.68 (m, 2H, H1 and H4), 7.22 (m, 2H, vinyl). 13
C
J¼7.1 Hz, 3H, CH3), 2.25 (s, 6H, CH3), 3.40 (s, 2H, CH2CO), 4.00 (q,
J¼7.1 Hz, 2H, OCH2), 5.90 (d, J¼3.0 Hz, 2H, furyl), 5.93 (d, J¼3.0 Hz,
2H, furyl), 7.11–7.15 (m, 2H, Ph), 7.21–7.29 (m, 3H, Ph). 13C NMR
NMR (75.5 MHz, CDCl3):
163.03.
d 14.06, 61.38, 85.06, 143.21, 152.66,
(75.5 MHz, CDCl3): d 13.61, 13.92, 43.10, 48.92, 60.15, 106.01, 108.98,
Acknowledgements
126.82, 127.56, 127.91, 143.46, 151.18, 154.25, 170.25. MS (EI, m/z
(relative intensity)): 338 (Mþ, 4), 252 (23), 251 (100), 208 (4), 179
(4), 178 (4), 165 (6), 118 (9). Anal. Calcd for C21H22O4: C, 74.54; H,
6.55. Found: C, 74.45; H, 6.61.
This work was supported by a Grant-in-Aid for Scientific Re-
search on Priority Areas ‘Advanced Molecular Transformations of
Carbon Resources’ from Ministry of Education, Culture, Sports,
Science and Technology, Japan. J.O. gratefully acknowledges JSPS
Research Fellowships for Young Scientists.
4.2.12. Ethyl 3,3-bis(2,5-dimethylfur-3-yl)propionate (6b)
Yellow liquid. 1H NMR (300 MHz, CDCl3):
d
1.16 (t, J¼7.1 Hz, 3H,
CH3), 2.18 (s, 6H, CH3), 2.19 (s, 6H, CH3), 2.70 (d, J¼7.8 Hz, 2H,
CH2CO), 4.05 (q, J¼7.1 Hz, 2H, OCH2), 4.07 (t, J¼7.8 Hz, 1H, CH), 5.84
References and notes
(s, 2H, furyl). 13C NMR (75.5 MHz, CDCl3):
d 11.47, 13.47, 14.05, 28.88,
1. (a) Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731–1769; (b) Dyker,
G. Angew. Chem., Int. Ed. 1999, 38, 1698–1712; (c) Kakiuchi, F.; Chatani, N. Adv.
Synth. Catal. 2003, 345, 1077–1101; (d) Kakiuchi, F.; Murai, S. Activation of C–H
bonds: Catalytic Reactions. In Activation of Unreactive Bonds and Organic Syn-
thesis; Murai, S., Ed.; Springer: Berlin, 1999; pp 47–79; (e) Shilov, A. E.; Shul’pin,
G. B. Chem. Rev. 1997, 97, 2879–2932; (f) Jia, C.; Kitamura, T.; Fujiwara, Y. Acc.
Chem. Res. 2001, 34, 633–639; (g) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35,
826–834; (h) Crabtree, R. H. J. Chem. Soc., Dalton Trans. 2001, 2437–2450; (i)
Guari, Y.; Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047–1055; (j)
Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013–3039.
2. Hong, P.; Cho, B.-R.; Yamazaki, H. Chem. Lett. 1980, 9, 507–510.
3. (a) Kakiuchi, F.; Yamamoto, Y.; Chatani, N.; Murai, S. Chem. Lett. 1995, 24, 681–
682; (b) Kakiuchi, F.; Sato, T.; Igi, K.; Chatani, N.; Murai, S. Chem. Lett. 2001, 30,
386–387.
4. (a) Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y. Org. Lett. 2000, 2, 2927–2930; (b)
Oyamada, J.; Lu, W.; Jia, C.; Kitamura, T.; Fujiwara, Y. Chem. Lett. 2002, 31, 20–21.
5. Reetz, M. T.; Sommer, K. Eur. J. Org. Chem. 2003, 3485–3496.
6. Tsuchimoto, T.; Hatanaka, K.; Shirakawa, E.; Kawakami, Y. Chem. Commun. 2003,
2454–2455.
41.12, 60.23, 105.34, 121.52, 144.72, 149.44, 171.80. IR (neat, cmꢂ1
)
2982, 2922, 1736 (C]O), 1639, 1582, 1442, 1372, 1259, 1222, 1172,
1037, 798. MS (EI, m/z (relative intensity)): 290 (Mþ, 24), 203 (100),
173 (13), 159 (22), 121 (25), 91 (10). Contamination of a trace
amount of impurities did not give a satisfactory analysis.
4.2.13. Ethyl (2Z)-3-(2,5-dimethylfur-3-yl)cinnamate (7a-Z)
Slightly yellow liquid. 1H NMR (300 MHz, CDCl3):
d 1.25 (t,
J¼7.1 Hz, 3H, CH3), 1.99 (s, 3H, CH3), 2.26 (s, 3H, CH3), 4.16 (q,
J¼7.1 Hz, 2H, OCH2), 5.83 (s, 1H, furyl), 6.21 (s, 1H, vinyl), 7.33–7.37
(m, 5H, Ph). 13C NMR (75.5 MHz, CDCl3):
d 12.80, 13.41, 14.24, 59.97,
108.55, 117.54, 118.22, 128.16, 128.31, 129.24, 140.92, 149.19, 149.29,
149.54, 165.89. MS (EI, m/z (relative intensity)): 270 (Mþ, 97), 253
(66), 227 (100), 225 (69), 199 (58), 195 (65), 182 (58), 181 (62), 153

J. Oyamada, T. Kitamura / Tetrahedron 65 (2009) 3842–3847
13. Speranza, M. J. Chem. Soc., Chem. Commun. 1981, 1177–1178.
3847
7. Tsukada, N.; Murata, K.; Inoue, Y. Tetrahedron Lett. 2005, 46, 7515–7517.
8. Li, Z.; Shi, Z.; He, C. J. Organomet. Chem. 2005, 690, 5049–5054.
9. Nakao, Y.; Kanyiva, K. S.; Oda, S.; Hiyama, T. J. Am. Chem. Soc. 2006,128, 8146–8147.
10. (a) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara, Y. Science 2000,
287, 1992–1995; (b) Jia, C.; Lu, W.; Oyamada, J.; Kitamura, T.; Matsuda, K.; Irie,
M.; Fujiwara, Y. J. Am. Chem. Soc. 2000, 122, 7252–7263.
14. Bagnoli, F.; Dell’Amico, D. B.; Calderazzo, F.; Englert, U.; Marchetti, F.; Merigo,
A.; Ramello, S. J. Organomet. Chem. 2001, 622, 180–189.
15. Murray, C. C.; Despinoy, X. L. M.; Gould, R. O.; McNab, H.; Parsons, S. Chem.
Commun. 1996, 1083–1084.
16. Sobral, A. J. F. N.; Rebanda, N. G. C. L.; da Silva, M.; Lampreia, S. H.; Silva, M. R.;
Beja, A. M.; Paixa˜o, J. A.; Gonsalves, A. M. d’A. R. Tetrahedron Lett. 2003, 44,
3971–3973.
11. (a) Oyamada, J.; Kitamura, T. Tetrahedron Lett. 2005, 46, 3823–3827; (b) Oya-
mada, J.; Kitamura, T. Chem. Lett. 2005, 34, 1430–1431.
12. (a) Hong, S.-J.; Jeong, S.-D.; Yoo, J.; Kim, J. S.; Yoon, J.; Lee, C.-H. Tetrahedron Lett.
2008, 49, 4137–4141; (b) Singh, K.; Behal, S.; Hundal, M. S. Tetrahedron 2005, 61,
6614–6622.
17. McCulloch, A. W.; McInnes, A. G. Can. J. Chem. 1974, 52, 143–150.
18. Safaei-Ghomi, J.; Tajbakhsh, M.; Kazemi-Kani, Z. Acta Chim. Slov. 2004, 51, 545–
550.