Highly efficient synthesis of multisubstituted furans through cupric halide-mediated intramolecular halocyclization of 1-(1-alkynyl)cyclopropyl ketones

Article abstract of DOI:10.1002/ejoc.201200601

A convenient and efficient method for the synthesis of 3-halofurans was developed by using a cascade reaction between 1-(1-alkynyl)cyclopropyl ketones and cupric halide. Under mild reaction conditions, both 3-chloro- and 3-bromofuran derivatives were obtained in high yields. The reaction involves consecutive multiple bond formations, includingC-O and C-Br bonds, with high regioselectivity. Mechanistic aspects are described. The selective synthesis of functionalized furans by using the cupric halide-mediated intramolecular halocyclization of 1-(1-alkynyl)cyclopropyl ketones is described. Under mild conditions, a series of 3-chloro- and 3-bromofuran derivatives were formed in 1 h in high yields (58-95 %). Copyright

Full text of DOI:10.1002/ejoc.201200601

Job/Unit: O20601
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FULL PAPER
DOI: 10.1002/ejoc.201200601
Highly Efficient Synthesis of Multisubstituted Furans through Cupric Halide-
Mediated Intramolecular Halocyclization of 1-(1-Alkynyl)cyclopropyl Ketones
Mei Zhu,[a] Wei-Jun Fu,*[a] Chen Xu,[a] Guang-Long Zou,[b] Zhi-Qiang Wang,[a] and
Bao-Ming Ji[a]
Keywords: Oxygen heterocycles / Cyclopropyl ketones / Copper / Halogenation / Cyclization
A convenient and efficient method for the synthesis of 3-
halofurans was developed by using a cascade reaction be-
tween 1-(1-alkynyl)cyclopropyl ketones and cupric halide.
Under mild reaction conditions, both 3-chloro- and 3-bromo-
furan derivatives were obtained in high yields. The reaction
involves consecutive multiple bond formations, including
C–O and C–Br bonds, with high regioselectivity. Mechanistic
aspects are described.
The CuX2-mediated intramolecular halocyclization of
nucleophiles,[12] such as oxygen,[13] nitrogen,[14] sulfur,[15] se-
lenium,[16] phosphorus,[17] and sp2-hybridized carbon,[18]
with alkynes or allenes has proven to be an effective method
for the syntheses of heterocyclic compounds. Many impor-
tant heterocycles, such as selenophenes, thiophenes, indoles,
phosphaisocoumarins, butenolides, azaanthraquinones, 5-
hydroxypyrrol-2(5H)-ones, benzo[b]thiophenes, and 2,5-di-
hydro[1,2]oxaphosphole 2-oxides have been synthesized on
the basis of this strategy. Meanwhile, 1-(1-alkynyl)cy-
clopropyl ketones have drawn much attention for their in-
creasing applications in the syntheses of highly substituted
furans and other cyclic compounds, using gold(I), cop-
per(I), or rhodium(I) complexes as catalysts.[19] Recently, we
reported the electrophilic cyclization of 1-(1-alkynyl)cy-
clopropyl ketones, using I+ or PhSe+ as the electrophilic
species, to afford the efficient syntheses of substituted iodo-
furans and chalcogenylfurans.[20] On the basis of the above
considerations and in the context of our efforts for de-
veloping new strategies toward heterocycles and related li-
braries,[21] we envisioned that the reaction of 1-(1-alkynyl)-
cyclopropyl ketones with CuX2 (X = Br and Cl) formed
bromo- and chlorofurans (see Scheme 1).
Introduction
Furans represent a class of heterocycles, which occur in
various natural products and biologically active com-
pounds.[1] Moreover, they are extensively used as important
reaction intermediates in the preparation of a variety of
heterocyclic and acyclic compounds.[2] In particular, halo-
furans are of special interest, because the halogen atom pro-
vides an opportunity for further functionalization through
transition-metal-catalyzed reactions to form a variety of C–
C, C–N, or C–S bonds, and halofurans also serve as build-
ing blocks in combinatorial chemistry.[3] As a consequence,
a number of efficient and selective methods have been de-
veloped to synthesize them.[4] Among the many methods
developed in past years, the most common synthetic
method for the construction of halofurans is the intramo-
lecular electrophilic cyclization of functionally substituted
alkynes, which includes the iodocyclizations of 3-alkyne-
1,2-diols,[5] 2,4-dialkenyl-1,3-dicarbonyls,[6] propargylic oxi-
rane,[7] 1,4-disubstituted but-3-yn-1-ones,[8] 2-(1-alkynyl)-
alk-2-en-1-ones,[9] and (Z)-1,4-disubstitutedbut-1-en-3-ynyl
acetates.[10] However, the chlorocyclization and bromocycli-
zation reactions are rarely reported, most likely because the
stability of the corresponding halonium intermediates de-
crease in the order I Ͼ Br Ͼ Cl.[11] Thus, continuous inter-
est has been directed to the development of new and ef-
ficient syntheses for chloro- and bromofurans.
[a] College of Chemistry and Chemical Engineering,
Luoyang Normal University,
Luoyang 471022, P. R. China
Fax: +86-379-69810261
E-mail: wjfu@lynu.edu.cn
[b] School of Chemistry and Environmental Science,
Guizhou University for Nationalities,
Guiyang 550025, P. R. China
Scheme 1. CuX2-mediated halocyclization of 1-(1-alkynyl)cy-
clopropyl ketones.
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200601.
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M. Zhu, W.-J. Fu, C. Xu, G.-L. Zou, Z.-Q. Wang, B.-M. Ji
FULL PAPER
groups were well tolerated to form the corresponding prod-
ucts in moderate to good yields. The procedure seemed in-
sensitive to the electronic nature of the substituents on the
aromatic ring. For example, cyclopropyl ketones 1 with
electron-withdrawing groups on the aromatic ring such as
para-chloro, -bromo, and -fluoro substituents gave the cor-
responding 3-halofurans in good yields (Table 2, Entries 3–
8). Substrates with a strong electron-donating methoxy
group at the para and meta positions of the aromatic ring
also provided 2e, 3e, 2f, and 3f in excellent yields (Table 2,
Entries 9–12). However, when a bulky 1-naphthyl group
was used as in the case of 1i, the desired products were
obtained in the slightly lower yields of 76 and 72% (Table 2,
Entries 17 and 18, respectively). Additionally, good results
were also obtained with alkyl substituents as in 1g and 1h
(Table 2, Entries 13–16). The molecular structure of repre-
sentative product 2e was determined by X-ray crystallogra-
phy (Figure 1).[22]
Results and Discussion
Our initial study began with the reaction of phenyl[1-(2-
phenylethynyl)cyclopropyl]methanone (1a), NBS (N-bro-
mosuccinimide, 1.0 equiv.), MeOH (10.0 equiv.), and
K2CO3 (1.0 equiv.) in CH2Cl2 at room temperature. Unfor-
tunately, NBS did not afford any furan product (Table 1,
Entry 1). When the reaction was performed with CuBr2
(2.5 equiv.), bromofuran 2a was obtained in 40% yield
along with a trace amount of 4a (Table 1, Entry 2). Con-
sidering the competing reactions between MeO– and Br–,
we then tried to use MeOH as the solvent. However, 2a was
again isolated as the major product (Table 1, Entry 3). In
the absence of MeOH, bromofuran 2a was synthesized in
60% yield within 12 h (Table 1, Entry 4). Further investiga-
tion showed that the reaction temperature and solvent were
important. We found that using DMSO (dimethyl sulfoxide)
as the solvent at an elevated reaction temperature (90 °C)
could shorten the reaction time, and the yield showed mod-
erate improvement (Table 1, Entry 5). To our delight, by
employing CH3CN as the solvent, 2a was obtained in 92%
yield (Table 1, Entry 6). Reducing the amount of CuBr2
(1.0 equiv.) led to a decrease in the chemical yield of 2a
(Table 1, Entry 7). Solvents such as DMF (dimethylform-
amide), THF (tetrahydrofuran), and toluene were found to
be less effective (Table 1, Entries 8–10). Additionally, under
similar reaction conditions, CuCl2 was used to generate
chlorofuran 3a in 90% yield (Table 1, Entry 11).
Table 2. CuX2-mediated halocyclization of 1 to halofurans.[a]
Entry
R1
R2
X
Yield [%][b]
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Cl
Br
Br
Cl
Br
2a, 92
3a, 90
2b, 88
3b, 74
2c, 86
3c, 80
2d, 78
3d, 73
2e, 93
3e, 95
2f, 90
3f, 89
2g, 91
3g, 90
2h, 90
3h, 92
2i, 76
3i, 72
2j, 84
3j, 88
2k, 93
3k, 86
2l, 87[c]
2m, 73
3m, 65
Table 1. CuX2-mediated halocyclization of 1a under various condi-
tions.[a]
4-ClC6H4
4-ClC6H4
4-BrC6H4
4-BrC6H4
4-FC6H4
4-FC6H4
4-CH3OC6H4
4-CH3OC6H4
3-CH3OC6H4
3-CH3OC6H4
nPr
nPr
C2H5
C2H5
1-naphthyl
1-naphthyl
4-ClC6H4
4-ClC6H4
C6H5
C6H5
C6H5
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
Entry CuX2
Solvent
T
t
[h]
Yield [%][b]
[°C]
2a
4a
1
2
none[c] CH2Cl2
r.t.
r.t.
r.t.
r.t.
90
90
90
90
90
90
90
24
12
12
12
3
1
1
1
3
3
1
0
40
35
60
[d]
CuBr2
CH2Cl2
trace
trace
3
4
5
6
CuBr2 CH3OH
CuBr2 CH2Cl2
CuBr2 DMSO
CuBr2 CH3CN
CuBr2 CH3CN
C6H5
82
4-CH3C6H4
4-CH3C6H4
2-CH3C6H4
2-CH3C6H4
4-CH3OC6H4
hexyl
92
7
43[e]
75
8
9
CuBr2
CuBr2
DMF
THF
68
70
90
10
11
CuBr2 toluene
CuCl2 CH3CN
4-CH3C6H4
4-CH3C6H4
4-CH3C6H4
hexyl
TMS
[d]
–
[a] Reagents and conditions: 1a (0.5 mmol), CuX2 (2.5 equiv.), sol-
vent (5 mL). [b] Isolated yield. [c] Reactions were performed using
1a (0.5 mmol), NBS (2.5 equiv.), MeOH (10 equiv.), and K2CO3
(1.0 equiv.). [d] MeOH (10 equiv.) and K2CO3 (1.0 equiv.) were
added. [e] CuBr2 (1.0 equiv.) was used.
[a] Reactions were performed using 1 (0.5 mmol) and CuX2
(2.5 equiv.) in CH3CN (5 mL) at 90 °C. [b] Isolated yield. [c] Reac-
tion was performed at room temperature. [d] A complex reaction
mixture was obtained.
To establish the scope of this halocyclization protocol,
Then, we elucidated the scope of the reaction by examin-
we tested a wide range of 1-(1-alkynyl)cyclopropyl ketones ing the effect of various R2 groups on the alkyne moiety.
(Table 2). First, the effect of various groups on the aromatic Substrates bearing para-methyl and -methoxy groups were
ring R1 was examined. As expected, various common func- subjected to the reaction conditions, and the corresponding
tionalities such as the chloro, bromo, fluoro, and methoxy products were obtained in moderate to excellent yields
2
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Synthesis of Multisubstituted Furans through Intramolecular Halocyclization
curred at the more substituted position of the cyclopropane
ring in all cases. However, when CuCl2 was used under the
same conditions, no desired product was obtained.
The generality of the method was also investigated by
using 1-phenylethynyl-bicyclo[4.1.0]heptan-2-one (1ab) un-
der the optimized conditions (Scheme 2). Fortuitously, the
expected products 2ab and 3ab were obtained in good
yields.
Scheme 2. Reaction between 1ab and CuX2.
The utility of the 3-bromofurans, produced by this chem-
istry, as useful synthetic intermediates for further elabora-
tion was briefly investigated. For example, 2m was success-
fully treated with 1-ethynyl-4-methylbenzene, and product 6
was obtained in 67% yield (Scheme 3).
Figure 1. X-ray crystal structure of 2e.
(Table 2, Entries 19, 20, and 23). The alkyne with the ortho-
methyl aromatic group was also a good substrate for this
transformation, and the desired 3-halofurans were obtained
in 93% and 86% yields, respectively (Table 2, Entries 21
and 22). Besides the different aromatic substituted alkynes,
we employed aliphatic and functionalized alkynes as well.
In contrast, the yields were lower than the yields with the
aromatic alkynes (Table 2, Entries 24 and 25). The use of
the trimethylsilylalkyne, however, gave no product, and the
reaction led mainly to degradation (Table 2, Entry 26).
Scheme 3. Sonogashira coupling reaction of 2m.
On the basis of the above results, a plausible mechanism
Following the successful halocyclization of 1-(1-alkynyl)- for the formation of 2 and 3 is depicted in Scheme 4. First,
cyclopropyl ketones, we decided to examine 2-substituted 1- the CuX2 species coordinates to the triple bond to generate
(1-alkynyl)cyclopropyl ketones to expand the scope of this intermediate A, which enhances the electrophilicity of the
methodology (Table 3). In general, the reaction of 2-substi- alkyne. The anti attack of the oxygen on the activated triple
tuted 1-(1-alkynyl)-cyclopropyl ketones with CuBr2 resulted bond leads to the formation of intermediate B, which can
in relatively lower yields (Table 3, Entries 1–5). This may be attacked by X– in a regioselective homo-Michael-type
be because of the steric effect of the phenyl group on the addition to give intermediate C. A reductive elimination re-
cyclopropane ring. Interestingly, nucleophilic addition oc- action of C provides 3-halofurans 2 or 3 and Cu0. The Cu0
can be oxidized by CuX2 to produce CuX.
Table 3. CuX2-mediated halocyclization of 2-substituted 1-(1-alk-
ynyl)cyclopropyl ketones.[a]
Entry
R1
R2
X
Yield [%][b]
1
2
3
4
5
6
7
C6H5
C6H5
C6H5
C6H5
n-C4H9
C6H5
C6H5
C6H5
4-CH3OC6H4
4-CH3C6H4
4-ClC6H4
C6H5
C6H5
4-CH3OC6H4
Br
Br
Br
Br
Br
Cl
Cl
4a, 65
4b, 72
4c, 70
4d, 58
4e, 67
N. R.[c]
N. R.[c]
Scheme 4. Plausible reaction mechanism.
Conclusions
[a] Reactions were performed using 2-substituted 1-(1-alkynyl)cy-
clopropyl ketone (0.5 mmol) and CuX2 (2.5 equiv.) in CH3CN
(5 mL) at 90 °C. [b] Isolated yield. [c] N. R. = no reaction.
In conclusion, an efficient process for the synthesis of 3-
halofurans was developed by the cascade cyclization–ad-
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M. Zhu, W.-J. Fu, C. Xu, G.-L. Zou, Z.-Q. Wang, B.-M. Ji
FULL PAPER
= 3.14–3.16 (t, J = 8.0 Hz, 2 H), 3.72–3.76 (t, J = 8.0 Hz, 2 H),
7.31–7.45 (m, 5 H), 7.61–7.63 (d, J = 8.0 Hz, 2 H), 7.95–7.97 (d, J
= 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.8,
146.6, 134.2, 129.3, 129.2, 128.8, 128.7, 128.3, 127.0, 125.2, 118.7,
114.4, 42.3, 27.8 ppm. MS: m/z (%) = 350 (100) [M]+. C18H13Cl3O
(351.65): calcd. C 61.48, H 3.73; found C 61.42, H 3.95.
dition–reductive elimination reactions of 1-(1-alkynyl)cy-
clopropyl ketones in the presence of cupric halide. The reac-
tion involves consecutive multiple bond formations, includ-
ing C–O and C–Br bonds, with high regioselectivity. This
process shows considerable synthetic advantages in terms
of product diversity, mild reaction conditions, simplicity of
the reaction procedure, and good-to-excellent yields. Fur-
ther studies to elucidate the precise mechanism of this reac-
tion and to extend the scope of its synthetic utility are in
progress in our laboratory.
3-Bromo-4-(2-bromoethyl)-5-(4-bromophenyl)-2-phenylfuran
(2c):
1
Colorless solid, m.p. 135–136 °C. H NMR (400 MHz, CDCl3): δ
= 3.22–3.26 (t, J = 8.0 Hz, 2 H), 3.54–3.58 (t, J = 8.0 Hz, 2 H),
7.33–7.36 (m, 1 H), 7.42–7.46 (m, 2 H), 7.53–7.59 (m, 4 H), 7.99–
8.01 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
148.1, 148.0, 132.2, 129.4, 129.2, 128.7, 128.5, 127.3, 125.7, 122.4,
121.0, 100.9, 29.7, 29.0 ppm. MS: m/z (%) = 484 (100) [M]+.
C18H13Br3O (485.01): calcd. C 44.58, H 2.70; found C 44.66, H
2.56.
Experimental Section
General Remarks: The chemicals were obtained from commercial
suppliers and used without further purification. 1-(1-Alkynyl)cy-
clopropyl ketones 1a–1l were prepared as described previously.[19a]
1H and 13C NMR spectroscopic data were measured in CDCl3 and
recorded with a Bruker Avance-400 spectrometer (400 MHz for 1H
NMR, 100 MHz for 13C NMR), using TMS as the internal stan-
dard. EI-MS were determined with an HP5989B mass spectrome-
ter. Elemental analyses were performed with an EA-1110 instru-
ment. Melting points were measured with a microscopic apparatus.
2-(4-Bromophenyl)-4-chloro-3-(2-chloroethyl)-5-phenylfuran
(3c):
1
Colorless solid, m.p. 128–130 °C. H NMR (400 MHz, CDCl3): δ
= 3.14–3.18 (t, J = 8.0 Hz, 2 H), 3.72–3.76 (t, J = 8.0 Hz, 2 H),
7.33–7.35 (m, 1 H), 7.42–7.56 (m, 6 H), 7.95–7.97 (d, J = 8.0 Hz,
2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.8, 146.6, 132.2,
129.3, 129.2, 128.8, 128.3, 127.3, 125.2, 122.4, 118.8, 114.4, 42.3,
27.7 ppm. MS: m/z (%) = 396 (100) [M]+. C18H13BrCl2O (396.11):
calcd. C 54.58, H 3.31; found C 54.47, H 3.53.
Typical Procedure for the CuBr2-Mediated Cyclization of 1-(1-Alk-
ynyl)cyclopropyl Ketones: To a solution of phenyl[1-(2-phenylethy-
nyl)cyclopropyl]methanone (1a, 0.5 mmol) in CH3CN (5 mL) was
added copper(II) bromide (2.5 equiv.). The resulting mixture was
stirred at 90 °C for 1 h, and then the reaction was quenched with
a saturated aqueous solution of NH4Cl. The mixture was then ex-
tracted with diethyl ether, and the combined organic layers were
dried with anhydrous MgSO4. The solvent was removed under re-
duced pressure, and the residue was purified by flash chromatog-
raphy on silica gel using hexane as the eluent to afford 2a as a
colorless solid. Compounds 2b–2l, 3a–3k, and 4a–4e were prepared
by the same method.
3-Bromo-4-(2-bromoethyl)-5-(4-fluorophenyl)-2-phenylfuran
(2d):
1
Colorless solid, m.p. 138–140 °C. H NMR (400 MHz, CDCl3): δ
= 3.20–3.24 (t, J = 8.0 Hz, 2 H), 3.54–3.58 (t, J = 8.0 Hz, 2 H),
7.12–7.16 (t, J = 8.0 Hz, 2 H), 7.31–7.35 (t, J = 8.0 Hz, 1 H), 7.41–
7.45 (t, J = 8.0 Hz, 2 H), 7.62–7.65 (t, J = 8.0 Hz, 2 H), 7.99–8.01
(d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 163.9,
161.4 (d, J = 248.0 Hz), 148.4, 147.8, 129.5, 128.7, 128.4, 127.91,
127.83 (d, J = 8.0 Hz), 126.60, 126.57 (d, J = 3.0 Hz), 125.7, 120.2,
116.27, 116.05 (d, J = 22.0 Hz), 100.8, 29.9, 29.0 ppm. MS: m/z (%)
= 424 (100) [M]+. C18H13Br2FO (424.10): calcd. C 50.98, H 3.09;
found C 51.21, H 3.26.
3-Chloro-4-(2-chloroethyl)-5-(4-fluorophenyl)-2-phenylfuran
(3d):
1
3-Bromo-4-(2-bromoethyl)-2,5-diphenylfuran (2a): Colorless solid,
m.p. 96–97 °C. 1H NMR (400 MHz, CDCl3): δ = 3.26–3.30 (t, J =
8.0 Hz, 2 H), 3.56–3.60 (t, J = 8.0 Hz, 2 H), 7.34–7.48 (m, 6 H),
7.67–7.69 (d, J = 8.0 Hz, 2 H), 8.02–8.04 (d, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 149.2, 147.8, 130.3, 129.7, 129.1,
128.7, 128.4, 128.3, 125.9, 125.7, 120.5, 100.9, 29.9, 29.1 ppm. MS:
m/z (%) = 406 (100) [M]+. C18H14Br2O (406.11): calcd. C 53.23, H
3.47; found C 53.47, H 3.30.
Colorless solid, m.p. 122–124 °C. H NMR (400 MHz, CDCl3): δ
= 3.16–3.20 (t, J = 8.0 Hz, 2 H), 3.75–3.78 (t, J = 8.0 Hz, 2 H),
7.14–7.18 (t, J = 8.0 Hz, 2 H), 7.32–7.35 (t, J = 8.0 Hz, 1 H), 7.43–
7.47 (t, J = 8.0 Hz, 2 H), 7.67–7.70 (t, J = 8.0 Hz, 2 H), 7.96–7.98
(d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
163.96, 161.48 (d, J = 248.0 Hz), 148.2, 146.4, 129.4, 128.8, 128.2,
128.0, 127.9, 127.6, 126.7, 125.8, 125.2, 118.0, 116.28, 116.06 (d, J
= 22.0 Hz), 114.2, 42.4, 27.8 ppm. MS: m/z (%) = 334 (100) [M]+.
C18H13Cl2FO (335.2): calcd. C 64.50, H 3.91; found C 64.63, H
3.81.
3-Chloro-4-(2-chloroethyl)-2,5-diphenylfuran (3a): Colorless solid,
m.p. 88–90 °C. 1H NMR (400 MHz, CDCl3): δ = 3.17–3.21 (t, J =
8.0 Hz, 2 H), 3.72–3.76 (t, J = 8.0 Hz, 2 H), 7.29–7.47 (m, 6 H),
7.68–7.70 (d, J = 8.0 Hz, 2 H), 7.97–7.99 (d, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 148.9, 146.3, 130.4, 129.4, 129.0,
128.7, 128.4, 128.1, 125.9, 125.2, 118.3, 114.3, 42.3, 27.8 ppm. MS:
m/z (%) = 316 (100) [M]+. C18H14Cl2O (317.21): calcd. C 68.15, H
4.45; found C 68.40, H 4.21.
3-Bromo-4-(2-bromoethyl)-5-(4-methoxyphenyl)-2-phenylfuran (2e):
1
Colorless solid, m.p. 116–117 °C. H NMR (400 MHz, CDCl3): δ
= 3.22–3.26 (t, J = 8.0 Hz, 2 H), 3.54–3.58 (t, J = 8.0 Hz, 2 H),
3.85 (s, 3 H), 6.98–7.00 (d, J = 8.0 Hz, 2 H), 7.30–7.45 (m, 3 H),
7.59–7.61 (d, J = 8.0 Hz, 2 H), 8.00–8.02 (d, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 159.8, 149.4, 147.2, 129.8, 128.6,
128.1, 127.5, 125.6, 123.1, 119.2, 114.5, 100.8, 55.5, 30.0, 29.1 ppm.
MS: m/z (%) = 436 (100) [M]+. C19H16Br2O2 (436.14): calcd. C
52.32, H 3.70; found C 52.54, H 3.93.
3-Bromo-4-(2-bromoethyl)-5-(4-chlorophenyl)-2-phenylfuran
(2b):
1
Colorless solid, m.p. 131–133 °C. H NMR (400 MHz, CDCl3): δ
= 3.22–3.25 (t, J = 8.0 Hz, 2 H), 3.53–3.57 (t, J = 8.0 Hz, 2 H),
7.32–7.45 (m, 5 H), 7.58–7.60 (d, J = 8.0 Hz, 2 H), 7.99–8.01 (d, J
= 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.1,
134.2, 129.4, 129.3, 128.7, 128.7, 128.5, 127.0, 125.7, 120.9, 100.9,
29.7, 29.0 ppm. MS: m/z (%) = 440 (100) [M]+. C18H13Br2ClO
(440.56): calcd. C 49.07, H 2.97; found C 49.15, H 3.11.
3-Chloro-4-(2-chloroethyl)-5-(4-methoxyphenyl)-2-phenylfuran (3e):
1
Colorless solid, m.p. 103–115 °C. H NMR (400 MHz, CDCl3): δ
= 3.03–3.07 (t, J = 8.0 Hz, 2 H), 3.58–3.62 (t, J = 8.0 Hz, 2 H),
3.80 (s, 3 H), 6.94–6.96 (d, J = 8.0 Hz, 2 H), 7.22–7.38 (m, 3 H),
7.59–7.63 (m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 159.2,
3-Chloro-4-(2-chloroethyl)-5-(4-chlorophenyl)-2-phenylfuran
Colorless solid, m.p. 108–110 °C. H NMR (400 MHz, CDCl3): δ
(3b): 149.2, 148.5, 131.3, 128.7, 127.3, 127.1, 125.7, 124.2, 119.7, 118.2,
1
114.5, 55.4, 43.1, 28.3 ppm. MS: m/z (%) = 346 (100) [M]+.
4
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/KAP1
Date: 10-07-12 16:45:37
Pages: 8
Synthesis of Multisubstituted Furans through Intramolecular Halocyclization
C19H16Cl2O2 (347.24): calcd. C 65.72, H 4.64; found C 65.83, H
4.90.
125.7, 122.9, 99.6, 30.4, 28.6 ppm. MS: m/z (%) = 456 (100) [M]+.
C22H16Br2O (456.17): calcd. C 57.92, H 3.54; found C 57.80, H
3.72.
3-Bromo-4-(2-bromoethyl)-5-(3-methoxyphenyl)-2-phenylfuran (2f):
1
Colorless solid, m.p. 117–118 °C. H NMR (400 MHz, CDCl3): δ
3-Chloro-4-(2-chloroethyl)-5-(naphthalen-1-yl)-2-phenylfuran (3i):
1
= 3.26–3.30 (t, J = 8.0 Hz, 2 H), 3.56–3.60 (t, J = 8.0 Hz, 2 H), Colorless solid, m.p. 89–90 °C. H NMR (400 MHz, CDCl3): δ =
3.86 (s, 3 H), 6.89–6.91 (d, J = 8.0 Hz, 1 H), 7.23–7.45 (m, 6 H),
8.01–8.03 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 160.0, 148.9, 147.7, 131.5, 130.1, 129.6, 128.6, 128.3, 125.7,
120.7, 118.3, 114.0, 111.4, 100.9, 55.5, 29.8, 29.1 ppm. MS: m/z (%)
= 436 (100) [M]+. C19H16Br2O2 (436.14): calcd. C 52.32, H 3.70;
found C 52.48, H 3.88.
2.98–3.01 (t, J = 8.0 Hz, 2 H), 3.62–3.65 (t, J = 8.0 Hz, 2 H), 7.30–
7.42 (m, 3 H), 7.52–7.61 (m, 4 H), 7.89–7.99 (m, 5 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 149.4, 147.1, 133.9, 132.3, 130.2,
129.6, 128.8, 128.7, 128.6, 128.1, 127.4, 127.0, 126.4, 125.7, 125.3,
125.2, 120.4, 113.4, 42.6, 27.6 ppm. MS: m/z (%) = 366 (100)
[M]+. C22H16Cl2O (367.27): calcd. C 71.95, H 4.39; found C 72.21,
H 4.30.
3-Chloro-4-(2-chloroethyl)-5-(3-methoxyphenyl)-2-phenylfuran (3f):
1
Colorless solid, m.p. 98–99 °C. H NMR (400 MHz, CDCl3): δ = 3-Bromo-4-(2-bromoethyl)-5-(4-chlorophenyl)-2-p-tolylfuran
(2j):
Colorless solid, m.p. 123–125 °C. H NMR (400 MHz, CDCl3): δ
= 2.38 (s, 3 H), 3.21–3.25 (t, J = 8.0 Hz, 2 H), 3.53–3.57 (t, J =
1
3.18–3.22 (t, J = 8.0 Hz, 2 H), 3.74–3.77 (t, J = 8.0 Hz, 2 H), 3.86
(s, 3 H), 6.89–6.91 (d, J = 8.0 Hz, 1 H), 7.25–7.43 (m, 6 H), 7.96–
7.98 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 8.0 Hz, 2 H), 7.23–7.25 (d, J = 8.0 Hz, 2 H), 7.40–7.42 (d, J =
160.1, 148.7, 146.3, 131.6, 130.1, 129.4, 128.7, 128.2, 125.2, 118.5,
8.0 Hz, 2 H), 7.58–7.60 (d, J = 8.0 Hz, 2 H), 7.88–7.90 (d, J =
118.3, 114.3, 113.9, 111.6, 55.5, 42.3, 27.8 ppm. MS: m/z (%) = 346
8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.3, 147.7,
(100) [M]+. C19H16Cl2O2 (347.24): calcd. C 65.72, H 4.64; found C 138.5, 134.1, 129.4, 129.2, 128.8, 126.9, 126.7, 125.7, 120.8, 100.2,
65.90, H 4.41.
29.7, 29.1, 21.5 ppm. MS: m/z (%) = 454 (100) [M]+. C19H15Br2ClO
(454.58): calcd. C 50.20, H 3.33; found C 50.45, H 3.51.
3-Bromo-4-(2-bromoethyl)-2-phenyl-5-propylfuran (2g): Colorless
1
oil. H NMR (400 MHz, CDCl3): δ = 0.94–0.98 (t, J = 8.0 Hz, 3 3-Chloro-4-(2-chloroethyl)-5-(4-chlorophenyl)-2-p-tolylfuran
(3j):
1
H), 1.67–1.72 (q, J = 8.0 Hz, 2 H), 2.60–2.63 (t, J = 8.0 Hz, 2 H),
2.92–2.95 (t, J = 8.0 Hz, 2 H), 3.45–3.49 (t, J = 8.0 Hz, 2 H), 7.24–
7.27 (t, J = 8.0 Hz, 1 H), 7.35–7.39 (t, J = 8.0 Hz, 2 H), 7.90–7.92
(d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.5,
Colorless solid, m.p. 107–108 °C. H NMR (400 MHz, CDCl3): δ
= 2.37 (s, 3 H), 3.12–3.16 (t, J = 8.0 Hz, 2 H), 3.71–3.74 (t, J =
8.0 Hz, 2 H), 7.22–7.24 (d, J = 8.0 Hz, 2 H), 7.38–7.40 (d, J =
8.0 Hz, 2 H), 7.59–7.61 (d, J = 8.0 Hz, 2 H), 7.82–7.84 (d, J =
146.8, 130.0, 128.5, 127.7, 125.2, 118.9, 98.7, 31.4, 28.7, 28.2 21.8, 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 147.4, 146.8,
13.9 ppm. MS: m/z (%) = 372 (100) [M]+. C15H16Br2O (372.09): 138.3, 134.0, 129.4, 129.2, 128.9, 126.9, 126.4, 125.1, 118.6, 113.6,
calcd. C 48.42, H 4.33; found C 48.30, H 4.48.
42.3, 27.8, 21.5 ppm. MS: m/z (%) = 364 (100) [M]+. C19H15Cl3O
(365.68): calcd. C 62.41, H 4.13; found C 62.63, H 4.32.
3-Chloro-4-(2-chloroethyl)-2-phenyl-5-propylfuran (3g): Colorless
1
oil. H NMR (400 MHz, CDCl3): δ = 0.96–0.99 (t, J = 8.0 Hz, 3 3-Bromo-4-(2-bromoethyl)-5-phenyl-2-o-tolylfuran (2k): Colorless
1
H), 1.68–1.74 (m, 2 H), 2.60–2.63 (t, J = 8.0 Hz, 2 H), 2.85–2.88 solid, m.p. 96–97 °C. H NMR (400 MHz, CDCl3): δ = 2.47 (s, 3
(t, J = 8.0 Hz, 2 H), 3.62–3.66 (t, J = 8.0 Hz, 2 H), 7.24–7.28 (m, H), 3.32–3.36 (t, J = 8.0 Hz, 2 H), 3.63–3.67 (t, J = 8.0 Hz, 2 H),
1 H), 7.37–7.41 (t, J = 8.0 Hz, 2 H), 7.87–7.89 (d, J = 8.0 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 152.4, 145.3, 129.8,
128.6, 127.5, 124.7, 116.8, 112.4, 43.4, 28.7, 27.1, 21.8, 13.9 ppm.
MS: m/z (%) = 282 (100) [M]+. C15H16Cl2O (283.19): calcd. C
63.62, H 5.69; found C 63.91.30, H 5.86.
7.29–7.35 (m, 3 H), 7.45–7.49 (t, J = 8.0 Hz, 2 H), 7.60–7.61 (d, J
= 4.0 Hz, 1 H), 7.67–7.69 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 149.9, 149.6, 137.8, 131.0, 130.5, 130.3,
129.5, 129.1, 128.8, 128.3, 125.8, 125.7, 119.39, 102.6, 30.0, 29.4,
20.9 ppm. MS: m/z (%) = 420 (100) [M]+. C19H16Br2O (420.14):
calcd. C 54.32, H 3.84; found C 54.49, H 3.62.
3-Bromo-4-(2-bromoethyl)-5-ethyl-2-phenylfuran (2h): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.27–1.30 (t, J = 8.0 Hz, 3 H), 3-Chloro-4-(2-chloroethyl)-5-phenyl-2-o-tolylfuran (3k): Colorless
1
2.68–2.74 (q, J = 8.0 Hz, 2 H), 2.95–2.99 (t, J = 8.0 Hz, 2 H), 3.49– solid, m.p. 90–92 °C. H NMR (400 MHz, CDCl3): δ = 2.46 (s, 3
3.53 (t, J = 8.0 Hz, 2 H), 7.25–7.31 (m, 1 H), 7.38–7.42 (t, J =
H), 3.20–3.24 (t, J = 8.0 Hz, 2 H), 3.76–3.80 (t, J = 8.0 Hz, 2 H),
8.0 Hz, 2 H), 7.92–7.94 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR 7.26–7.35 (m, 3 H), 7.42–7.45 (t, J = 8.0 Hz, 2 H), 7.57–7.59 (d, J
(100 MHz, CDCl3): δ = 153.7, 146.8, 130.1, 128.6, 127.8, 125.7, = 8.0 Hz, 1 H), 7.65–7.67 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR
118.2, 98.8, 31.6, 28.2, 20.3, 13.1 ppm. MS: m/z (%) = 358 (100) (100 MHz, CDCl3): δ = 149.3, 148.1, 137.5, 131.0, 130.6, 129.8,
[M]+. C14H14Br2O (358.07): calcd. C 46.96, H 3.94; found C 46.85,
H 4.09.
129.3, 129.0, 128.3, 125.7, 117.1, 115.3, 42.43, 28.0, 20.9 ppm. MS:
m/z (%) = 330 (100) [M]+. C19H16Cl2O (330.24): calcd. C 68.89, H
4.87; found C 68.63, H 4.71.
3-Chloro-4-(2-chloroethyl)-5-ethyl-2-phenylfuran (3h): Colorless oil.
1H NMR (400 MHz, CDCl3): δ = 1.26–1.30 (t, J = 8.0 Hz, 3 H), 3-Bromo-4-(2-bromoethyl)-2-(4-methoxyphenyl)-5-phenylfuran (2l):
1
2.65–2.69 (m, 2 H), 2.86–2.89 (t, J = 8.0 Hz, 2 H), 3.63–3.67 (t, J
Colorless solid, m.p. 105–106 °C. H NMR (400 MHz, CDCl3): δ
= 8.0 Hz, 2 H), 7.24–7.29 (m, 1 H), 7.38–7.42 (t, J = 8.0 Hz, 2 H), = 3.24–3.28 (t, J = 8.0 Hz, 2 H), 3.55–3.59 (t, J = 8.0 Hz, 2 H),
7.87–7.89 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 153.5, 145.3, 129.9, 128.6, 127.5, 124.7, 116.0, 112.5, 43.5, 27.1,
3.84 (s, 3 H), 6.95–6.97 (d, J = 8.0 Hz, 2 H), 7.32–7.36 (t, J =
8.0 Hz, 1 H), 7.43–7.47 (t, J = 8.0 Hz, 2 H), 7.65–7.67 (d, J =
20.2, 13.0 ppm. MS: m/z (%) = 268 (100) [M]+. C14H14Cl2O 8.0 Hz, 2 H), 7.94–7.96 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR
(269.17): calcd. C 62.47, H 5.24; found C 62.58, H 5.44.
(100 MHz, CDCl3): δ = 159.6, 148.5, 147.9, 130.4, 129.0, 128.2,
127.3, 125.8, 122.5, 120.4, 114.1, 99.4, 55.4, 29.9, 29.2 ppm. MS:
m/z (%) = 436 (100) [M]+. C19H16Br2O2 (436.14): calcd. C 52.32,
H 3.70; found C 52.53, H 3.85.
3-Bromo-4-(2-bromoethyl)-5-(naphthalen-1-yl)-2-phenylfuran (2i):
1
Colorless solid, m.p. 113–115 °C. H NMR (400 MHz, CDCl3): δ
= 3.03–3.06 (t, J = 8.0 Hz, 2 H), 3.44–3.48 (t, J = 8.0 Hz, 2 H),
7.33–7.43 (m, 4 H), 7.52–7.65 (m, 3 H), 7.84–8.04 (m, 5 H) ppm. 3-Bromo-4-(2-bromoethyl)-2-hexyl-5-p-tolylfuran (2m): Oil. 1H
13C NMR (100 MHz, CDCl3): δ = 149.7, 148.7, 133.5, 132.4, 130.2, NMR (400 MHz, CDCl3): δ = 0.87–0.92 (m, 3 H), 1.25–1.40 (m, 6
129.5, 128.8, 128.7, 128.7, 128.4, 127.9, 127.8, 127.5, 127.0, 126.3,
H), 1.64–1.68 (m, 2 H), 2.35 (s, 3 H), 2.62–2.66 (t, J = 7.2 Hz, 2
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5

Job/Unit: O20601
/KAP1
Date: 10-07-12 16:45:37
Pages: 8
M. Zhu, W.-J. Fu, C. Xu, G.-L. Zou, Z.-Q. Wang, B.-M. Ji
FULL PAPER
H), 2.92–2.96 (t, J = 7.2 Hz, 2 H), 3.46–3.50 (t, J = 7.2 Hz, 2 H), 3,5-Dibromo-5,6,7,8-tetrahydro-2-phenyl-4H-cyclohepta[b]furan
1
7.18–7.20 (d, J = 8.0 Hz, 2 H), 7.79–7.81 (d, J = 8.0 Hz, 2 H) ppm. (2ab): Oil. H NMR (400 MHz, CDCl3): δ = 1.66–1.69 (m, 1 H),
13C NMR (100 MHz, CDCl3): δ = 152.3, 147.0, 137.6, 129.2, 127.3, 2.00–2.10 (m, 2 H), 2.43–2.45 (m, 1 H), 2.75–2.85 (m, 3 H), 2.96–
125.2, 118.5, 98.0, 31.7, 31.4, 29.0, 28.5, 28.3, 26.8, 22.7, 21.4,
3.00 (m, 1 H), 4.10–4.15 (m, 1 H), 7.21–7.23 (d, J = 8.0 Hz, 1 H),
14.2 ppm. MS: m/z (%) = 428 (81) [M]+. C19H24Br2O (428.20): 7.34–7.38 (t, J = 8.0 Hz, 2 H), 7.51–7.56 (t, J = 8.0 Hz, 2 H) ppm.
calcd. C 53.29, H 5.65; found C 53.60, H 5.83.
13C NMR (100 MHz, CDCl3): δ = 152.9, 146.9, 135.9, 131.6, 128.6,
126.9, 125.6, 100.6, 41.4, 34.0, 28.3, 28.2, 24.7 ppm. MS: m/z (%)
= 370 (100) [M]+. C15H14Br2O (370.08): calcd. C 48.68, H 3.81;
found C 48.81, H 3.54.
3-Chloro-4-(2-chloroethyl)-2-hexyl-5-p-tolylfuran (3m): Oil. 1H
NMR (400 MHz, CDCl3): δ = 0.87–0.90 (m, 3 H), 1.31–1.36 (m, 6
H), 1.64–1.68 (m, 2 H), 2.35 (s, 3 H), 2.60–2.64 (t, J = 7.2 Hz, 2
H), 2.84–2.88 (t, J = 7.2 Hz, 2 H), 3.62–3.66 (t, J = 7.2 Hz, 2 H),
7.19–7.23 (d, J = 8.0 Hz, 2 H), 7.75–7.77 (d, J = 8.0 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 152.1, 145.5, 137.4, 129.3, 127.1,
124.7, 116.4, 111.7, 43.4, 31.7, 29.0, 28.5, 27.2, 26.7, 22.7, 21.4,
14.2 ppm. MS: m/z (%) = 338 (65) [M]+. C19H24Cl2O (339.30):
calcd. C 67.26, H 7.13; found C 67.43, H 6.95.
3-Bromo-4-(2-bromo-2-phenylethyl)-2,5-diphenylfuran (4a): Oil. 1H
NMR (400 MHz, CDCl3): δ = 3.52–3.58 (m, 1 H), 3.68–3.74 (m, 1
H), 5.32–5.36 (t, J = 7.6 Hz, 1 H), 7.19–7.20 (m, 3 H), 7.29–7.35
(m, 4 H), 7.39–7.42 (m, 4 H), 7.57–7.59 (d, J = 8.0 Hz, 2 H), 7.99–
8.02 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
149.7, 147.7, 140.9, 130.5, 129.7, 128.8, 128.63, 128.6, 128.5, 128.4,
128.2, 127.5, 126.5, 125.7, 119.9, 100.9, 52.7, 36.0 ppm. MS: m/z
(%) = 482 (78) [M]+. C24H18Br2O (482.20): calcd. C 59.78, H 3.76;
found C 60.05, H 3.49.
3,5-Dichloro-5,6,7,8-tetrahydro-2-phenyl-4H-cyclohepta[b]furan
1
(3ab): Oil. H NMR (400 MHz, CDCl3): δ = 1.66–1.99 (m, 3 H),
2.75–3.07 (m, 5 H), 4.26–4.31 (m, 1 H), 7.22–7.24 (d, J = 8.0 Hz,
1 H), 7.33–7.37 (t, J = 8.0 Hz, 2 H), 7.51–7.56 (t, J = 8.0 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 153.1, 146.9, 135.9,
131.6, 128.6, 126.9, 125.6, 115.9, 42.3, 34.8, 28.3, 28.2, 25.8 ppm.
MS: m/z (%) = 280 (100) [M]+. C15H14Cl2O (281.18): calcd. C
64.07, H 5.02; found C 64.28, H 5.35.
3-(2-Bromoethyl)-5-hexyl-2-p-tolyl-4-(2-p-tolylethynyl)furan (6): Oil.
1H NMR (400 MHz, CDCl3): δ = 0.77–0.81 (t, J = 8.0 Hz, 3 H),
1.38–1.40 (br. s, 6 H), 1.66–1.69 (m, 2 H), 2.28 (s, 3 H), 2.30 (s, 3
H), 2.58–2.61 (m, J = 7.2 Hz, 2 H), 2.67–2.70 (t, J = 7.6 Hz, 2 H),
3.39–3.43 (t, J = 7.6 Hz, 2 H), 7.02–7.04 (d, J = 8.0 Hz, 2 H), 7.07–
7.09 (d, J = 7.6 Hz, 2 H), 7.24–7.26 (d, J = 7.6 Hz, 2 H), 7.95–7.97
(d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 148.7,
130.4, 130.3, 128.9, 128.7, 128.1, 127.9, 127.3, 125.4, 124.0, 108.4,
100.2, 51.8, 40.5, 35.2, 29.6, 22.0, 14.1 ppm. MS: m/z (%) = 462
(86) [M]+. C22H22Br2O (462.21): calcd. C 57.17, H 4.80; found C
57.38, H 4.59.
3-Bromo-4-(2-bromo-2-phenylethyl)-2-(4-methoxyphenyl)-5-phen-
1
ylfuran (4b): Oil. H NMR (400 MHz, CDCl3): δ = 3.49–3.55 (m,
1 H), 3.66–3.72 (m, 1 H), 3.78 (s, 3 H), 5.32–5.36 (t, J = 7.6 Hz, 1
H), 6.92–6.94 (t, J = 8.4 Hz, 2 H), 7.18 (br. s, 3 H), 7.30 (br. s, 3
H), 7.36–7.40 (t, J = 8.0 Hz, 2 H), 7.55–7.57 (d, J = 7.2 Hz, 2 H),
7.91–7.93 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 159.5, 149.0, 147.8, 141.0, 130.6, 128.7, 128.54, 128.50, 128.1,
127.5, 127.2, 126.3, 122.5, 119.7, 114.0, 99.3, 55.4, 52.8, 35.9 ppm.
MS: m/z (%) = 512 (71) [M]+. C25H20Br2O2 (512.23): calcd. C
58.62, H 3.94; found C 58.81, H 3.76.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, characterization data, and 1H NMR
and 13C NMR spectra.
Acknowledgments
3-Bromo-4-(2-bromo-2-phenylethyl)-5-phenyl-2-p-tolylfuran (4c):
Oil. H NMR (400 MHz, CDCl3): δ = 2.32 (s, 3 H), 3.48–3.54 (m,
We are grateful to the National Natural Science Foundation of
China (Project Nos. 20902042 and 20902043) and the Foundation
of HeЈnan Educational Committee (No. 2010B150020).
1
1 H), 3.65–3.71 (m, 1 H), 5.31–5.35 (t, J = 7.2 Hz, 1 H), 7.13–7.19
(m, 5 H), 7.27–7.29 (m, 3 H), 7.35–7.39 (t, J = 7.2 Hz, 2 H), 7.54–
7.56 (d, J = 7.6 Hz, 2 H), 7.86–7.88 (d, J = 7.6 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 149.3, 147.9, 140.9, 138.0, 130.5,
129.3, 128.7, 128.5, 128.4, 128.1, 127.5, 126.9, 126.4, 122.6, 119.8,
100.2, 52.8, 35.9, 21.5 ppm. MS: m/z (%) = 496 (83) [M]+.
C25H20Br2O (496.23): calcd. C 60.51, H 4.06; found C 60.35, H
3.88.
[1] a) A. R. Katritzky, Advances in Heterocyclic Chemistry, Aca-
demic Press, New York, 1982; b) M. V. Sargent, F. M. Dean in
Comprehensive Heterocyclic Chemistry (Eds.: A. R. Katritzky,
C. W. Rees), Pergamon Press, New York, 1984, vol. 4, pp. 599–
656; c) K. Nakanishi, Natural Products Chemistry, Kodansha,
Tokyo, 1974; d) C. W. Bird, G. W. H. Cheeseman, Comprehen-
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3-Bromo-4-(2-bromo-2-phenylethyl)-2-(4-chlorophenyl)-5-phen-
1
ylfuran (4d): Oil. H NMR (400 MHz, CDCl3): δ = 3.46–3.52 (m,
1 H), 3.64–3.69 (m, 1 H), 5.27–5.31 (t, J = 7.6 Hz, 1 H), 7.16–7.18
(m, 3 H), 7.27–7.40 (m, 7 H), 7.53–7.55 (d, J = 7.6 Hz, 2 H), 7.88–
7.90 (d, J = 7.6 Hz, 2 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
149.9, 146.6, 140.9, 133.8, 130.2, 128.83, 128.81, 128.6, 128.5,
128.1, 127.5, 126.7, 126.4, 120.0, 101.4, 52.6, 35.9 ppm. MS: m/z
(%) = 516 (74) [M]+. C24H17Br2ClO (516.65): calcd. C 55.79, H
3.32; found C 55.58, H 3.60.
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1H NMR (400 MHz, CDCl3): δ = 0.99–1.02 (t, J = 7.2 Hz, 3 H),
1.44–1.51 (m, 2 H), 1.68–1.72 (m, 2 H), 2.85–2.88 (t, J = 7.6 Hz, 2
H), 3.35–3.40 (m, 1 H), 3.53–3.58 (m, 1 H), 5.02–5.06 (t, J = 7.6 Hz,
1 H), 7.38–7.44 (m, 5 H), 7.72–7.79 (m, 5 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 148.7, 130.4, 130.3, 128.9, 128.7, 128.1,
127.9, 127.3, 125.4, 124.0, 108.4, 100.2, 51.8, 40.5, 35.2, 29.6, 22.0,
14.1 ppm. MS: m/z (%) = 462 (86) [M]+. C22H22Br2O (462.21):
calcd. C 57.17, H 4.80; found C 57.38, H 4.59.
6
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Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20601
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Date: 10-07-12 16:45:37
Pages: 8
Synthesis of Multisubstituted Furans through Intramolecular Halocyclization
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Received: May 7, 2012
Published Online: ᭿
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
7

Job/Unit: O20601
/KAP1
Date: 10-07-12 16:45:37
Pages: 8
M. Zhu, W.-J. Fu, C. Xu, G.-L. Zou, Z.-Q. Wang, B.-M. Ji
FULL PAPER
Halofuran Synthesis
The selective synthesis of functionalized
furans by using the cupric halide-mediated
intramolecular halocyclization of 1-(1-alk-
ynyl)cyclopropyl ketones is described. Un-
der mild conditions, a series of 3-chloro-
and 3-bromofuran derivatives were formed
in 1 h in high yields (58–95%).
M. Zhu, W.-J. Fu,* C. Xu, G.-L. Zou,
Z.-Q. Wang, B.-M. Ji ....................... 1–8
Highly Efficient Synthesis of Multisubsti-
tuted Furans through Cupric Halide-Me-
diated Intramolecular Halocyclization of 1-
(1-Alkynyl)cyclopropyl Ketones
Keywords: Oxygen heterocycles / Cyclo-
propyl ketones / Copper / Halogenation /
Cyclization
8
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