Synthesis of Furans and Pyrroles from 2-Alkoxy-2,3-dihydrofurans Through a Nucleophilic Substitution-Triggered Heteroaromatization

Article abstract of DOI:10.1002/adsc.201500993

An effective method to synthesize α-functionalized furan and pyrrole derivatives was developed using 2-alkoxy-2,3-dihydrofurans as modular precursors. This protocol featured a previously unreported tandem nucleophilic substitution/heteroaromatization reaction. Nucleophiles such as indole, α-oxoketene dithioacetal, trimethoxybenzene, and dimethoxynaphthalene can react readily with 2-alkoxy-2,3-dihydrofurans to afford α-functionalized five-membered ring heterocycles in the presence of acid catalysts, such as copper bromide and iron chloride. The mechanism of the reaction was also discussed, in which the first step, nucleophilic substitution, is the key in triggering the succeeding heteroaromatization. This method can also be extended to the synthesis of dihydrothiophenes.

Full text of DOI:10.1002/adsc.201500993

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DOI: 10.1002/adsc.201500993
Synthesis of Furans and Pyrroles from 2-Alkoxy-2,3-dihydrofurans
Through a Nucleophilic Substitution-Triggered Heteroaromatiza-
tion
Changhui Liu,a Li Zhou,a Wenbo Huang,a Man Wang,a and Yanlong Gua,b,*
a
Key laboratory of Material Chemistry for Energy Conversion and Storage, Ministry of Education, Hubei Key Laboratory
of Material Chemistry and Service Failure, School of Chemistry and Chemical Engineering, Huazhong University of
Science and Technology (HUST), 1037 Luoyu road, Hongshan District, Wuhan 430074, People’s Republic of China
Fax: (+86) 27-87 54 45 32; Phone: (+86) 27-87 54 37 32; e-mail: klgyl@hust.edu.cn
b
State Key Laboratory for Oxo Synthesis and Selective Oxidation, Lanzhou Institute of Chemical Physics, Lanzhou,
730000, People’s Republic of China
Received: October 28, 2015; Revised: December 5, 2015; Published online: February 17, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201500993.
Abstract: An effective method to synthesize a-func- catalysts, such as copper bromide and iron chloride.
tionalized furan and pyrrole derivatives was devel- The mechanism of the reaction was also discussed, in
oped using 2-alkoxy-2,3-dihydrofurans as modular which the first step, nucleophilic substitution, is the
precursors. This protocol featured a previously unre- key in triggering the succeeding heteroaromatization.
ported tandem nucleophilic substitution/heteroaro- This method can also be extended to the synthesis of
matization reaction. Nucleophiles such as indole, a- dihydrothiophenes.
oxoketene dithioacetal, trimethoxybenzene, and di-
methoxynaphthalene can react readily with 2-alkoxy-
2,3-dihydrofurans to afford a-functionalized five- Keywords: dihydrothiophenes; furans; heteroaroma-
membered ring heterocycles in the presence of acid tization; indoles; pyrroles; a-oxoketene dithioacetal
Introduction
lished on the basis of an intramolecular condensation-
pull reaction manner. Furthermore, redox reactions,
Furans, pyrroles, and thiophenes are naturally occur- which can enrich the product diversity significantly,
ring heterocycles. Some of these functional groups are have been rarely applied in the construction of a het-
important biologically active pharmaceuticals.[1] Al- erocyclic scaffold from nucleophilic substitution.[6]
though myriad methods are known to accomplish the
We reported a ring-opening reaction of 2-substitut-
synthesis of these heterocycles, sustained efforts have ed 3,4-dihydropyrans with indoles, which provided
been made to develop efficient synthetic methods a convenient method to synthesize 2-[3-(indol-3-yl)-
under manageable conditions.[2] On the other hand, propyl]-1,3-dicarbonyl compounds.[7] In continuation
carbon–carbon bond formation through a nucleophilic of our research to explore new reactions using cyclic
substitution reaction is a fundamental pathway to acetals as building blocks, we recognized the value of
construct complex organic molecules.[3] Tandem or investigating the reactions of 2-alkoxy-2,3-dihydrofur-
cascade reactions, which are hot research topics of ans.[8] Herein, we report, for the first time, a nucleo-
modern organic chemistry, often employ nucleophilic philic substitution-triggered heteroaromatization reac-
substitution as a key step because the conditions for tion of 2-alkoxy-2,3-dihydrofurans with aromatic nu-
implementing these reactions are compatible with cleophiles that produces furan and pyrrole derivatives.
many others.[4] By the rational design of organic sub- Dihydrothiophenes could also be synthesized with
strates, many important heterocycles could be synthe- a similar procedure.
sized through nucleophilic substitution-triggered reac-
tion sequences.[5] However, the potential capacity of
this type of sequential reaction in creating molecular
complexity and diversity has not been fully exploited,
because most of the reported examples were estab-
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Synthesis of Furans and Pyrroles
Results and Discussion
to 11). A weak Lewis acid, MnCl2·4H2O, was also em-
ployed, but only a trace amount of 3a was formed
Initially, a dihydrofuran derivative 1a was treated (entry 12).
with 2-methylindole 2a (Table 1). The reaction was
The effect of the solvent on the model reaction was
performed at room temperature in nitromethane. No then investigated. Nitromethane prominently cooper-
product was formed in the absence of catalyst ated with the CuBr2 catalyst, followed by acetonitrile,
(entry 1). When FeCl3·6H2O was employed as cata- 1,4-dioxane, and chlorobenzene to a distant second
lyst, 1a was consumed rapidly. However, the expected place (entries 13 to 15). By contrast, toluene, di-
oxidative substitution product 3a was obtained only chloromethane, and ethanol were found to be inap-
at a 15% yield (entry 2). The formation of a ring- propriate for this reaction (entries 16 to 18). Further
opening product 4a was predominant. To improve the investigations revealed that the reaction was also af-
yield of 3a, various Lewis acids were employed. Nota- fected significantly by the catalyst amount. When the
bly, when CuBr2 was used, 3a reached a 95% yield amount of catalyst was increased, the maximum yield
(entry 3). Many other copper salts were also screened. was reached sooner. With 20 mol% of catalyst, the re-
CuCl2 and Cu(OTf)2 were found to be less effective action time was halved compared with that of the use
(entries 4 and 5), and 3a was obtained at 55% and of 5 mol% of CuBr2 (entry 19). However, with a high
23% yields, respectively. CuSO4·5H2O and CuBr catalyst loading, the reaction selectivity dropped
cannot catalyze this reaction (entries 6 and 7). When slightly because of the formation of some inseparable
strong acids, such as para-toluenesulfonic acid products. Finally, the optimal reaction conditions
(PTSA), AlCl3, Sc(OTf)3, and I2 were employed as were confirmed as the following: 5 mol% of CuBr2
catalysts, 1a was consumed rapidly. However, 3a was catalyst, nitromethane solvent, and 1 h reaction time
scarcely detected, and only 4a was obtained (entries 8 at room temperature.
Table 1. Synthesis of 3a from 1a and 2a.[a]
entry
catalyst (5 mol%)
–
FeCl3 6H2O
CuBr2
solvent
Yield (%)
3a
4a
1
2
3
4
5
6
7
8
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3NO2
CH3CN
1,4-dioxane
PhCl
0
15
0
65
–
22
.
95 (92)[b]
55
CuCl2
Cu(OTf)2
23
52
.
CuSO4 5H2O
trace
trace
trace
trace
trace
trace
trace
65
59
55
11
trace
trace
85
trace
trace
68
58
45
53
10
15
13
24
25
trace
trace
trace
CuBr
PTSA
AlCl3
Sc(OTf)3
I2
9
10
11
12
13
14
15
16
17
18
19[c]
.
MnCl2 4H2O
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
CuBr2
toluene
DCM
EtOH
CH3NO2
[a]
Conditions unless specified otherwise: 1a, 0.2 mmol; 2a, 0.2 mmol; catalyst, 0.01 mmol; solvent, 1 mL; room temperature,
1 h, under air.
Reaction scale: 10 mmol.
Catalyst amount, 20 mol%, 0.04 mmol, 30 min.
[b]
[c]
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Under the optimized conditions, we probed the are rather reluctant to participate in the reaction, and
scope of the reaction with respect to both the dihy- moderate yields were obtained even though the reac-
drofuran and the indole components. As demonstrat- tion time was increased to 12 h (3k to 3n). By sharp
ed by the results in Figure 1, various indoles reacted contrast, excellent yields were obtained when the di-
with 1a readily, affording the C3-furanyl substituted hydrofurans with phenyl or n-propyl group in C2 posi-
indole derivatives in good to excellent yields (3b–f). tion were employed (3n–3o). The discrepancy be-
The presence of a phenyl group in the C2 position of tween the reactivities is likely due to the possible
the indole ring enabled more efficient reactions than steric hindrance associated with these groups. Despite
the congeners with methyl group (3j, 3l, 3n). The obtaining only a 68% yield from the synthesis of 3k,
scope of this oxidative substitution reaction with re- considering the fact that cyclopropane scaffold is
spect to the dihydrofuran component was next stud- amenable to many transformations,[9] the present re-
ied. Many 2-butoxy-2,3-dihydrofurans with ester or action is quite interesting. This reaction enabled the
ether moieties were proven to be viable substrates synthesis of a C5-substituted fused furan 3s, which
(3g–3u). However, an unexpected subtle influence of has been proven to possess promising biological activ-
a bulky group in the C2 position of the skeleton on ity.[10] The catalytic activity of CuBr2 was not affected
the reactivity of the molecule was observed. 2-Isopro- by the existence of a pyridyl group in the skeleton of
pyl- or 2-cyclopropyl-substituted 2,3-dihydrofurans dihydrofuran. Owing to this unique ability of CuBr2,
Figure 1. Substrate scope of the reaction between 2-butoxy-2,3-dihydrofurans and indoles.
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Synthesis of Furans and Pyrroles
a tricyclic compound 3u can be obtained at a 78%
yield.
Notably, the productꢁs skeleton contains an indole
ring system, which has become an important structur-
al component in many pharmaceutical agents.[11] Par-
ticularly, indoles substituted with aromatic heterocy-
clic rings at the C3 position have been found in a fasci-
nating array of bioactive natural products and phar-
maceutical compounds.[12] However, we found that
the synthesis of these compounds is challenging be-
cause the reported arylation methods suffered from
Scheme 1. Synthesis of 3a from 4a.
either insufficient reaction or the use of expensive re- with PTSA in reflux benzene resulted in the forma-
agents. For example, with the classical carbon–carbon tion of methyl 2-methyl-3-furancarboxylate. However,
cross-coupling strategy (Suzuki–Miyaura, Stille, this compound was found to be highly stable in
Kumada, and Negishi reactions), the overall process a cross-dehydrogenative coupling reaction (CDC) in
includes the prefunctionalization of the substrates as the presence of 2-methylindole under previous reac-
nucleophilic and electrophilic reagents, which is gen- tion conditions (see the Supporting Information,
erally less efficient with the heteroaryl analogues.[13] Scheme S1). This precludes the possibility of forming
A direct arylation involving a C–H activation reaction 3a through a CDC reaction. We then treated 4a in
allows the use of a simple unfunctionalized arene as the presence of CuBr2. Intriguingly, 3a was formed
substrate.[14] However, the reactions with indoles are rapidly (Scheme 1). A low yield of 25% was obtained
limited to the use of homoaryl halides as the electro- after inducing the same reaction under argon. This
philic component; furthermore, the regioselectivity of implies that molecular oxygen is important for render-
the arylation depends on the protecting group of the ing the reaction possible. On the basis of these results,
indole nitrogen atom.[15] The model reaction in we proposed a mechanism depicted in Figure 2. Ini-
Table 1 not only allowed the addition of a nucleophile tially, CuBr2 may have activated the dihydrofuran 1a
moiety to the skeleton of a five-membered heterocy- through coordination with the ketone carbonyl. Then,
cle in a convenient and efficient way, but also avoided 2-methylindole may have acted as a nucleophile to
the use of expensive catalysts and harsh reaction con- attack the anomeric carbon of 1a. Both of the endo-
À
À
ditions. The reaction can also be scaled up effectively cyclic C O and exocyclic C O bonds are fairly sensi-
with similar efficiency. In particular, the reaction of tive to acid; hence the nucleophilic substitution may
1a (10 mmol) with 2a (10 mmol) gave the corre- have occurred twice, thereby forming 4a. The good
sponding product 3a at a 92% yield (Table 1, leaving ability of 2-methylindole 2a[17] leads to the
entry 3).
formation of the alkylideneindolenine intermediate
To gain insight into this reaction, several controlled (I).[11b,18] (I) may have instigated an intramolecular
experiments were conducted. 2-Alkoxy-2,3-dihydro- nucleophilic substitution, in which a OH group in the
furans are known to be rather susceptible to acidic enol form of 1,3-dicarbonyl fragment of 4a served as
conditions.[16] For instance, treating a dihydrofuran 1b a nucleophile. An intermediate (II) was therefore
Figure 2. Proposed mechanism for the synthesis of furan derivatives.
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mation rate of the final product 3a should be under
the control of this apparent nucleophilic substitution.
Considering the success of the earlier experiments,
we were prompted to use other nucleophiles in this
type of reaction. We found that a-oxoketene dithioa-
cetals, which have recently emerged as important
building blocks,[20] can react with our dihydrofurans
easily in the presence of CuBr2 catalyst at 608C. This
result is reasonable because the a-carbon of the
Scheme 2. CuBr2-catalyzed aromatization of 5a.
generated. Finally, 3a may have been formed through double bond that is close to the carbonyl group is
a CuBr2-induced heteroaromatization.[19] All of our fairly reactive because of the presence of electron-re-
earlier attempts at isolating intermediate (II) from leasing alkylthiol groups (p-p conjugation). The sub-
the reaction system failed. Hence, to verify the ame- strate scope was also found to be excellent (Figure 3).
nability of (II) for the heteroaromatization reaction, Reasonable yields were obtained regardless of the
a similar C5-aryl-substituted 2,3-dihydrofuran 5a was nature of the substituent present on the a-oxoketene
synthesized and subjected to the conditions of the thioacetal (electron-donating or electron-withdraw-
model reaction (Scheme 2). As we expected, 5a was ing). Cyclopropyl, difluoromethyl, and double bonds
easily converted to 6a at 608C. These results suggest in the substrates can all be delivered uneventfully
that the heteroaromatization of (II) may indeed be into the structure of final products (8 f, 8k, and 8q).
the last step of the mechanism. Interestingly, the for- The synthesis of 8a and 8q scaled up to 5 mmol pro-
mation of (II) starting from the dihydrofuran 1a ap- vided uniform results.
pears to involve a nucleophilic substitution, in which
Trimethoxybenzenes 9a, 9b, and dimethoxynaph-
the butoxy group acted as the leaving group. The het- thalene 11a reacted readily with 1b to form a-aryl-
eroaromatization step is rather fast; therefore, the for- functionalized furan derivatives (Scheme 3). Particu-
Figure 3. a-Ketene dithioacetal reactions with 2-alkoxy-2,3-dihydrofuran to produce corresponding furan derivatives.
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Synthesis of Furans and Pyrroles
could be synthesized through an alternative two-step
method as shown in Scheme 4. In the first step, 1c
reacts readily with 2.0 equivalents of 2a with the aid
·
of the catalyst FeCl3 6H2O, affording a ring-opening
product 4b in almost quantitative yield. Treatment of
4b with 13a in the presence of Al(OTf)3 catalyst pro-
duced 14a in 82% yield. The addition of Al(OTf)3 as
catalyst in the second step is necessary because 14a
cannot be obtained in the absence of Al(OTf)3
·
(Scheme 4). When FeCl3 6H2O was used instead of
Al(OTf)3, only 3h was obtained, and aniline remained
unchanged at the end of the reaction (Scheme 4).
In these consecutive steps, the same solvent nitro-
methane was used. To simplify the operational proce-
dure, we also attempted to perform the reaction in
a one-pot stepwise manner. First, 1c was treated with
·
2.0 equivalents of 2a in the presence of FeCl3 6H2O in
nitromethane. After 30 min of stirring at 608C, by
monitoring the reaction with thin layer chromatogra-
phy (TLC), we found that both 1c and 2a were com-
pletely consumed. Then, 13a was added along with
the Al(OTf)3 catalyst. After 6 h of reaction, 14a was
obtained in 76% yield. With this procedure, various
C3-pyrrolylated indoles could be obtained. Random
combinations of the three starting substrates could
Scheme 3. Reactions of 1b with 9a, 9b and 11a.
larly, when 1,3,5-trimethoxybenzene 9a was used as provide final products with up to 88% yield
nucleophile, the desired product 10a was obtained in (Figure 4). The reaction with the 5 mmol scale also
an almost quantitative yield within 30 min. The inferi- proceeded successfully. Previous methods employed
or reaction yield of 1,2,4-trimethoxybenzene 9b with to access this kind of pyrrole/indole hybrid molecular
respect to that of 9a may be due to the low nucleo- scaffold were not easy and suffered from either the
philicity in the former compound.
difficulty of preparing the starting substrate[22] or the
2-Alkoxy-2,3-dihydrofuran is well known to react use of harsh conditions.[23]
with amines to generate pyrrole.[21] Thus, we estab-
To understand the exact role of these two catalysts,
lished a three-component reaction of dihydrofuran several controlled experiments were performed
1c, aniline 13a, and 2a, with which a pyrrole deriva- (Scheme 5). In the skeleton of 4b, two active sites
tive is expected to be synthesized. Although 1c was that can potentially react with 13a. The diketone
consumed in some cases, we failed to obtain the an- moiety may react with 13a to form an enamine. In its
À
ticipated assembly product 14a. Nevertheless, 14a opposite side, a cleavage of a C C bond may also
Scheme 4. Synthesis of 14a via a two-step method.
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Figure 4. Scope of one-pot, stepwise, multicomponent reactions of indoles, 2-butoxy-2,3-dihydrofurans and anilines.
occur, enabling the formation of a nucleophilic substi- molecular enamination. The following heteroaromati-
tution product with the removal of one molecule of zation of (V) would then result in the formation of
2a. To determine the favorability of the reaction, 3- 14a. (V) is difficult to isolate from the reaction mix-
methyl-2,4-pentane 15a was treated with 13a under ture; hence, to clarify the exact contribution of each
our conditions. However, no reaction occurred when component of the catalyst in the heteroaromatization
·
FeCl3 6H2O or Al(OTf)3 was used as catalyst. A com- reaction, a dihydropyrrole 19a was used as an alterna-
·
bination of FeCl3 6H2O and Al(OTf)3 also gave the tive model to (V) in the controlled experiments. The
same result. Afterward, a diindolylmethane derivative oxidation of 19a proceeded favorably in the presence
17a was subjected to our reaction conditions. An in- of FeCl3·H2O, and the expected pyrrole derivative
termolecular nucleophilic substitution product 18a 20a was obtained in 82% yield. By contrast, the reac-
was then generated in 78% yield when Al(OTf)3 was tion over Al(OTf)3 proceeded sluggishly, and the
·
used as catalyst. FeCl3 6H2O was demonstrated to be yield of 20a reached only 35% under identical condi-
less efficient in this reaction, and the yield of 18a in tions. These results led us to conclude that in the het-
this case reached only 15% under identical condi- eroaromatization step, the main driving force is the
tions. These results imply that the initial step in the catalytic effect of the iron salt.
reaction of 4b and 13a might be a pseudo-nucleophil-
This one-pot stepwise method was also proven to
ic substitution to form intermediate (IV). In this step, be applicable in the synthesis of a dihydrothiophene
the Al(OTf)3 catalyst plays an important role derivative 21a (Figure 6). After finishing the electro-
(Figure 5). Once (IV) is formed, it might be rapidly philic ring-opening of 1b with 2a, P2S5 was added into
converted to a dihydropyrrole (V) through an intra- the reaction system. Compound 21a was obtained in
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Synthesis of Furans and Pyrroles
Conclusions
A novel nucleophilic substitution-triggered heteroaro-
matization reaction of 2-butoxy-2,3-dihydrofuran was
developed by using metal Lewis acids as catalysts.
With this method, many nucleophiles that have conju-
gated systems, such as indole, a-oxoketene dithioace-
tal, trimethoxybenzene and dimethoxynaphthalene
could be installed into C2 position of the furan skele-
ton with the aid of CuBr2 catalyst. Thanks to the good
leaving ability of 2-methylindole, stepwise approaches
for the synthesis of pyrrole and dihydrothiophene de-
rivatives were also developed. These reactions offered
effective means to heteroarylate some commonly
used nucleophiles. Given the large number of com-
mercially available nucleophiles and the easy access
to the dihydrofurans, the present method should be
applicable to the synthesis of a-functionalized furans,
pyrroles and dihydrothiophenes. Particularly, it should
be useful for establishing some indole/five-membered
heterocycle hybrid molecule libraries with high diver-
sity.
Scheme 5. Control experiments.
Experimental Section
95% yield within 1 h of reaction at 608C. The resist-
ance of the dihydrothiophene derivative against the General
heteroaromatization reaction may partially result
Melting points were determined by microscopic melting
from the existence of sulfur that significantly dimin-
ishes the catalytic ability of Fe3+ in promoting an oxi-
dation reaction.[24] A reaction in the 5 mmol scale also
proceeded successfully, indicating the usefulness of
this reaction for practical synthesis. Notably, the
methods to access C3-thiophenyl-substituted indole
derivatives have been rarely reported,[25] although this
scaffold has often been employed in the production of
medicines and pesticides.[26]
pointmeter and were uncorrected. IR spectra were recorded
on a FT-IR Bruker (EQUINOX 55) using KBr pellets or
neat liquid technology. 1H and 13C NMR spectra were re-
corded on a Bruker AV-400 or 600. Chemical shifts were ex-
pressed in ppm relative to Me4Si in solvent. All chemicals
used were of reagent grade and were used as received with-
out further purification. 2-Alkoxy-2,3-dihydrofuran were
prepared according to previously reported methods.[8] In the
most cases, the reactions were conducted in a 10 mL of V-
type flask equipped with triangle magnetic stirring.
Figure 5. Proposed mechanism for the synthesis of pyrrole derivatives.
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Figure 6. Synthesis of thiophene derivatives.
A typical procedure for the reaction of dihydrofuran and
indole. In a typical reaction, 1a (0.20 mmol) was mixed with
2a (0.20 mmol) and CuBr2 (5 mol%) in nitromethane
(1.0 mL). The mixture was then stirred at room temperature
for one hour. After reaction, the product was obtained by
isolation with preparative TLC (eluting solution: petroleum
ether/ethyl acetate=5:1 (v/v)). Tests for substrate scope
were all performed with an analogous procedure. Com-
pound 4a was obtained in 65% yield by changing the cata-
the product was obtained by isolation with preparative TLC
(eluting solution: petroleum ether/ethyl acetate=5:1 (v/v)).
Tests for substrate scope were all performed with an analo-
gous procedure.
Large-scale synthesis of 8a and 8n. In a 100 mL of round-
bottom flask, dihydrofuran 1b (5.0 mmol) was mixed with
a-oxoketene dithioacetal (5.0 mmol) and CuBr2 (5 mol%)
in nitromethane (20.0 mL). The mixture was then stirred at
608C for 2 h. After completion of the reaction, brine
(20 mL) was added. And then, the aqueous phase was ex-
tracted by ethyl acetate (20 mL ” 3). The acquired organic
phase was dried over anhydrous Na2SO4. After removing
volatile components, the organic residue was submitted to
an isolation with silica gel column chromatography (eluting
solution: petroleum ether/ethyl acetate=10:1 (v/v)). Large
scale synthesis of compound 8n was implemented according
to an analogous procedure.
Synthesis of 10a, 10b and 12a. Dihydrofuran 1b
(0.2 mmol, 42.8 mg) was mixed with 1,3,5-trimethoxyben-
zene 9a (0.2 mmol, 33.6 mg) and CuBr2 (0.01 mmol, 2.2 mg,
5 mol%) in nitromethane (1 mL). Then, the mixture was
stirred at room temperature for 0.5 h. After reaction, 10a
was obtained by isolation with preparative TLC (eluting so-
lution: petroleum ether/ethyl acetate=5:1 (v/v)) in 98%
yield (0.2 mmol, 60.0 mg). 10b and 12a were synthesized ac-
cording to an analogous procedure.
.
lyst to FeCl3 6H2O (5 mol%).
Large-scale synthesis of 4a. In a 100 mL of round-bottom
flask, 1a (10.0 mmol) was mixed with 2a (10.0 mmol), and
CuBr2 (5 mol%) in nitromethane (30.0 mL). The mixture
was then stirred at room temperature for one hour. After
completion of the reaction, brine (30 mL) was added. And
then the aqueous phase was extracted by ethyl acetate
(30 mL ” 3). The acquired organic phase was dried over an-
hydrous Na2SO4. After removing volatile components, the
organic residue was submitted to an isolation with silica gel
column chromatography (eluting solution: petroleum ether/
ethyl acetate=10:1 (v/v)).
Synthesis of 6a. Compound 5a was synthesized from 4-
methylstyrene and methyl acetylacetonate by using I2 as cat-
alyst and TBPB as oxidant.[27] 5a (0.2 mmol, 46.4 mg) was
mixed with CuBr2 (0.01 mmol, 2.2 mg) in nitromethane
(1 mL). The mixture was then stirred at 608C for 3 h. After
reaction, the product was obtained by isolation with prepa-
rative TLC (eluting solution: petroleum ether/ethyl ace-
tate=5:1 (v/v)) in 85% yield (0.17 mmol, 39.3 mg).
Synthesis of 14a in a two-step method. Dihydrofuran 1c
(0.2 mmol, 45.6 mg) was mixed with 2a (0.4 mmol, 52.4 mg)
.
and FeCl3 6H2O (0.01 mol, 2.7 mg) in nitromethane (1 mL).
A typical procedure for the reaction of 2-butoxy-2,3-dihy-
drofuran and a-ketene dithioacetal. In a typical reaction, 1a
(0.20 mmol) was mixed with a-ketene dithioacetal
(0.20 mmol), CuBr2 (5 mol%) in nitromethane (1.0 mL).
The mixture was then stirred at 608C for 2 h. After reaction,
The mixture was then stirred at 608C for 30 min. After reac-
tion, the mixture was cooled to room temperature, and the
product 4b was obtained by isolation with preparative TLC
(eluting solution: petroleum ether/ethyl acetate=3:1 (v/v))
in 99% yield (0.2 mmol, 82.4 mg). Compound 4b (0.2 mmol,
908
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Synthesis of Furans and Pyrroles
.
82.4 mg) was mixed with aniline (0.2 mmol, 18.6 mg) and
Al(OTf)3 (0.01 mmol, 4.7 mg) in nitromethane (1 mL). The
mixture was then stirred at 608C for 12 h. After reaction,
the mixture was cooled to room temperature, and the prod-
uct 14a was obtained by isolation with preparative TLC
(eluting solution: petroleum ether/ethyl acetate=5:1 (v/v))
in 82% yield (0.16 mmol, 58.7 mg).
and FeCl3 6H2O (0.25 mmol) in nitromethane (20 mL). The
mixture stirred at 608C for 30 min. Then, P2S5 (1.11 g,
5 mmol) and Al(OTf)3 (118.5 mg, 0.25 mmol) were added to
the reaction system. The mixture was stirred at 608C for
one hour. After completion of the reaction, brine (20 mL)
was added. And then, the aqueous phase was extracted by
ethyl acetate (20 mL ” 3). The acquired organic phase was
dried over anhydrous Na2SO4. After removing volatile com-
ponents, the organic residue was submitted to an isolation
with silica gel column chromatography (eluting solution: pe-
troleum ether/ethyl acetate=10/1 (v/v)). Compound 15a
was obtained in 93% yield.
A typical procedure for the one-pot stepwise three-com-
ponent reaction of dihydrofuran, indole and aniline. Dihy-
drofuran 1b (0.2 mmol) was mixed with 2a (0.4 mmol) and
.
FeCl3 6H2O (5 mol%) in nitromethane (1 mL). The reaction
was then stirred at 608C. After completion of the reaction
monitored by TLC, aniline 13a (0.2 mmol) and Al(OTf)3
(5 mol%) were added to the flask. Then, the mixture sub-
mitted to the specified conditions of the second step. Finally
the mixture was cooled to room temperature, and the prod-
uct was obtained by isolation with preparative TLC (eluting
solution: petroleum ether/ethyl acetate=5:1 (v/v)). Tests for
substrate scope were all performed with an analogous proce-
dure.
All spectroscopic data of obtained compounds
1-(2-Methyl-5-(2-methyl-1H-indol-3-yl)furan-3-yl)ethanone
(3a) (0.19 mmol, 48.1 mg, 95%): brown oil; 1H NMR
(400 MHz, DMSO-d6, 258C) d=11.36 (s, 1H), 7.81 (d, J=
7.1 Hz, 1H), 7.33 (d, J=7.1 Hz, 1H), 7.12–7.04 (m, 2H),
6.76 (s, 1H), 2.63 (s, 3H), 2.57 (s, 3H), 2.46 ppm (s, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=199.2, 160.0,
154.3, 140.2, 138.9, 130.6, 127.8, 126.3, 124.9, 124.1, 116.1,
108.8, 107.5, 34.5, 19.3, 18.3 ppm; IR (KBr) v: 3396, 2927,
2859, 1699, 1459, 1226, 742 cmÀ1; HRMS (TOF, ESI): m/z
calcd for C16H16NO2, [M+H]+ 254.1181, found 254.1183.
1-(2-Methyl-5-(2-phenyl-1H-indol-3-yl)furan-3-yl)etha-
none (3b) (0.19 mmol, 60.5 mg, 96%): light yellow solid,
Large scale synthesis of 14b. In a 100 mL of round-
bottom flask, 1b (5 mmol) was mixed with 2a (10 mmol)
.
and FeCl3 6H2O (0.25 mmol) in nitromethane (20 mL), the
mixture was allowed to stir at 608C for 30 min. Then, aniline
(465.0 mg, 5 mmol) and Al(OTf)3 (0.25 mmol) were added
to the reaction system. The mixture was stirred at 608C
again for 6 h. After completion of the reaction, brine
(20 mL) was added. And then, the aqueous phase was ex-
tracted by ethyl acetate (20 mL ” 3). The acquired organic
phase was dried over anhydrous Na2SO4. After removing
volatile components, the organic residue was submitted to
an isolation with silica gel column chromatography (eluting
solution: petroleum ether/ethyl acetate=10:1 (v/v)). Com-
pound 14b was obtained in 69% yield.
Synthesis of 18a. Compound 17a was synthesized accord-
ing to a literature method (se the Supporting Informa-
tion).[28]. Compound 17a (0.2 mmol, 85.6 mg) was mixed
with aniline 13a (0.2 mmmol, 18.6 mg) and Al(OTf)3
(0.02 mmol, 9.5 mg) in nitromethane (1 mL). The mixture
was stirred at 608C for 3 h. After reaction, the product was
obtained by isolation with preparative TLC (eluting solu-
tion: petroleum ether/ethyl acetate=5:1 (v/v)) in 78% yield
(0.16 mmol, 60.8 mg).
1
mp: 155–1578C; H NMR (400 MHz, DMSO-d6, 258C) d=
12.53 (s, 1H), 8.24 (d, J=7.5 Hz, 1H), 7.73–7.67 (m, 2H),
7.66–7.60 (m, 3H), 7.50 (d, J=7.6 Hz, 1H), 7.33–7.24 (m,
2H), 6.79 (s, 1H), 2.28 (s, 3H), 1.79 ppm (s, 3H); 13C NMR
(100 MHz, DMSO-d6, 258C) d=202.9, 197.9, 185.1, 147.6,
147.6, 136.4, 135.8, 132.3, 130.9, 130.6, 129.2, 127.5, 124.3,
123.1, 122.0, 115.1, 112.5, 31.3, 26.3 ppm; IR (KBr) v: 3293,
2956, 2925, 2855, 1658, 1568, 1453, 1234, 950, 744 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C21H18NO2, [M+H]+
316.1338, found: 316.1352.
1-(2-Methyl-5-(1-methyl-2-phenyl-1H-indol-3-yl)furan-3-
yl)ethanone (3c) (0.17 mmol, 56.6 mg, 86%): brown oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=7.96 (d, J=7.9 Hz,
1H), 7.57–7.52 (m, 4H), 7.48 (dd, J=6.8, 2.8 Hz, 2H), 7.29
(t, J=7.6 Hz, 1H), 7.21 (t, J=7.5 Hz, 1H), 6.20 (s, 1H), 3.57
(s, 3H), 2.48 (s, 3H), 2.28 ppm (s, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=198.6, 160.4, 153.4, 143.1, 141.8, 136.3,
135.8, 134.2, 133.8, 129.8, 127.8, 127.6, 125.8, 125.2, 115.6,
109.5, 108.8, 35.9, 34.2, 19.3 ppm; IR (KBr) v: 3054, 2926,
Synthesis of 20a. Compound 19a was synthesized accord-
ing to a literature method.[29] Compound 19a (0.2 mmol,
.
61.4 mg) was mixed with FeCl3 6H2O (54.0 mg, 0.2 mmol) in
nitromethane (1 mL). The mixture was stirred at 608C for
6 h. After reaction, the product was obtained by isolation
with preparative TLC (eluting solution: petroleum ether/
ethyl acetate=5:1 (v/v)) in 82% yield (0.16 mmol, 50.0 mg).
A typical procedure for the synthesis of dihydrothiophene
derivatives. Dihydrofuran 1b (0.2 mmol) was mixed with 2a
2854, 1674, 1572, 1467, 1227, 1093, 948, 744, 702 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C22H20NO2, [M+H]+
330.1494, found: 330.1503.
1-(5-(1-Ethyl-2-phenyl-1H-indol-3-yl)-2-methylfuran-3-
yl)ethanone (3d) (0.17 mmol, 57.6 mg, 84%): light yellow
oil; 1H NMR (400 MHz, DMSO-d6, 258C) d=8.32 (d, J=
7.7 Hz, 1H), 7.74–7.61 (m, 6H), 7.39 (t, J=7.5 Hz, 1H), 7.33
(t, J=7.4 Hz, 1H), 6.56 (s, 1H), 4.05 (q, J=7.1 Hz, 2H),
2.21 (s, 3H), 1.70 (s, 3H), 1.19 ppm (t, J=7.2 Hz, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=202.7, 198.0,
184.7, 148.3, 147.5, 136.1, 135.5, 131.2, 131.1, 130.9, 129.6,
126.8, 124.6, 123.7, 122.3, 116.0, 111.6, 31.2, 26.1, 15.3 ppm;
IR (KBr) v: 3053, 2929, 2868, 1674, 1672, 1462, 1226, 1098,
744, 703 cmÀ1; HRMS (TOF, ESI): m/z calcd for C23H22NO2,
[M+H]+ 344.1651, found: 344.1659.
.
(0.4 mmol) and FeCl3 6H2O (0.01 mmol, 5 mol%). The mix-
ture was stirred at 608C for 0.5 h. Then, P2S5 (0.2 mmol,
44.4 mg) and Al(OTf)3 (0.01 mmol, 5 mmol%) were added
to the flask. The mixture was submitted to one hour of stir-
ring at 608C. The product was obtained by isolation with
preparative TLC (eluting solution: petroleum ether/ethyl
acetate=5:1 (v/v)). Tests for substrate scope were all per-
formed with an analogous procedure.
Large scale synthesis of 15a. In a 100 mL of round-
bottom flask, 1b (5 mmol) was mixed with 2a (10 mmol)
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Changhui Liu et al.
1-(5-(2,5-Dimethyl-1H-indol-3-yl)-2-methylfuran-3-yl)-
ethanone (3e) (0.18 mmol, 49.7 mg, 93%): light yellow
solid, mp: 155–1578C; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=8.05 (s, 1H), 7.61 (s, 1H), 7.19 (d, J=8.2 Hz, 1H),
7.01 (dd, J=8.2, 1.1 Hz, 1H), 6.59 (s, 1H), 2.69 (d, J=
6.6 Hz, 3H), 2.59 (s, 3H), 2.50 (s, 3H), 2.48 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=194.6, 156.2,
149.1, 133.3, 133.0, 129.8, 126.4, 123.4, 122.9, 119.1, 110.1,
104.3, 103.6, 29.3, 21.7, 14.6, 13.2 ppm; IR (KBr) v: 3224,
2-Methoxyethyl 2-methyl-5-(2-phenyl-1H-indol-3-yl)furan-
3-carboxylate (3j) (0.20 mmol, 74.3 mg, 99%): yellowish oil;
1H NMR (400 MHz, CD3Cl, TMS, 258C) d=8.47 (s, 1H),
7.85 (d, J=7.7 Hz, 1H), 7.53 (dd, J=8.0, 1.5 Hz, 2H), 7.43–
7.32 (m, 4H), 7.29–7.15 (m, 2H), 6.57 (s, 1H), 4.41–4.35 (m,
2H), 3.71–3.64 (m, 2H), 3.40 (s, 3H), 2.57 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=164.3, 157.9,
147.9, 135.7, 135.6, 132.4, 128.65, 128.5, 128.4, 127.3, 123.0,
120.9, 120.3, 114.5, 111.0, 106.8, 104.2, 70.7, 63.2, 59.0,
13.9 ppm; IR (KBr) v: 3350, 2926, 1712, 1459, 1230, 1090,
2918, 2850, 1653, 1570, 1233, 1014, 908, 796, 725, 628 cmÀ1
;
1035, 744 cmÀ1
; HRMS (TOF, ESI): (m/z) calcd for
HRMS (TOF, ESI): m/z calcd for C17H18NO2, [M+H]+
268.1338, found: 268.1339.
C23H21NNaO4, [M+Na]+ 398.1368, found398.1365.
Methyl 2-isopropyl-5-(2-methyl-1H-indol-3-yl)furan-3-car-
boxylate (3k) (0.08 mmol, 24.9 mg, 42%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.38 (s, 1H), 7.74
(dd, J=6.0, 2.3 Hz, 1H), 7.34 (dd, J=6.1, 2.5 Hz, 1H), 7.12–
7.04 (m, 2H), 3.79 (s, 4H), 3.78–3.72 (m, 1H), 2.56 (s, 3H),
1.32 ppm (d, J=6.9 Hz, 6H); 13C NMR (100 MHz, DMSO-
d6, 258C) d=164.2, 164.1, 149.8, 135.5, 134.3, 125.8, 121.6,
120.3, 119.1, 112.6, 111.5, 103.2, 102.9, 51.8, 27.10, 21.3,
13.6 ppm; IR (KBr) v: 3399, 2969, 2932, 2873, 1716, 1587,
1461, 1230, 1064, 743 cmÀ1; HRMS (TOF, ESI): (m/z) calcd
for C18H19NNaO3, [M+Na]+ 320.1263, found 320.1268.
Methyl 2-isopropyl-5-(2-phenyl-1H-indol-3-yl)furan-3-car-
boxylate (3l) (0.14 mmol, 50.3 mg, 70%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.78 (s, 1H), 7.73
(d, J=7.9 Hz, 1H), 7.58 (d, J=7.0 Hz, 2H), 7.52–7.40 (m,
4H), 7.24–7.17 (m, 1H), 7.18–7.10 (m, 1H), 6.55 (s, 1H),
3.76 (s, 3H), 3.74–3.64 (m, 1H), 1.14 ppm (d, J=6.9 Hz,
6H); 13C NMR (100 MHz, DMSO-d6, 258C) d=165.0, 164.0,
148.2, 136.5, 136.4, 132.7, 129.1, 128.9, 128.7, 126.8, 122.8,
120.8, 119.7, 112.6, 112.1, 105.7, 102.9, 51.8, 27.0, 21.2 ppm;
IR (KBr) v: 3399, 2969, 2932, 2873, 1716, 1587, 1461, 1230,
1-(5-(5-Fluoro-2-methyl-1H-indol-3-yl)-2-methylfuran-3-
yl)ethanone (3 f) (0.18 mmol, 48.2 mg, 89%): brown solid,
mp: 178–1808C, 1H NMR (400 MHz, CDCl3, TMS, 258C)
d=8.13 (s, 1H), 7.77 (dd, J=8.6, 5.3 Hz, 1H), 7.00 (dd, J=
9.3, 1.9 Hz, 1H), 6.94 (td, J=9.3, 2.0 Hz, 1H), 6.59 (s, 1H),
2.70 (s, 3H), 2.59 (s, 3H), 2.49 ppm (s, 3H); 13C NMR
(100 MHz, DMSO-d6, 258C) d=199.2, 162.7 (d, J=
230.0 Hz), 160.1, 153.7, 141.0, 136.9, 133.4, 132.6, 131.0,
130.9, 130.8, 127.8, 117.1 (d, J=10.0 Hz), 114.2 (d, J=
26.0 Hz), 109.1 (d, J=24.0 Hz), 108.91, 108.0 (d, J=4.0 Hz),
34.5, 19.2, 18.4 ppm. 19F NMR (377 MHz, CDCl3, TMS,
258C) d=À121.1 ppm; IR (KBr) v: 3240, 2955, 2923, 2853,
1659, 1570, 1464, 1240, 1138, 958, 776 cmÀ1; HRMS (TOF,
ESI): m/z calcd for C16H15FNO2, [M+H]+ 272.1087, found:
272.1102.
Methyl
2-methyl-5-(2-methyl-1H-indol-3-yl)furan-3-car-
boxylate (3g) (0.18 mmol, 49.5 mg, 92%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.37 (s, 1H), 7.76
(d, J=7.2 Hz, 1H), 7.33 (d, J=7.1 Hz, 1H), 7.13–7.02 (m,
2H), 6.56 (s, 1H), 3.79 (s, 2H), 2.63 (s, 3H), 2.55 ppm (s,
3H); 13C NMR (100 MHz, DMSO-d6, 258C) d=164.3, 156.5,
150.0, 135.5, 134.3, 125.8, 121.6, 120.2, 119.3, 114.4, 111.4,
103.5, 102.7, 51.7, 13.9, 13.5 ppm; IR (KBr) v: 3317, 2954,
1064, 743 cmÀ1
; HRMS (TOF, ESI): (m/z) calcd for
C23H21NNaO3, [M+Na]+ 382.1419, found 382.1413.
Methyl 2-cyclopropyl-5-(2-methyl-1H-indol-3-yl)furan-3-
carboxylate (3m) (0.07 mmol, 20.7 mg, 35%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.36 (s, 1H), 7.64
(d, J=8.1 Hz, 1H), 7.32 (d, J=6.9 Hz, 1H), 7.13–7.01 (m,
2H), 6.54 (s, 1H), 3.81 (s, 3H), 2.83–2.74 (m, 1H), 2.51 (s,
3H), 1.17–1.06 ppm (m, 4H); 13C NMR (100 MHz, DMSO-
d6, 258C) d=164.0, 159.7, 148.5, 135.0, 133.8, 125.3, 121.1,
119.9, 118.5, 113.5, 111.0, 103.0, 102.2, 51.3, 13.1, 9.0,
8.3 ppm; IR (KBr) v: 3324, 2925, 2854, 1694, 1591, 1459,
1236, 1072, 741 cmÀ1; HRMS (TOF, ESI): (m/z) calcd for
C18H17NNaO3, [M+Na]+ 318.1106, found 318.1101.
2924, 2853, 1692, 1591, 1444, 1255, 1095, 1041, 761 cmÀ1
;
HRMS (TOF, ESI): (m/z) calcd for C16H15NNaO3, [M+
Na]+ 292.0950, found 292.0959.
Ethyl 2-methyl-5-(2-methyl-1H-indol-3-yl)furan-3-carbox-
ylate (3h) (0.19 mmol, 53.2 mg, 94%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.38 (s, 1H), 7.76
(d, J=7.2 Hz, 1H), 7.34 (d, J=7.1 Hz, 1H), 7.13–7.03 (m,
2H), 6.55 (s, 1H), 4.26 (q, J=7.1 Hz, 2H), 2.63 (s, 3H), 2.55
(s, 3H), 1.31 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=163.9, 156.4, 149.9, 135.5, 134.3, 125.9,
121.6, 120.2, 119.3, 114.7, 111.4, 103.5, 102.1, 60.3, 14.7, 14.0,
13.5 ppm; IR (KBr) v: 3319, 2925, 2854, 1961, 1590, 1460,
1233, 1095, 1038, 743 cmÀ1; HRMS (TOF, ESI): (m/z) calcd
for C17H17NNaO3, [M+Na]+ 306.1106, found 306.1109.
2-Methoxyethyl 2-methyl-5-(2-methyl-1H-indol-3-yl)fur-
an-3-carboxylate (3i) (0.16 mmol, 50.7 mg, 81%), light
Methyl 2-cyclopropyl-5-(2-phenyl-1H-indol-3-yl)furan-3-
carboxylate (3n) (0.14 mmol, 48.6 mg, 68%): yellowsih oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.75 (s, 1H), 7.67
(d, J=7.9 Hz, 1H), 7.57–7.52 (m, 2H), 7.49 (t, J=7.3 Hz,
2H), 7.46–7.41 (m, 2H), 7.20 (t, J=7.0 Hz, 1H), 7.13 (t, J=
7.0 Hz, 1H), 6.56 (s, 1H), 3.78 (s, 3H), 2.76–2.64 (m, 1H),
0.98 (dt, J=6.4, 3.9 Hz, 2H), 0.77–0.67 ppm (m, 2H);
13C NMR (100 MHz, DMSO-d6, 258C) d=164.4, 161.1,
147.3, 136.4, 132.7, 129.1, 128.9, 128.7, 126.6, 122.8, 120.8,
119.6, 114.0, 112.1, 105.9, 102.7, 51.7, 9.4, 9.0 ppm; IR (KBr)
1
yellow oil; H NMR (400 MHz, DMSO-d6, 258C) d=11.38
(s, 1H), 7.76 (d, J=7.1 Hz, 1H), 7.34 (d, J=7.1 Hz, 1H),
7.14–7.03 (m, 2H), 6.54 (s, 1H), 4.40–4.29 (m, 2H), 3.69–
3.60 (m, 2H), 3.31 (s, 3H), 2.64 (s, 3H), 2.55 ppm (s, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=163.3, 156.1,
149.6, 135.0, 133.8, 125.4, 121.1, 119.8, 118.8, 114.0, 110.9,
103.0, 102.2, 69.9, 62.9, 58.1, 13.5, 13.1 ppm; IR(KBr) v:
3350, 2926, 1712, 1459, 1230, 1090, 1035, 744 cmÀ1; HRMS
(TOF, ESI): (m/z) calcd for C18H19NNaO4, [M+Na]+
336.1212, found 336.1219.
v: 3324, 2925, 2854, 1694, 1591, 1459, 1236, 1072, 741 cmÀ1
;
HRMS (TOF, ESI): (m/z) calcd for C23H19NNaO3, [M+
Na]+ 380.1263, found 380.1261.
Methyl
2-methyl-5-(2-phenyl-1H-indol-3-yl)furan-3-car-
boxylate (3o) (0.18 mmol, 58.9 mg, 89%) : yellowish oil;
1H NMR (400 MHz, CDCl3, TMS, 258C) d=8.33 (s, 1H),
910
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Synthesis of Furans and Pyrroles
7.89 (d, J=7.7 Hz, 1H), 7.56 (d, J=6.8 Hz, 2H), 7.46–7.38
(m, 4H), 7.30–7.18 (m, 2H), 6.58 (s, 1H), 3.82 (s, 3H),
2.59 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, TMS, 258C)
d=164.9, 157.7, 147.9, 135.7, 135.5, 132.4, 128.7, 128.5, 128.4,
127.3, 123.0, 120.9, 120.4, 114.5, 111.0, 106.7, 104.3, 51.3,
13.8 ppm; IR (KBr) v: 3395, 2928, 2862, 1695, 1459, 1234,
742 cmÀ1; HRMS (TOF, ESI): (m/z) calcd for C21H17NNaO3,
[M+Na]+ 354.1106, found 354.1116.
Ethyl 2-methyl-5-(2-phenyl-1H-indol-3-yl)furan-3-carbox-
ylate (3p) (0.17 mmol, 60.0 mg, 87%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.78 (s, 1H), 7.73
(d, J=7.9 Hz, 1H), 7.60 (d, J=7.1 Hz, 2H), 7.53–7.39 (m,
4H), 7.20 (t, J=7.0 Hz, 1H), 7.12 (t, J=7.0 Hz, 1H), 6.48 (s,
1H), 4.22 (q, J=7.1 Hz, 2H), 2.55 (s, 3H), 1.27 ppm (t, J=
7.1 Hz, 3H); 13C NMR (100 MHz, DMSO-d6, 258C) d=
163.7, 157.3, 148.5, 136.4, 132.5, 129.0, 128.9, 128.8, 127.1,
122.8, 120.8, 119.9, 114.7, 112.1, 106.3, 102.7, 60.3, 14.7,
14.0 ppm; IR (KBr) v: 3393, 2922, 2864, 1699, 1459, 1234,
742 cmÀ1.HRMS (TOF, ESI): (m/z) calcd for C22H19NNaO3,
[M+Na]+ 368.1263, found 368.1256.
8.8, 5.4 Hz, 3H), 7.66 (d, J=6.8 Hz, 2H), 7.56–7.46 (m, 4H),
7.26 (t, J=9.0 Hz, 3H), 7.22–7.17 (m, 1H), 6.76 (s, 1H), 4.24
(q, J=7.1 Hz, 2H), 1.26 ppm (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, DMSO-d6, 258C) d=163.3, 162.6 (d, J=
246.0 Hz), 153.5, 149.8, 137.1, 136.5, 132.7, 130.5, 130.4,
129.3, 129.1, 129.0, 126.5, 126.3, 123.0, 121.1, 119.7, 115.7 (d,
J=21.7 Hz), 115.3, 112.3, 108.0, 102.5, 60.8, 14.5 ppm;
19F NMR (377 MHz, DMSO-d6, 258C) d=À111.4 ppm; IR
(KBr) v: 3331, 2980, 2932, 1071, 1598, 1502, 1454, 1234,
1092, 1028, 840, 744 cmÀ1; HRMS (TOF, ESI): (m/z) calcd
for C27H20FNNaO3, [M+Na]+ 448.1325, found 448.1327.
Ethyl
2-(2,6-dichloro-5-fluoropyridin-3-yl)-5-(2-phenyl-
1H-indol-3-yl)furan-3-carboxylate (3u) (0.16 mmol, 77.1 mg,
78%); 1H NMR (400 MHz, DMSO-d6, 258C) d=11.95 (s,
1H), 8.41 (d, J=8.3 Hz, 1H), 7.84 (d, J=7.9 Hz, 1H), 7.65
(d, J=7.1 Hz, 2H), 7.57–7.43 (m, J=15.9, 7.4 Hz, 4H), 7.23
(t, J=7.1 Hz, 1H), 7.16 (t, J=7.3 Hz, 1H), 6.74 (s, 1H), 4.16
(q, J=7.1 Hz, 2H), 1.13 ppm (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, DMSO-d6, 258C) d=162.2, 153.5 (d, J=
258.0 Hz), 152.3, 147.9, 143.2, 137.6, 137.3, 136.4, 132.3,
131.1 (d, J=22.0 Hz), 129.2 (d, J=12.0 Hz), 127.3 (d, J=
4.0 Hz), 126.7, 123.1, 121.1, 119.9 (d, J=16.0 Hz), 112.3,
106.8, 102.0, 61.0, 14.2 ppm; 19F NMR (377 MHz, DMSO-d6,
258C) d=À122.7, À122.8 ppm; IR (KBr) v: 3395, 3334,
2962, 2928, 1708, 1696, 1453, 1230, 1048, 743 cmÀ1; HRMS
(TOF, ESI): (m/z) calcd for C26H17Cl2FN2NaO3, [M+Na]+
517.0498, found 517.0494.
3-(2,2-Bis(2-methyl-1H-indol-3-yl)ethyl)pentane-2,4-dione
(mixture of enol and ketone, the ratio approximately : enol/
ketone=3/2) (4a) (0.13 mmol, 50.2 mg, 65%): brown oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=17.03 (s, 0.57H),
10.72 (d, J=12.0 Hz, 2H), 7.53 (d, J=8.0 Hz, 0.82H), 7.44
(d, J=8.0 Hz, 1.17H), 7.23 (dd, J=8.0, 4.0 Hz, 2H), 6.98–
6.94 (m, 2H), 6.87 (t, J=8.0 Hz, 0.87H),6.81 (t, J=8.0 Hz,
1.22H), 4.31–4.27 (m, 1H), 3.71 (t, J=6.9 Hz, 0.43H), 3.32
(d, J=8.0 Hz, 1.22H), 2.84 (t, J=8.0 Hz, 0.8H), 2.31 (s,
6H), 1.98 (s, 3H), 1.65 ppm (s, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=204.7, 191.9, 135.1, 131.5, 128.2, 120.8,
120.7, 119.4, 119.3, 119.3, 119.1, 113.0, 110.4, 67.5, 32.8, 29.1,
22.6, 12.7, 12.4 ppm; IR (KBr) v: 3240, 2956, 2923, 2853,
1707, 1658, 1570, 1460, 1248, 939, 736, 636 cmÀ1; HRMS
(TOF, ESI): m/z calcd for C25H26N2NaO2, [M+Na]+
409.1892, found 409.1904.
Ethyl 2-acetyl-4,4-bis(2-methyl-1H-indol-3-yl)butanoate
(4b) (0.20 mmol, 82.4 mg, 99%): brown oil; 1H NMR
(400 MHz, CDCl3, TMS, 258C) d=7.70 (s, 1H), 7.68 (s,
1H), 7.65–7.59 (m, 2H), 7.15 (d, J=9.5 Hz, 2H), 7.01 (dt,
J=16.1, 7.4 Hz, 4H), 4.44 (t, J=8.3 Hz, 1H), 4.16–4.02 (m,
2H), 3.52 (t, J=7.0 Hz, 1H), 3.04–2.91 (m, 2H), 2.18 (s,
3H), 2.15 (s, 3H), 2.04 (s, 3H), 1.19 ppm (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=203.7, 170.1,
135.2, 135.1, 131.6, 131.4, 128.2, 128.1, 120.6, 120.6, 119.3,
119.3, 119.2, 113.1, 113.0, 110.4, 110.3, 61.3, 58.5, 32.7, 32.6,
29.1, 14.0, 12.6, 12.4 ppm; IR (KBr) v: 3394, 2935, 2864,
1705, 1616, 1460, 1305, 1224, 911, 747 cmÀ1; HRMS (TOF,
ESI): m/z calcd for C26H28N2NaO3, [M+Na]+ 439.1998,
found 439.1998.
Ethyl 2-phenyl-5-(2-phenyl-1H-indol-3-yl)furan-3-carbox-
ylate (3q) (0.18 mmol, 70.0 mg, 86%): light yellow solid,
1
mp: 168–1708C, H NMR (400 MHz, DMSO-d6, 258C) d=
11.89 (s, 1H), 7.85 (d, J=7.7 Hz, 1H), 7.78 (dd, J=7.8,
1.8 Hz, 2H), 7.66 (d, J=6.8 Hz, 2H), 7.51 (dt, J=20.5,
7.3 Hz, 4H), 7.45–7.38 (m, 3H), 7.28–7.16 (m, 2H), 6.77 (s,
1H), 4.25 (q, J=7.1 Hz, 2H), 1.26 ppm (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=163.4, 154.3,
149.7, 137.1, 136.5, 132.7, 129.8, 129.6, 129.3, 129.1, 129.0,
128.7, 128.1, 126.5, 123.0, 121.1, 119.7, 115.5, 112.3, 108.1,
102.5, 60.8, 14.5 ppm; IR (KBr) v: 3406, 3058, 2980, 1714,
1489, 1452, 1235, 1091, 1033, 744 cmÀ1; HRMS (TOF, ESI):
(m/z) calcd for C27H21NNaO3, [M+Na]+ 430.1419, found
430.1415.
Ethyl 5-(2-phenyl-1H-indol-3-yl)-2-propylfuran-3-carbox-
ylate (3r) (0.18 mmol, 68.6 mg, 92%): yellowish oil;
1H NMR (400 MHz, DMSO-d6, 258C) d=11.79 (s, 1H), 7.71
(d, J=7.9 Hz, 1H), 7.58 (d, J=7.0 Hz, 2H), 7.50–7.39 (m,
4H), 7.20 (t, J=7.6 Hz, 1H), 7.13 (t, J=7.9 Hz, 1H), 6.54 (s,
1H), 4.23 (q, J=7.1 Hz, 2H), 2.92 (t, J=7.3 Hz, 2H), 1.65–
1.53 (m, 2H), 1.27 (t, J=7.1 Hz, 3H), 0.87 (t, J=7.4 Hz,
3H); 13C NMR (100 MHz, DMSO-d6, 258C) d=163.6, 160.8,
148.4, 136.4, 132.6, 129.0, 128.9, 128.7, 128.2, 127.1, 122.8,
120.8, 119.7, 114.7, 112.1, 106.2, 102.8, 60.3, 29.3, 21.6, 14.7,
13.9 ppm; IR (KBr) v: 3398, 3344, 2963, 2931, 1712, 1691,
1453, 1230, 1050, 743 cmÀ1; HRMS (TOF, ESI): (m/z) calcd
for C24H23NNaO3, [M+Na]+ 396.1576, found 396.1578.
6,6-Dimethyl-2-(2-phenyl-1H-indol-3-yl)-6,7-dihydroben-
zofuran-4(5H)-one (3s) (0.18 mmol, 62.5 mg, 88%): yellow-
1
ish oil; H NMR (400 MHz, DMSO-d6, 258C) d=11.82 (s,
1H), 7.76 (d, J=7.9 Hz, 1H), 7.59 (d, J=7.0 Hz, 2H), 7.54–
7.42 (m, 4H), 7.21 (t, J=7.0 Hz, 1H), 7.13 (t, J=7.5 Hz,
1H), 6.45 (s, 1H), 2.79 (s, 2H), 2.35 (s, 2H), 1.08 ppm (s,
6H); 13C NMR (100 MHz, DMSO-d6, 258C) d=193.5, 165.3,
151.0, 136.7, 136.4, 132.5, 129.0, 129.0, 128.9, 127.0, 122.9,
120.9, 120.8, 120.0, 112.1, 102.7, 101.5, 51.9, 36.9, 35.4,
28.5 ppm; IR (KBr) v: 3311, 2958, 2871, 1661, 1583, 1451,
1327, 1220, 1114,1032, 744 cmÀ1; HRMS (TOF, ESI): (m/z)
calcd for C24H21NNaO2, [M+Na]+ 378.1470, found 378.1474.
Ethyl 2-(4-fluorophenyl)-5-(2-phenyl-1H-indol-3-yl)furan-
3-carboxylate (3t) (0.16 mmol, 69.7 mg, 82%): 1H NMR
(400 MHz, DMSO-d6, 258C) d=11.89 (s, 1H), 7.84 (dd, J=
Methyl 2-methyl-5-(p-tolyl)-4,5-dihydrofuran-3-carboxyl-
ate (5a) (7.5 mmol, 1.74 g, 75%): colorless oil; 1H NMR
(400 MHz, CDCl3, TMS, 258C) d=7.22 (d, J=8.1 Hz, 2H),
7.17 (d, J=8.1 Hz, 2H), 5.55 (dd, J=10.6, 8.4 Hz, 1H), 3.71
(s, 3H), 3.29 (ddd, J=14.4, 10.7, 1.6 Hz, 1H), 2.91 (ddd, J=
Adv. Synth. Catal. 2016, 358, 900 – 918
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911

FULL PAPERS
Changhui Liu et al.
14.5, 8.3, 1.6 Hz, 1H), 2.35 (s, 3H), 2.27 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d 168.0, 166.5,
138.4, 138.0, 129.4, 125.8, 101.5, 83.3, 50.8, 37.8, 21.2,
14.1 ppm; IR (KBr) v: 2953, 2925, 2855, 1705, 1649, 1438,
1382, 1224, 1088, 984, 763 cmÀ1; IR (KBr) v: 3009, 2952,
39.3, 35.9, 13.7 ppm; IR (KBr) v: 3059, 2926, 1715, 1624,
1571, 1448, 1273, 1226, 1103, 1027, 696 cmÀ1; HRMS (TOF,
ESI): m/z calcd for C21H22NaO5S2, [M+Na]+ 441.0806,
found 441.0821.
Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenyleth-
2862, 1708, 1564, 1511, 1437, 1325, 1211, 1122, 826, 731 cmÀ1
;
yl)-2-isopropylfuran-3-carboxylate (8e) (0.15 mmol, 56.6 mg,
HRMS (TOF, ESI): m/z calcd for C14H16NaO3, [M+Na]+
73%): yellowish oil; H NMR (400 MHz, DMSO-d6, 258C)
1
255.0997, found 255.1020.
d=7.44–7.39 (m, 1H), 7.37–7.30 (m, 4H), 6.61 (s, 1H), 3.73
(s, 3H), 3.61–3.54 (m, 2H), 3.51–3.47 (m, 3H), 0.84 (s, 3H),
0.82 ppm (s, 3H); 13C NMR (100 MHz, DMSO-d6, 258C)
d=189.2, 170.4, 165.6, 163.6, 149.5, 140.1, 131.4, 128.6, 127.9,
114.3, 112.4, 110.7, 51.9, 36.3, 26.8, 24.6, 20.7 ppm; IR (KBr)
v: 2970, 2929, 2871, 1715, 1623, 1569, 1448, 1272, 1227, 1063,
699 cmÀ1; HRMS (TOF, ESI): m/z calcd for C20H20NaO4S2,
[M+Na]+ 411.0701, found 411.0691.
Methyl
2-methyl-5-(p-tolyl)furan-3-carboxylate
(6a)
(0.17 mmol, 39.3 mg, 85%): colorless oil; 1H NMR
(400 MHz, CDCl3, TMS, 258C) d=7.53 (d, J=8.1 Hz, 2H),
7.19 (d, J=8.0 Hz, 2H), 6.81 (s, 1H), 3.85 (s, 3H), 2.64 (s,
3H), 2.36 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, TMS,
258C) d=164.6, 158.4, 152.0, 137.6, 129.4, 127.4, 123.6,
115.0, 104.4, 51.4, 21.3, 13.9 ppm; IR (KBr) v: 3012, 2932,
2862, 1708, 1568, 1437, 1325, 1122, 826, 731 cmÀ1.HRMS
(TOF, ESI): m/z calcd for C14H15O3, [M+H]+ 231.1021,
found 231.1028.
Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenyleth-
yl)-2-cyclopropylfuran-3-carboxylate
(8 f)
(0.11 mmol,
1
42.5 mg, 55%): yellowish oil; H NMR (400 MHz, DMSO-
d6, 258C) d=7.44 (t, J=6.9 Hz, 1H), 7.38–7.31 (m, 4H),
6.65 (s, 1H), 3.74 (s, 3H), 3.62–3.54 (m, 2H), 3.52–3.45 (m,
2H), 3.14 (t, J=6.7 Hz, 2H), 2.90 (t, J=7.1 Hz, 2H), 1.74–
1.64 ppm (m, 1H); 13C NMR (100 MHz, CDCl3, TMS, 258C)
d=188.9, 171.4, 163.5, 159.9, 150.3, 139.8, 131.7, 128.6, 128.0,
114.7, 114.1, 111.1, 52.0, 36.3, 33.7, 30.9, 25.8 ppm; IR (KBr)
v: 2926, 2854, 1712, 1625, 1571, 1447, 1272, 1230, 1096, 803,
698 cmÀ1; HRMS (TOF, ESI): m/z calcd for C20H18NaO4S2,
[M+Na]+ 409.0544, found 409.0534.
Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenyleth-
yl)-2-methylfuran-3-carboxylate (8a) (0.16 mmol, 58.3 mg,
81%): yellowish oil; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=7.47 (d, J=7.1 Hz, 2H), 7.37 (t, J=6.8 Hz, 1H),
7.26 (t, J=7.6 Hz, 2H), 6.59 (s, 1H), 3.80 (s, 3H), 3.53–3.46
(m, 2H), 3.42–3.35 (m, 2H), 2.39 ppm (s, 3H);13C NMR
(100 MHz, CDCl3, TMS, 258C) d=189.5, 169.4, 164.3, 158.3,
149.4, 139.2, 131.2, 128.4, 127.9, 115.2, 114.4, 111.2, 51.4,
39.3, 35.9, 13.6 ppm; IR (KBr) v: 2949, 2925, 1716, 1618,
1446, 1274, 1228, 1105, 775, 697 cmÀ1; HRMS (TOF, ESI):
m/z calcd for C18H16NaO4S2, [M+ Na]+ 383.0388, found
383.0390.
Ethyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenylethyl)-
2-propylfuran-3-carboxylate (8g) (0.16 mmol, 64.3 mg,
80%): yellowish oil; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=7.50–7.43 (m, 2H), 7.36 (t, J=7.4 Hz, 1H), 7.26 (t,
J=7.6 Hz, 2H), 6.63 (s, 1H), 4.26 (q, J=7.1 Hz, 2H), 3.54–
3.48 (m, 2H), 3.40 (t, J=6.3 Hz, 2H), 2.79 (t, J=7.3 Hz,
2H), 1.35–1.30 (m, 5H), 0.72 ppm (t, J=7.4 Hz, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=189.7, 169.1,
163.9, 162.0, 149.3, 139.5, 131.0, 128.5, 128.3, 127.9, 127.9,
114.5, 111.2, 108.3, 60.2, 39.2, 35.9, 29.2, 21.2, 14.3, 13.5 ppm;
IR (KBr) v: 2964, 2929, 2872, 1712, 1623, 1570, 1452, 1274,
1226, 1109, 1050, 803, 697 cmÀ1; HRMS (TOF, ESI): m/z
calcd for C21H22NaO4S2, [M+Na]+ 425.0857, found 425.0865.
Ethyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenylethyl)-
2-phenylfuran-3-carboxylate (8h) (0.15 mmol, 65.4 mg,
75%): yellow solid, mp: 99–1018C, 1H NMR (400 MHz,
CDCl3, TMS, 258C) d=7.54 (t, J=7.3 Hz, 4H), 7.39 (t, J=
7.3 Hz, 1H), 7.34–7.27 (m, 5H), 6.81 (s, 1H), 4.28 (q, J=
7.1 Hz, 2H), 3.54–3.48 (m, 2H), 3.45–3.40 (m, 2H),
1.32 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3,
TMS, 258C) d=189.8, 168.7, 163.4, 156.0, 150.0, 139.5, 131.3,
129.4, 129.2, 128.4, 128.3, 128.1, 127.9, 115.1, 114.9, 113.2,
60.6, 39.2, 36.1, 14.2 ppm; IR (KBr) v: 3059, 2978, 2927,
Ethyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenylethyl)-
2-methylfuran-3-carboxylate (8b) (0.17 mmol, 64.3 mg,
86%): yellowish oil; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=7.51–7.45 (m, 2H), 7.37 (t, J=7.4 Hz, 1H), 7.26 (t,
J=7.6 Hz, 2H), 6.60 (s, 1H), 4.26 (q, J=7.1 Hz, 2H), 3.49
(t, J=6.3 Hz, 2H), 3.38 (t, J=6.2 Hz, 2H), 2.39 (s, 3H),
1.33 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3,
TMS, 258C) d=189.5, 169.3, 163.9, 158.1, 149.3, 139.2, 131.2,
128.4, 127.9, 115.3, 114.7, 111.3, 60.2, 39.3, 35.9, 14.3,
13.6 ppm; IR (KBr) v: 2979, 2927, 1712, 1617, 1572, 1449,
1273, 1227, 1103, 1066, 696 cmÀ1; HRMS (TOF, ESI): m/z
calcd for C19H18NaO4S2, [M+Na]+ 397.0544, found 397.0532.
2-(4-Acetyl-5-methylfuran-2-yl)-2-(1,3-dithiolan-2-yli-
dene)-1-phenylethanone (8c) (0.14 mmol, 48.8 mg, 71%):
1
yellowish oil; H NMR (400 MHz, DMSO-d6, 258C) d=7.42
(dt, J=13.5, 4.3 Hz, 3H), 7.37–7.30 (m, 2H), 6.74 (s, 1H),
3.59–3.54 (m, J=7.1, 4.8 Hz, 2H), 3.50–3.46 (m, 2H), 2.34 (s,
3H), 2.34 ppm (s, 3H); 13C NMR (100 MHz, DMSO-d6,
258C) d=198.7, 193.7, 175.6, 161.7, 154.2, 144.2, 136.5,
133.3, 133.1, 127.7, 119.1, 116.2, 41.1, 34.3, 19.0 ppm; IR
(KBr) v: 2973, 2931, 2870, 1715, 1623, 1569, 1464, 1270,
1227, 1063, 695 cmÀ1; HRMS (TOF, ESI): m/z calcd for
C18H16NaO3S2, [M+Na]+ 367.0439, found 367.0433.
1716, 1623, 1487, 1449, 1270, 1242, 1103, 1023, 764, 694 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C24H20NaO4S2, [M+Na]+
459.0701, found 459.0691.
2-(1,3-Dithiolan-2-ylidene)-2-(4-(2-(2-methoxyethoxy)ace-
tyl)-5-methylfuran-2-yl)-1-phenylethanone (8d) (0.18 mmol,
73.6 mg, 88%): yellowish oil; 1H NMR (400 MHz, CDCl3,
TMS, 258C) d=7.48 (d, J=7.1 Hz, 2H), 7.37 (t, J=7.4 Hz,
1H), 7.26 (t, J=7.6 Hz, 2H), 6.62 (s, 1H), 4.40–4.33 (m,
2H), 3.70–3.63 (m, 2H), 3.49 (dd, J=11.8, 4.9 Hz, 2H),
3.43–3.35 (m, 5H), 2.40 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS, 258C) d=189.5, 169.4, 163.8, 158.5, 149.4,
139.2, 131.2, 128.4, 127.9, 115.2, 114.4, 111.3, 70.5, 63.3, 59.0,
Ethyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenylethyl)-
2-(4-fluorophenyl)furan-3-carboxylate
(8i)
(0.15 mmol,
68.1 mg, 75%): yellow solid, mp: 131–1328C, 1H NMR
(400 MHz, CDCl3, TMS, 258C) d=7.53 (dd, J=8.0, 6.4 Hz,
4H), 7.40 (t, J=7.4 Hz, 1H), 7.31 (t, J=7.5 Hz, 2H), 6.97 (t,
J=8.8 Hz, 2H), 4.28 (q, J=7.1 Hz, 1H), 3.55–3.50 (m, 2H),
3.46–3.42 (m, 2H), 1.33 ppm (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3, TMS, 258C) d=189.8, 168.6, 163.1 (d, J=
248.0 Hz), 163.4, 155.1, 145.0, 139.6, 131.3, 130.4, 130.3,
912
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FULL PAPERS
Synthesis of Furans and Pyrroles
128.4, 128.1, 125.6, 125.6, 115.0 (d, J=22.0 Hz), 114.9 (d, J=
37.0 Hz), 113.2, 60.7, 39.2, 36.2, 14.2 ppm; IR (KBr) v: 3059,
2978, 2927, 1714, 1623, 1486, 1448, 1271, 1232, 1113, 1023,
163.3, 157.8, 149.2, 137.8, 136.0, 129.7, 128.2, 113.9, 113.3,
111.0, 51.4, 35.9, 13.2 ppm; IR (KBr) v: 2952, 2926, 2854,
1717, 1616, 1587, 1443, 1274, 1229, 1104, 1013, 775 cmÀ1
;
764, 697 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for
HRMS (TOF, ESI): m/z calcd for C18H15ClNaO4S2, [M+
C24H19FNaO4S2, [M+Na]+ 477.0606, found 477.0596.
Na]+ 416.9998, found 416.9986.
2-(1-(1,3-Dithiolan-2-ylidene)-2-oxo-2-phenylethyl)-6,6-di-
methyl-6,7-dihydrobenzofuran-4(5H)-one (8j) (0.16 mmol,
59.9 mg, 78%): yellowsih oil; 1H NMR (400 MHz, CDCl3,
TMS, 258C) d=7.46 (d, J=7.3 Hz, 2H), 7.36 (t, J=7.4 Hz,
1H), 7.24 (t, J=7.6 Hz, 2H), 6.67 (s, 1H), 3.52 (t, J=6.3 Hz,
2H), 3.40 (t, J=6.3 Hz, 2H), 2.50 (s, 2H), 2.35 (s, 2H),
1.06 ppm (s, 6H); 13C NMR (100 MHz, CDCl3, TMS, 258C)
d=193.8, 189.3, 170.1, 165.4, 152.2, 139.4, 131.1, 128.3, 127.8,
120.9, 115.0, 106.8, 51.9, 39.3, 37.2, 35.9, 35.3, 28.4 ppm; IR
(KBr) v: 2958, 2929, 2870, 1675, 1626, 1447, 1274, 1217,
1114, 1029, 802, 729 cmÀ1; HRMS (TOF, ESI): m/z calcd for
C21H20NaO3S2, [M+Na]+ 407.0752, found 407.0749.
Ethyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-2-phenylethyl)-
2-(difluoromethyl)furan-3-carboxylate (8k) (0.13 mmol,
53.3 mg, 65%): yellowish oil; 1H NMR (400 MHz, CDCl3,
TMS, 258C) d=7.47–7.42 (m, 2H), 7.38 (t, J=7.4 Hz, 1H),
7.28 (t, J=7.5 Hz, 2H), 7.21 (s, 0.25H), 7.08 (s, 0.5H), 6.95
(s, 0.25H), 6.61 (s, 1H), 4.31 (q, J=7.1 Hz, 2H), 3.55–3.49
(m, 2H), 3.46–3.40 (m, 2H), 1.35 ppm (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=184.6, 167.5,
157.0, 148.4, 143.0 (t, J=23.0 Hz), 134.2, 126.6, 123.4, 123.3,
115.5, 109.3, 106.3, 104.0, 101.7, 99.3, 56.6, 34.5, 31.5,
9.4 ppm; 19F NMR (377 MHz, CDCl3, TMS, 258C) d=
À121.8, À122.0 ppm.IR (KBr) v: 2951, 2926, 2853, 1717,
1597, 1445, 1272, 1229, 1104, 1065, 851, 775 cmÀ1; HRMS
(TOF, ESI): m/z calcd for C19H16F2NaO4S2, [M+Na]+
433.0356, found 433.0349.
Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-(4-fluorophenyl)-
2-oxoethyl)-2-methylfuran-3-carboxylate (8o) (0.12 mmol,
45.4 mg, 60%): yellowish oil; H NMR (400 MHz, DMSO-
1
d6, 258C) d=7.46 (dd, J=8.8, 5.6 Hz, 2H), 7.17 (t, J=
8.9 Hz, 2H), 6.61 (s, 1H), 3.74 (s, 3H), 3.58–3.54 (m, 2H),
3.50–3.45 (m, 2H), 2.35 ppm (s, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=186.9, 171.2, 163.6, 163.3 (d, J=
249.0 Hz), 157.7, 149.3, 135.5, 135.5, 130.6 (d, J=9.0 Hz),
115.1 (d, J=21.0 Hz), 113.9, 113.5, 110.8, 51.4, 35.9,
13.2 ppm; 19F NMR (377 MHz, DMSO-d6, 258C) d=
À108.2 ppm; IR (KBr) v: 2951, 2926, 2853, 1717, 1597, 1445,
1272, 1229, 1104, 1065, 851, 775 cm-1; HRMS (TOF, ESI):
m/z calcd for C18H15FNaO4S2, [M+Na]+ 401.0293, found
401.0312.
Methyl
5-(1-(1,3-dithiolan-2-ylidene)-2-oxopropyl)-2-
methylfuran-3-carboxylate (8p) (0.15 mmol, 45.3 mg, 76%):
1
yellowish oil; H NMR (400 MHz, CDCl3, TMS, 258C) d=
6.66 (s, 1H), 3.85 (s, 3H), 3.49 (t, J=6.4 Hz, 2H), 3.29 (t,
J=6.4 Hz, 2H), 2.62 (s, 3H), 2.11 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3, TMS, 258C) d=188.4, 165.9, 159.5, 154.2,
144.8, 111.1, 109.6, 106.9, 46.7, 35.0, 30.6, 23.2, 9.1 ppm; IR
(KBr) v: 2952, 2854, 1717, 1616, 1587, 1443, 1274, 1229,
1104, 1013, 775 cmÀ1; HRMS (TOF, ESI): m/z calcd for
C13H14NaO4S2, [M+Na]+ 321.0231, found 321.0229.
(E)-Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-oxo-4-phenyl-
but-3-en-1-yl)-2-methylfuran-3-carboxylate (8q) (0.15 mmol,
58.7 mg, 76%): yellow solid, mp: 117–1198C; 1H NMR
(400 MHz, CDCl3, TMS, 258C) d=7.71 (d, J=15.6 Hz, 1H),
7.44 (dd, J=6.3, 3.0 Hz, 2H), 7.38–7.31 (m, 3H), 6.69 (d, J=
16.8 Hz, 2H), 3.86 (s, 3H), 3.54–3.49 (m, 2H), 3.36–3.30 (m,
2H), 2.65 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, TMS,
258C) d=183.9, 164.4, 159.3, 148.9, 143.0, 135.2, 130.1,
128.8, 128.3, 123.2, 116.5, 114.5, 112.2, 51.5, 39.7, 35.6,
13.9 ppm; IR (KBr) v: 2951, 2925, 1716, 1642, 1588, 1448,
1332, 1279, 1233, 1092, 979, 772, 717 cmÀ1; HRMS (TOF,
ESI): m/z calcd for C20H18NaO4S2, [M+Na]+ 409.0544,
found 409.0546.
Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-(4-methoxyphen-
yl)-2-oxoethyl)-2-methylfuran-3-carboxylate
(8l)
(0.17 mmol, 64.7 mg, 83%): yellowish oil; 1H NMR
(400 MHz, CDCl3, TMS, 258C) d=7.51 (d, J=8.9 Hz, 2H),
6.77 (d, J=8.9 Hz, 2H), 6.59 (s, 1H), 3.81 (d, J=2.3 Hz,
6H), 3.50–3.44 (m, 2H), 3.42–3.36 (m, 2H), 2.45 ppm (s,
3H); 13C NMR (100 MHz, CDCl3, TMS, 258C) d=183.7,
161.5, 159.6, 157.6, 153.6, 144.9, 126.7, 126.3, 110.7, 109.7,
108.5, 106.1, 50.6, 46.6, 34.3, 31.4, 8.9 ppm; IR (KBr) v:
2951, 2927, 2841, 1716, 1599, 1443, 1308, 1253, 1171, 1104,
1028, 846, 774 cmÀ1; HRMS (TOF, ESI): m/z calcd for
C19H18NaO5S2, [M+Na]+ 413.0493, found 413.0482.
Methyl
2-methyl-5-(2,4,6-trimethoxyphenyl)furan-3-car-
boxylate (10a) (0.2 mmol, 60.0 mg, 98%): light yellow oil;
1H NMR (400 MHz, CDCl3, TMS, 258C) d=6.65 (s, 1H),
6.17 (s, 2H), 3.84 (s, 3H), 3.82 (s, 3H), 3.78 (s, 6H),
2.62 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, TMS, 258C)
d=164.9, 161.9, 159.7, 158.4, 145.2, 114.1, 110.9, 101.8, 90.9,
56.0, 55.4, 51.2, 14.0 ppm; IR (KBr) v: 2948, 2842, 1715,
1601, 1463, 1228, 1126, 1023, 950, 813, 799, 631 cmÀ1; HRMS
(TOF, ESI): (m/z) calcd for C16H18NaO6, [M+Na]+
329.1001, found 329.1009.
Methyl 5-(1-(1,3-dithiolan-2-ylidene)-2-(4-nitrophenyl)-2-
oxoethyl)-2-methylfuran-3-carboxylate (8m) (0.14 mmol,
55.1 mg, 68%): deep yellow solid, mp: 156–1588C; H NMR
1
(400 MHz, CDCl3, TMS, 258C) d=8.12 (d, J=8.3 Hz, 2H),
7.58 (d, J=8.4 Hz, 2H), 6.61 (s, 1H), 3.81 (s, 3H), 3.58 (t,
J=6.5 Hz, 2H), 3.43 (t, J=6.5 Hz, 2H), 2.39 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=182.3, 169.6,
159.3, 153.8, 144.0, 143.8, 140.4, 124.3, 118.4, 109.9, 109.5,
107.3, 46.7, 34.9, 31.2, 8.9 ppm; IR (KBr) v: 2952, 2926,
2853, 1716, 1597, 1521, 1442, 1347, 1275, 1228, 1105, 1066,
Methyl
2-methyl-5-(2,4,5-trimethoxyphenyl)furan-3-car-
865, 754 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for
boxylate (10b) (0.16 mmol, 49.6 mg, 81%): light yellow
solid, mp: 118–1208C; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=7.32 (s, 1H), 7.02 (s, 1H), 6.58 (s, 1H), 3.92 (s,
9H), 3.85 (s, 3H), 2.65 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS, 258C) d=164.8, 157.3, 150.2, 149.1, 148.1,
143.1, 115.1, 111.1, 109.3, 108.6, 97.5, 56.6, 56.1, 51.3,
13.8 ppm; IR (KBr) v: 2992, 2945, 2839, 1714, 1609, 1519,
1446, 1290, 1209, 1095, 1030, 818, 776 cmÀ1; HRMS (TOF,
C18H15NNaO6S2, [M+Na]+ 428.0238, found 428.0245.
Methyl 5-(2-(4-chlorophenyl)-1-(1,3-dithiolan-2-ylidene)-
2-oxoethyl)-2-methylfuran-3-carboxylate (8n) (0.12 mmol,
1
48.1 mg, 61%): yellowish oil; H NMR (400 MHz, DMSO-
d6, 258C) d=7.39 (s, 4H), 6.60 (s, 1H), 3.73 (s, 3H), 3.59–
3.55 (m, 2H), 3.50–3.46 (m, 2H), 2.35 ppm (s, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=187.0, 172.3,
Adv. Synth. Catal. 2016, 358, 900 – 918
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913

FULL PAPERS
Changhui Liu et al.
ESI): (m/z) calcd for C16H18NaO6, [M+Na]+ 329.1001,
found 329.1009.
2925, 2859, 1678, 1516, 1459, 1232, 1092, 744 cmÀ1; HRMS
(TOF, ESI): m/z calcd for C24H25N2O2, [M+H]+ 373.1916,
found 373.1941.
Methyl 5-(2,7-dimethoxynaphthalen-1-yl)-2-methylfuran-
3-carboxylate (12a) (0.14 mmol, 44.3 mg, 68%): light yellow
oil; 1H NMR (400 MHz, DMSO-d6, 258C) d=7.97 (d, J=
9.0 Hz, 1H), 7.84 (d, J=8.6 Hz, 1H), 7.35 (d, J=9.1 Hz,
1H), 7.09–7.03 (m, 2H), 6.78 (s, 1H), 3.87 (s, 3H), 3.80 (s,
3H), 3.76 (s, 3H), 2.64 ppm (s, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=164.2, 158.8, 156.7, 147.2, 134.7, 131.6,
130.4, 128.6, 127.9, 126.2, 124.3, 116.4, 114.4, 111.7, 111.5,
111.4, 103.4, 56.9, 55.4, 51.8, 14.0 ppm; IR (KBr) v: 3058,
Ethyl
1-(4-methoxyphenyl)-2-methyl-5-(2-methyl-1H-
(14e) (0.14 mmol,
indol-3-yl)-1H-pyrrole-3-carboxylate
1
53.5 mg, 69%): yellowish oil; H NMR (400 MHz, DMSO-
d6, 258C) d=10.94 (s, 1H), 7.17 (d, J=7.9 Hz, 1H), 7.12 (d,
J=7.8 Hz, 1H), 7.07 (d, J=8.7 Hz, 2H), 6.95–6.91 (m, 1H),
6.84 (d, J=7.5 Hz, 1H), 6.80 (d, J=8.9 Hz, 2H), 6.42 (s,
1H), 4.22 (q, J=7.0 Hz, 2H), 3.67 (s, 3H), 2.34 (s, 3H), 2.09
(s, 3H), 1.28 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=165.2, 158.8, 136.7, 135.5, 135.3, 130.8,
129.3, 129.3, 127.7, 120.8, 119.3, 118.3, 114.3, 112.0, 110.9,
110.9, 104.1, 59.3, 55.6, 22.9, 15.0, 13.0, 12.5 ppm; IR (KBr)
v: 3396, 2927, 2855, 1697, 1678, 1513, 1243, 1090, 1070,
744 cmÀ1; HRMS (TOF, ESI): m/z calcd for C24H25N2O3,
[M+H]+ 389.1865, found 389.1892.
2955, 1734, 1628, 1587, 1510, 1387, 1208, 1147, 818, 743 cmÀ1
;
HRMS-ESI (m/z) calcd for C19H18NaO5, [M+Na]+
349.1052, found 349.1043.
Ethyl 2-methyl-5-(2-methyl-1H-indol-3-yl)-1-phenyl-1H-
pyrrole-3-carboxylate (14a) (0.16 mmol, 58.7 mg, 82%): yel-
1
lowish oil; H NMR (400 MHz, DMSO-d6, 258C) d=10.94
(s, 1H), 7.30–7.22 (m, 3H), 7.19–7.09 (m, 4H), 6.92 (t, J=
7.0 Hz, 1H), 6.82 (t, J=7.9 Hz, 1H), 6.45 (s, 1H), 4.23 (q,
J=7.1 Hz, 2H), 2.36 (s, 3H), 2.07 (s, 3H), 1.28 ppm (t, J=
7.1 Hz, 3H); 13C NMR (100 MHz, DMSO-d6, 258C) d=
165.2, 138.1, 136.4, 135.5, 135.3, 129.1, 128.2, 127.5, 120.8,
119.3, 118.3, 112.3, 111.1, 110.9, 104.0, 59.3, 15.0, 13.0,
12.4 ppm; IR (KBr) v: 3394, 3337, 2927, 2858, 1678, 1457,
1231, 1086, 745, 700 cmÀ1; HRMS (TOF, ESI): m/z calcd for
C23H22N2NaO2, [M+Na]+ 381.1579, found 381.1581.
Ethyl 1-(4-fluorophenyl)-2-methyl-5-(2-methyl-1H-indol-
3-yl)-1H-pyrrole-3-carboxylate (14 f) (0.16 mmol, 60.9 mg,
81%): yellowish oil; H NMR (400 MHz, DMSO-d6, 258C)
1
d=10.98 (s, 1H), 7.21 (dd, J=8.9, 5.1 Hz, 2H), 7.17 (d, J=
8.0 Hz, 1H), 7.11 (t, J=8.9 Hz, 3H), 6.96–6.90 (m, 1H), 6.82
(t, J=7.5 Hz, 1H), 6.45 (s, 1H), 4.23 (q, J=7.1 Hz, 2H),
2.36 (s, 3H), 2.11 (s, 3H), 1.29 ppm (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=165.1, 135.9 (d,
J=128.0 Hz), 135.60, 130.39, 130.30, 128.97, 127.66, 120.84,
119.32, 118.25, 116.12, 115.89, 112.30, 111.0 (d, J=5.0 Hz),
103.80, 59.34, 14.97, 12.96, 12.42 ppm; 19F NMR (377 MHz,
DMSO-d6, 258C) d=À113.9, À114.0 ppm; IR (KBr) v:
3397, 2927, 2855, 1698, 1679, 1511, 1422, 1221, 1091, 1016,
746 cmÀ1; HRMS (TOF, ESI): m/z calcd for C23H22FN2O2,
[M+H]+ 377.1665, found 377.1689.
Methyl 2-methyl-5-(2-methyl-1H-indol-3-yl)-1-phenyl-1H-
pyrrole-3-carboxylate (14b) (0.15 mmol, 50.9 mg, 74%): yel-
1
lowish oil; H NMR (400 MHz, DMSO-d6, 258C) d=10.94
(s, 1H), 7.29–7.22 (m, 3H), 7.17–7.13 (m, 3H), 7.10 (d, J=
7.8 Hz, 1H), 6.92 (t, J=8.0 Hz, 1H), 6.82 (t, J=7.5 Hz, 1H),
6.46 (s, 1H), 3.75 (s, 3H), 2.36 (s, 1H), 2.07 ppm (s, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=165.6, 138.1,
136.5, 135.5, 135.3, 129.2, 129.1, 128.2, 127.6, 120.8, 119.3,
118.3, 111.9, 111.0, 110.9, 104.0, 51.1, 13.0, 12.4 ppm; IR
(KBr) v: 3396, 2925, 2854, 1701, 1548, 1443, 1233, 1092, 744,
701 cmÀ1; HRMS (TOF, ESI): m/z calcd for C22H21N2O2,
[M+H]+ 345.1603, found 345.1603.
Ethyl 1-(3-fluorophenyl)-2-methyl-5-(2-methyl-1H-indol-
3-yl)-1H-pyrrole-3-carboxylate (14g) (0.17 mmol, 63.2 mg,
1
84%): yellowish oil; H NMR (600 MHz, DMSO-d6, 258C)
d=11.00 (s, 1H), 7.30 (dd, J=14.7, 8.1 Hz, 1H), 7.17 (d, J=
8.0 Hz, 1H), 7.13 (d, J=9.8 Hz, 1H), 7.12–7.08 (m, 2H),
6.99 (d, J=8.0 Hz, 1H), 6.93 (t, J=7.5 Hz, 1H), 6.82 (t, J=
7.8 Hz, 1H), 6.46 (s, 1H), 4.23 (q, J=7.1 Hz, 2H), 2.39 (s,
3H), 2.12 (s, 3H), 1.29 ppm (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, DMSO-d6, 258C) d=165.1, 161.9 (d, J=
243.0 Hz), 139.6 (d, J=10.0 Hz), 136.5, 135.6, 135.3, 130.7
(d, J=9.0 Hz), 128.9, 127.6, 124.7, 120.9, 119.3, 118.2, 115.7
(d, J=23.0 Hz), 115.3 (d, J=21.0 Hz), 112.5, 111.1 (d, J=
23.0 Hz), 103.7, 59.4, 15.0, 13.0, 12.4 ppm; 19F NMR
(377 MHz, DMSO-d6, 258C) d=À112.2 ppm; IR (KBr) v:
3398, 2926, 2855, 1676, 1606, 1456, 1240, 1178, 1085,
745 cmÀ1; HRMS (TOF, ESI): m/z calcd for C23H22FN2O2,
[M+H]+ 377.1665, found 377.1682.
2-Methoxyethyl
2-methyl-5-(2-methyl-1H-indol-3-yl)-1-
phenyl-1H-pyrrole-3-carboxylate (14c) (0.16 mmol, 60.5 mg,
1
78%): yellowish oil; H NMR (400 MHz, DMSO-d6, 258C)
d=10.93 (s, 1H), 7.31–7.24 (m, 3H), 7.18–7.14 (m, 3H), 7.12
(d, J=7.9 Hz, 1H), 6.95–6.90 (m, 1H), 6.82 (t, J=7.8 Hz,
1H), 6.46 (s, 1H), 4.33–4.29 (m, 2H), 3.65–3.60 (m, 2H),
3.30 (s, 3H), 2.36 (s, 3H), 2.07 ppm (s, 3H); 13C NMR
(100 MHz, DMSO-d6, 258C) d=165.0, 138.1, 136.6, 135.5,
135.3, 129.2, 128.2, 127.6, 120.8, 119.3, 118.3, 112.0, 111.1,
110.9, 103.9, 70.7, 62.6, 58.6, 13.0, 12.4 ppm; IR (KBr) v:
3397, 2927, 1698, 1497, 1458, 1227, 1082, 745, 701 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C24H25N2O3, [M+H]+
389.1865, found 389.1870.
Ethyl 1-(2-bromophenyl)-2-methyl-5-(2-methyl-1H-indol-
3-yl)-1H-pyrrole-3-carboxylate (14h) (0.17 mmol, 73.2 mg,
Ethyl 2-methyl-5-(2-methyl-1H-indol-3-yl)-1-(p-tolyl)-1H-
pyrrole-3-carboxylate (14d) (0.12 mmol, 43.2 mg, 58%): yel-
1
83%): yellowish oil; H NMR (400 MHz, DMSO-d6, 258C)
1
d=10.98 (s, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.48 (d, J=7.8 Hz,
1H), 7.34–7.24 (m, 2H), 7.20 (t, J=7.0 Hz, 1H), 7.14 (d, J=
8.0 Hz, 1H), 6.91 (t, J=7.0 Hz, 1H), 6.83 (t, J=7.1 Hz, 1H),
6.45 (s, 1H), 4.23 (q, J=7.1 Hz, 2H), 2.24 (d, J=4.0 Hz,
6H), 1.29 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz,
DMSO-d6, 258C) d=165.1, 137.4, 136.7, 136.2, 135.2, 133.4,
131.6, 131.0, 129.1, 128.7, 127.7, 123.3, 120.7, 119.1, 118.8,
112.4, 111.5, 110.9, 103.5, 59.4, 15.0, 12.8, 12.7 ppm; IR
(KBr) v: 3399, 3341, 2925, 1679, 1482, 1457, 1231, 1071,
lowish oil; H NMR (400 MHz, DMSO-d6, 258C) d=10.95
(s, 1H), 7.17 (d, J=7.8 Hz, 1H), 7.13 (d, J=7.8 Hz, 1H),
7.06 (d, J=8.0 Hz, 2H), 7.02 (d, J=8.0 Hz, 2H), 6.93 (t, J=
7.5 Hz, 1H), 6.84 (t, J=7.4 Hz, 1H), 6.44 (s, 1H), 4.22 (q,
J=7.1 Hz, 2H), 2.34 (s, 3H), 2.20 (s, 3H), 2.07 (s, 3H),
1.28 ppm (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, DMSO-
d6, 258C) d=169.9, 142.4, 141.3, 140.3, 140.2, 140.0, 134.4,
134.0, 132.7, 132.3, 125.5, 124.1, 123.1, 116.9, 115.8, 115.7,
108.8, 64.0, 25.7, 19.7, 17.8, 17.2 ppm; IR (KBr) v: 3397,
914
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ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2016, 358, 900 – 918

FULL PAPERS
Synthesis of Furans and Pyrroles
744 cmÀ1; HRMS (TOF, ESI): m/z calcd for C23H22BrN2O2,
[M+H]+ 437.0865, found 437.0877.
HRMS (TOF, ESI): m/z calcd for C23H20BrFN2NaO2, [M+
Na]+ 477.0590, found 477.0587.
Ethyl 5-(5-methoxy-2-methyl-1H-indol-3-yl)-2-methyl-1-
Ethyl
1-(3,4-difluorophenyl)-2-methyl-5-(2-methyl-1H-
phenyl-1H-pyrrole-3-carboxylate
(14m)
(0.14 mmol,
indol-3-yl)-1H-pyrrole-3-carboxylate
(14i) (0.16 mmol,
1
1
55.1 mg, 71%): yellowish oil; H NMR (400 MHz, DMSO-
d6, 258C) d=10.80 (s, 1H), 7.30–7.23 (m, 3H), 7.19 (d, J=
7.1 Hz, 2H), 7.03 (d, J=9.4 Hz, 1H), 6.54–6.50 (m, 2H),
6.44 (s, 1H), 4.23 (q, J=7.1 Hz, 2H), 3.62 (s, 3H), 2.37 (s,
3H), 2.11 (s, 3H), 1.29 ppm (t, J=7.1 Hz, 3H); 13C NMR
(1–0 MHz, DMSO-d6, 258C) d=165.2, 153.7, 138.2, 136.3,
136.1, 130.2, 129.3, 129.1, 128.3, 127.8, 112.3, 111.5, 110.9,
110.7, 104.0, 100.3, 59.3, 55.6, 15.0, 13.1, 12.5 ppm; IR (KBr)
62.2 mg, 79%): yellowish oil; H NMR (600 MHz, DMSO-
d6, 258C) d=11.03 (s, 1H), 7.50–7.44 (m, 1H), 7.34 (dd, J=
19.2, 9.0 Hz, 1H), 7.18 (d, J=8.0 Hz, 1H), 7.09 (d, J=
7.9 Hz, 1H), 7.01 (d, J=8.6 Hz, 1H), 6.94 (t, J=7.5 Hz,
1H), 6.83 (t, J=7.4 Hz, 1H), 6.45 (s, 1H), 4.23 (q, J=
7.1 Hz, 2H), 2.39 (s, 3H), 2.16 (s, 3H), 1.28 ppm (t, J=
7.1 Hz, 3H); 13C NMR (150 MHz, DMSO-d6, 258C) d=
165.0, 136.7–135.3 (m, 2C), 128.8, 127.7, 120.9, 119.4, 118.2
(d, J=32.7 Hz), 117.9, 112.5, 111.1 (d, J=17.6 Hz), 103.5,
59.4, 15.0, 12.9, 12.4 ppm; 19F NMR (377 MHz, DMSO-d6,
258C) d=À136.9, À137.0, À138.8, À138.9 ppm; IR (KBr) v:
3396, 2926, 1681, 1518, 1243, 1216, 1076, 745 cmÀ1; HRMS
(TOF, ESI): m/z calcd for C23H21F2N2O2, [M+H]+ 395.1571,
found 395.1601.
v: 3396, 2926, 1695, 1675, 1484, 1227, 1085, 1030, 774 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C24H25N2O3, [M+H]+
389.1865, found 389.1884.
3,3’-((2-bromophenyl)methylene)bis(2-methyl-1H-indole)
(17a)[27] (0.95 mmol, 406.6 mg, 95%): white solid, mp: 140–
1428C, 1H NMR (400 MHz, DMSO-d6, 258C) d=10.80 (s,
2H), 7.61 (d, J=7.8 Hz, 1H), 7.32–7.21 (m, 4H), 7.19–7.14
(m, 1H), 6.91 (t, J=7.3 Hz, 2H), 6.79 (d, J=7.7 Hz, 2H),
6.70 (t, J=7.3 Hz, 2H), 6.06 (s, 1H), 2.02 ppm (s, 6H);
13C NMR (100 MHz, DMSO-d6, 258C) d=143.7, 135.5,
133.1, 132.8, 131.5, 128.9, 128.7, 127.7, 125.1, 120.1, 118.6,
118.4, 111.1, 110.9, 12.2 ppm.
Ethyl 2-methyl-5-(2-methyl-1H-indol-3-yl)-1-(4-(trifluoro-
methoxy)phenyl)-1H-pyrrole-3-carboxylate
(14j)
(0.16 mmol, 72.5 mg, 82%): yellowish oil; 1H NMR
(600 MHz, DMSO-d6, 258C) d=11.00 (s, 1H), 7.29 (q, J=
9.0 Hz, 4H), 7.17 (d, J=8.0 Hz, 1H), 7.08 (d, J=7.8 Hz,
1H), 6.93 (t, J=7.5 Hz, 1H), 6.82 (t, J=7.4 Hz, 1H), 6.47 (s,
1H), 4.23 (q, J=7.1 Hz, 2H), 2.39 (s, 3H), 2.08 (s, 3H),
1.29 ppm (t, J=7.1 Hz, 3H); 13C NMR (150 MHz, DMSO-
d6, 258C) d=165.1, 147.7 (d, J=0.9 Hz), 137.1, 136.4, 135.5,
135.3, 130.3, 128.8, 127.6, 121.7, 120.9, 119.3, 118.2, 112.6,
111.1 (d, J=23.7 Hz), 103.6, 59.4, 15.0, 13.0, 12.4 ppm;
19F NMR (377 MHz, DMSO-d6, 258C) d=À57.0 ppm; IR
N-((2-bromophenyl)(2-methyl-1H-indol-3-yl)methyl)ani-
line (18a) (0.16 mmol, 60.8 mg, 78%), white solid, mp: 149–
1518C; 1H NMR (400 MHz, CDCl3, TMS, 258C) d=7.89
(dd, J=7.8, 1.5 Hz, 1H), 7.73 (s, 1H), 7.52 (dd, J=7.9,
1.1 Hz, 1H), 7.36 (d, J=7.9 Hz, 1H), 7.28 (td, J=7.6,
1.0 Hz, 1H), 7.21 (d, J=8.2 Hz, 1H), 7.14–7.04 (m, 4H),
6.95 (t, J=8.0 Hz, 1H), 6.69 (t, J=7.3 Hz, 1H), 6.46 (d, J=
7.7 Hz, 2H), 5.87 (s, 1H), 4.29 (s, 1H), 2.27 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=147.4, 140.5,
135.1, 133.4, 133.2, 129.5, 129.3, 128.7, 127.4, 127.3, 123.7,
121.3, 119.7, 118.8, 117.5, 113.2, 110.9, 110.4, 55.5, 12.7 ppm;
IR (KBr) v: 3394, 3348, 2949, 2921, 1691, 1454, 1438, 1244,
(KBr) v: 3397, 2928, 1681, 1512, 1259, 1072, 746 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C24H22F3N2O3, [M+H]+
443.1583, found 443.1505.
Ethyl 1-(3-chloro-2-methylphenyl)-2-methyl-5-(2-methyl-
1H-indol-3-yl)-1H-pyrrole-3-carboxylate (14k) (0.18 mmol,
1
71.4 mg, 88%): yellowish oil; H NMR (400 MHz, DMSO-
1063, 608 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for
d6, 258C) d=11.00 (s, 1H), 7.38 (dd, J=12.3, 8.0 Hz, 2H),
7.23–7.13 (m, 3H), 6.93 (t, J=7.5 Hz, 1H), 6.85 (t, J=
7.4 Hz, 1H), 6.48 (s, 1H), 4.23 (q, J=7.1 Hz, 2H), 2.22 (s,
3H), 2.16 (s, 3H), 1.79 (s, 3H), 1.29 ppm (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, DMSO-d6, 258C) d=165.1, 138.7,
136.7, 135.8, 135.2, 134.9, 134.2, 129.9, 129.0, 128.8, 127.8,
127.6, 120.9, 119.3, 118.4, 112.4, 111.4, 111.0, 103.5, 59.4,
15.5, 14.9, 12.6, 12.5 ppm; IR (KBr) v: 3335, 2926, 1696,
1679, 1463, 1237, 1073, 1029, 745 cmÀ1; HRMS (TOF, ESI):
m/z calcd for C24H24ClN2O2, [M+H]+ 407.1526, found
407.1544.
C22H19BrN2Na, [M+Na]+ 413.0629, found 413.0622.
Methyl 2-methyl-1-phenyl-5-(p-tolyl)-4,5-dihydro-1H-pyr-
role-3-carboxylate (19a) colorless oil; (0.85 mmol, 261.0 mg,
85%); 1H NMR (400 MHz, CDCl3, TMS, 258C) d=7.24–
7.17 (m, 2H), 7.14 (d, J=8.1 Hz, 2H), 7.08 (t, J=7.8 Hz,
3H), 6.94–6.87 (m, 2H), 5.01 (dd, J=11.3, 8.3 Hz, 1H), 3.69
(s, 2H), 3.36 (ddd, J=14.7, 11.4, 1.2 Hz, 1H), 2.78 (ddd, J=
14.8, 8.3, 1.4 Hz, 1H), 2.29 (s, 2H), 2.24 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS, 258C) d=204.3, 167.5,
159.0, 141.5, 139.9, 137.1, 129.3, 128.9, 126.8, 125.8, 125.6,
120.2, 98.6, 69.0, 50.4, 38.3, 21.1, 14.2 ppm; IR (KBr) v:
2961, 2922, 1699, 1597, 1458, 1435, 1243, 1063, 742 cmÀ1
;
Ethyl 1-(2-bromo-4-fluorophenyl)-2-methyl-5-(2-methyl-
1H-indol-3-yl)-1H-pyrrole-3-carboxylate (14l) (0.16 mmol,
HRMS (TOF, ESI): m/z calcd for C20H21NNaO2, [M+Na]+
1
71.7 mg, 79%): yellowish oil; H NMR (400 MHz, DMSO-
330.1470, found 330.1463.
d6, 258C) d=11.03 (s, 1H), 7.66–7.53 (m, 2H), 7.26 (d, J=
7.9 Hz, 1H), 7.24–7.18 (m, 1H), 7.16 (d, J=8.0 Hz, 1H),
6.93 (t, J=7.0 Hz, 1H), 6.84 (t, J=7.9 Hz, 1H), 6.45 (s, 1H),
4.23 (q, J=7.1 Hz, 2H), 2.26 (s, 6H), 1.29 ppm (t, J=7.1 Hz,
3H); 13C NMR (150 MHz, DMSO-d6, TMS, 258C) d=165.1,
161.6 (d, J=249.0 Hz), 136.9, 136.3, 135.2, 134.2, 132.9 (d,
J=9.0 Hz), 129.0, 127.9, 124.2 (d, J=10.0 Hz), 120.8, 120.5
(d, J=26.0 Hz), 119.2, 118.7, 115.7 (d, J=22.0 Hz), 112.5,
111.5, 110.6, 103.3, 59.5, 14.9, 12.8, 12.6 ppm; 19F NMR
(377 MHz, DMSO-d6, 258C) d=À110.5 ppm; IR (KBr) v:
Methyl
2-methyl-1-phenyl-5-(p-tolyl)-1H-pyrrole-3-car-
boxylate (20a) colorless oil; (0.16 mmol, 50.0 mg, 82%);
1H NMR (400 MHz, CDCl3, TMS, 258C) d=7.43–7.35 (m,
3H), 7.17–7.10 (m, 2H), 6.98–6.90 (m, 4H), 6.74 (s, 1H),
3.85 (s, 3H), 2.39 (s, 3H), 2.25 ppm (s, 3H); 13C NMR
(100 MHz, CDCl3, TMS, 258C) d=166.1, 138.2, 138.0, 136.3,
134.1, 129.5, 129.2, 128.8, 128.5, 128.2, 128.0, 112.4, 109.5,
50.9, 21.1, 12.5 ppm; IR (KBr) v: 2961, 2922, 2911, 1703,
1597, 1452, 1439, 1240, 1061, 742 cmÀ1; HRMS (TOF, ESI):
m/z calcd for C20H19NNaO2, [M+Na]+ 328.1313, found
328.1301.
3396, 2926, 1695, 1675, 1484, 1227, 1085, 1030, 774 cmÀ1
;
Adv. Synth. Catal. 2016, 358, 900 – 918
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
915

FULL PAPERS
Changhui Liu et al.
Methyl 2-methyl-5-(2-methyl-1H-indol-3-yl)-4,5-dihydro-
thiophene-3-carboxylate (21a) (0.19 mmol, 54.2 mg, 95%):
brown oil; H NMR (400 MHz, DMSO-d6, 258C) d=10.96
43.86, 43.56, 16.58, 12.10 ppm; IR (KBr) v: 3394, 3348, 2949,
2921, 1699, 1597, 1458, 1438, 1244, 1063, 608, 744 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C17H20NO3S, [M+H]+
318.1164, found 318.1161.
1
(s, 1H), 7.53 (d, J=7.8 Hz, 1H), 7.29 (d, J=7.9 Hz, 1H),
7.02 (t, J=7.0 Hz, 1H), 6.95 (t, J=7.0 Hz, 1H), 5.39 (t, J=
9.8 Hz, 1H), 3.65 (s, 3H), 3.41–3.34 (m, 2H), 2.36 ppm (s,
6H); 13C NMR (100 MHz, DMSO-d6, 258C) d=164.2, 157.0,
136.0, 133.4, 126.7, 120.9, 119.2, 119.1, 118.9, 111.3, 109.9,
51.4, 43.9, 43.7, 16.6, 11.9 ppm; IR (KBr) v: 3394, 3348,
Methyl 5-(5-fluoro-2-methyl-1H-indol-3-yl)-2-methyl-4,5-
dihydrothiophene-3-carboxylate (21 f) (90%, 0.18 mmol,
57.1 mg), light yellow oil; 1H NMR (400 MHz, DMSO-d6,
258C) d=11.09 (s, 1H), 7.26 (dd, J=8.7, 4.7 Hz, 1H), 7.19
(dd, J=10.3, 2.4 Hz, 1H), 6.85 (td, J=9.3, 2.5 Hz, 1H), 5.35
(t, J=9.7 Hz, 1H), 3.65 (s, 3H), 3.42–3.35 (m, 1H), 3.28
(ddd, J=16.0, 9.2, 1.9 Hz, 1H), 2.35 ppm (d, J=3.5 Hz,
6H); 13C NMR (100 MHz, DMSO-d6, 258C) d=164.1, 156.9
(d, J=229.0 Hz), 156.8, 135.8, 132.6, 126.9 (d, J=10.0 Hz),
119.1, 112.1 (d, J=10.0 Hz), 110.4 (d, J=4.0 Hz), 108.6 (d,
J=25.0 Hz), 103.9 (d, J=23.0 Hz), 51.4, 43.8, 43.3, 16.6,
12.0 ppm; 19F NMR (377 MHz, DMSO-d6, 258C) d=
À124.7 ppm.IR (KBr) v: 3394, 3348, 2951, 2920, 1702, 1592,
1458, 1435, 1244, 1063, 742 cmÀ1; HRMS (TOF, ESI): m/z
calcd for C16H17FNO2S, [M+H]+ 306.0964, found 306.0961.
2949, 2924, 1699, 1597, 1458, 1435, 1244, 1063, 742 cmÀ1
;
HRMS (TOF, ESI): m/z calcd for C16H18NO2S, [M+H]+
288.1058, found 288.1030.
Ethyl
2-methyl-5-(2-methyl-1H-indol-3-yl)-4,5-dihydro-
thiophene-3-carboxylate (21b) (0.19 mmol, 56.0 mmol,
93%), light yellow oil; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=7.97 (s, 1H), 7.72 (d, J=7.5 Hz, 1H), 7.23 (d, J=
7.5 Hz, 1H), 7.16–7.04 (m, 2H), 5.27 (t, J=10.1 Hz, 1H),
4.18 (qd, J=7.1, 1.3 Hz, 2H), 3.55 (ddd, J=16.1, 10.1,
1.9 Hz, 1H), 3.43 (ddd, J=16.2, 10.2, 1.4 Hz, 1H), 2.42 (s,
3H), 2.34 (s, 3H), 1.26 ppm (t, J=7.1 Hz, 3H); 13C NMR
(100 MHz, CDCl3, TMS, 258C) d=164.4, 157.5, 135.5, 132.1,
126.8, 121.4, 119.7, 119.4, 119.4, 110.7, 110.6, 59.9, 43.9, 43.9,
16.6, 14.4, 12.0 ppm; IR (KBr) v: 3392, 3351, 2939, 2922,
1699, 1596, 1455, 1436, 1242, 1066, 742 cmÀ1; HRMS (TOF,
ESI): m/z calcd for C17H20NO2S, [M+H]+ 302.1215, found
302.1203.
2-Methoxyethyl 2-methyl-5-(2-methyl-1H-indol-3-yl)-4,5-
dihydrothiophene-3-carboxylate (21c) (0.18 mmol, 60.9 mg,
92%), light yellow oil; 1H NMR (400 MHz, CDCl3, TMS,
258C) d=7.93 (s, 1H), 7.72 (d, J=7.7 Hz, 1H), 7.26 (d, J=
7.3 Hz, 1H), 7.11 (dtd, J=15.9, 7.1, 1.0 Hz, 2H), 5.27 (t, J=
10.2 Hz, 1H), 4.34–4.22 (m, 2H), 3.61 (t, J=4.8 Hz, 2H),
3.59–3.51 (m, 1H), 3.49–3.41 (m, 1H), 3.37 (s, 3H), 2.42 (s,
2H), 2.37 ppm (s, 3H); 13C NMR (100 MHz, CDCl3, TMS,
258C) d=164.1, 158.4, 135.5, 132.0, 126.8, 121.4, 119.7,
119.5, 119.0, 110.6, 110.5, 70.7, 63.0, 59.0, 44.1, 43.7, 16.6,
12.0 ppm; IR (KBr) v: 3392, 3351, 2948, 2921, 1701, 1598,
1456, 1431, 1249, 1061, 742 cmÀ1; HRMS (TOF, ESI): m/z
calcd for C18H22NO3S, [M+H]+ 332.1320, found 332.1304.
Acknowledgements
Financial support from National Natural Science Foundation
of China for the financial support (21173089 and 21373093),
the Fundamental Research Funds for the Central Universities
of China (2014ZZGH019) and the Cooperative Innovation
Center of Hubei Province are greatly appreciated. The au-
thors are also grateful for all the staff members in the Analyt-
ical and Testing Center of HUST, for their contributions to
our works.
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5-(2-methyl-1H-indol-3-yl)-2-phenyl-4,5-dihydro-
thiophene-3-carboxylate (21d) (0.18 mmol, 64.6 mg, 89%),
light yellow oil; 1H NMR (400 MHz, CDCl3, TMS, 258C)
d=7.92 (s, 1H), 7.89–7.84 (m, 1H), 7.47 (dd, J=6.5, 3.1 Hz,
2H), 7.34 (dd, J=5.0, 1.9 Hz, 3H), 7.26–7.21 (m, 1H), 7.16–
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16.5, 10.1 Hz, 1H), 2.38 (s, 3H), 1.05 ppm (t, J=7.1 Hz,
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IR (KBr) v: 3395, 3341, 2944, 2928, 1699, 1596, 1457, 1435,
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Methyl 5-(5-methoxy-2-methyl-1H-indol-3-yl)-2-methyl-
4,5-dihydrothiophene-3-carboxylate (21e) (87%, 0.17 mmol,
1
55.2 mg), light yellow oil; H NMR (400 MHz, CDCl3, TMS,
258C) d=7.88 (s, 1H), 7.15 (d, J=2.3 Hz, 1H), 7.12 (d, J=
8.7 Hz, 1H), 6.77 (dd, J=8.7, 2.4 Hz, 1H), 5.21 (t, J=
9.6 Hz, 1H), 3.81 (s, 3H), 3.71 (s, 3H), 3.53–3.40 (m, 2H),
2.42 (s, 3H), 2.34 ppm (s, 3H); 13C NMR (100 MHz, CDCl3.
TMS, 258C) d=164.73, 157.89, 153.73, 132.78, 130.57,
127.10, 119.06, 111.23, 111.04, 110.90, 102.20, 55.87, 51.10,
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