Multicomponent reaction of imidazo[1,5- a ]pyridine carbenes with aldehydes and dimethyl acetylenedicarboxylate or allenoates: A straightforward approach to fully substituted furans

Article abstract of DOI:10.1021/jo1014933

The facile three-component reactions of N,N-substituted imidazo[1,5-a]pyridine carbenes, namely imidazo[1,5-a]pyridin-3-ylidenes, with aldehydes and DMAD or allenoates were disclosed. Both reactions proceeded via tandem nucleophilic addition, [3 + 2]-cycloaddition, and ring transformation to produce different 4-[(2-pyridyl)methyl]aminofuran derivatives generally in moderate yields. This work not only 'rovided the first example of the application of imidazo[1,5-a]pyridin-3-ylidenes in organic synthesis but also developed a straightforward approach to fully substituted furans that are not easily accessible by other methods.

Full text of DOI:10.1021/jo1014933

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Multicomponent Reaction of Imidazo[1,5-a]pyridine Carbenes with
Aldehydes and Dimethyl Acetylenedicarboxylate or Allenoates:
A Straightforward Approach to Fully Substituted Furans
Huan-Rui Pan, Yong-Jia Li, Cai-Xia Yan, Juan Xing, and Ying Cheng*
College of Chemistry, Beijing Normal University, Beijing 100875, China
ycheng2@bnu.edu.cn
Received July 29, 2010
The facile three-component reactions of N,N-substituted imidazo[1,5-a]pyridine carbenes, namely
imidazo[1,5-a]pyridin-3-ylidenes, with aldehydes and DMAD or allenoates were disclosed. Both
reactions proceeded via tandem nucleophilic addition, [3 þ 2]-cycloaddition, and ring transformation
to produce different 4-[(2-pyridyl)methyl]aminofuran derivatives generally in moderate yields. This
work not only provided the first example of the application of imidazo[1,5-a]pyridin-3-ylidenes in
organic synthesis but also developed a straightforward approach to fully substituted furans that are
not easily accessible by other methods.
Introduction
ligands in organometallics2 but also organocatalysts3 and
unique building blocks in organic synthesis.4 Although
numerous studies on the reactivity and synthetic applications
of nucleophilic carbenes, mainly N-heterocyclic carbenes,
have been reported, the multicomponent reaction of car-
benes remained largely unexplored until the 2000s. Since
Nair and co-workers reported the first three-component
reaction of dimethoxycarbene with dimethyl acetylenedicar-
boxylate (DMAD) and aldehydes or quinones in 2001,5 a
series of multicomponent reactions of nucleophilic carbenes
have appeared in the field of carbene chemistry.6,7 Most of
the known MCRs participated by a carbene intermediate
comprised of a nucleophilic carbene, an activated alkyne,
and a carbonyl compound including aldehyde, ketone,
anhydride, and ketene.5,6 These three-component reactions
proceeded either via the nucleophilic addition of a carbene
to the triple bond of the alkyne followed by cycloaddition
of the zwitterions intermediate with the carbonyl group or
Multicomponent reactions (MCRs) in which three or
more reactants are connected sequentially in a one-pot
reaction have attracted considerable attention owing to high
synthetic efficiency, and, in many cases, the facile construc-
tion of complex organic compounds.1 Nucleophilic carbenes
are versatile and valuable intermediates not only as the
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2005, 44, 1602–1634. (c) Zhu, J. Eur. J. Org. Chem. 2003, 1133–1144.
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2006, 8, 507–509. (c) Enders, D.; Balensiefer, T. Acc. Chem. Res. 2004, 37,
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6644 J. Org. Chem. 2010, 75, 6644–6652
Published on Web 09/10/2010
DOI: 10.1021/jo1014933
r
2010 American Chemical Society

Pan et al.
JOCArticle
TABLE 1. Reaction of 2-Phenylimidazo[1,5-a]pyridinium Salt 1a with Benzaldehyde 3a and Dimethyl Acetylenedicarboxylate 4 in the Presence of NaH
under Different Conditions
yield (%)
entry
1a: 3a: 4: NaH
solvent
THF
THF
THF
THF
CH2Cl2
ClCH2CH2Cl
CH3COCH3
CH3CN
CH3Ph
T (°C)
time (h)
5a
6a
1
2
3
4
5
6
7
8
9
1:1.1:1.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
1:1.5:2.2:1.5
rt
rt
12
12
12
12
12
12
12
12
12
10
26
42
3
51
45
24
21
4
12
32
11
16
10
8
9
8
3
-20
reflux
-20
-20
-20
-20
-20
through the nucleophilic addition of a carbene to the carbo-
nyl group and then to the triple bond of the alkyne. Both
reaction routes generally led to the formation of furan or
furanone derivatives. Although the known three-component
reactions of carbenes are successful, both types of carbenes
and reactions of MCRs are still rather limited.
Our interest in nucleophilic carbenes and their applica-
tions in organic synthesis8 has led us to investigate multi-
component reactions of N-heterocyclic carbenes.7 Our atten-
tion had been drawn to imidazo[1,5-a]pyridin-1-ylidenes and
imidazo[1,5-a]pyridin-3-ylidenes, the carbon and nitrogen
atom substituted and two nitrogen atom substituted imi-
dazo[1,5-a]pyridine carbenes reported in 2005 by Lassaletta9
and Glorius.10 Both types of imidazo[1,5-a]pyridine carbenes
have been shown to be strong C-ligands to Ag, Rh, Ir, and Pd
cations and elemental Se;9,10 however, their reactions and
applications as organic intermediates remain unexplored.
Very recently, we studied the reaction of electron-deficient
alkynes with the dipoles that were derived from the reaction
of imidazo[1,5-a]pyridin-1-ylidenes with aryl isothiocyanates.11
After that, our attention was turned to the reactions of
imidazo[1,5-a]pyridin-3-ylidenes. We envisioned that the
multicomponent reactions of imidazo[1,5-a]pyridine car-
benes might afford novel spiro-, fused, or monoheterocycles.
We report herein our investigation on the three-component
reactions of imidazo[1,5-a]pyridin-3-ylidenes with aldehydes
and DMAD or allenoates. The reactions provided a straight-
forward route to fully substituted furans.
Results and Discussion
We started the investigation with the reaction of
2-phenylimidazo[1,5-a]pyridin-3-ylidene 2a with benzalde-
hyde 3a and DMAD 4. The 2-phenylimidazo[1,5-a]pyridin-
3-ylidene 2a was generated in situ from its precursor, 2-phen-
ylimidazo[1,5-a]pyridinium salt 1a, which was prepared from
pyridine-2-carbaldehyde and aniline via a POCl3-mediated
cyclization of a formamide intermediate (see the Supporting
Information).9,10 Initially, the reaction of 2-phenylimidazo-
[1,5-a]pyridinium salt 1a with benzaldehyde 3a and DMAD
4 in the presence of NaH (1a/3a/4/NaH = 1:1.1:1.2:1.5) was
examined in dry THF at room temperature. After reaction
for 12 h, a pair of isomeric products 5a and 6a were isolated in
10% and 12% yields, respectively (Table 1, entry 1). Having
realized the products 5 and 6 were the 1 þ 1 þ 2 adducts of
carbene 2a with benzaldehyde 3a and DMAD 4, the reaction
employing 1a, 3a, and 4 in a ratio of 1:1.5:2.2 was optimized
by varying solvents and reaction temperature. As indicated
in Table 1, the reaction at -20 °C in dry THF produced 42%
yield of 5a along with 11% yield of 6a, while at ambient
temperature the reaction gave total yields of 5a and 6a
similar to those at -20 °C albeit with poor selectivity
between 5a and 6a. The further increase of reaction tempera-
ture to around 60 °C led to diminished yields of 5a and 6a.
The reaction was then examined at -20 °C in different
solvents including dichloromethane, 1,2-dichloromethane,
acetone, acetonitrile, and toluene. The best yield of 5a (51%)
(6) (a) Nair, V.; Sreekumar, V.; Bindu, S.; Suresh, E. Org. Lett. 2005, 7,
2297–2300. (b) Nair, V.; Bindu, S.; Sreekumar, V.; Chiaroni, A. Org. Lett.
2002, 4, 2821–2823. (c) Nair, V.; Bindu, S.; Sreekumar, V.; Rath, N. P. Org.
Lett. 2003, 5, 665–667. (d) Nair, V.; Deepthi, A.; Poonoth, M.; Santhamma,
B. J. Org. Chem. 2006, 71, 2313–2319. (e) Ma, C.; Ding, H.; Wu, G.; Yang, Y.
J. Org. Chem. 2005, 70, 8919–8923. (f) Nair, V.; Bindu, S.; Sreekumar, V.;
Balagopal, L. Synthesis 2003, 1446–1456. (g) Nair, V.; Mathew, S. C.;
Vellalath, S.; Pillai, A. N.; Suresh, E. Synthesis 2008, 551–554. (h) Ma, C.;
Yang, Y. Org. Lett. 2005, 7, 1343–1345. (i) Nair, V.; Beneesh, P. B.;
Sreekumar, V.; Bindu, S.; Menon, R. S.; Deepthi, A. Tetrahedron Lett.
2005, 46, 201–203. (j) Ma, C.; Ding, H.; Zhang, Y.; Bian, M. Angew. Chem.,
Int. Ed. 2006, 45, 7793–7797. (k) Ding, H.; Zhang, Y.; Bian, M.; Yao, W.;
Ma, C. J. Org. Chem. 2008, 73, 578–584.
(7) Wang, B.; Li, J.-Q.; Cheng, Y. Tetrahedron Lett. 2008, 49, 485–489.
(8) (a) Cheng, Y.; Zhu, Q.; Li, Q.-S.; Meth-Cohn, O. J. Org. Chem. 2005,
70, 4840–4846. (b) Cheng, Y.; Wang, B.; Cheng, L.-Q. J. Org. Chem. 2006,
71, 4418–4427. (c) Liu, M.-F.; Wang, B.; Cheng, Y. Chem. Commun. 2006,
1215–1217. (d) Cheng, Y.; Liu, M.-F.; Fang, D.-C.; Lei, X.-M. Chem.;Eur.
J. 2007, 13, 4282–4292. (e) Cheng, Y.; Ma, Y.-G.; Wang, X.-R.; Mo, J.-M.
J. Org. Chem. 2009, 74, 850–855. (f) Cheng, Y.; Wang, B.; Wang, X.-R.;
Zhang, J.-H.; Fang, D.-C. J. Org. Chem. 2009, 74, 2357–2367. (g) Mo, J.-M.;
Ma, Y.-G.; Cheng, Y. Org. Biomol. Chem. 2009, 7, 5010–5019. (h) Li, J.-Q.;
Liao, R.-Z.; Ding, W.-J.; Cheng, Y. J. Org. Chem. 2007, 72, 6266–6269.
(9) Alcarazo, M.; Roseblade, S. J.; Cowley, A. R.; Fernandez, R.; Brown,
J. M.; Lassaletta, J. M. J. Am. Chem. Soc. 2005, 127, 3290–3291.
(10) Burstein, C.; Lehmann, C. W.; Glorius, F. Tetrahedron 2005, 61,
6207–6217.
(11) Cheng, Y.; Peng, J.-H.; Li, J.-Q. J. Org. Chem. 2010, 75, 2382–2388.
J. Org. Chem. Vol. 75, No. 19, 2010 6645

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TABLE 2. Reaction of Imidazo[1,5-a]pyridinium Salts 1 with Aldehydes 3 and Dimethyl Acetylenedicarboxylate 4 in the Presence of NaH under
Optimized Conditions
yield (%)
entry
1
Ar (R)
Ph
Ph
Ph
Ph
3
Ar1
time (h)
5
6
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1a
1a
1a
1a
1a
1b
1c
1d
1e
1f
3a
3b
3c
3d
3e
3f
3f
3f
3f
3f
3f
3e
3g
Ph
12
10
10
12
8
10
10
12
12
12
12
8
5a: 51
5b: 26
5c: 53
5d: 15
5e: 50
5f: 55
5g: 63
5h: 42
5i: 45
5j: 42
5k: 47
5l: 66
a
6a: 10
6b: 12
6c: 16
6d: 54
6e: 7
6f: 14
6g: 8
6h: 26
a
p-CH3OPh
p-BrPh
p-NO2Ph
2-furyl
p-ClPh
p-ClPh
p-ClPh
p-ClPh
p-ClPh
p-ClPh
2-furyl
n-Pr
Ph
Ph
p-CH3OPh
p-ClPh
p-CF3Ph
i-Pr
Bn
p-CH3Ph
Ph
a
6k: 6
6l: 10
6m: 42
1g
1a
12
aA small amount of byproduct was detected by TLC without isolation.
TABLE 3. Reaction of Imidazo[1,5-a]pyridinium Salts 1 with Aromatic
Aldehydes 3 and Dimethyl Acetylenedicarboxylate 4 in the Presence of
NaH and DBU under Optimized Conditions
was obtained from the reaction in dichloromethane, along
with 10% yield of 6a.
The generality of the reaction was studied under the
optimized conditions using imidazo[1,5-a]pyridinium salts
1 and aldehydes 3 bearing different substituents. As shown in
Table 2, the structures of aldehydes 3 strongly influenced the
outcomes of the reactions. For example, when different aro-
matic aldehydes 3 reacted with 2-phenylimidazo[1,5-a]pyridin-
3-ylidene 2a and DMAD, 4-methoxybenzaldehyde 3b
afforded a much lower total yield of products 5b and 6b than
other aromatic aldehydes including 3a and 3c-f (Table 2,
entries 1-6). In addition, the reaction of carbene 2a with
DMAD and 4-nitrobenzaldehyde 3d, or aliphatic n-butyr-
aldehyde 3g, produced isomer 6 rather than 5 as the major
product (Table 2, entries 4 and 13). The lower reactivity of
4-methoxybenzaldehyde 3b in the reaction can be explained
by the electron-donating effect of the methoxy group that
deactivates the aldehyde toward nucleophilic carbenes.
On the other hand, the reaction of 4-nitrobenzaldehyde 3d
with carbene 2a and DMAD produced 6d instead of 5d
as the major product, probably because a strong electron-
withdrawing substituent enhanced the acidity of allyl proton
of 5 and promoted the isomerization of 5 to 6 (vide infra).
The fact that the reaction of carbene 2a with butyraldehyde
3g and DMAD preferred to give isomer 6m rather than 5m is
intriguing. Possibly, the unconjugated 5-alkylfuran is less
stable than the aryl-aryl conjugated 5-arylfuran. Therefore,
the isomerization of 5-propylfuran 5m into more conjugated
product 6m probably took place much easier than that of
5-arylfurans 5a-l. Being different from the influences of
substituents of aldehydes, the N-substituents of carbene
reactants showed small effects on the reaction. For instance,
imidazo[1,5-a]pyridin-3-ylidenes 2 bearing either an alkyl
including isopropyl and benzyl or a phenyl substituted
by an electron-donating or electron-withdrawing group,
reacted efficiently with 4-chlorobenzaldehyde 3f and DMAD
entry
1
Ar (R)
3
Ar1
time (h) yield of 6 (%)
1
2
3
4
5
6
7
8
9
10
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
3a Ph
12
10
10
12
8
10
10
12
12
8
6a: 44
6b: 26
6c: 52
6d: 73
6e: 59
6f: 56
6g: 40
6h: 48
6k: 42
6l: 55
3b p-CH3OPh
3c p-BrPh
3d p-NO2Ph
3e 2-furyl
3f p-ClPh
1b p-CH3OPh 3f p-ClPh
1c p-ClPh
1f Bn
1g p-CH3Ph
3f p-ClPh
3f p-ClPh
3e 2-furyl
toproduce 5 and 6 in41-63% and 0-26%yields, respectively
(Table 2, entries 6-11).
Having realized the compounds 6 were isomerized pro-
ducts of 5 by shifting the carbon-carbon double bond of
maleate moiety of 5, we considered that a base might
promote the isomerization of 5 to 6 through deprotonation
of the allyl proton of 5. Thus, the reaction of imidazo[1,5-a]-
pyridinium salts 1 with aromatic aldehydes 3 and DMAD 4
was examined again in the presence of both NaH and 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) under the same con-
ditions as those without DBU. To our delight, except the
reaction of carbene 2a with 4-methoxybenzaldehyde 3b and
DMAD that gave low yield of 6b, all reactions afforded pro-
ducts 6 in moderate to good yields (Table 3), while none or a
tiny amount of 5 were detected by TLC. The isomerization of
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TABLE 4. Reaction of Imidazo[1,5-a]pyridinium Salts 1 with Aromatic Aldehydes 3 and Allenoates 7 in the Presence of NaH
yield (%)
entry
1
Ar
3
Ar1
7
R1
time (h)
8
9
1
2
3
4
5
6
7
8
9
1a
1a
1a
1a
1a
1a
1b
1g
1c
Ph
Ph
Ph
Ph
Ph
Ph
3c
3c
3c
3f
3f
3g
3f
3c
3f
p-BrPh
p-BrPh
p-BrPh
p-ClPh
p-ClPh
o-FPh
p-ClPh
p-BrPh
p-ClPh
7a
7b
7c
7a
7c
7c
7c
7b
7c
Me
Et
10
10
10
11
10
8
10
10
8
8a: 45
8b: 53
8c: 47
8d: 42
8e: 54
8f: 41
8g: 40
8h: 44
8i: 49
a
a
9c:11
a
9e: 6
a
a
a
a
Bn
Me
Bn
Bn
Bn
Et
p-CH3OPh
p-CH3Ph
p-ClPh
Bn
aA small amount of byproduct was detected by TLC without isolation.
SCHEME 1. Proposed Mechanisms for the Reaction of Imidazo[1,5-a]pyridin-3-ylidenes 2 with Aldehydes 3 and Dimethyl Acetylene-
dicarboxylate 4 in the Presence of NaH or NaH and DBU
5 to 6 by the action of a base has also be confirmed through
stirring the mixture of 5g (0.2 mmol) with DBU (1 mmol) in
CH2Cl2 (10 mL) at room temperature for 12 h, which afforded
6g in 73% yield.
and vinyl protons of compounds 5 appeared as two singlet
signals around 6.0 and 6.3 ppm, respectively, while the
isomers 6 showed the allylic methylene protons as singlet
signals at about 3.5 ppm. On the other hand, in the 1H NMR
spectra of 8, only one singlet signal of CH2 appeared at
4.6-4.8 ppm corresponding to the methylene protons adja-
cent to the pyridyl group, while isomers 9 have two singlet
signals of CH2 corresponding to the methylene protons
adjacent to the pyridyl and carbonyl groups, respectively.
To account for the formation of [(2-pyridyl)methyl]-
aminofuran derivatives 5 and 6 or 8 and 9 from the reaction
of imidazo[1,5-a]pyridin-3-ylidenes 2 with aldehydes 3 and
DMAD or allenoates 7, two tandem reaction mechanisms
comprising nucleophilic addition of imidazo[1,5-a]pyridine
carbene, [3 þ 2]-cycloaddition, and ring transformation were
proposed. As depicted in Scheme 1, imidazo[1,5-a]pyridin-3-
ylidenes 2 undergo a nucleophilic addition to aldehydes 3 to
form dipolar intermediates 10. The consecutive [3 þ 2]
cycloaddition of dipoles 10 with DMAD 4 produces the
spiro-dihydrofuran intermediates 11. Deaminative aromati-
zation of the dihydrofuran intermediates 11 gives rise to the
opening of the imidazole ring to form carbanions 12. The
nucleophilic addition of carbanions 12 to DMAD affords
products 5. The isomerization of compounds 5 to 6 took
To further extend the application of imidazo[1,5-a]pyridine
carbenes, we next explored the reaction of imidazo[1,5-a]-
pyridine carbenes 2 with aromatic aldehydes 3 and electron-
deficient allenes 7. Under the similar conditions as that of the
reaction with DMAD, 2-arylimidazo[1,5-a]pyridin-3-ylidenes
2 reacted with aromatic aldehydes 3 and allenoates 7, both
bearing different substituents, to produce products 8 in
40-54% yields along with a little amount of byproducts 9
(around 10% yields) (Table 4). Being different from com-
pounds 5 and 6 that were 1 þ 1 þ 2 adducts of carbenes 2 with
aldehyde 3 and DMAD, products 8 and 9 are constitutional
isomers derived from addition of carbenes 2 to aldehyde 3
and allenes 7 in a ratio of 1:1:1 determined by the spectro-
scopic data.
The structures of all products 5, 6, 8, and 9 were ascertained
by spectroscopic methods, and the final proofs for the assigned
structures of 6a and 8e were obtained by single-crystal X-ray
analyses (see Figure S1 in the Supporting Information). The
constitutional isomers 5 and 6 or 8 and 9 can be easily
identified by the 1H NMR spectra. For example, the methine
J. Org. Chem. Vol. 75, No. 19, 2010 6647

Pan et al.
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SCHEME 2. Proposed Mechanisms for the Reaction of
Imidazo[1,5-a]pyridin-3-ylidenes 2 with Aromatic Aldehydes 3
and Allenoates 7 in the Presence of NaH
furan-2,3-dicarboxylates, respectively, as major products
generally in moderate to good yields. While reacting with
aldehydes and allenoates, imidazo[1,5-a]pyridin-3-ylidenes
produced 4-(2-pyridylmethyl)aminofuran-3-carboxylates in
moderate yields. Two tandem nucleophilic addition, [3 þ 2]-
cycloaddition and ring transformation mechanisms, were
proposed for the formation of products. This work not only
provided the first example of the synthetic application of
imidazo[1,5-a]pyridin-3-ylidenes but also developed a straight-
forward approach to fully substituted furans that are not
easily accessible by other methods and are potentially amen-
able to further transformations.
Experimental Section
General Procedure for the Reaction of 2-Aryl(2-alkyl)imidazo-
[1,5-a]pyridinium Salts 1 and Aldehydes 3 with DMAD 4 in the
Presence of NaH (Method A). Under nitrogen atmosphere and
at -20 °C, imidazo[1,5-a]pyridinium salts 1 (1.0 mmol), alde-
hydes 3 (1.5 mmol), and DMAD (2.2 mmol) were mixed in dry
dichloromethane (60 mL). To this mixture was added NaH
(1.5 mmol), and the reaction mixture was then stirred at -20 °C
for 8-12 h. After removal of the excess NaH and NaCl by
filtration and evaporation of the solvent under vacuum, the
residue was chromatographed on a silica gel column eluting with
a mixture of petroleum ether (30-60 °C) and ethyl acetate
(5:1-2:1) to afford white crystallines 5 and 6.
General Procedure for the Reaction of Imidazo[1,5-a]-
pyridinium Salts 1 and Aromatic Aldehydes 3 with DMAD 4 in
the Presence of NaH and DBU (Method B). Under nitrogen
atmosphere and at -20 °C, imidazo[1,5-a]pyridinium salts 1
(1.0 mmol), aromatic aldehydes 3 (1.5 mmol), and DMAD
(2.2 mmol) were mixed in dry dichloromethane (60 mL),
and then NaH (1.5 mmol) and DBU (1.5 mmol) were added.
The reaction mixture was stirred at -20 °C for 8-12 h. After
removal of the excess NaH and NaCl by filtration and evapora-
tion of the solvent under vacuum, the residue was chromato-
graphed on a silica gel column eluting with a mixture of petro-
leum ether (30-60 °C) and ethyl acetate (5:1-2:1) to afford
products 6.
(Z)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)allyl)-
N-phenylamino)-5-phenylfuran-2,3-dicarboxylate (5a):51% (method
A); white crystals (CH2Cl2, petroleum ether, ethyl acetate); mp
127-128 °C; νmax/cm-1 1729, 1656, 1598; δH (400 MHz, CDCl3)
8.13 (dd, J = 4.0, 0.7 Hz, 1H), 7.46 (dd, J = 7.8, 2.0 Hz, 2H), 7.32
(dt, J = 7.7, 1.8 Hz, 1H), 7.24-7.28 (m, 3H), 7.16 (dd, J = 7.3, 1.5
Hz, 2H), 7.03 (d, J = 7.8 Hz, 1H), 6.92 (ddd, J = 7.4, 4.8, 0.8 Hz,
1H), 6.80-6.85 (m, 3H), 6.22 (s, 1H), 5.92 (s, 1H), 3.81 (s, 3H), 3.72
(s, 3H), 3.60 (s, H), 3.49 (s, 3H); δC (100 MHz, CDCl3) 167.3, 165.5,
163.0, 157.9, 154.3, 154.0, 149.1, 146.8, 145.1, 139.7, 135.9, 129.7,
129.1, 128.5, 128.2, 127.9, 126.6, 126.1, 125.0, 123.6, 123.0, 120.1,
115.9, 68.5, 52.7, 52.4 (2 C), 51.9; MS (EI) 175 (87), 204 (100), 351
(90), 584 (Mþ, 10). Anal. Calcd for C32H28N2O9: C, 65.75; H, 4.83;
N, 4.79. Found: C, 65.62; H, 4.59; N, 4.74.
(E)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)prop-
1-enyl)-N-phenylamino)-5-phenylfuran-2,3-dicarboxylate (6a): 10%
(method A); 44% (method B), white crystals (CH2Cl2, petroleum
ether, ethyl acetate); mp 165-167 °C; νmax/cm-1 1740, 1715, 1612,
1594; δH (400 MHz, CDCl3) 8.41 (dd, J = 3.9, 0.7 Hz, 1H), 7.69
(dd, J = 6.1, 3.6 Hz, 2H), 7.46 (dt, J = 7.7, 1.7 Hz, 1H), 7.29-7.31
(m, 4H), 7.03-7.18 (m, 5H), 6.90-6.94 (m, 1H), 3.88 (s, 3H), 3.68
(s, 3H), 3.52 (s, 2H), 3.43 (s, 3H), 3.37 (s, 3H); δC (100 MHz,
CDCl3) 170.2, 169.8, 162.7, 157.8, 155.1, 150.7, 150.3, 148.8, 145.7,
139.2, 135.5, 129.5, 129.2, 128.2, 127.4, 126.7, 126.3, 126.0, 124.6,
123.6, 123.2, 122.3, 116.5, 52.7, 52.4, 51.7, 51.5, 35.9; MS (ESI) 585
(M þ 1), 607 (M þ Naþ). Anal. Calcd for C32H28N2O9: C, 65.75;
H, 4.83; N, 4.79. Found: C, 65.41; H, 5.10; N, 4.53.
place most likely through deprotonation of the acidic proton
adjacent to the carbonyl and pyridyl groups of 5 by a base,
followed by shifting of the carbon-carbon double bonds
and reprotonation of allyl anions. In the reaction of carbenes
2 withaldehydes3 and allenoates 7, dipoles 10undergo [3 þ 2]-
cycloaddition with either the C2-C3 double bond or C3-C4
double bond of allenoates 7 to form spiro-tetrahydrofuran
intermediates 13 or 14, respectively. In the presence of a base,
the transformations of spiro-tetrahydrofurans 13 and 14 to
furan carbanions 15 and 16, respectively, were furnished by
aromatization of tetrahydrofuran moieties of 13 and 14
through deamination and rearrangement of the exocyclic
carbon-carbon double bonds to the endocyclic double
bonds (Scheme 2). Being different from the carbanions 12 that
undergo a nucleophilic addition to DMAD (Scheme 1), the
carbanions 15 and 16 did not attack the allenoates 7, pro-
bably because allenoates are less reactive and more stereo-
hindered than DMAD. In results, the protonation of carba-
nions 15 and 16 led to the formation of products 8 and 9,
respectively. The predominant formation of products 8
rather than 9 was most probably because the ester carbonyl
substituted C2-C3 double bond is more active than alkyl
substituted C3-C4 double bond toward nucleophilic addi-
tion of dipoles 10.
Conclusion
In summary, we have studied two three-component reac-
tions of imidazo[1,5-a]pyridine carbenes. In the absence or
presence of DBU, the reaction of imidazo[1,5-a]pyridin-3-
ylidenes with aldehydes and DMAD produced 4-(2,3-dimethox-
ycarbonyl-1-(2-pyridyl)allyl)aminofuran-2,3-dicarboxylates or
4-(2,3-dimethoxycarbonyl-1-(2-pyridyl)prop-1-enyl)amino-
6648 J. Org. Chem. Vol. 75, No. 19, 2010

Pan et al.
(Z)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)allyl)-
JOCArticle
for C32H27N3O11: C, 61.05; H, 4.32; N, 6.67. Found: C, 60.90; H,
4.14; N, 6.42.
(E)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)-
prop-1-enyl)-N-phenylamino)-5-(p-nitrophenyl)furan-2,3-dicarbo-
xylate (6d): 54% (method A), 73% (method B); yellow crystals
N-phenylamino)-5-(p-methoxyphenyl)furan-2,3-dicarboxylate (5b):
26% (method A); white crystals (CH2Cl2, petroleum ether, ethyl
acetate); mp 174-176 °C; νmax/cm-1 1721, 1608, 1597; δH (400
MHz, CDCl3) 8.15 (d, J = 3.9 Hz, 1H), 7.38 (d, J = 8.3 Hz, 3H),
7.15 (d, J = 7.9 Hz, 2H), 7.11 (br, 1H), 6.96 (br, 1H), 6.76-6.82
(m, 5H), 6.23 (s, 1H), 5.95 (s, 1H), 3.80 (s, 3H), 3.73 (s, 6H), 3.59
(s, 3H), 3.48 (s, 3H); δC (100 MHz, CDCl3) 167.3, 165.5, 163.1,
160.7, 158.0, 154.3, 148.9, 146.8, 145.0, 138.9, 136.0, 129.1,
128.4, 128.2, 125.1, 124.6, 123.6, 123.1, 120.5, 120.0, 115.8,
114.0, 68.5, 55.3, 52.7, 52.4, 52.3, 51.9; HRMS (ESI) 615.1982
(M þ 1), calcd for C33H31N2O10 615.1979 (M þ 1).
(CH2Cl2, petroleum ether, ethyl acetate); mp 165-167 °C; νmax
/
cm-1 1738, 1730, 1714, 1597; δH (400 MHz, CDCl3) 8.39 (d, J =
4.6 Hz, 1H), 8.14 (d, J = 9.0 Hz, 2H), 7.99 (d, J = 8.9 Hz, 2H),
7.58 (t, J = 7.6 Hz, 1H), 7.40 (d, J = 6.5 Hz, 1H), 7.10-7.23 (m,
4H), 7.00 (d, J = 7.8 Hz, 1H), 6.93 (t, J = 7.2 Hz, 1H), 3.90 (s,
3H), 3.73 (s, 3H), 3.54 (s, 2H), 3.44 (s, 3H), 3.41 (s, 3H); δC (100
MHz, CDCl3) 169.9, 169.4, 162.2, 157.4, 154.7, 149.8, 148.9,
147.5, 146.8, 145.2, 140.5, 135.9, 132.9, 129.4, 129.3, 129.0,
127.2, 126.0, 125.1, 124.1, 123.6, 123.4, 122.7, 122.1, 117.9,
52.9, 52.6, 51.8, 51.7, 35.9; MS (ESI) 630 (M þ 1), 652 (M þ
Naþ). Anal. Calcd for C32H27N3O11: C, 61.05; H, 4.32; N 6.67.
Found: C, 61.26; H, 4.30; N, 6.60.
(E)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)prop-
1-enyl)-N-phenylamino)-5-(p-methoxyphenyl)furan-2,3-dicarbo-
xylate (6b): 26% (method B), 12% (method A); white crystals
(CH2Cl2, petroleum ether, ethyl acetate); mp 158-159 °C; νmax
/
cm-1 1736, 1713, 1608; δH (400 MHz, CDCl3) 8.42 (d, J = 4.4
Hz, 1H), 7.66 (d, J = 8.9 Hz, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.31
(d, J = 7.9 Hz, 1H), 7.17 (brs, 2H), 7.06-7.14 (m, 2H), 7.01 (d,
J = 7.1 Hz, 1H), 6.89-6.93 (m, 1H), 6.82 (d, J = 8.9 Hz, 2H),
3.87 (s, 3H), 3.80 (s, 3H), 3.70 (s, 3H), 3.51 (s, 2H), 3.44 (s, 3H),
3.39 (s, 3H); δC (125 MHz, CD3COCD3) 169.6, 169.1, 162.6,
160.7, 157.3, 155.4, 150.2, 150.1, 148.7, 146.0, 138.3, 135.5,
129.1, 128.5, 126.6, 124.8, 123.3, 123.1, 122.0, 121.5, 120.2,
117.3, 113.7, 54.8, 52.1, 51.7, 50.9, 50.6, 35.6; MS (ESI) 615
(M þ 1). Anal. Calcd for C33H30N2O10: C, 64.49; H, 4.92; N,
4.56. Found: C, 64.14; H, 4.85; N, 4.18.
(Z)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)allyl)-
N-phenylamino)-5-(2-furyl)furan-2,3-dicarboxylate (5e): 50%
(method A), pale yellow crystals (CH2Cl2, petroleum ether,
ethyl acetate); mp 165-166 °C; νmax/cm-1 1725, 1657, 1596;
δH (400 MHz, CDCl3) 8.26 (d, J = 4.2 Hz, 1H), 7.40 (s, 2H), 7.20
(br, 1H), 7.11 (t, J = 8.9 Hz, 2H), 7.00 (br, 1H), 6.78 (d, J = 8.0
Hz, 2H), 6.77 (t, J = 7.8 Hz, 1H), 6.52 (d, J = 2.8 Hz, 1H), 6.45
(s, 1H), 6.36 (dd, J = 3.4, 1.6 Hz, 1H), 6.07 (br, 1H), 3.80 (s, 3H),
3.75 (s, 3H), 3.61 (s, 3H), 3.52 (s, 3H); δC (100 MHz, CDCl3)
167.4, 165.7, 162.6, 157.7, 154.5, 149.1, 146.7, 146.4, 144.8,
144.0, 142.8, 139.4, 136.2, 128.9, 128.0, 125.7, 125.0, 123.9,
123.2, 120.1, 116.2, 111.8, 111.5, 68.1, 52.8, 52.41, 52.39, 51.9;
MS (EI) 341 (100), 574 (Mþ, 5). Anal. Calcd for C30H26N2O10:
C, 62.72; H, 4.56; N, 4.88. Found: C, 62.62; H, 4.32; N, 4.63.
(E)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)prop-
1-enyl)-N-phenylamino)-5-(2-furyl)furan-2,3-dicarboxylate (6e):
59% (method B), 7% (method A); pale yellow crystals (CH2Cl2,
petroleum ether, ethyl acetate); mp 151-153 °C; νmax/cm-1
1749, 1732, 1703, 1596; δH (400 MHz, CDCl3) 8.41 (d, J = 4.7
Hz, 1H), 7.71 (d, J = 8.6 Hz, 2H), 7.51(t, J = 7.8 Hz, 1H), 7.32
(d, J = 8.0 Hz, 1H), 7.25 (s, 1H), 7.18 (d, J = 4.0 Hz, 2H), 7.11 (t,
J = 7.4 Hz, 2H), 6.98 (d, J = 8.1 Hz, 1H), 6.91-6.94 (m, 1H),
3.88 (s, 3H), 3.72 (s, 3H), 3.51 (s, 2H), 3.43 (s, 3H), 3.40 (s, 3H);
δC (100 MHz, CDCl3) 170.1, 169.5, 162.6, 157.6, 154.9, 150.3,
148.6, 145.4, 139.3, 136.1, 135.5, 129.3, 128.5, 128.0, 126.5,
126.2, 125.7, 125.0, 123.8, 123.4, 122.4, 122.1, 117.0, 52.8,
52.4, 51.7, 51.6, 35.8; HRMS (ESI) 575.1642 (M þ 1), calcd
for C30H27N2O10 575.1666 (M þ 1).
(Z)-Dimethyl 5-(p-bromophenyl)-4-(N-(2,3-dimethoxycarbonyl-
1-(2-pyridyl)allyl)-N-phenylamino)furan-2,3-dicarboxylate (5c).
53% (method A), white crystals (CH2Cl2, petroleum ether, ethyl
acetate); mp 151-153 °C; νmax/cm-1 1727, 1657, 1589; δH (400
MHz, CDCl3) 8.22 (s, 1H), 7.44-7.49 (m, 5H), 7.23 (d, J = 7.4
Hz, 2H), 7.22 (brs, 1H), 7.05 (brs, 1H), 6.91 (d, J = 7.4 Hz, 1H),
6.88 (d, J = 8.2 Hz, 2H), 6.29 (s, 1H), 6.04 (s, 1H), 3.89 (s, 3H),
3.80 (s, 3H), 3.69 (s, 3H), 3.58 (s, 3H); δC (100 MHz, CDCl3)
167.2, 165.4, 162.9, 157.8, 154.2, 152.9, 149.1, 146.5, 144.7,
139.7, 136.1, 131.8, 129.2, 128.3, 128.0, 126.7, 126.5, 125.0,
124.2, 123.8, 123.2, 120.4, 115.9, 68.2, 52.8, 52.5, 52.4, 52.0;
MS (ESI) 663 (M þ 1), 685 (M þ Naþ). Anal. Calcd for
C32H27BrN2O9: C, 57.93; H, 4.10; N, 4.22. Found: C, 57.79;
H, 3.78; N, 4.19.
(E)-Dimethyl 5-(p-bromophenyl)- 4-(N-(2,3-dimethoxycarbo-
nyl-1-(2-pyridyl)prop-1-enyl)-N-phenylamino)furan-2,3-dicarboxy-
late (6c): 52% (method B), 16% (method A); white crystals
(CH2Cl2, petroleum ether, ethyl acetate); mp 147-149 °C; νmax
/
cm-1 1729, 1705, 1590; δH (400 MHz, CDCl3) 8.38 (d, J = 4.4
Hz, 1H), 7.61 (d, J = 8.6 Hz, 2H), 7.50 (t, J = 6.2 Hz, 1H), 7.39
(d, J = 8.6 Hz, 2H), 7.31 (d, J = 7.1 Hz, 1H), 7.15 (brs, 2H), 7.08
(t, J = 7.4 Hz, 2H), 6.96 (d, J = 8.1 Hz, 1H), 6.90 (t, J = 8.0 Hz,
1H), 3.85 (s, 3H), 3.69 (s, 3H), 3.48 (s, 2H), 3.41 (s, 3H), 3.38 (s,
3H); δC (125 MHz, CD3COCD3) 169.5, 169.0, 162.3, 157.2,
155.2, 149.8, 148.8, 148.2, 145.6, 139.3, 135.7, 131.3, 129.2,
129.1, 128.5, 126.9, 126.7, 126.2, 125.0, 123.5, 123.4, 123.1,
122.4, 121.6, 117.9, 52.2, 51.9, 51.0, 50.7, 35.6; MS (ESI) 663
(M þ 1), 685 (M þ Naþ). Anal. Calcd for C32H27BrN2O9: C,
57.93; H, 4.10; N, 4.22. Found: C, 57.98; H, 4.01; N, 3.92.
(Z)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)allyl)-
N-phenylamino)-5-(p-nitrophenyl)furan-2,3-dicarboxylate (5d): 15%
(method A), yellow crystals (CH2Cl2, petroleum ether, ethyl acetate);
mp 179-181 °C; νmax/cm-1 1728, 1657, 1599; δH (400 MHz,
CDCl3) 8.21 (d, J = 8.9 Hz, 2H), 8.17 (d, J = 4.6 Hz, 1H), 7.85
(d, J = 8.8 Hz, 2H), 7.50 (t, J = 7.6 Hz, 1H), 7.24-7.30 (m, 3H),
7.06 (t, J = 6.8 Hz, 1H), 6.93 (d, J = 7.4 Hz, 1H), 6.90 (d, J = 8.0
Hz, 2H), 6.29 (s, 1H), 6.10 (s, 1H), 3.91 (s, 3H), 3.79 (s, 3H), 3.69 (s,
3H), 3.59 (s, 3H); δC (100 MHz, CDCl3) 167.1, 165.3, 162.6, 157.5,
154.2, 151.2, 149.2, 147.8, 146.1, 144.3, 140.9, 136.4, 133.4, 129.3,
129.0, 128.1, 127.2, 125.0, 124.2, 123.7, 123.4, 120.9, 116.3, 68.0, 52.9,
52.6, 52.5, 52.0; MS (EI) 93 (100), 181 (25), 629 (Mþ, 1). Anal. Calcd
(Z)-Dimethyl 5-(p-chlorophenyl)-4-(N-(2,3-dimethoxycarbo-
nyl-1-(2-pyridyl)allyl)-N-phenylamino)furan-2,3-dicarboxylate (5f):
55% (method A), white crystals (CH2Cl2, petroleum ether, ethyl
acetate); mp 146-148 °C; νmax/cm-1 1727, 1594; δH (400 MHz,
CDCl3) 8.16 (d, J = 4.3 Hz, 1H), 7.44 (d, J = 8.5 Hz, 3H), 7.43
(brs, 1H), 7.24 (d, J = 8.6 Hz, 2H), 7.15 (d, J = 7.4 Hz, 2H), 7.01
(brs, 1H), 6.82 (d, J = 7.3 Hz, 1H), 6.79 (d, J = 8.3 Hz, 2H), 6.25
(s, 1H), 6.03 (s, 1H), 3.81 (s, 3H), 3.73 (s, 3H), 3.60 (s, 3H), 3.48
(s, 3H); δC (100 MHz, CDCl3) 167.2, 165.4, 162.9, 157.8, 154.2,
152.9, 148.9, 146.4, 144.6, 139.7, 136.3, 135.8, 129.2, 128.8,
128.2, 127.8, 126.4, 126.2, 125.1, 124.0, 123.2, 120.4, 115.9,
68.2, 52.8, 52.5, 52.4, 52.0; MS (EI): 93 (99), 181 (100), 618
(Mþ, 5). Anal. Calcd for C32H27ClN2O9: C, 62.09; H, 4.40; N,
4.53. Found: C, 61.99; H, 4.09; N, 4.44.
(E)-Dimethyl 5-(p-chlorophenyl)-4-(N-(2,3-dimethoxycarbo-
nyl-1-(2-pyridyl)prop-1-enyl)-N-phenylamino)furan-2,3-dicarbo-
xylate (6f): 52% (method B), 14% (method A); white crystals
(CH2Cl2, petroleum ether, ethyl acetate); mp 153-154 °C; νmax
/
cm-1 1730, 1706, 1593; δH (400 MHz, CDCl3) 8.41 (d, J = 4.3
Hz, 1H), 7.71 (d, J = 8.7 Hz, 2H), 7.52 (t, J = 7.1 Hz, 1H), 7.33
(d, J = 7.7 Hz, 1H), 7.26 (d, J = 8.6 Hz, 2H), 7.18 (brs, 2H),
7.09-7.11 (m, 2H), 6.99 (d, J = 7.9 Hz, 1H), 6.90-6.94 (m, 1H),
3.88 (s, 3H), 3.72 (s, 3H), 3.51 (s, 2H), 3.44 (s, 3H), 3.40 (s, 3H);
J. Org. Chem. Vol. 75, No. 19, 2010 6649

Pan et al.
JOCArticle
δC (125 MHz, CD3COCD3) 169.6, 169.1, 162.4, 157.2, 155.2,
149.8, 148.8, 148.2, 145.7, 139.3, 135.7, 134.7, 129.2, 129.1,
128.3, 126.8, 126.4, 126.1, 125.0, 123.5, 123.4, 123.3, 122.3,
121.6, 117.9, 52.2, 51.8, 51.0, 50.7, 35.7; MS (EI) 181 (100),
618 (Mþ, 5). Anal. Calcd for C32H27ClN2O9: C, 62.09; H, 4.40;
N, 4.53. Found: C, 62.05; H, 4.16; N, 4.30.
(Z)-Dimethyl 5-(p-chlorophenyl)-4-(N-(2,3-dimethoxycarbo-
nyl-1-(2-pyridyl)allyl)-N-(p-methoxyphenyl)amino)furan-2,3-
dicarboxylate (5g): 63% (method A); white crystals (CH2Cl2,
petroleum ether, ethyl acetate); mp 106-107 °C; νmax/cm-1
1727, 1667, 1588; δH (400 MHz, CDCl3) 8.25 (s, 1H), 7.62 (d,
J = 8.4 Hz, 2H), 7.51 (br, 1H), 7.35 (d, J = 8.5 Hz, 2H), 7.28
.(br, 1H), 7.09 (br, 1H), 6.84 (d, J = 9.2 Hz, 2H), 6.79 (d, J = 9.2
Hz, 2H), 6.35 (br, 1H), 6.06 (br, 1H), 3.89 (s, 3H), 3.81 (s, 3H), 3.75
(s, 3H), 3.68 (s, 3H), 3.56 (s, 3H); δC (100 MHz, CDCl3) 167.3,
165.4, 163.1, 157.8, 154.5, 153.8, 152.6, 149.0, 145.0, 140.2, 139.6,
136.2, 135.7, 128.8, 128.1, 127.8, 127.5, 126.4, 125.0, 123.9, 123.2,
117.7, 114.5, 68.3, 55.5, 53.4, 52.7, 52.4, 51.9; MS (ESI) 649
(M þ 1). Anal. Calcd for C33H29ClN2O10: C, 61.07; H, 4.50; N,
4.32. Found: C, 61.15; H, 4.53; N, 4.06.
(E)-Dimethyl 5-(p-chlorophenyl)-4-(N-(2,3-dimethoxycarbo-
nyl-1-(2-pyridyl)prop-1-enyl)-N-(p-methoxyphenyl)amino)furan-
2,3-dicarboxylate (6g). 40% (method B), 8% (method A); white
crystals (CH2Cl2, petroleum ether, ethyl acetate); mp 142-143
°C; νmax/cm-1 1732, 1713, 1608, 1596, 1579; δH (400 MHz,
CDCl3) 8.42 (d, J = 4.4 Hz, 1H), 7.74 (d, J = 8.7 Hz, 2H), 7.50
(t, J = 9.2 Hz, 1H), 7.32 (br, 1H), 7.29 (d, J = 8.6 Hz, 2H), 7.09
(d, J = 6.4 Hz, 2H), 6.96 (d, J = 7.5 Hz, 1H), 6.68 (d, J = 9.2 Hz,
1H), 6.65 (d, J = 9.0 Hz, 1H), 3.88 (s, 3H), 3.71 (s, 3H), 3.70 (s,
3H), 3.51 (s, 2H), 3.44 (s, 3H), 3.37 (s, 3H); δC (125 MHz,
CD3COCD3) 169.8, 169.2, 162.4, 157.2, 156.3, 155.4, 150.8,
148.7, 147.8, 139.2, 138.7, 135.6, 134.6, 128.4, 127.6, 126.4, 126.0,
125.1, 124.6, 124.1, 123.3, 115.9, 114.3, 114.1, 54.9, 52.1, 51.8, 50.9,
50.5, 35.3; MS (ESI) 649 (M þ 1). Anal. Calcd for C33H29ClN2O10:
C, 61.07; H, 4.50; N, 4.32. Found: C, 60.74; H, 4.40; N, 4.11.
(Z)-Dimethyl 5-(p-chlorophenyl)-4-(N-(p-chlorophenyl)-N-(2,3-
dimethoxycarbonyl-1-(2-pyridyl)allyl)amino)furan-2,3-dicarboxy-
late (5h): 41% (method A); white crystals (CH2Cl2, petroleum
ether, ethyl acetate); mp 139-140 °C; νmax/cm-1 1727, 1657,
1593; δH (400 MHz, CDCl3) 8.22 (d, J = 3.5 Hz, 1H), 7.52 (d,
J = 8.3 Hz, 2H), 7.48 (brs, 1H), 7.32 (d, J = 8.6 Hz, 2H), 7.23 (d,
J = 7.5 Hz, 2H), 7.05 (brs, 1H), 6.91 (d, J = 7.5 Hz, 1H), 6.88 (d,
J = 8.3 Hz, 2H), 6.30 (s, 1H), 6.05 (s, 1H), 3.89 (s, 3H), 3.80 (s,
3H), 3.69 (s, 3H), 3.58 (s, 3H); δC (100 MHz, CDCl3) 167.2,
165.4, 162.9, 157.8, 154.2, 152.9, 149.2, 146.5, 144.8, 139.7,
136.1, 135.8, 129.2, 128.8, 128.2, 127.8, 126.4, 126.2, 125.0,
123.7, 123.2, 120.3, 115.9, 68.3, 52.8, 52.4 (2C), 52.0; MS (ESI)
653 (M þ 1). Anal. Calcd for C32H26Cl2N2O9: C, 58.82; H, 4.01;
N, 4.29. Found: C, 58.47; H, 4.27; N, 4.18.
(E)-Dimethyl 5-(p-chlorophenyl)-4-(N-(p-chlorophenyl)-N-(2,3-
dimethoxycarbonyl-1-(2-pyridyl)prop-1-enyl)amino)furan-2,3-
dicarboxylate (6h): 48% (method B), 26% (method A); white
crystals (CH2Cl2, petroleum ether, ethyl acetate); mp 154-155
°C; νmax/cm-1 1729, 1706, 1592; δH (400 MHz, CDCl3) 8.43 (d,
J = 4.4 Hz, 1H), 7.70 (d, J = 8.6 Hz, 2H), 7.57 (brs, 1H), 7.38
(brs, 1H), 7.28 (d, J = 7.2 Hz, 2H), 7.10-7.18 (m, 3H), 7.01 (d,
J = 5.8 Hz, 1H), 6.92 (t, J = 6.5 Hz, 1H), 3.89 (s, 3H), 3.72 (s,
3H), 3.52 (s, 2H), 3.44 (s, 3H), 3.42 (s, 3H); δC (100 MHz,
CDCl3) 170.4, 169.9, 163.2, 158.1, 156.1, 150.7, 149.7, 149.1,
146.6, 140.2, 136.6, 135.6, 130.0, 130.04, 129.97, 129.3, 129.2,
127.7, 127.3, 127.0, 125.9, 124.34, 124.26, 123.3, 122.5, 118.8,
53.1, 52.7, 51.9, 51.5, 36.5; HRMS (ESI) 653.1088 (M þ 1),
C32H27Cl2N2O9 requires 653.1094 (M þ 1). Anal. Calcd for
C32H26Cl2N2O9: C, 58.82; H, 4.01; N, 4.29. Found: C, 58.41; H,
4.05; N, 4.07.
petroleum ether, ethyl acetate); mp 167-169 °C; νmax/cm-1
1729, 1660, 1616, 1586; δH (400 MHz, CDCl3) 8.23 (s, 1H),
7.50 (d, J = 8.3 Hz, 2H), 7.47 (br, 1H), 7.43 (d, J = 6.6 Hz, 2H),
7.33 (d, J = 8.4 Hz, 2H), 7.17 (brs, 1H), 7.08 (brs, 1H), 6.93 (d,
J = 8.7 Hz, 2H), 6.24 (s, 1H), 6.06 (s, 1H), 3.91 (s, 3H), 3.84 (s,
3H), 3.70 (s, 3H), 3.58 (s, 3H); δC (100 MHz, CDCl3) 166.8,
165.2, 162.7, 157.7, 153.6, 153.0, 149.2, 148.9, 143.4, 140.3,
136.6, 136.2, 129.0, 127.7, 126.6, 126.5, 125.9, 125.8, 125.1,
123.5, 123.1, 122.6, 122.2, 121.9, 115.2, 68.1, 52.9, 52.5, 52.1;
HRMS (ESI) 687.1349 (M þ 1), C33H27ClF3N2O9 required
687.1345 (M þ 1).
(Z)-Dimethyl 5-(p-chlorophenyl)-4-(N-isopropyl-N-(2,3-dimeth-
oxycarbonyl-1-(2-pyridyl)allylamino)furan-2,3-dicarboxylate (5j):
42% (method A); colorless crystals (CH2Cl2, petroleum ether,
ethyl acetate); mp 141-142 °C; νmax/cm-11748, 1732, 1646,
1589; δH (400 MHz, CD3COCD3) 8.53 (d, J = 8.7 Hz, 2H), 8.33
(brs, 1H), 7.63 (t, J = 7.4 Hz, 1H), 7.53 (d, J = 8.8 Hz, 3H), 7.13
(brs, 1H), 6.62 (s, 1H), 5.66 (s, 1H), 3.90 (s, 3H), 3.83 (s, 3H), 3.80
(br, 1H), 3.65 (s, 6H), 1.02 (d, J = 6.2 Hz, 3H), 0.89 (d, J = 6.6
Hz, 3H); δH (100 MHz, CD3COCD3) 167.6, 165.6, 165.5, 158.4,
158.1, 153.1, 149.7, 149.4, 140.8, 137.0, 135.2, 129.9, 129.3,
129.2, 129.0, 127.4, 125.5, 124.8, 123.7, 70.7, 53.0, 52.6, 52.5,
52.2, 52.1, 20.7, 18.5; HRMS (TOF-ESI) 585.1634 (M þ 1),
C29H30ClN2O9 required 585.1640 (M þ 1).
(Z)-Dimethyl 4-(N-benzyl-N-(2,3-dimethoxycarbonyl-1-(2-pyr-
idyl)allylamino)-5-(p-chlorophenyl)furan-2,3-dicarboxylate (5k):
47% (method A); white crystals (CH2Cl2, petroleum ether, ethyl
acetate); mp 141-142 °C; νmax/cm-1 1728, 1587; δH (400 MHz,
CDCl3) 8.31 (d, J = 4.4 Hz, 1H), 7.50 (d, J = 8.6 Hz, 2H), 7.45
(br, 1H), 7.24 (br, 1H), 7.13 (d, J = 8.6 Hz, 2H), 7.04 (br, 1H),
6.93 (s, 5H), 6.52 (br, 1H), 5.34 (br, 1H), 4.23 (d, J = 12.5 Hz,
1H), 4.05 (d, J = 12.5 Hz, 1H), 3.91 (s, 3H), 3.74 (s, 3H), 3.62 (s,
3H), 3.60 (s, 3H); δC (100 MHz, CDCl3) 167.2, 165.2, 164.7,
158.0, 156.1, 151.2, 149.3, 147.8, 139.5, 136.2, 135.9, 134.8,
129.9, 129.0, 128.4, 127.9, 127.8, 127.4, 127.0, 126.2, 124.2,
124.1, 123.1, 72.3, 57.0, 52.9, 52.3, 52.0; MS (ESI) 633 (M þ
1). Anal. Calcd for C33H29ClN2O9: C, 62.61; H, 4.62; N, 4.43.
Found: C, 62.47; H, 4.42; N, 4.30.
(E)-Dimethyl 4-(N-benzyl-N-(2,3-dimethoxycarbonyl-1-(2-pyr-
idyl)prop-1-enyl)amino)-5-(p-chlorophenyl)furan-2,3-dicarboxy-
late (6k): 42% (method B), 6% (method A); white crystals
(CH2Cl2, petroleum ether, ethyl acetate); mp 116-118 °C;
ν
max/cm-1 1730, 1689, 1597, 1564; δH (400 MHz, CDCl3) 8.66
(d, J = 4.2 Hz, 1H), 7.99 (d, J = 8.6 Hz, 2H), 7.51 (t, J = 7.4 Hz,
1H), 7.38 (d, J = 8.6 Hz, 2H), 7.21 (t, J = 6.9 Hz, 2H),
7.03-7.09 (m, 3H), 6.98 (d, J = 5.8 Hz, 2H), 4.52 (s, 2H),
3.90 (s, 3H), 3.87 (s, 3H), 3.63 (s, 2H), 3.44 (s, 3H), 3.25 (s, 3H);
δC (125 MHz, CD3COCD3) 170.4, 169.3, 163.2, 157.3, 155.8,
155.0, 148.9, 147.8, 139.7, 136.7, 135.9, 134.7, 129.0, 128.6,
128.4, 127.9, 127.5, 127.2, 126.9, 126.2, 125.2, 123.6, 109.1,
56.2, 52.5, 51.9, 50.8, 50.3, 34.8; HRMS (TOF-ESI) 633.1620
(M þ 1), C33H30ClN2O9 requires 633.1640 (M þ 1).
(Z)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)allyl)-
N-(p-methylphenyl)amino)-5-(2-furyl)furan-2,3-dicarboxylate (5l):
66% (method A); mp 153-155 °C; νmax/cm-1 1720, 1652, 1576;
δH (400 MHz, CDCl3) 8.33 (d, J = 4.4 Hz, 1H), 7.48 (s, 2H), 7.27
(br, 1H), 7.05 (br, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.77 (d, J = 8.6
Hz, 2H), 6.61 (d, J = 3.4 Hz, 1H), 6.51 (s, 1H), 6.44 (dd, J = 3.4,
1.7 Hz, 1H), 6.09 (brs, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.69 (s, 3H),
3.60 (s, 3H), 2.23 (s, 3H); δC (100 MHz, CDCl3) 167.4, 165.7,
162.6, 157.7, 154.6, 149.1, 146.3, 145.1, 144.3, 144.0, 142.8,
139.3, 136.1, 129.5, 129.3, 128.0, 126.0, 124.9, 123.8, 123.1,
116.2, 111.8, 111.5, 68.1, 52.8, 52.4, 51.93, 51.89, 20.4; MS
(ESI) 589 (M þ 1). Anal. Calcd for C31H28N2O10: C, 63.26; H,
4.80; N, 4.76. Found: C, 63.10; H, 5.03; N, 4.70.
(Z)-Dimethyl 5-(p-chlorophenyl)-4-(N-(2,3-dimethoxycarbo-
nyl-1-(2-pyridyl)allyl)-N-(p-trifluoromethylphenyl)amino)furan-
2,3-dicarboxylate (5i): 45% (method A); white crystals (CH2Cl2,
(E)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)prop-
1-enyl)-N-(p-methylphenyl)amino)-5-(2-furyl)furan-2,3-dicarboxy-
late (6l): 55% (method B), 10% (method A); mp 183-184 °C;
6650 J. Org. Chem. Vol. 75, No. 19, 2010

Pan et al.
max/cm-1 1735, 1725, 1692; δH (400 MHz, CDCl3) 8.39 (d, J =
JOCArticle
ν
(t, J = 8.1 Hz, 2H); δC (100 MHz, CDCl3) 163.1, 162.1, 158.4,
148.9, 148.4, 146.9, 140.5, 136.4, 131.6, 129.1, 128.5, 128.4, 127.9,
127.8, 127.0, 126.3, 122.6, 122.0, 118.5, 113.9, 113.0, 59.4, 51.2,
34.2, 30.4; HRMS (ESI) 567.1266 (M þ 1), C32H28BrN2O3
requires 567.1283 (M þ 1). Anal. Calcd for C32H27BrN2O3: C,
67.73; H, 4.80; N, 4.94. Found: C, 67.32; H, 4.96; N, 4.74.
Methyl 2-(3-benzyl-5-(p-bromophenyl)-4-(N-phenyl-N-(2-pyr-
idylmethyl)amino)(2-furyl)acetate (9c): 11%; oil; νmax/cm-11743,
1596; δH (400 MHz, CDCl3) 8.37 (d, J = 4.5 Hz, 1H), 7.34 (d, J =
8.7 Hz, 2H), 7.29 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 8.6 Hz, 2H),
7.07 (d, J = 7.3 Hz, 2H), 7.02-7.06 (m, 4H), 6.93 (d, J = 7.0 Hz,
2H), 6.72 (t, J = 7.8 Hz, 1H), 6.71 (d, J = 8.6 Hz, 2H), 4.62 (s,
2H), 3.61 (s, 3H), 3.53 (s, 2H), 3.43 (s, 2H); δC (100 MHz, CDCl3)
169.5, 158.1, 148.7, 147.5, 146.3, 144.5, 138.6, 136.7, 131.6, 129.8,
129.3, 128.6, 128.5, 128.4, 126.5, 126.3, 122.5, 122.3, 122.1, 121.4,
118.5, 113.7, 58.3, 52.3, 33.0, 29.1; HRMS (TOF-ESI): 567.1286
(M þ 1), C32H28BrN2O3 requires 567.1283 (M þ 1).
4.3 Hz, 1H), 7.45 (br, 1H), 7.38 (br, 1H), 7.36 (s, 1H), 7.03 (br,
1H), 6.83-6.88 (m, 4H), 6.60 (d, J = 2.5 Hz, 1H), 6.36 (dd, J =
3.4, 1.6 Hz, 1H), 3.81 (s, 3H), 3.53 (s, 2H), 3.49 (s, 3H), 3.35 (s,
3H), 3.32 (s, 3H), 2.14 (s, 3H); δC (100 MHz, CDCl3) 170.3,
170.0, 162.3, 157.6, 154.7, 150.7, 148.6, 143.8, 142.6, 142.3,
139.2, 135.9, 133.5, 129.63, 129.57, 126.0, 124.9, 124.6, 123.4,
122.8, 116.9, 111.9, 111.5, 52.6, 52.4, 51.6, 35.8, 20.7; MS (ESI)
589 (M þ 1). Anal. Calcd for C31H28N2O10: C, 63.26; H, 4.80; N,
4.76. Found: C, 63.09; H, 4.87; N, 4.70.
(E)-Dimethyl 4-(N-(2,3-dimethoxycarbonyl-1-(2-pyridyl)prop-
1-enyl)-N-(p-methylphenyl)amino)-5-(n-propyl)furan-2,3-dicarbo-
xylate (6m): 42% (method A); νmax/cm-1 1735, 1594, 1584,
1564; δH (400 MHz, CD3COCD3) 8.50 (d, J = 4.1 Hz, 1H), 7.66
(dt, J = 7.8, 1.7 Hz, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.20-7.24 (m,
1H), 7.18 (br, 2H), 7.00 (br, 2H), 6.94 (t, J = 7.4 Hz, 1H), 3.81 (s,
3H), 3.58 (s, 2H), 3.46 (s, 3H), 3.38 (s, 3H), 3.33 (s, 3H), 2.63 (t,
J = 7.3 Hz, 2H), 1.62-1.69 (m, 2H), 0.93 (t, J = 7.4 Hz, 3H); δH
(100 MHz, CD3COCD3) 170.8, 170.2, 163.3, 158.2, 156.3, 155.5,
151.4, 149.7, 146.5, 140.2, 136.7, 129.8, 128.0, 125.6, 124.3,
123.9, 123.1, 122.5, 118.8, 52.43, 52.36, 51.8, 51.4, 36.3, 28.6,
21.0, 14.1; HRMS (TOF-ESI) 551.2022 (M þ 1), C29H31N2O9
requires 551.2030 (M þ 1).
Methyl 5-(p-chlorophenyl)-2-ethyl-4-(N-phenyl-N-(2-pyridyl-
methyl)amino)furan-3-carboxylate (8d): 42%; white crystals
(CH2Cl2, petroleum ether); mp 147-148 °C; νmax/cm-1 1719,
1594, 1568; δH (400 MHz, CDCl3) 8.29 (d, J = 4.2 Hz, 1H), 7.38
(d, J = 8.6 Hz, 2H), 7.26 (dt, J = 7.7, 1.7 Hz, 1H), 7.05-7.08 (m,
2H), 7.02 (t, J = 8.0 Hz, 2H), 6.90 (dd, J = 7.0, 5.3 Hz, 1H), 6.63
(d, J = 7.3 Hz, 1H), 6.61 (d, J = 8.2 Hz, 3H), 4.64 (br, 2H), 3.44
(s, 3H), 2.91 (q, J = 7.6 Hz, 2H), 1.18 (t, J = 7.6 Hz, 3H); δC (100
MHz, CDCl3) 164.3, 163.3, 158.6, 149.0, 148.5, 146.6, 136.2,
133.7, 129.1, 128.6, 127.8, 127.6, 122.4, 122.0, 118.4, 113.8,
111.9, 59.7, 51.2, 22.0, 12.1; MS (ESI) 447 (M þ 1). Anal. Calcd
for C26H23ClN2O3: C, 69.87; H, 5.19; N, 6.27. Found: C, 69.77;
H, 5.43; N, 6.18.
Methyl 5-(p-chlorophenyl)-2-phenethyl-4-(N-phenyl-N-(2-pyr-
idylmethyl)amino)furan-3-carboxylate (8e): 54%; white crystals
(CH2Cl2, petroleum ether); mp 145-146 °C; νmax/cm-1 1716,
1592, 1568; δH (400 MHz, CDCl3) 8.40 (d, J = 4.7 Hz, 1H), 7.41
(d, J = 8.6 Hz, 2H), 7.38 (br, 1H), 7.10-7.23 (m, 10H), 7.02 (br,
1H), 6.73 (t, J = 7.2 Hz, 1H), 6.69 (d, J = 8.3 Hz, 2H), 4.76 (br,
2H), 3.51 (s, 3H), 3.30 (t, J = 8.2 Hz, 2H), 3.00 (t, J = 8.1 Hz, 2H);
δC (100 MHz, CDCl3) 163.1, 162.0, 158.5, 149.0, 148.5, 146.9,
140.6, 136.3, 133.8, 129.1, 128.6, 128.5, 128.4, 127.6, 127.4, 126.7,
126.3, 122.5, 122.0, 118.5, 113.9, 113.0, 59.5, 51.2, 34.3, 30.4; MS
(ESI) 523 (M þ 1), 545 (M þ Naþ). Anal. Calcd for
C32H27ClN2O3: C, 73.49; H, 5.20; N, 5.36. Found: C, 73.35; H,
4.89; N, 5.34.
Methyl 2-(3-benzyl-5-(p-chlorophenyl)-4-(N-phenyl-N-(2-pyr-
idylmethyl)amino) (2-furyl)acetate (9e): 6%; oil; νmax/cm-1 1743,
1596; δH (400 MHz, CDCl3) 8.36 (d, J = 4.7 Hz, 1H), 7.40 (d, J =
8.5 Hz, 2H), 7.32 (d, J = 7.6 Hz, 1H), 6.99-7.15 (m, 9H), 6.94 (d,
J = 7.4 Hz, 2H), 6.72 (t, J = 5.2Hz, 1H), 6.71 (d, J = 8.1 Hz, 2H),
4.62 (s, 2H), 3.61 (s, 3H), 3.53 (s, 2H), 3.43 (s, 2H); δC (100 MHz,
CDCl3) 169.4, 158.1, 148.5, 147.6, 146.3, 144.4, 138.6, 136.7,
133.2, 129.7, 129.3, 128.6, 128.5, 128.3, 128.2, 126.3, 126.2,
122.4, 122.3, 122.1, 118.5, 113.7, 58.2, 52.2, 33.0, 29.1; HRMS
(TOF-ESI) 523.1796 (M þ 1), C32H28ClN2O3 required 523.1788
(M þ 1).
General Procedure for the Reaction of Imidazo[1,5-a]pyridin-
ium Salts 1 and Aromatic Aldehydes 3 with Allenoates 7 in the
Presence of NaH. Imidazo[1,5-a]pyridinium salts 1 (1.0 mmol),
aromatic aldehydes 3 (1.5 mmol), and allenoates 7 (1.5 mmol)
were mixed in dry dichloromethane (60 mL) at room tempera-
ture. Under nitrogen atmosphere and at -20 °C, NaH (1.5
mmol) was added to the reaction mixture, and the mixture was
then stirred at -20 °C for 8-12 h. After removal of the excess
NaH and NaCl by filtration and evaporation of the solvent
under vacuum, the residue was chromatographed on a silica gel
column eluting with a mixture of petroleum ether (30-60 °C)
and ethyl acetate (8:1-5:1) to afford colorless, crystalline 8 and 9.
Methyl 5-(p-bromophenyl)-2-ethyl-4-(N-phenyl-N-(2-pyridyl-
methyl)amino)furan-3-carboxylate (8a): 45%; white crystals
(CH2Cl2, petroleum ether); mp 151-153 °C; νmax/cm-1 1717,
1594, 1571; δH (400 MHz, CDCl3) 8.47 (d, J = 4.7 Hz, 1H), 7.49
(d, J = 8.2 Hz, 2H), 7.45 (t, J = 7.8 Hz, 1H), 7.40 (d, J = 8.1 Hz,
2H), 7.26 (brs, 1H), 7.20 (t, J = 7.6 Hz, 2H), 7.09 (t, J = 5.6 Hz,
1H), 6.80 (t, J = 6.8 Hz, 3H), 4.82 (br, 2H), 3.62 (s, 3H), 3.09 (q,
J = 7.5 Hz, 2H), 1.35 (t, J = 7.5 Hz, 3H); δC (100 MHz, CDCl3)
164.4, 163.3, 158.5, 148.9, 148.4, 146.6, 136.4, 131.6, 129.1,
128.0, 127.9, 126.9, 122.5, 122.0, 121.9, 118.5, 113.8, 111.9,
59.5, 51.2, 22.1, 12.1; MS (ESI) 490 (M þ 1). Anal. Calcd for
C26H23BrN2O3: C, 63.55; H, 4.72; N, 5.70. Found: C, 63.37; H,
4.79; N, 5.52.
Methyl 5-(p-bromophenyl)-4-(N-phenyl-N-(2-pyridylmethyl)-
amino)-2-propylfuran-3-carboxylate (8b): 53%; white crystals
(CH2Cl2, petroleum ether); mp 142-144 °C; νmax/cm-1 1716,
1591, 1571; δH (400 MHz, CDCl3) 8.47 (d, J = 4.4 Hz, 1H),
7.44-7.50 (m, 3H), 7.40 (d, J = 8.3 Hz, 2H), 7.25 (br, 1H), 7.20
(t, J = 7.8 Hz, 2H), 7.08-7.11 (m, 1H), 6.78-6.82 (m, 3H), 4.85
(br, 2H), 3.62 (s, 3H), 3.04 (t, J = 7.5 Hz, 2H), 1.80 (sextet, J =
7.4 Hz, 2H), 1.03 (t, J = 7.4 Hz, 3H); δC (100 MHz, CDCl3)
163.4, 163.3, 158.5, 149.0, 148.5, 146.7, 136.2, 131.6, 129.1,
128.0, 127.8, 126.9, 122.5, 122.0, 118.4, 113.8, 112.5, 59.5,
51.2, 30.3, 21.3, 13.8; MS (ESI) 505 (M þ 1). Anal. Calcd for
C27H25BrN2O3: C, 64.16; H, 4.99; N, 5.54. Found: C, 64.12; H,
5.35; N, 5.35.
Methyl 5-(o-fluorophenyl)-2-phenethyl-4-(N-phenyl-N-(2-pyr-
idylmethyl)amino)furan-3-carboxylate (8f): 41%; white crystals
(CH2Cl2, petroleum ether); mp 100-102 °C; νmax/cm-1 1700,
1599, 1581, 1495; δH (400 MHz, CDCl3) 8.39 (d, J = 4.4 Hz, 1H),
7.20-7.29 (m, 5H), 7.13-7.16 (m, 3H), 7.07-7.11 (m, 3H),
6.96-7.00 (m, 3H), 6.70 (t, J = 7.3 Hz, 1H), 6.60 (d, J = 8.2
Hz, 2H), 4.71 (br, 2H), 3.46 (s, 3H), 3.30 (t, J = 8.2 Hz, 2H), 3.00
(t, J = 8.2 Hz, 2H); δC (100 MHz, CDCl3) 162.8, 161.0, 158.8,
158.5, 149.0, 148.8, 143.8, 140.6, 136.3, 130.64, 130.56, 130.3,
130.2, 129.8, 128.8, 128.5, 128.4, 126.2, 124.02, 123.98, 121.8,
121.7, 118.3, 117.5, 117.3, 116.2, 116.0, 114.0, 112.3, 59.5, 51.1,
34.1, 30.4; MS (EI) 123 (100), 506 (Mþ, 80). Anal. Calcd for
C32H27FN2O3: C, 75.87; H, 5.37; N, 5.53. Found: C, 75.56; H,
5.20; N, 5.20.
Methyl 5-(p-bromophenyl)-2-phenethyl-4-(N-phenyl-N-(2-pyr-
idylmethyl)amino)furan-3-carboxylate (8c): 47%; white crystals
(CH2Cl2, petroleum ether); mp 140-141 °C; νmax/cm-1 1705,
1622, 1594, 1572; δH (400 MHz, CDCl3) 8.47 (d, J = 4.5 Hz, 1H),
7.38-7.48 (m, 5H), 7.30 (t, J = 8.0 Hz, 2H), 7.18-7.25 (m, 6H),
7.10 (t, J = 5.5 Hz, 1H), 6.80 (t, J = 7.2 Hz, 1H), 6.77 (d, J = 8.2
Hz, 2H), 4.83 (br, 2H), 3.59 (s, 3H), 3.38 (t, J = 7.4 Hz, 2H), 3.08
J. Org. Chem. Vol. 75, No. 19, 2010 6651

Pan et al.
JOCArticle
Methyl 5-(p-chlorophenyl)-4-(N-(p-methoxyphenyl)-N-(2-pyr-
idylmethyl)amino)-2-phenethylfuran-3-carboxylate (8g):40%; white
crystals (CH2Cl2, petroleum ether); mp 97-98 °C; νmax/cm-1
1708, 1623, 1594; δH (400 MHz, CDCl3) 8.49 (d, J = 4.8 Hz,
1H), 7.53 (d, J = 8.4 Hz, 2H), 7.46 (t, J = 7.6 Hz, 1H), 7.21-7.32
(m, 8H), 7.09 (t, J = 6.9 Hz, 1H), 6.77 (d, J = 9.2 Hz, 2H), 6.69 (d,
J = 8.9 Hz, 2H), 4.78 (br, 2H), 3.75 (s, 3H), 3.61 (s, 3H), 3.36 (t,
J = 8.1 Hz, 2H), 3.07 (t, J = 8.2 Hz, 2H); δC (100 MHz, CDCl3)
163.2, 162.0, 158.8, 152.5, 149.0, 146.8, 142.6, 140.6, 136.3, 133.7,
128.6, 128.5, 128.4, 128.3, 127.5, 126.7, 126.3, 122.4, 122.0, 114.9,
114.5, 113.0, 59.9, 55.6, 51.3, 34.3, 30.5; HRMS (TOF-ESI)
553.1881 (M þ 1), C33H30ClN2O4 requires 553.1894 (M þ 1).
Methyl 5-(p-bromophenyl)-2-propyl-4-(N-(2-pyridylmethyl)-
N-(p-tolyl)amino)furan-3-carboxylate (8h): 44%; white crystals
(CH2Cl2, petroleum ether); mp 151-153 °C; νmax/cm-1 1707,
1626, 1611, 1593; δH (400 MHz, CDCl3) 8.47 (d, J = 4.8 Hz,
1H), 7.51 (d, J = 8.2 Hz, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.40 (d,
J = 8.3 Hz, 2H), 7.26 (d, J = 6.8 Hz, 1H), 7.07 (t, J = 6.7 Hz,
1H), 6.99 (d, J = 8.2 Hz, 2H), 6.68 (d, J = 8.2 Hz, 2H), 4.81 (br,
2H), 3.63 (s, 3H), 3.02 (t, J = 7.5 Hz, 2H), 2.24 (s, 3H), 1.80
(sextet, J = 7.4 Hz, 2H), 1.02 (t, J = 7.4 Hz, 3H); δC (100 MHz,
CDCl3) 163.4, 163.3, 158.7, 148.8, 146.6, 146.1, 136.4, 131.5,
129.7, 128.1, 128.05, 127.5, 126.9, 122.6, 122.0, 121.9, 113.8,
112.6, 59.5, 51.2, 30.3, 21.3, 20.4, 13.8; MS (ESI) 519 (M þ 1).
Anal. Calcd for C28H27BrN2O3: C, 64.74; H, 5.24; N, 5.39.
Found: C, 64.76; H, 5.57; N, 5.23.
Methyl 5-(p-chlorophenyl)-4-(N-(p-chlorophenyl)-N-(2-pyridyl-
methyl)amino)-2-phenethylfuran-3-carboxylate (8i): 49%; white
crystals (CH2Cl2, petroleum ether); mp 109-110 °C; νmax/cm-1
1709, 1592, 1569, 1493; δH (400 MHz, CDCl3) 8.48 (d, J = 4.8 Hz,
1H), 7.46 (dd, J = 6.8, 1.8 Hz, 2H), 7.45-7.50 (m, 1H), 7.19-7.32
(m, 8H), 7.13 (dd, J = 9.0, 2.0 Hz, 2H), 7.12-7.15 (m, 1H), 6.70
(dd, J = 7.0, 2.1 Hz, 2H), 4.8 (br, 2H), 3.61 (s, 3H), 3.38 (t, J = 8.0
Hz, 2H), 3.08 (t, J = 7.4 Hz, 2H); δC (100 MHz, CDCl3) 162.9,
162.1, 157.9, 149.0, 147.1, 147.0, 140.4, 136.4, 134.0, 129.0, 128.7,
128.5, 128.4, 127.22, 127.18, 126.6, 126.3, 123.4, 122.6, 122.2,
115.0, 112.8, 59.5, 51.3, 34.2, 30.4; HRMS (TOF-ESI) 557.1396
(M þ 1), C32H27Cl2N2O3 requires 557.1399 (M þ 1).
Acknowledgment. This work was supported by the National
Natural Science Foundation of China (No. 20832006), the
Ministry of Science and Technology of China (2009ZX09501-
006), Beijing Municipal Commission of Education, and the
Scientific Research Foundation of Beijing Normal University
(2009SC-1).
Supporting Information Available: General procedure for
the preparation of 2-aryl (alkyl)imidazo[1,5-a]pyridinium salts
1, copies of 1H NMR and 13C NMR spectra of products 5, 6, 8,
and 9 excluding those byproducts without full characterization,
as well as single-crystal data of 6a and 8e (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
6652 J. Org. Chem. Vol. 75, No. 19, 2010