Synthesis of 3,4-dihalogenated furan-2-(5H)-ones by electrophilic cyclization of 4-hydroxy-2-alkynoates

Article abstract of DOI:10.1002/asia.201200137

Functionalized 3,4-dihalogenated furan-2(5H)-ones can be readily prepared in moderate to good yields by treating 4-hydroxy-4-arylbut-2-ynoate derivatives with ICl, IBr, and I₂. Both halogen atoms of the electrophile are incorporated in the product. The resulting halides can further afford polycyclic aromatic compounds using known palladium-catalyzed coupling reactions.

Full text of DOI:10.1002/asia.201200137

DOI: 10.1002/asia.201200137
Synthesis of 3,4-Dihalogenated Furan-2-(5H)-ones by Electrophilic
Cyclization of 4-Hydroxy-2-alkynoates
Hai-Tao Zhu,[a] Li-Jing Wang,[a] Ke-Gong Ji,[a] Xue-Yuan Liu,[a] and Yong-Min Liang*[a, b]
Abstract: Functionalized 3,4-dihalogenated furan-2ACTHNUTRGNEUG(N 5H)-ones can be readily pre-
pared in moderate to good yields by treating 4-hydroxy-4-arylbut-2-ynoate deriva-
tives with ICl, IBr, and I2. Both halogen atoms of the electrophile are incorporated
in the product. The resulting halides can further afford polycyclic aromatic com-
pounds using known palladium-catalyzed coupling reactions.
Keywords: allenes
cyclization furan-2
palladium · propargylic alcohol
·
electrophilic
·
U
Introduction
tive for the synthesis of these furan-2ACTHNGUTERNNU(G 5H)-ones, but there
are some drawbacks such as long reaction sequences, low
temperatures, and the use of expensive metals. Thus, the de-
velopment of concise and efficient methods for the synthesis
Furan-2ACHTUNGTRENNUNG(5H)-one is a key structural subunit prevalent in nu-
merous natural products and plays an important role in
pharmaceutical chemistry.[1] For example, it has been report-
ed that rubrolide O (1) has anti-inflammatory properties[2]
and caucanolide C (3) shows in vitro antiplasmodial activity
against the malaria parasite, plasmodium falciparum
(Figure 1).[3] Therefore, many synthetic methods for the con-
of functionalized furan-2
The electrophilic cyclization of allenes to effectively pro-
vide furan-2(5H)-ones has been explored, and the mecha-
ACHTUNGERTN(NUNG 5H)-ones is necessary.
AHCTUNGTRENNUNG
nism of this process has been studied by Ma et al.[8] Never-
theless, the use of unstable allenes as the starting materials
poses some challenges. Only recently has the electrophilic
cyclization of an allene cation derived from propargylic al-
cohols proven to be a very powerful tool for the synthesis of
heterocyclic and carbocyclic compounds, owing to its clean
and very mild reaction conditions.[9–14] Also, it has been re-
ported that various fundamental heterocycles and carbocy-
cles, such as furans,[9] dihydrofurans,[10a] dihydropyrroles,[10a]
dihydrothiophenes,[10b] benzenes,[11] dihydronaphthalenes or
indenes,[12] naphthalenes,[13] and fluoranthenes[14] have been
produced with this strategy. This chemistry is generally be-
lieved to proceed through a stepwise mechanism that in-
cludes the formation, in the presence of electrophiles, of the
allene cation I which can be readily trapped by nucleophiles
(e.g., Cl, Br, I), and electrophilic activation of the halogen-
ated allene intermediate followed by intramolecular nucleo-
philic attack on the cationic intermediate II (Scheme 1a).
Our previous success in employing this process for the
synthesis of 2,5-dihydrofurans and 2,5-dihydropyrroles[15]
(Scheme 1b) inspired us to explore the possibility of prepar-
struction of furan-2ACHTUNGTRENNUNG(5H)-ones have been described in detail
by Ma,[4] Takahashi,[5] Marinelli,[6] and other research
groups.[7] These classical methods have proven to be effec-
Figure 1. Two representative natural products containing a furan-2
one skeleton.
ACHTUNGTNER(NUNG 5H)-
ing furan-2ACTHNUGRTNEUNG(5H)-ones with this methodology. We envisioned
[a] Dr. H.-T. Zhu, L.-J. Wang, Dr. K.-G. Ji, Prof. Dr. X.-Y. Liu,
Prof. Dr. Y.-M. Liang
that 4-hydroxy-2-alkynoates as substrates would undergo the
identical isomerization process in the presence of the elec-
trophilic reagent (e.g., ICl, IBr, I2) and then cyclize to give
Department of Chemistry
State Key Laboratory of Applied Organic Chemistry
Lanzhou University, Lanzhou 730000 (China)
Fax : (+86)931-8915557
3,4-dihalogenated furan-2
we report an effective method for the synthesis of highly
substituted 3,4-dihalogenated furan-2(5H)-ones by an elec-
ACHTUNGTNER(NUNG 5H)-ones (Scheme 1c). Herein,
E-mail: liangym@lzu.edu.cn
AHCTUNGTRENNUNG
[b] Prof. Dr. Y.-M. Liang
trophilic cyclization of 4-hydroxy-2-alkynoates under mild
reaction conditions.
Key Laboratory of Solid Lubrication
Lanzhou Institute of Chemical Physics
Chinese Academy of Science
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia.201200137.
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ents on the aromatic R2 groups.
Using substituted tertiary alco-
hols as substrates, electron-do-
nating groups showed better re-
sults than electron-withdrawing
ones (2c vs 2h). However, sub-
stituted secondary alcohols as
substrates, decreased the yield
(2p vs 2s). Better results were
obtained (2j vs 2k) when the
aliphatic chain of R1 was ex-
tended.
To further explore the scope
of this electrophilic cyclization,
the reactions of 4-hydroxy-4-ar-
ylpent-2-ynoate derivatives with
IBr have been studied under
similar conditions, as depicted
Scheme 1. The electrophilic cyclization of propargylic alcohol derivatives.
Results and Discussion
Table 1. Optimization of the electrophilic cyclization of methyl-4-hy-
droxy-4-phenylpent-2-ynoate 1.[a]
Initially, we used methyl-4-hydroxy-4-phenylpent-2-ynoate
(1a; 0.2 mmol) in the presence of ICl (1.5 equiv) in
ClCH2CH2Cl (4 mL) at room temperature; to our delight,
the desired product 3-chloro-4-iodo-5-methyl-5-phenyl-
furan-2ACHTUNGTRENNUNG(5H)-one (2a) was isolated in 71% yield, after
1 hour (Table 1, entry 1). Increasing the amount of ICl to
two equivalents afforded 2a in 81% yield (Table 1, entry 2).
However, increasing the amount of ICl to three equivalents
did not improve the yield (Table 1, entry 3). The study of
the influence of different reaction media showed that
CH3CN, CH2Cl2, and CH3NO2 were less effective (Table 1,
entries 4–6), whereas methanol proved to be ineffective
(Table 1, entry 7). Prolonging the reaction did not provide
better results (Table 1, entries 8 and 9). By using anhydrous
ClCH2CH2Cl as the solvent, afforded the desired product 2a
in 75% yield (Table 1, entry 10).
After having established the optimized reaction condi-
tions for the present reaction, various 4-hydroxy-4-arylpent-
2-ynoate derivatives 1a–s were subjected to the standard re-
action conditions, as depicted in Table 2. Thus, the tandem
carbon–oxygen bond formations of 4-hydroxy-4-arylpent-2-
ynoate derivatives 1a–s proceeded smoothly to provide the
corresponding products 2a–s in moderate to good yields.
The structure of the representative product 2a was deter-
mined by X-ray crystallographic analysis (see the Supporting
Information).[16] The reaction can tolerate various substitu-
Entry
Solvent
ICl [equiv]
t [h]
Yield [%][b]
1
2
3
4
5
6
7
8
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
CH3CN
CH2Cl2
CH3NO2
1.5
2.0
3.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
1
1
1
1
1
1
1
2
6
1
71
81
80
63
68
61
MeOH
nr[c]
73
ClCH2CH2Cl
ClCH2CH2Cl
ClCH2CH2Cl
9
10
66
75[d]
[a] All reactions were run under the following conditions, unless other-
wise indicated: 1 (0.2 mmol) with ICl (2.0 equiv) in wet ClCH2CH2Cl
(4 mL) with 0.05% water content at room temperature. [b] Yield of iso-
lated product. [c] nr=no reaction. [d] Anhydrous ClCH2CH2Cl.
in Table 3. Substrate 1a gave the desired 3-bromo-4-iodofur-
an-2ACTHUNRTGNEUNG(5H)-one (3a) in 65% yield. Similarly, methyl-4-hy-
droxy-4-phenylhex-2-ynoate (1j) led to the desired product
3j in 87% yield. Substituted secondary alcohols 1m, 1o, and
1q, which have phenyl, p-methoxyphenyl, and m-methyl
substituents, produced the five-membered dihalogenated ox-
acyclic compounds in 34%, 73%, and 66% yield, respec-
tively.
The reaction of 4-hydroxy-2-alkynoates 1 with diverse
substitutions on the R1 and R2 moieties was also examined
in the presence of molecular iodine. Secondary and tertiary
alcohols both afforded the desired products, but the tertiary
alcohol gave better results (Table 4, 1a vs 1n). Electron-rich
aryl groups give better results than those with an electron-
withdrawing group in this tandem reaction (1 f vs 1v). Infe-
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Synthesis of 3,4-Dihalogenated Furan-2-(5H)-ones
Table 2. Cascade synthesis of 3-chloro-4-iodofuran-2
(5H)-ones 2 from 4-
Table 4. Synthesis of 3,4-diiodofuran-2ACTHUNGETRN(UNG 5H)-ones 4 from 4-hydroxy-4-ar-
hydroxy-4-arylpent-2-ynoate derivatives 1.[a]
ylpent-2-ynoate derivatives 1.[a]
Entry Substrate (R1, R2)
Product Yield [%][b]
Entry
Substrate (R1, R2)
Product
Yield [%][b]
1
2
3
4
5
6
7
8
R1 =Me, R2 =Ph 1a
2a
2b
2c
2d
2e
2 f
2g
2h
2i
2j
2k
2l
2m
2n
2o
2p
2q
2r
81
69
77
61
57
93
97
35
65
70
89
74
1
2
3
4
5
6
7
8
R1 =Me, R2 =Ph 1a
4a
4 f
4h
4k
4l
4n
4o
4s
4t
70
57
71
38
78
58
31
50
57[c]
68
65
R1 =Me, R2 =p-MeC6H4 1b
R1 =Me, R2 =p-MeOC6H4 1c
R1 =Me, R2 =m-BrC6H4 1d
R1 =Me, R2 =o-MeOC6H4 1e
R1 =Me, R2 =p-ClC6H4 1 f
R1 =Me, R2 =p-BrC6H4 1g
R1 =Me, R2 =p-ClC6H4 1 f
R1 =Me, R2 =benzo
ACTHUNGTERNNU[G 1,3]dioxole 1h
R1 =nBu, R2 =Ph 1k
R1 =Ph, R2 =Ph 1l
R1 =H, R2 =p-MeC6H4 1n
R1 =H, R2 =p-MeOC6H4 1o
R1 =Me, R2 =benzo
E
R1 =H, R2 =benzo
ACTHUNGTERNNU[G 1,3]dioxole 1s
9
R1 =Me, R2 =m-MeOC6H4 1i
9
10
11
R1 =Me, R2 =furyl 1t
10
11
12
13
14
15
16
17
18
19
R1 =Et, R2 =Ph 1j
R1 =Ph, R2 =ethynyl 1u
4u
R1 =nBu, R2 =Ph 1k
R1 =Me, R2 =3,4-dimethoxybenzene 1v 4v
R1 =Ph, R2 =Ph 1l
[a] All reactions were run under the following conditions, unless other-
wise indicated: 1 (0.2 mmol) with I2 (2.0 equiv) in wet CH3CN (4 mL)
with 0.05% water content at 808C. [b] Yield of isolated product. [c] The
reaction temperature is 408C.
R1 =H, R2 =Ph 1m
50[c]
80[c]
73[c]
37[c]
59[c]
31[c]
86[c]
R1 =H, R2 =p-MeC6H4 1n
R1 =H, R2 =p-MeOC6H4 1o
R1 =H, R2 =p-BrC6H4 1p
R1 =H, R2 =m-MeC6H4 1q
R1 =H, R2 =o-MeOC6H4 1r
R1 =H, R2 =benzo
N
2s
[a] All reactions were run under the following conditions, unless other-
wise indicated: 1 (0.2 mmol) with ICl (2.0 equiv) in wet ClCH2CH2Cl
(4 mL) with 0.05% water content at room temperature. [b] Yield of iso-
lated product. [c] Wet CH2Cl2 with 0.05% water content.
Table 3. Synthesis of 3-bromo-4-iodofuran-2ACHTUNGTRNE(NGU 5H)-ones 3 from 4-hy-
droxy-4-arylpent-2-ynoate derivatives 1.[a]
Substrate (R1, R2)
Product
Yield [%][b]
Scheme 2. Proposed reaction mechanism.
Entry
1
2
3
4
5
R1 =Me, R2 =Ph 1a
3a
3j
3m
3o
3q
65[c]
87
34
73
66
R1 =Et, R2 =Ph 1j
R1 =H, R2 =Ph 1m
R1 =H, R2 =p-MeOC6H4 1o
R1 =H, R2 =m-MeC6H4 1q
then the intermediate allene cation B is afforded along with
an unstable hypoiodous acid (HOI).[13] The intermediate B
then reacts with a halide anion to give C, which is activated
by an iodonium cation. Nucleophilic attack by the oxygen of
the carbonyl group on the activated allene is followed by
SN2 attack of the halide anion on the methyl group to give
[a] All reactions were run under the following conditions, unless other-
wise indicated: 1 (0.2 mmol) with IBr (2.0 equiv) in wet CH2Cl2 (4 mL)
with 0.05% water content at room temperature. [b] Yield of isolated
product. [c] The solvent is wet CH3NO2 with 0.05% water content.
the methyl halide and dihalogenated furan-2ACHTNUTRGNE(UNG 5H)-one D.
A standard feature of this process is the fact that the diha-
logenated heterocyclic compounds produced by electro-
philes (e.g., I2, IBr, and ICl) can be further elaborated by
using various palladium-catalyzed processes. For example,
the Sonagashira[17] coupling of 3-bromo-5-ethyl-4-iodo-5-
rior results were obtained (1a vs 1k) when the aliphatic
chain of R1 was extended. Substrate 1t with a furyl on R2
can also lead to the desired product. Interestingly, a substrate
such as 1u with an ethynyl group can also give the corre-
sponding furan-2
G
phenylfuran-2
N
ACHTUNGTREN[NGNU 1,3]dioxol-5-
On the basis of the above observations, we propose the
following mechanism for this iodocyclization (Scheme 2).
Presumably, in the presence of Lewis acidic iodine, the
propargyl hydroxy group of substrate A is activated and
yl)-3,4-diiodo-5-methylfuran-2ACTHUNGTRENNNUG
afforded the corresponding products 5j and 8h in 52% and
59% yield, respectively. The Suzuki[18] coupling of 3-bromo-
5-ethyl-4-iodo-5-phenylfuran-2ACHTUNTRGNEUNG(5H)-one 3j also obtained
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(3ꢁ15 mL), washed with water, saturated brine, dried over Na2SO4, and
evaporated under reduced pressure. The residue was purified by chroma-
tography on silica gel to afford the corresponding dihalogenated-hetero-
cyclic compounds.
3-Chloro-4-iodo-5-methyl-5-phenylfuran-2ACHTNUTRGNE(NUG 5H)-one (2a)
White solid; m.p. 94–968C; Reaction time: 1 h. 1H NMR (400 MHz,
CDCl3): d=7.42–7.39 (m, 3H), 7.37–7.33 (m, 2H), 1.97 ppm (s, 3H).
13C NMR (100 MHz, CDCl3): d=166.4, 136.1, 134.9, 129.3, 128.8, 125.6,
121.8, 92.2, 24.4 ppm. IR (neat): n˜ =1753, 1593, 1252, 1028, 845, 692 cmÀ1
.
HRMS (ESI): m/z: calcd for C11H12ClINO2: 351.9596 [M+NH4]; found:
351.9604.
Acknowledgements
We thank the National Science Foundation (NSF-21072080) and the Na-
tional Basic Research Program of China (973 Program) 2010CB8-33203
for financial support. We also acknowledge the support by the “111”
Project.
[1] For reviews, see: a) A. D. Wright, R. D. Nys, C. K. Angerhofer, J. M.
Pezzuto, M. Gurrath, J. Nat. Prod. 2006, 69, 1180–1187; b) R. S.
El Dine, A. M. El Halawany, C.-M. Ma, M. Hattori, J. Nat. Prod.
2009, 72, 2019–2023; c) A. O. Brachmann, S. Forst, G. M. Furgani,
A. Fodor, H. B. Bode, J. Nat. Prod. 2006, 69, 1830–1832; d) M.
Hentzer, K. Riedel, T. B. Rasmussen, A. Heydorn, J. B. Andersen,
M. R. Parsek, S. A. Rice, L. Eberl, S. Molin, N. Hoiby, S. Kjelleberg,
M. Givskov, Microbiology 2002, 148, 87–102; e) T. Olpp, R. Bruck-
ner, Angew. Chem. 2005, 117, 1577–1581; Angew. Chem. Int. Ed.
2005, 44, 1553–1557; f) M. Inoue, T. Sato, M. Hirama, Angew.
Chem. 2006, 118, 4961–4966; Angew. Chem. Int. Ed. 2006, 45, 4843–
4848; g) T. J. Donohoe, R. M. Harris, J. Burrows, J. Parker, J. Am.
Chem. Soc. 2006, 128, 13704–13705.
[2] A. N. Pearce, E. W. Chia, M. V. Berridge, E. W. Maas, M. J. Page,
V. L. Webb, J. L. Harper, B. R. Copp, J. Nat. Prod. 2007, 70, 111–
113.
Scheme 3. Palladium-catalyzed coupling reactions.
[3] C. A. Ospina, A. D. Rodriguez, J. A. Sanchez, E. Ortega-Barria,
T. L. Capson, A. M. S. Mayer, J. Nat. Prod. 2005, 68, 1519–1526.
[4] a) S. Ma, D. Duan, Zh. Shi, Org. Lett. 2000, 2, 1419–1422; b) G.
Chen, R. Zeng, Z. Gu, C. Fu, S. Ma, Org. Lett. 2008, 10, 4235–4238;
c) S. Ma, Z. Yu, J. Org. Chem. 2003, 68, 6149–6152.
the desired products 6j and 7j in 95% and 72% yield, re-
spectively (Scheme 3).
[5] E. Yoneda, Sh.-W. Zhang, D.-Y. Zhou, K. Onitsuka, S. Takahashi, J.
Org. Chem. 2003, 68, 8571–8576.
[6] M. Alfonsi, A. Arcadi, M. Chiarini, F. Marinelli, J. Org. Chem. 2007,
72, 9510–9517.
Conclusions
[7] a) Q. Zhang, M. Cheng, X. Hu, B.-G. Li, J.-X. Ji, J. Am. Chem. Soc.
2010, 132, 7256–7257; b) A. Takahashi, H. Yanai, M. Zhang, T.
Sonoda, M. Mishima, T. Taguchi, J. Org. Chem. 2010, 75, 1259–
1265; c) P. Langer, Synlett 2006, 20, 3369–3381; d) S. Protti, M. Fag-
noni, A. Albini, J. Am. Chem. Soc. 2006, 128, 10670–10671; e) Y.
Harada, Y. Fukumoto, N. Chatani, Org. Lett. 2005, 7, 4385–4387;
f) T. G. Elford, Y. Arimura, S.-H. Yu, D. G. Hall, J. Org. Chem.
2007, 72, 1276–1284; g) M. Takimoto, M. Kawamura, M. Mori, Org.
Lett. 2003, 5, 2599–2601; h) L.-B. Huang, H.-F. Jiang, Ch.-R. Qi, X.-
H. Liu, J. Am. Chem. Soc. 2010, 132, 17652–17654.
In conclusion, we have developed an efficient synthesis of
substituted dihalogenated furan-2ACTHNUTRGNEUNG(5H)-ones in moderate to
good yields from simple 4-hydroxy-2-alkynoates under mild
reaction conditions. The dihalogenated moiety can be readi-
ly introduced into the heterocycle in a position not easily
obtained previously. Also, in this reaction, both halogen
atoms can be used effectively.
[8] a) S. Ma, Z. Shi, Z. Yu, Tetrahedron Lett. 1999, 40, 2393–2396; b) S.
Ma, Z. Shi, Z. Yu, Tetrahedron 1999, 55, 12137–12148; c) C. Fu, S.
Ma, Eur. J. Org. Chem. 2005, 3942–3945; d) S. Ma, F. Pan, X. Hao,
X. Huang, Synlett 2004, 85–88; e) C. Zhou, Z. Ma, Z. Gu, C. Fu, S.
Ma, J. Org. Chem. 2008, 73, 772–774; f) S. Ma, Acc. Chem. Res.
2009, 42, 1679–1688.
[9] F. Yang, T. Jin, M. Bao, Y. Yamamoto, Chem. Commun. 2011, 47,
4541–4543.
[10] a) K.-G. Ji, H.-T. Zhu, F. Yang, X.-Z. Shu, S.-C. Zhao, A. Shaukat,
X.-Y. Liu, Y.-M. Liang, Chem. Eur. J. 2010, 16, 6151–6154; b) F.
Experimental Section
General procedure for synthesis of 3, 4-dihalogenated furan-2ACTHUNRGTNE(NUG 5H)-ones
The corresponding electrophile (0.4 mmol) was added to a solution of 4-
hydroxy-2-alkynoates 1 (0.20 mmol) in wet solvent with 0.05% water
content (4 mL). When the reaction was considered complete as deter-
mined by TLC analysis, the reaction mixture was quenched by addition
of saturated aqueous sodium thiosulfate and extracted with ethyl acetate
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Synthesis of 3,4-Dihalogenated Furan-2-(5H)-ones
Yang, T. Jin, M. Bao, Y. Yamamoto, Tetrahedron 2011, 67, 10147–
10155.
[11] F. Yang, K.-G. Ji, H.-T. Zhu, A. Shaukat, X.-Y. Liu, Y.-M. Liang,
Chem. Eur. J. 2011, 17, 4986–4990.
[17] For reviews, see: a) The Sonogashira Cu–Pd-Catalyzed Alkyne
Coupling Reaction. I. B. Campbell in Organocopper Reagents (Ed.:
R. T. K. Taylor), Oxford, UK, 1994, pp. 217–235; b) K. Sonogashira,
S. Takahashi, Yuki Gosei Kagaku Kyokaishi 1993, 51, 1053; c) K. So-
nogashira in Comprehensive Organic Synthesis, Vol. 3 (Eds: B. M.
Trost, I. Fleming), Pergamon, Oxford, 1991, pp. 521–549.
[18] For reviews, see: a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95,
2457–2483; b) A. Suzuki, J. Organomet. Chem. 1999, 576, 147–168;
c) A. Suzuki in Metal-Catalyzed Cross-Coupling Reactions (Eds.: F.
Diederich, P. J. Stang), Wiley-VCH, New York, 1998, Chap. 2.
[12] H.-T. Zhu, K.-G. Ji, F. Yang, L.-J. Wang, Sh.-Ch. Zhao, A. Shaukat,
X.-Y. Liu, Y.-M. Liang, Org. Lett. 2011, 13, 684–687.
[13] F. Yang, T. Jin, M. Bao, Y. Yamamoto, Chem. Commun. 2011, 47,
4013–4015.
[14] X. Chen, P. Lu, Y. Wang, Chem. Eur. J. 2011, 17, 8105–8114.
[15] K.-G. Ji, H.-T. Zhu, F. Yang, A. Shaukat, X.-F. Xia, Y.-F. Yang, X.-
Y. Liu, Y.-M. Liang, J. Org. Chem. 2010, 75, 5670–5678.
[16] CCDC 861426 (2a) contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.a-
c.uk/data_request/cif.
Received: February 11, 2012
Revised: March 19, 2012
Published online: && &&, 0000
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Cyclization Reactions
Hai-Tao Zhu, Li-Jing Wang,
Ke-Gong Ji, Xue-Yuan Liu,
Yong-Min Liang*
&&&& — &&&&
Synthesis of 3,4-Dihalogenated Furan-
2-(5H)-ones by Electrophilic Cycliza-
tion of 4-Hydroxy-2-alkynoates
Three amigos: Functionalized 3,4-diha-
logenated furan-2(5H)-ones can be
readily prepared in moderate to good
yields by treating 4-hydroxy-4-arylbut-
2-ynoate derivatives with ICl, IBr, and
I2. Both halogen atoms of the electro-
phile are incorporated in the product
(see scheme).
AHCTUNGTRENNUNG
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