Phosphane-mediated domino synthesis of tetrasubstituted furans from simple terminal activated olefins

Article abstract of DOI:10.1002/ejoc.201200945

Convenient and highly efficient syntheses of tetrasubstituted furans with flexible substituent patterns from simple and readily available starting materials have been developed. Under very mild conditions, with the mediation of stoichiometric nBu₃P, simple terminal activated olefins and acyl chlorides or anhydrides smoothly furnish tetrasubstituted furans in modest to excellent yields. This synthetic strategy features a flexible selection of substituent pattern and a C-acylation/O-acylation/C-acylation/intramolecular Wittig reaction multiple domino assembly sequence. Simplicity can give rise to flexibility and efficiency. Convenient and highly efficient syntheses of tetrasubstituted furans from simple terminal activated olefins through phosphane-mediated multiple domino assembly sequences (such as C-acylation/O-acylation/C-acylation/intramolecular Wittig reaction) have been achieved.

Full text of DOI:10.1002/ejoc.201200945

Job/Unit: O20945
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Date: 10-09-12 10:58:00
Pages: 10
FULL PAPER
DOI: 10.1002/ejoc.201200945
Phosphane-Mediated Domino Synthesis of Tetrasubstituted Furans from
Simple Terminal Activated Olefins
Jianfang Wang,[a] Rong Zhou,[a] Zheng-Rong He,[b] and Zhengjie He*[a]
Keywords: Polysubstituted furans / Activated olefins / Domino reactions / Oxygen heterocycles / Phosphanes
Convenient and highly efficient syntheses of tetrasubstituted
furans with flexible substituent patterns from simple and
readily available starting materials have been developed.
Under very mild conditions, with the mediation of stoichio-
metric nBu3P, simple terminal activated olefins and acyl
chlorides or anhydrides smoothly furnish tetrasubstituted fur-
ans in modest to excellent yields. This synthetic strategy fea-
tures a flexible selection of substituent pattern and a C-acyl-
ation/O-acylation/C-acylation/intramolecular Wittig reaction
multiple domino assembly sequence.
polysubstituted furans, the development of new synthetic
methods that allow facile assembly of polysubstituted fur-
ans under mild conditions from simple and readily available
starting materials remains an important objective.
Introduction
Polysubstituted furans are an important class of hetero-
cyclic compounds. Their importance stems primarily from
their ubiquity as structural components in naturally occur-
ring products and artificial pharmaceuticals,[1,2] and also
from their usefulness as synthetic building blocks.[3] Al-
though many classical and well-established methods have
proven very effective for the synthesis of furan derivatives,
efficient synthesis of polysubstituted furans with flexible
substituent patterns has long been a challenging goal.[4]
During the past decade, many transition-metal-catalyzed
annulations of alkynyl, allenyl, or cyclopropyl ketones or
other derivatives have provided powerful means of access
to diversely substituted furans.[5] Most of them, however,
are unable to provide furans with high flexibility in terms of
substituent patterns. Most recently, non-metal-mediated –
particularly phosphane-enabled – cyclizations have emerged
as new and efficient synthetic routes to polysubstituted fur-
ans.[6] Remarkably, a stoichiometric phosphane-mediated
domino synthetic strategy pioneered by Lin et al. has
proven to be highly effective for the synthesis of polysubsti-
tuted furans.[6b] Tetrasubstituted furans could be conve-
niently prepared from activated trisubstituted olefins
through an nBu3P-based O-acylation/intramolecular Wittig
reaction sequence [Scheme 1, Equation (1)]. Although sig-
nificant progress has been witnessed in the synthesis of
Scheme 1. Phosphane-mediated domino synthesis of tetrasubsti-
tuted furans.
As part of our ongoing efforts in exploring stoichiomet-
ric phosphane-mediated synthetic reactions, with particular
regard to phosphorus ylides generated in situ,[7] and also
[a] The State Key Laboratory of Elemento-Organic Chemistry and inspired by a successful sequential synthesis of polysubsti-
Department of Chemistry, Nankai University,
tuted furans through intramolecular Wittig reactions re-
94 Weijin Road, Tianjin 300071, People’s Republic of China
ported by Lin,[6b] we set out to investigate the feasibility of
Fax: +86-22-23501520
E-mail: zhengjiehe@nankai.edu.cn
Homepage: http://skleoc.nankai.edu.cn/professors/hezhengjie/
hezhengjie.htm
phosphane-triggered domino assembly of tetrasubstituted
furans from simple and readily available terminal activated
olefins [Scheme 1, Equation (2)]. The purpose of the utiliza-
tion of terminal activated olefins was to allow a more flexi-
ble selection of substituent pattern in the synthesis of tetra-
substituted furans.
[b] Department of Chemistry, Xiaogan University,
272 Jiaotong Road, Xiaogan 432000, People’s Republic of
China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200945.
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J. Wang, R. Zhou, Z.-R. He, Z. He
FULL PAPER
yields (Entries 1–6). The inferior yield in the case of 2d
could be attributed to the significant steric hindrance of the
ortho-chlorine substituent (Entry 4). Heteroaroyl chlorides
such as 2-furoyl chloride (2g) and 2-thenoyl chloride (2h)
were also effective, providing the corresponding polysubsti-
tuted furans 3ag and 3ah in modest yields (Entries 7, 8).
Variation of the alkyl group in acrylates 1 did not substan-
tially interfere with the formation of furan product. Methyl,
ethyl, and n-butyl acrylates 1b–d all delivered the expected
furan products with selected benzoyl chlorides in excellent
yields (Entries 9–14). Acrylonitrile (1e) also proved to be a
good activated olefin in the reaction. With representative
benzoyl chlorides 2, acrylonitrile (1e) smoothly gave the ex-
pected furans 3 in very good yields (Entries 15–17). Both
aliphatic and aromatic anhydrides 2Ј were found to be effec-
tive acylation agents, readily delivering alkyl- and aryl-sub-
stituted furans 3 in acceptable yields in their reactions with
acrylate 1a (Entries 18–20).
Results and Discussion
Our investigation started with a model reaction between
tert-butyl acrylate (1a, Table 1) and benzoyl chloride (2a).
Initial results (Entries 1–6) revealed that, under mild condi-
tions and in the presence of NEt3 in excess (2.25 mmol),
tetrasubstituted furan 3aa bearing 3- and 4-functional
groups was smoothly formed in modest yields from acrylate
1a (1.0 mmol) and benzoyl chloride (2a, 1.5 mmol) with me-
diation by nBu3P (0.6 mmol). The 1,4-dicarbonyl com-
pound 4 was also isolated as a byproduct in low yield in
each case (Entries 1–6). Other phosphanes such as PPh3,
Ph2PMe, and PhPMe2 were totally ineffective for the trans-
formation. Other bases such as DBU, DMAP, and K2CO3
were also screened: DBU and DMAP were not as effective
as NEt3, and K2CO3 did not work at all. The substrate
molar ratio of 1a/2a/phosphane/NEt3 was found to have a
significant impact on the yields both of 3aa and of 4 (En-
tries 7–10). When acrylate 1a was employed in excess with
regard to benzoyl chloride (2a), byproducts[8] such as 4 were
formed in appreciable yields (Entries 1–9). In contrast, the
use of benzoyl chloride (2a) in 20% excess relative to acry-
late 1a gratifyingly resulted in a 92% yield of 3aa (En-
try 10). A new and efficient phosphane-mediated synthesis
of tetrasubstituted furans from acrylates and acyl chlorides
had thus been achieved.
Table 2. Synthesis of tetrasubstituted furans 3 from olefins 1 and
acyl chlorides 2 or anhydrides 2Ј.[a]
Table 1. Brief survey of the model reaction conditions.[a]
Entry
EWG in 1
R in 2 or 2Ј
3 (yield [%][b]
)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
CO2Me (1b)
CO2Me (1b)
CO2Et (1c)
CO2Et (1c)
CO2nBu (1d)
CO2nBu (1d)
CN (1e)
Ph (2a)
3aa (92)
3ab (99)
3ac (99)
3ad (36)
3ae (97)
3af (80)
3ag (50)
3ah (48)
3bb (94)
3be (90)
3cb (98)
3ce (96)
3db (96)
3de (92)
3ea (96)
3eb (88)
3ee (99)
3aaЈ (40)
3abЈ (36)
3aa (48)
4-ClC6H4 (2b)
3-ClC6H4 (2c)
2-ClC6H4 (2d)
4-MeC6H4 (2e)
4-NO2C6H4 (2f)
2-furyl (2g)
Entry
Solvent
Substrate molar ratio[d]
3aa
4
2-thienyl (2h)
4-ClC6H4 (2b)
4-MeC6H4 (2e)
4-ClC6H4 (2b)
4-MeC6H4 (2e)
4-ClC6H4 (2b)
4-MeC6H4 (2e)
Ph (2a)
[%][e]
[%][e]
1
2
3
4
5
6
7
THF
CH2Cl2
toluene
hexanes
1,4-dioxane
CH3CN
THF
1.0:1.5:0.6:2.25
1.0:1.5:0.6:2.25
1.0:1.5:0.6:2.25
1.0:1.5:0.6:2.25
1.0:1.5:0.6:2.25
1.0:1.5:0.6:2.25
1.5:1.5:0.6:2.25
1.5:1.5:0.9:2.25
0.5:1.0:0.6:1.5
0.5:1.8:0.6:2.7
73
54
30
72
55
71
47
56
29
92
14
12
34
11
21
7
27
34
26
–
CN (1e)
4-ClC6H4 (2b)
4-MeC6H4 (2e)
Me (2Јa)
CN (1e)
8
THF
THF
THF
CO2tBu (1a)
CO2tBu (1a)
CO2tBu (1a)
9[f]
10
Et (2Јb)
Ph (2Јc)
[a] Typical conditions: a mixture of 1a/2a/phosphane/base in the
specified molar ratio was stirred in the solvent (2.0 mL) under N2
at room temp. for 24 h. [b] Other phosphanes such as PPh3,
Ph2PMe, and PhPMe2 were found ineffective. [c] Bases such as
DBU, DMAP, and K2CO3 were also screened but gave inferior re-
sults. [d] Refers to 1a/2a/phosphane/base. [e] Isolated yield. [f] By-
product tert-butyl 2,5-diphenylfuran-3-carboxylate (5) was isolated
in 13% yield (see ref.[8]).
[a] Optimized conditions: alkene 1 (0.5 mmol) and either acyl
chloride 2 or anhydride 2Ј (1.8 mmol) were added to THF (2.0 mL)
under N2 at room temp., followed by addition of PBu3 (0.6 mmol)
and NEt3 (2.7 mmol); the resulting mixture was stirred at room
temp. for 24 h. [b] Isolated yield based on 1.
The scope of the activated olefins 1 was further exam-
ined. Other electron-deficient olefins were also found to be
Under the optimized conditions, the substrate scopes good candidates in the reaction. Under the standard condi-
with respect to terminal activated olefins 1 and acylation tions with a modified substrate molar ratio, both diethyl
agents 2 were examined (Table 2). With use of tert-butyl maleate (1f, Scheme 2) and alkyl 2-acylacrylates 1g–i
acrylate (1a), a series of substituted benzoyl chlorides 2, (Scheme 3, Table 3) could produce tetrasubstituted furans
with the exception of o-chlorobenzoyl chloride (2d), readily in modest to excellent yields in their reactions with various
afforded the corresponding tetrasubstituted furans 3 in high acyl chlorides 2. With representative benzoyl chlorides 2,
2
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Domino Synthesis of Tetrasubstituted Furans
maleate 1f afforded symmetric tetrasubstituted furans 3fa– Table 3. Synthesis of tetrasubstituted furans 3 from olefins 1 and
acyl chlorides 2.[a]
fe in modest yields (Scheme 2). 2-Acylacrylates 1g–i can be
regarded as C-benzoylation derivatives of the correspond-
ing acrylates. Gratifyingly, the PBu3-mediated furan-form-
ing reactions between 1g–i and acyl chlorides 2b–j took
place smoothly, providing a facile synthetic route to tetra-
substituted furans such as 3gb–ie, bearing four different
substituents (Table 3). Other aromatic acyl chlorides 2, with
the exception of o-chlorobenzoyl chloride, afforded good
yields. With olefin 1g, both aliphatic acyl chlorides 2i,j and
anhydrides 2Јa,b readily afforded the corresponding furans
3gi and 3gj, but in inferior yields [Table 3, Entries 8 and
9 and Scheme 3, Equation (1)]. Under similar conditions,
however, styryl ketone 1j exclusively delivered trisubstituted
furan 3jb in 95% yield [Scheme 3, Equation (2)].[9] The for-
mation of 3jb is presumably through an O-acylation/intra-
molecular Wittig reaction sequence, just as disclosed in re-
cent work by Lin.[6c]
Time 3 (yield [%]
Entry
R1 in 1
R2 in 2
[b]
[h]
)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
C6H5 (1g)
C6H5 (1g)
4-ClC6H4 (2b)
3-ClC6H4 (2c)
2-ClC6H4 (2d)
4-MeC6H4 (2e)
24
13
22
13
3gb (88)
3gc (81)
3gd (30)
3ge (76)
3gf (69)
3gg (80)
3gh (76)
3gi (25)
3gj (14)
3hb (88)
3he (94)
3hg (86)
3ib (83)
3ie (82)
C6H5 (1g)
C6H5 (1g)
C6H5 (1g)
4-NO2C6H4 (2f) 15
C6H5 (1g)
2-furyl (2g)
2-thienyl (2h)
Me (2i)
13
9
C6H5 (1g)
C6H5 (1g)
24
48
16
14
18
10
12
C6H5 (1g)
Et (2j)
4-FC6H4 (1h)
4-FC6H4 (1h)
4-FC6H4 (1h)
4-MeOC6H4 (1i)
4-MeOC6H4 (1i)
4-ClC6H4 (2b)
4-MeC6H4 (2e)
2-furyl (2g)
4-ClC6H4 (2b)
4-MeC6H4 (2e)
[a] Conditions: alkene 1 (0.5 mmol) and acyl chloride 2 (1.2 mmol)
were added to THF (2.0 mL) under N2 at room temp., followed by
addition of PBu3 (0.6 mmol) and NEt3 (1.8 mmol); the resulting
mixture was stirred for the time specified. [b] Isolated yield based
on 1.
compounds provides effective access to substituted furans
by a Paal–Knorr process,[4a] byproduct 4 as a 1,4-dicarb-
onyl compound failed to give either tetrasubstituted furan
3aa or trisubstituted furan 5. In addition, byproduct 5
could not be converted into the tetrasubstituted furan 3aa
under the standard conditions by acylation either. Appar-
ently, compounds 4 and 5 were competitively formed by-
products and not intermediates in the formation of tetra-
substituted furan 3aa.
Scheme 2. Synthesis of tetrasubstituted furans 3 from diethyl male-
ate (1f).
Scheme 3. Polysubstituted furans 3 from other activated olefins.
The structures of compounds 3, 4, and 5 were identified
Scheme 4. Control experiments.
1
by H NMR, 13C NMR, and HRMS (ESI) measurements.
Compound 3aa was further confirmed by X-ray crystallo-
graphic analysis.
From the experimental results in this work, a multiple
domino process that accounts for the formation of tetrasub-
To allow better understanding of the nature of this stituted furans 3 is proposed. As shown in Scheme 5, nu-
nBu3P-mediated convergent synthesis of tetrasubstituted cleophilic addition of PBu3 to acrylate 1a could initially
furans 3, two control experiments were conducted generate a zwitterion A, which could undergo a C-acylation
(Scheme 4). Byproducts 4 and 5, isolated from the model reaction with acyl chloride 2 to give a phosphonium chlor-
reaction during the conditions survey (Table 1), were each ide B. In the presence of NEt3 as base, phosphonium salt B
treated with benzoyl chloride (2a) under the standard con- could be converted into a phosphonium enolate C, which
ditions. Although the cyclocondensation of 1,4-dicarbonyl could lead to a phosphonium chloride D through an O-
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J. Wang, R. Zhou, Z.-R. He, Z. He
FULL PAPER
acylation reaction with acyl chloride 2. Phosphonium salt pattern in the synthesis of polysubstituted furans. Further-
D could generate a phosphorus ylide E through the action more, this method provides easy access to 3,4-function-
of NEt3. Ylide E could undergo another C-acylation reac- alized furans, which often display important biological ac-
tion with 2 to give a phosphonium chloride F, which could tivities.[12] The introduction of functional groups at the 3-
subsequently be converted into an ylide G through the ac- and 4-positions of furan rings by classical synthetic meth-
tion of NEt3. Finally, ylide G could accomplish the domino ods is difficult because of the inherent properties of furans,
assembly of tetrasubstituted furan 3 through an intramolec- such as the regiopreference for the 2- and 5-positions in
ular Wittig reaction. Formation of the tetrasubstituted fur- electrophilic substitution.[4e] Future efforts in our labora-
ans 3 from acrylate 1a is therefore presumably through a tory will be directed towards further investigation of the
quadruple domino C-acylation/O-acylation/C-acylation/in- feasibility of this protocol in the construction of other het-
tramolecular Wittig reaction sequence (Scheme 5).
erocyclic structures.
Experimental Section
General: Unless otherwise noted, all reactions were carried out un-
der nitrogen and under anhydrous conditions. Solvents were puri-
fied by standard procedures prior to use. 1H and 13C NMR spectra
were recorded in CDCl3 with tetramethylsilane (TMS) as the in-
ternal standard. Column chromatography was performed on silica
gel (200–300 mesh) with a mixture of petroleum ether (60–90 °C)/
ethyl acetate as the eluent. 2-Acyl acrylates 1g–i were prepared by
the reported procedure.[13] CCDC-861370 (for 3aa) 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.ac.uk/data_request/cif.
Typical Procedure for the Synthesis of Tetrasubstituted Furans 3:
PBu3 (150 μL, 0.6 mmol) and Et3N (375 μL, 2.7 mmol) were se-
quentially added by microsyringe under N2 to a solution of the
activated olefin 1a (64 mg, 0.5 mmol) and acylation agent 2a
(253 mg, 1.8 mmol) in THF (2.0 mL). The resulting reaction mix-
ture was stirred at room temperature. After completion of the reac-
tion as monitored by TLC, water (10 mL) was added. The mixture
was extracted with CH2Cl2 (3ϫ10 mL). The combined organic lay-
ers were washed with saturated brine (10 mL) and dried with anhy-
drous sodium sulfate. After filtration, the solvent was removed in
a rotary evaporator under reduced pressure, and the residue was
subjected to column chromatographic isolation on silica gel with
elution with petroleum ether/ethyl acetate (20:1–40:1) to give furan
3aa (195 mg) in 92% yield. Other furans 3 were synthesized simi-
larly, under the conditions listed in Tables 2, 3, Schemes 2, 3.
Scheme 5. Proposed mechanism for the formation of furans 3 from
acrylate 1a.
Although verification of the above mechanism needs
more evidence, the formation of tetrasubstituted furans 3
from 2-acylacrylates 1g–i under the standard conditions
(Table 3) strongly implies that the C-acylation of the acti-
vated olefin 1a should be the first step in the quadruple
domino sequence. According to the proposed mechanism,
furans 3gb–ie are generated through a triple domino O-
acylation/C-acylation/intramolecular Wittig reaction se-
quence (Table 3), and furans 3fa–fe from diethyl maleate
(1f) are presumably formed through another C-acylation/O-
acylation/intramolecular Wittig reaction triple domino pro-
cess (Scheme 2). The formation of byproducts 4 and 5
(Table 1) could be also explained by this proposed mecha-
nism: 4 could be formed through a water-involving re-
ductive hydrolysis of the phosphonium salt F,[10,11] whereas
trisubstituted furan 5 could result from a competing intra-
molecular Wittig reaction of intermediate E (Scheme 5).
tert-Butyl 4-Benzoyl-2,5-diphenylfuran-3-carboxylate (3aa): tert-
Butyl acrylate (1a, 0.5 mmol, 73 μL) and benzoyl chloride (2a,
1.8 mmol, 209 μL) were employed in the typical procedure to give
1
the product 3aa (200 mg, 92%); white solid; m.p. 181–182 °C. H
NMR (400 MHz, CDCl3): δ = 7.93–7.98 (m, 4 H), 7.55–7.57 (m, 2
H), 7.49 (t, J = 7.4 Hz, 1 H), 7.36–7.43 (m, 5 H), 7.19–7.25 (m, 3
H), 1.08 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 192.0,
161.8, 155.4, 150.0, 137.6, 133.6, 129.6, 129.6, 129.1, 128.9, 128.8,
128.7, 128.7, 128.40, 128.3, 126.0, 121.9, 117.0, 82.3, 27.4 ppm.
HRMS (MALDI): calcd. for C28H24O4Na [M + Na]+ 447.1567;
found 447.1563.
Conclusions
tert-Butyl 4-(4-Chlorobenzoyl)-2,5-bis(4-chlorophenyl)furan-3-carb-
oxylate (3ab): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 4-
chlorobenzoyl chloride (2b, 1.8 mmol, 229 μL) were employed in
the typical procedure to give the product 3ab (260 mg, 96%); yellow
A general and convenient phosphane-mediated domino
synthesis of tetrasubstituted furans from simple terminal
activated olefins has been successfully developed. This syn-
thetic method involves a highly efficient multiple domino
sequence consisting of C-acylation, O-acylation, and intra-
molecular Wittig reaction as key unit steps. As demon-
strated in this work, the use of simple terminal activated
1
solid; m.p. 198–200 °C. H NMR (400 MHz, CDCl3): δ = 8.00 (d,
J = 8.7 Hz, 2 H), 7.92 (d, J = 8.7 Hz, 2 H), 7.53 (d, J = 8.7 Hz, 2
H), 7.46 (d, J = 8.7 Hz, 2 H), 7.44 (d, J = 8.7 Hz, 2 H), 7.30 (d, J
= 8.7 Hz, 2 H), 1.19 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 190.5, 161.3, 154.7, 149.1, 140.4, 136.0, 135.7, 135.1, 130.9,
olefins allows a more flexible selection of substituent 129.8, 129.2, 129.1, 128.6, 127.3, 127.2, 127.1, 121.9, 117.3, 82.9,
4
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Domino Synthesis of Tetrasubstituted Furans
27.5 ppm. HRMS (MALDI): calcd. for C28H21Cl3O4Na [M +
Na]+ 549.0398; found 549.0402.
82.1, 27.6 ppm. HRMS (MALDI): calcd. for C22H18O7Na [M +
Na]+ 417.0945; found 417.0940.
tert-Butyl 4-(3-Chlorobenzoyl)-2,5-bis(3-chlorophenyl)furan-3-carb-
oxylate (3ac): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 3-
chlorobenzoyl chloride (2c, 1.8 mmol, 231 μL) were employed in
tert-Butyl 2,5-Di(thien-2-yl)-4-(thien-2-ylcarbonyl)furan-3-carboxyl-
ate (3ah): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 2-thenoyl
chloride (2h, 1.8 mmol, 178 μL) were employed in the typical pro-
cedure to give the product 3ah (106 mg, 48%); oil. 1H NMR
the typical procedure to give the product 3ac (261 mg, 99%); yellow
1
solid; m.p. 110–111 °C. H NMR (400 MHz, CDCl3): δ = 8.04 (s, (400 MHz, CDCl3): δ = 8.10 (dd, J = 3.8, 1.0 Hz, 1 H), 7.70 (dd,
1 H), 7.98 (s, 1 H), 7.95 (t, J = 4.4 Hz, 2 H), 7.83 (d, J = 7.8 Hz, J = 4.0, 0.9 Hz, 1 H), 7.60 (dd, J = 3.8, 0.9 Hz, 1 H), 7.49 (dd, J
1 H), 7.67 (s, 1 H), 7.55 (d, J = 8.2 Hz, 1 H), 7.38–7.46 (m, 4 H),
= 5.0, 1.0 Hz, 1 H), 7.45 (dd, J = 4.7, 0.9 Hz, 1 H), 7.33 (dd, J =
7.22–7.29 (m, 2 H), 1.23 (s, 9 H) ppm. 13C NMR (100 MHz, 5.0, 0.9 Hz, 1 H), 7.16 (dd, J = 5.0, 3.9 Hz, 1 H), 7.09 (dd, J = 4.7,
CDCl3): δ = 190.1, 161.1, 154.0, 149.2, 138.8, 135.1, 134.8, 134.2,
133.7, 130.3, 130.1, 130.1, 130.1, 129.9, 129.6, 129.2, 129.1, 128.4,
127.6, 126.6, 126.0, 124.2, 122.4, 117.9, 83.0, 27.5 ppm.
C28H21Cl3O4 (527.83): calcd. C 63.71, H 4.01; found C 63.41, H
3.67.
4.0 Hz, 1 H), 7.02 (dd, J = 5.0, 3.8 Hz, 1 H), 1.25 (s, 9 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 182.0, 160.6, 149.9, 144.9, 144.2,
133.6, 133.5, 129.4, 129.2, 128.4, 127.6, 127.3, 126.8, 126.6, 126.1,
125.7, 119.3, 113.8, 81.4, 26.5 ppm. HRMS (MALDI): calcd. for
C22H18S3O4Na [M + Na]+ 465.0529; found 465.0527.
tert-Butyl 4-(2-Chlorobenzoyl)-2,5-bis(2-chlorophenyl)furan-3-carb-
oxylate (3ad): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 2-
chlorobenzoyl chloride (2d, 1.8 mmol, 229 μL) were employed in
the typical procedure to give the product 3ad (96 mg, 36%); yellow
solid; m.p. 118–120 °C. 1H NMR (400 MHz, CDCl3): δ = 7.66 (dd,
J = 7.6, 1.8 Hz, 1 H), 7.61 (dd, J = 7.4, 1.8 Hz, 1 H), 7.61 (td, J =
7.6, 1.8 Hz, 2 H), 7.36–7.42 (m, 2 H), 7.28–7.34 (m, 2 H), 7.25–
7.28 (m, 2 H), 7.18–7.24 (m, 2 H), 1.22 (s, 9 H) ppm. 13C NMR
Methyl
4-(4-Chlorobenzoyl)-2,5-bis(4-chlorophenyl)furan-3-carb-
oxylate (3bb): Methyl acrylate (1b, 0.5 mmol, 45 μL) and 4-
chlorobenzoyl chloride (2b, 1.8 mmol, 229 μL) were employed in
the typical procedure to give the product 3bb (227 mg, 94%); yellow
1
solid; m.p. 185–186 °C. H NMR (400 MHz, CDCl3): δ = 7.99 (d,
J = 8.4 Hz, 2 H), 7.87 (d, J = 8.4 Hz, 2 H), 7.55 (d, J = 8.4 Hz, 2
H), 7.46 (d, J = 8.4 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.31 (d, J
= 8.4 Hz, 2 H), 3.50 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3):
(100 MHz, CDCl3): δ = 188.4, 161.2, 153.4, 152.9, 137.1, 134.2, δ = 190.6, 162.6, 155.1, 149.7, 140.3, 136.2, 135.7, 135.3, 130.4,
134.0, 133.2, 132.5, 132.3, 132.2, 131.5, 131.0, 130.8, 129.7, 129.7, 129.7, 129.2, 129.1, 128.7, 127.3, 127.0, 126.8, 122.0, 115.6,
129.7, 128.8, 128.0, 126.4, 126.3, 126.2, 124.9, 119.1, 81.8, 51.8 ppm. HRMS (MALDI): calcd. for C25H15Cl3O4Na [M +
27.6 ppm. HRMS (MALDI): calcd. for C28H21Cl3O4Na [M +
Na]+ 506.9928; found 506.9926.
Na]+ 549.0398; found 549.0392.
Methyl 4-(4-Methylbenzoyl)-2,5-di-p-tolylfuran-3-carboxylate (3be):
tert-Butyl
4-(4-Methylbenzoyl)-2,5-di-p-tolylfuran-3-carboxylate Methyl acrylate (1b, 0.5 mmol, 45 μL) and p-toluoyl chloride (2e,
(3ae): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 4-toluoyl chlor-
ide (2e, 1.8 mmol, 238 μL) were employed in the typical procedure
to give the product 3ae (230 mg, 97%); white solid; m.p. 160–
162 °C. 1H NMR (400 MHz, CDCl3): δ = 7.84 (d, J = 8.2 Hz, 2
H), 7.79 (d, J = 8.1 Hz, 2 H), 7.41 (d, J = 8.2 Hz, 2 H), 7.15 (d, J
1.8 mmol, 238 μL) were employed in the typical procedure to give
the product 3be (189 mg, 90%); yellow solid; m.p. 185–186 °C. H
1
NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.0 Hz, 2 H), 7.85 (d,
J = 7.9 Hz, 2 H), 7.53 (d, J = 8.0 Hz, 2 H), 7.28 (d, J = 7.9 Hz, 2
H), 7.22 (d, J = 7.9 Hz, 2 H), 7.10 (d, J = 7.9 Hz, 2 H), 3.46 (s, 3
= 8.1 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 6.97 (d, J = 8.0 Hz, 2 H), 2.41 (s, 3 H), 2.37 (s, 3 H), 2.29 (s, 3 H) ppm. 13C NMR
H), 2.27 (s, 3 H), 2.24 (s, 3 H), 2.15 (s, 3 H), 1.06 (s, 9 H) ppm.
(100 MHz, CDCl3): δ = 192.1, 163.1, 155.9, 150.1, 144.2, 140.0,
13C NMR (100 MHz, CDCl3): δ = 191.8, 161.8, 155.4, 149.6, 144.3, 138.8, 135.2, 129.3, 129.3, 129.2, 129.0, 128.2, 126.2, 126.1, 125.8,
139.6, 138.6, 135.2, 129.6, 129.2, 129.2, 128.8, 128.2, 126.4, 126.2,
125.7, 121.4, 116.3, 81.9, 27.4, 21.6, 21.3, 21.1 ppm. HRMS
(MALDI): calcd. for C31H30O4Na [M + Na]+ 489.2036; found
489.2035.
121.39, 114.8, 51.4, 21.6, 21.4, 21.2 ppm. HRMS (MALDI): calcd.
for C28H24O4 [M]+ 424.1669; found 424.1667.
Ethyl 4-(4-Chlorobenzoyl)-2,5-bis(4-chlorophenyl)furan-3-carboxyl-
ate (3cb): Ethyl acrylate (1c, 0.5 mmol, 55 μL) and 4-chlorobenzoyl
chloride (2b, 1.8 mmol, 229 μL) were employed in the typical pro-
cedure to give the product 3cb (243 mg, 98%); white solid; m.p.
177–178 °C. 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.4 Hz,
2 H), 7.90 (d, J = 8.4 Hz, 2 H), 7.54 (d, J = 8.4 Hz, 2 H), 7.46 (t,
tert-Butyl
4-(4-Nitrobenzoyl)-2,5-bis(4-nitrophenyl)furan-3-carb-
oxylate (3af): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 4-nitro-
benzoyl chloride (2f, 1.8 mmol, 0.334 g) were employed in the typi-
cal procedure to give the product 3af (223 mg, 80%); yellow solid;
m.p. 179–180 °C. 1H NMR (400 MHz, CDCl3): δ = 8.38 (t, J = J = 8.4 Hz, 2 H), 7.44 (t, J = 8.4 Hz, 2 H),7.31 (d, J = 8.4 Hz, 2
8.6 Hz, 2 H), 8.36 (t, J = 8.6 Hz, 2 H), 8.30 (d, J = 8.6 Hz, 2 H),
H), 4.00 (q, J = 7.1 Hz, 2 H), 0.93 (t, J = 7.1 Hz, 3 H) ppm. 13C
8.23 (d, J = 8.6 Hz, 2 H), 8.18 (d, J = 8.6 Hz, 2 H), 7.79 (d, J = NMR (100 MHz, CDCl3): δ = 190.7, 162.1, 155.2, 149.4, 140.3,
8.6 Hz, 2 H), 1.22 (s, 9 H) ppm. 13C NMR (100 MHz, CDCl3): δ 136.2, 135.7, 135.2, 130.6, 129.8, 129.2, 129.1, 128.6, 127.2, 127.1,
= 189.3, 160.4, 156.4, 154.3, 150.9, 149.1, 148.4, 147.9, 141.1, 133.9,
133.5, 130.4, 129.5, 126.7, 124.4, 124.2, 123.7, 119.6, 84.2,
27.6 ppm. C28H21N3O10 (559.49): calcd. C 60.11, H 3.78, N 7.51;
found C 59.85, H 3.94, N 7.53.
126.9, 121.9, 115.8, 61.2, 13.4 ppm. HRMS (MALDI): calcd. for
C26H17Cl3O4Na [M + Na]+ 521.0085; found 521.0078.
Ethyl 4-(4-Methylbenzoyl)-2,5-di-p-tolylfuran-3-carboxylate (3ce):
Ethyl acrylate (1c, 0.5 mmol, 55 μL) and 4-toluoyl chloride (2e,
1.8 mmol, 238 μL) were employed in the typical procedure to give
the product 3ce (209 mg, 96%); white solid; m.p. 134–136 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 7.9 Hz, 2 H), 7.88 (d,
J = 7.9 Hz, 2 H), 7.53 (d, J = 7.9 Hz, 2 H), 7.28 (d, J = 7.9 Hz, 2
tert-Butyl
2,5-Di(furan-2-yl)-4-(furan-2-ylcarbonyl)furan-3-carb-
oxylate (3ag): tert-Butyl acrylate (1a, 0.5 mmol, 73 μL) and 2-furoyl
chloride (2g, 1.8 mmol, 178 μL) were employed in the typical pro-
cedure to give the product 3ag (100 mg, 50%); oil. 1H NMR
(400 MHz, CDCl3): δ = 7.60 (dd, J = 16.0, 6.7 Hz, 3 H), 7.45 (s, 1 H), 7.23 (d, J = 7.9 Hz, 2 H), 7.10 (d, J = 7.9 Hz, 2 H), 3.97 (q, J
H), 7.13 (s, 1 H), 6.87 (d, J = 3.1 Hz, 1 H), 6.55–6.58 (m, 2 H),
6.45 (d, J = 1.4 Hz, 1 H), 1.29 (s, 9 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 177.4, 160.9, 153.3, 147.1, 146.8, 144.0, 143.8, 143.5,
143.4, 143.2, 119.5, 119.1, 114.8, 114.2, 112.51, 112.0, 111.6, 110.4,
= 7.0 Hz, 2 H), 2.41 (s, 3 H), 2.38 (s, 3 H), 2.29 (s, 3 H), 0.90 (t, J
= 7.0 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 192.2,
162.7, 156.0, 149.9, 144.3, 139.9, 138.8, 135.3, 129.4, 129.3, 129.3,
128.9, 128.4, 126.2, 126.1, 125.8, 121.4, 114.9, 60.7, 21.7, 21.4, 21.2,
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O20945
/KAP1
Date: 10-09-12 10:58:00
Pages: 10
J. Wang, R. Zhou, Z.-R. He, Z. He
FULL PAPER
13.2 ppm. HRMS (MALDI): calcd. for C29H26O4Na [M + Na]+
461.1723; found 461.1719.
tert-Butyl 4-Acetyl-2,5-dimethylfuran-3-carboxylate (3aaЈ): tert-
Butyl acrylate (1a, 0.5 mmol, 73 μL) and acetic anhydride (2Јa,
1.8 mmol, 171 μL) were employed in the typical procedure to give
Butyl 4-(4-Chlorobenzoyl)-2,5-bis(4-chlorophenyl)furan-3-carboxyl-
ate (3db): n-Butyl acrylate (1d, 0.5 mmol, 72 μL) and 4-chlorobenz-
oyl chloride (2b, 1.8 mmol, 229 μL) were employed in the typical
procedure to give the product 3db (254 mg, 96%); yellow solid; m.p.
142–143 °C. 1H NMR (400 MHz, CDCl3): δ = 8.01 (d, J = 8.6 Hz,
2 H), 7.91 (d, J = 8.6 Hz, 2 H), 7.54 (d, J = 8.7 Hz, 2 H), 7.46 (d,
J = 8.7 Hz, 2 H), 7.44 (d, J = 8.7 Hz, 2 H),7.31 (d, J = 8.7 Hz, 2
H), 3.96 (t, J = 6.6 Hz, 2 H), 1.23–1.30 (m, 2 H), 1.03–1.12 (m, 2
H), 0.78 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 190.7, 162.2, 155.3, 149.3, 140.4, 136.2, 135.6, 135.2, 130.7,
129.9, 129.2, 129.2, 128.6, 127.2, 127.1, 126.9, 121.9, 115.8, 65.2,
30.1, 19.0, 13.5 ppm. HRMS (MALDI): calcd. for C28H21Cl3O4Na
[M + Na]+ 549.0398; found 549.0398.
1
the product 3aaЈ (47 mg, 40%); colorless oil. H NMR (400 MHz,
CDCl3): δ = 2.46 (s, 3 H), 2.43 (s, 3 H), 2.34 (s, 3 H), 1.55 (s, 9 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 197.1, 163.0, 156.1, 152.9,
122.8, 114.2, 81.5, 31.0, 28.1, 13.4, 12.8 ppm. HRMS (MALDI):
calcd. for C13H18O4Na [M + Na]+ 261.1097; found 261.1090.
tert-Butyl 2,5-Diethyl-4-propionylfuran-3-carboxylate (3abЈ): tert-
Butyl acrylate (1a, 0.5 mmol, 73 μL) and propionic anhydride (2Јb,
1.8 mmol, 232 μL) were employed in the typical procedure to give
1
the product 3abЈ (50 mg, 36%); colorless oil. H NMR (400 MHz,
CDCl3): δ = 2.88 (q, J = 7.6 Hz, 2 H), 2.75 (q, J = 7.3 Hz, 2 H),
2.66 (q, J = 7.5 Hz, 2 H), 1.53 (s, 9 H), 1.23 (t, J = 7.6 Hz, 3 H),
1.20 (t, J = 7.5 Hz, 3 H), 1.13 (t, J = 7.3 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 201.1, 163.0, 161.0, 156.1, 121.7, 113.1,
81.3, 36.8, 28.1, 21.0, 20.4, 12.6, 12.4, 8.2 ppm. HRMS (MALDI):
calcd. for C16H25O4 [M + H]+ 281.1747; found 281.1755.
Butyl 4-(4-Methylbenzoyl)-2,5-di-p-tolylfuran-3-carboxylate (3de):
n-Butyl acrylate (1d, 0.5 mmol, 72 μL) and 4-toluoyl chloride (2e,
1.8 mmol, 238 μL) were employed in the typical procedure to give
the product 3de (214 mg, 92%); white solid; m.p. 120–121 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.1 Hz, 2 H), 7.88 (d,
J = 8.0 Hz, 2 H), 7.51 (d, J = 8.1 Hz, 2 H), 7.27 (d, J = 8.1 Hz, 2
H), 7.22 (d, J = 8.0 Hz, 2 H), 7.09 (d, J = 8.1 Hz, 2 H), 3.93 (t, J
= 6.5 Hz, 2 H), 2.40 (s, 3 H), 2.37 (s, 3 H), 2.27 (s, 3 H), 1.20–1.27
(m, 2 H), 1.02–1.11 (m, 2 H), 0.74 (t, J = 7.3 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 192.1, 162.8, 156.1, 149.7, 144.3,
139.9, 138.7, 135.1, 129.5, 129.3, 129.3, 128.9, 128.4, 126.3, 126.1,
125.7, 121.3, 115.0, 64.7, 30.0, 21.6, 21.4, 21.2, 18.9, 13.5 ppm.
HRMS (MALDI): calcd. for C31H30O4Na [M + Na]+ 489.2036;
found 489.2033.
Diethyl 2,5-Diphenylfuran-3,4-dicarboxylate (3fa):[15] Diethyl male-
ate (1f, 0.5 mmol, 81 μL) and benzoyl chloride (2a, 1.2 mmol,
140 μL) were employed in the typical procedure to give the product
1
3fa (59 mg, 33%); colorless oil. H NMR (400 MHz, CDCl3): δ =
7.86 (d, J = 7.3 Hz, 4 H), 7.43 (m, 6 H), 4.35 (q, J = 7.1 Hz, 4 H),
1.34 (t, J = 7.1 Hz, 6 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
163.7, 153.2, 129.4, 128.9, 128.4, 127.3, 115.5, 61.4, 14.0 ppm.
Diethyl 2,5-Bis(4-chlorophenyl)furan-3,4-dicarboxylate (3fb): Di-
ethyl maleate (1f, 0.5 mmol, 81 μL) and 4-chlorobenzoyl chloride
(2b, 1.2 mmol, 153 μL) were employed in the typical procedure to
give the product 3fb (108 mg, 50%); white solid; m.p. 113–114 °C.
1H NMR (400 MHz, CDCl3): δ = 7.80 (d, J = 8.4 Hz, 2 H), 7.42
(d, J = 8.4 Hz, 2 H), 4.35 (q, J = 7.1 Hz, 2 H), 1.34 (t, J = 7.1 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 163.4, 152.4, 135.7,
128.8, 128.7, 127.2, 116.1, 61.6, 14.0 ppm. HRMS (MALDI):
calcd. for C22H18Cl2O5Na [M + Na]+ 455.0424; found 455.0423.
4-Benzoyl-2,5-diphenylfuran-3-carbonitrile (3ea):[14] Acrylonitrile
(1e, 0.5 mmol, 33 μL) and benzoyl chloride (2a, 1.8 mmol, 209 μL)
were employed in the typical procedure to give the product 3ea
(167 mg, 96%); white solid; m.p. 152–154 °C. 1H NMR (400 MHz,
CDCl3): δ = 8.12 (d, J = 8.0 Hz, 2 H), 7.88 (d, J = 8.0 Hz, 2 H),
7.52–7.59 (m, 6 H), 7.39 (t, J = 7.5 Hz, 2 H), 7.31 (d, J = 6.9 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 189.2, 159.0, 153.8,
136.3, 134.0, 130.8, 130.0, 129.9, 129.2, 128.7, 128.7, 127.8, 127.4,
127.3, 125.7, 122.1, 113.4, 94.2 ppm.
Diethyl 2,5-Bis(3-chlorophenyl)furan-3,4-dicarboxylate (3fc): Di-
ethyl maleate (1f, 0.5 mmol, 81 μL) and 3-chlorobenzoyl chloride
(2c, 1.2 mmol, 154 μL) were employed in the typical procedure to
give the product 3fc (110 mg, 51%); white solid; m.p. 72–73 °C. 1H
NMR (400 MHz, CDCl3): δ = 7.86 (s, 2 H), 7.75 (m, 2 H), 7.39
(m, 4 H), 4.37 (q, J = 7.1 Hz, 2 H), 1.36 (t, J = 7.2 Hz, 3 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 163.2, 151.9, 134.5, 130.2, 129.8,
129.6, 127.3, 125.5, 116.6, 61.7, 14.0 ppm. HRMS (MALDI):
calcd. for C22H18Cl2O5Na [M + Na]+ 455.0424; found 455.0421.
4-(4-Chlorobenzoyl)-2,5-bis(4-chlorophenyl)furan-3-carbonitrile
(3eb): Acrylonitrile (1e, 0.5 mmol, 33 μL) and 4-chlorobenzoyl
chloride (2b, 1.8 mmol, 229 μL) were employed in the typical pro-
cedure to give the product 3eb (198 mg, 88%); yellow solid; m.p.
181–182 °C. 1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.6 Hz,
2 H), 7.81 (d, J = 8.6 Hz, 2 H), 7.53 (d, J = 8.3, Hz, 2 H), 7.51 (d,
J = 8.3, Hz, 2 H), 7.41 (d, J = 8.6 Hz, 2 H), 7.33 (d, J = 8.6 Hz, 2
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 187.5, 158.1, 152.9,
141.0, 137.2, 136.6, 134.4, 131.2, 129.7, 129.3, 129.2, 128.6, 127.0,
125.9, 125.4, 122.1, 112.9, 94.5 ppm. HRMS (MALDI): calcd. for
C24H12Cl3NO2Na [M + Na]+ 473.9826; found 473.9824.
Diethyl 2,5-Di-p-tolylfuran-3,4-dicarboxylate (3fe): Diethyl maleate
(1f, 0.5 mmol, 81 μL) and 4-toluoyl chloride (2e, 1.2 mmol, 259 μL)
were employed in the typical procedure to give the product 3fe
1
(57 mg, 29%); white solid; m.p. 113–115 °C. H NMR (400 MHz,
CDCl3): δ = 7.75 (d, J = 8.2 Hz, 2 H), 7.25 (d, J = 8.2 Hz, 2 H),
4.34 (q, J = 7.1 Hz, 2 H), 1.34 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 163.9, 153.3, 139.6, 129.1, 127.3, 126.2,
61.3, 21.4, 14.0 ppm. HRMS (MALDI): calcd. for C24H24O5Na [M
+ Na]+ 415.1516; found 415.1523.
4-(4-Methylbenzoyl)-2,5-di-p-tolylfuran-3-carbonitrile (3ee): Acrylo-
nitrile (1e, 0.5 mmol, 33 μL) and 4-toluoyl chloride (2e, 1.8 mmol,
238 μL) were employed in the typical procedure to give the product
3ee (195 mg, 99%); yellow solid; m.p. 165–167 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.90 (d, J = 8.1 Hz, 2 H), 7.71 (d, J =
Ethyl 4-(4-Chlorobenzoyl)-5-(4-chlorophenyl)-2-phenylfuran-3-carb-
oxylate (3gb): 2-Acyl acrylate 1g (0.5 mmol, 102 mg) and 4-chloro-
8.0 Hz, 2 H), 7.39 (d, J = 8.1 Hz, 2 H), 7.22 (d, J = 8.0 Hz, 2 H), benzoyl chloride (2b, 1.2 mmol, 153 μL) were employed in the
7.11 (d, J = 8.0 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 2 H), 2.33 (s, 3 H),
2.29 (s, 3 H), 2.23 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ
= 189.0, 158.8, 153.2, 145.1, 141.1, 140.0, 133.9, 130.1, 129.8, 129.4,
129.3, 127.1, 125.6, 125.2 124.7, 121.5, 113.7, 93.3, 21.7, 21.5,
21.3 ppm. HRMS (MALDI): calcd. for C27H21NO2Na [M + Na]+
414.1465; found 414.1460.
typical procedure to give the product 3gb (204 mg, 88%); yellow
solid; m.p. 135–136 °C. 1H NMR (400 MHz, CDCl3): δ = 7.94 (dd,
J = 7.8, 16.8 Hz, 2 H), 7.84–7.80 (m, 2 H), 7.50–7.44 (m, 2 H), 7.39
(t, J = 6.0 Hz, 3 H), 7.37–7.30 (m, 2 H), 7.25–7.18 (m, 2 H), 3.91
(q, J = 7.1 Hz, 2 H), 0.85 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 190.8, 162.2, 156.4, 149.2, 140.2, 135.8,
6
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O20945
/KAP1
Date: 10-09-12 10:58:00
Pages: 10
Domino Synthesis of Tetrasubstituted Furans
135.0, 130.6, 130.1, 129.1, 129.1, 128.6, 128.5, 128.3, 127.1, 127.1,
121.9, 115.4, 61.1, 13.4 ppm. HRMS (MALDI): calcd. for
C26H18Cl2O4 [M]+ 464.0577; found 464.0583.
153.2, 146.8, 144.1, 143.8, 143.6, 129.9, 128.5, 128.4, 128.3, 120.0,
118.8, 114.9, 112.5, 111.6, 110.5, 61.0, 13.5 ppm. HRMS
(MALDI): calcd. for C22H16O6Na [M + Na]+ 399.0839; found
399.0840.
Ethyl 4-(3-Chlorobenzoyl)-5-(3-chlorophenyl)-2-phenylfuran-3-carb-
oxylate (3gc): 2-Acylacrylate 1g (0.5 mmol, 102 mg) and 3-chloro-
benzoyl chloride (2c, 1.2 mmol, 154 μL) were employed in the typi-
cal procedure to give the product 3gc (188 mg, 81%); yellow solid;
m.p. 60–62 °C. 1H NMR (400 MHz, CDCl3): δ = 8.04 (dd, J = 7.8,
1.7 Hz, 2 H), 7.97 (t, J = 1.7 Hz, 1 H), 7.81 (d, J = 7.8 Hz, 1 H),
7.68 (d, J = 1.7 Hz, 1 H), 7.62–7.47 (m, 4 H), 7.47–7.36 (m, 2 H),
7.33–7.21 (m, 2 H), 4.01 (q, J = 7.1 Hz, 2 H), 0.94 (t, J = 7.1 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 190.6, 162.1, 156.7,
148.9, 139.0, 135.2, 134.9, 133.6, 130.2, 130.2, 130.1, 130.1, 129.1,
129.0, 128.7, 128.5, 128.3, 127.5, 125.9, 124.1, 122.3, 115.4, 61.2,
13.4 ppm. HRMS (MALDI): calcd. for C26H18Cl2O4Na [M + Na]
Ethyl
2-Phenyl-5-(thien-2-yl)-4-(thien-2-ylcarbonyl)furan-3-carb-
oxylate (3gh): 2-Acylacrylate 1g (0.5 mmol, 102 mg) and 2-thenoyl
chloride (2h, 1.2 mmol, 119 μL) were employed in the typical pro-
cedure to give the product 3gh (155 mg, 76%); brown oil. 1H NMR
(400 MHz, CDCl3): δ = 8.05 (d, J = 6.6 Hz, 2 H), 7.69 (d, J =
4.8 Hz, 1 H), 7.59 (d, J = 3.1 Hz, 1 H), 7.45–7.50 (m, 4 H), 7.33
(d, J = 4.8 Hz, 1 H), 7.09 (t, J = 4.5 Hz, 1 H), 7.02 (t, J = 4.5 Hz,
1 H), 4.02 (q, J = 7.1 Hz, 2 H), 0.97 (t, J = 7.1 Hz, 3 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 183.1, 162.5, 155.4, 147.0, 145.0,
134.7, 134.2, 130.3, 129.9, 128.6, 128.4, 128.3, 128.3, 127.8, 127.2,
126.8, 120.5, 115.2, 61.1, 13.3 ppm. HRMS (MALDI): calcd. for
C22H16O4S2Na [M + Na]+ 431.0382; found 431.0380.
+
487.0474; found 487.0478.
Ethyl 4-(2-Chlorobenzoyl)-5-(2-chlorophenyl)-2-phenylfuran-3-carb-
oxylate (3gd): 2-Acylacrylate 1g (0.5 mmol, 102 mg) and 2-chloro-
benzoyl chloride (2d, 1.8 mmol, 153 μL) were employed in the t
ypical procedure to give the product 3gd (70 mg, 30%); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 7.2 Hz, 2 H), 7.54
(d, J = 7.6 Hz, 2 H), 7.42–7.46 (m, 4 H), 7.32 (d, J = 8.0 Hz, 2 H),
7.23–7.28 (m, 3 H), 7.12–7.20 (m, 2 H), 4.15 (q, J = 7.1 Hz, 2 H),
1.18 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
188.2, 163.6, 154.7, 152.9, 137.2, 133.9, 132.6, 132.4, 132.1, 131.1,
130.7, 130.5, 129.7, 128.6, 128.5, 127.8, 127.5, 126.3, 126.3, 126.3,
125.7, 114.7, 61.5, 13.7 ppm. HRMS (MALDI): calcd. for
C26H18Cl2O4Na [M + Na]+ 487.0474; found 487.0470.
Ethyl 4-Acetyl-5-methyl-2-phenylfuran-3-carboxylate (3gi): 2-Acyl-
acrylate 1g (0.5 mmol, 102 mg) and acetyl chloride (2i, 1.2 mmol,
85 μL) were employed in the typical procedure to give the product
3gi (34 mg, 25%); white solid; m.p. 35–37 °C. 1H NMR (400 MHz,
CDCl3): δ = 7.71 (d, J = 7.4 Hz, 2 H), 7.48–7.33 (m, 3 H), 4.35 (q,
J = 7.1 Hz, 2 H), 2.57 (s, 3 H), 2.44 (s, 3 H), 1.32 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.3, 164.8, 155.6,
152.1, 129.2, 129.0, 128.4, 126.9, 123.8, 113.9, 61.6, 30.1, 14.0,
13.9 ppm. HRMS (ESI): calcd. for C16H17O4 [M + H]+ 273.1121;
found 273.1117.
Ethyl 5-Ethyl-2-phenyl-4-propionylfuran-3-carboxylate (3gj): 2-
Acylacrylate 1g (0.5 mmol, 102 mg) and propionyl chloride (2j,
1.2 mmol, 105 μL) were employed in the typical procedure to give
the product 3gj (21 mg, 14%); white solid; m.p. 65–67 °C. 1H NMR
(400 MHz, CDCl3): δ = 7.74 (d, J = 7.7 Hz, 2 H), 7.48–7.33 (m, 3
H), 4.33 (q, J = 7.1 Hz, 2 H), 2.89 (q, J = 7.5 Hz, 3 H), 2.75 (q, J
= 7.2 Hz, 2 H), 1.31 (t, J = 7.5 Hz, 3 H), 1.30 (t, J = 7.2 Hz, 3 H)
1.17 (t, J = 7.2 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ = 198.3,
164.7, 159.08, 152.6, 129.2, 128.4, 128.4, 127.2, 122.8, 113.6, 61.5,
35.8, 21.2, 13.9, 12.5, 8.1 ppm. HRMS (ESI): calcd. for C18H21O4
[M + H]+ 301.1434; found 301.1435.
Ethyl
4-(4-Methylbenzoyl)-2-phenyl-5-p-tolylfuran-3-carboxylate
(3ge): 2-Acylacrylate 1g (0.5 mmol, 102 mg) and 4-toluoyl chloride
(2e, 1.2 mmol, 259 μL) were employed in the typical procedure to
give the product 3ge (161 mg, 76%); white solid; m.p. 129–130 °C.
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 7.2 Hz, 2 H), 7.88
(d, J = 8.1 Hz, 2 H), 7.53 (d, J = 8.1 Hz, 2 H), 7.41–7.49 (m, 3 H),
7.23 (d, J = 7.9 Hz, 2 H), 7.11 (d, J = 8.1 Hz, 2 H), 3.97 (q, J =
7.2 Hz, 2 H), 2.39 (s, 3 H), 2.30 (s, 3 H), 0.90 (t, J = 7.2 Hz, 3 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 192.1, 162.6, 155.6, 150.3,
144.4, 138.9, 135.2, 129.7, 129.5, 129.4, 129.4, 129.1, 128.4, 128.2,
126.1, 125.8, 121.4, 115.5, 60.8, 21.7, 21.2, 13.3 ppm. HRMS
(MALDI): calcd. for C28H24O4Na [M + Na]+ 447.1567; found
447.1562.
Methyl 4-(4-Chlorobenzoyl)-5-(4-chlorophenyl)-2-(4-fluorophenyl)-
furan-3-carboxylate (3hb): 2-Acylacrylate 1h (0.5 mmol, 104 mg)
and 4-chlorobenzoyl chloride (2b, 1.2 mmol, 153 μL) were em-
ployed in the typical procedure to give the product 3hb (206 mg,
88%); yellow solid; m.p. 159–160 °C. 1H NMR (400 MHz, CDCl3):
δ = 8.08–8.01 (m, 2 H), 7.88 (d, J = 8.5 Hz, 2 H), 7.56 (d, J =
8.6 Hz, 2 H), 7.44 (d, J = 8.5 Hz, 2 H), 7.31 (d, J = 8.6 Hz, 2 H),
7.19 (t, J = 8.6 Hz, 2 H), 3.49 (s, 3 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 190.8, 163.7 (J = 251.7 Hz), 162.6, 155.5, 149.4, 140.2,
135.8, 135.2, 130.7 (J = 8.6 Hz), 130.4, 129.2, 129.1, 127.2, 126.9,
124.8, 121.8, 115.6 (J = 21.9 Hz), 115.1, 51.7 ppm. HRMS (ESI):
calcd. for C25H16Cl2FO4 [M + H]+ 469.0404; found 469.0408.
Ethyl
4-(4-Nitrobenzoyl)-5-(4-nitrophenyl)-2-phenylfuran-3-carb-
oxylate (3gf): 2-Acylacrylate 1g (0.5 mmol, 102 mg) and 4-nitro-
benzoyl chloride (2f, 1.8 mmol, 223 mg) were employed in the
typical procedure to give the product 3gh (168 mg, 69%); brown
1
solid; m.p. 147–149 °C. H NMR (400 MHz, CDCl3): δ = 8.34 (d,
J = 8.7 Hz, 2 H), 8.21 (d, J = 8.8 Hz, 2 H), 8.15 (d, J = 8.7 Hz, 2
H), 8.05 (dd, J = 6.3, 3.1 Hz, 2 H), 7.79 (d, J = 8.8 Hz, 2 H), 7.54
(t, J = 3.1 Hz, 3 H), 4.02 (q, J = 7.1 Hz, 2 H), 0.96 (t, J = 7.1 Hz,
3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 190.1, 161.6, 158.0,
150.7, 148.0, 147.6, 141.5, 134.0, 130.8, 130.1, 128.9, 128.5, 128.0,
126.4, 124.3, 124.2, 124.1, 115.7, 61.5, 13.5 ppm. HRMS (ESI):
calcd. for C26H19N2O8 [M + H]+ 487.1136; found 487.1143.
Methyl
2-(4-Fluorophenyl)-4-(4-methylbenzoyl)-5-p-tolylfuran-3-
carboxylate (3he): 2-Acyl acrylate 1h (0.5 mmol, 104 mg) and 4-
toluoyl chloride (2e, 1.2 mmol, 259 μL) were employed in the typi-
cal procedure to give the product 3he (201 mg, 94%); white solid;
Ethyl
3-(Furan-2-ylcarbonyl)-5-phenyl-2,2Ј-bifuran-4-carboxylate
1
(3gg): 2-Acylacrylate 1g (0.5 mmol, 102 mg) and 2-furoyl chloride
(2g, 1.2 mmol, 119 μL) were employed in the typical procedure to
give the product 3gg (150 mg, 80%); brown solid; m.p. 104–105 °C.
1H NMR (400 MHz, CDCl3): δ = 8.03 (dd, J = 7.9, 1.6 Hz, 2 H),
m.p. 153–154 °C. H NMR (400 MHz, CDCl3): δ = 8.04–8.08 (m,
2 H), 7.84 (d, J = 7.9 Hz, 2 H), 7.52 (d, J = 7.9 Hz, 2 H), 7.24 (d,
J = 7.9 Hz, 2 H), 7.17 (t, J = 8.6 Hz, 2 H), 7.12 (d, J = 7.9 Hz, 2
H), 2.40 (s, 3 H), 2.31 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
7.61 (s, 1 H), 7.44–7.50 (m, 4 H), 7.18 (d, J = 3.5 Hz, 2 H), 6.91 δ = 192.00, 163.5 (J = 250.9 Hz), 163.1, 154.7, 150.5, 144.4, 139.1,
(d, J = 3.5 Hz, 2 H), 6.55 (dd, J = 3.5, 1.6 Hz, 1 H), 6.46 (dd, J =
3.5, 1.6 Hz, 1 H), 4.06 (q, J = 7.1 Hz, 2 H), 1.00 (t, J = 7.1 Hz, 3
H) ppm. 13C NMR (100 MHz, CDCl3): δ = 177.4, 162.6, 155.5,
135.2, 130.5 (J = 8.4 Hz), 129.4, 129.3, 125.9, 125.3, 125.2, 121.4,
115.4 (J = 21.9 Hz), 115.1, 51.5, 21.7, 21.3 ppm. HRMS (ESI):
calcd. for C27H22FO4 [M + H]+ 429.1497; found 429.14.97.
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O20945
/KAP1
Date: 10-09-12 10:58:00
Pages: 10
J. Wang, R. Zhou, Z.-R. He, Z. He
FULL PAPER
Methyl
5-(4-Fluorophenyl)-3-(furan-2-ylcarbonyl)-2,2Ј-bifuran-4-
NMR (100 MHz, CDCl3): δ = 162.8, 155.9, 152.1, 130.0, 129.9,
129.1, 128.8, 128.5, 128.0, 127.9, 123.9, 117.37, 108.2, 81.2,
28.2 ppm. HRMS (ESI): calcd. for C21H20O3Na [M + Na]+
343.1305; found 343.1306.
carboxylate (3hg): 2-Acylacrylate 1h (0.5 mmol, 104 mg) and 2-fu-
royl chloride (2g, 1.2 mmol, 119 μL) were employed in the typical
procedure to give the product 3hg (163 mg, 86%); yellow solid; m.p.
129–130 °C. 1H NMR (400 MHz, CDCl3): δ = 8.01–8.09 (m, 2 H),
7.61 (s, 1 H), 7.45 (s, 1 H), 7.15–7.20 (m, 2 H), 6.91 (d, J = 3.4 Hz,
1 H), 6.56 (dd, J = 3.6, 1.7 Hz, 1 H), 6.46 (dd, J = 3.6, 1.7 Hz, 1
H), 3.56 (s, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 177.2
163.6 (J = 251.1 Hz), 163.1, 154.7, 153.2, 146.9, 144.3, 143.9, 143.4,
130.6 (J = 8.6 Hz), 124.8, 119.9, 118.6, 115.5 (J = 21.9 Hz), 114.5,
112.5, 111.7, 110.8, 51.9 ppm. HRMS (ESI): calcd. for C21H13FO6
[M + H]+ 381.0769; found 381.0775.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of H and 13C NMR spectra for compounds 3, 4, and
5 and ORTEP drawing of the crystal structure for 3aa.
Acknowledgments
Financial support from the National Natural Science Foundation
of China (Grant nos. 20872063; 21072100; 21121002) is gratefully
acknowledged.
Ethyl 4-(4-Chlorobenzoyl)-5-(4-chlorophenyl)-2-(4-methoxyphenyl)-
furan-3-carboxylate (3ib): 2-Acylacrylate 1i (0.5 mmol, 117 mg) and
4-chlorobenzoyl chloride (2b, 1.2 mmol, 153 μL) were employed in
the typical procedure to give the product 3ib (205 mg, 83%); yellow
[1] a) F. M. Dean, Naturally Occurring Oxygen Ring Compounds,
Butterworths, London, 1963, pp. 1–28; b) D. M. X. Donnelly,
M. J. Meegan, in Comprehensive Heterocyclic Chemistry, vol. 4
(Ed.: A. R. Katrizky), Pergamon Press, New York, 1984,
pp. 657–712.
[2] a) J. K. Landquist, in Comprehensive Heterocyclic Chemistry,
vol. 1 (Ed.: A. R. Katrizky), Pergamon Press, New York, 1984,
pp. 144–184; b) S. Cacchi, J. Organomet. Chem. 1999, 576, 42.
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Y. Yang, Tetrahedron 1994, 50, 9583; c) H.-K. Lee, K.-F. Chan,
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Chem. 2005, 77, 139.
1
solid; m.p. 150–151 °C. H NMR (400 MHz, CDCl3): δ = 8.03 (d,
J = 8.8 Hz, 2 H), 7.91 (d, J = 8.5 Hz, 2 H), 7.54 (d, J = 8.6 Hz, 2
H), 7.43 (d, J = 8.6 Hz, 2 H), 7.29 (d, J = 8.6 Hz, 2 H), 7.01 (d, J
= 8.8 Hz, 2 H), 3.99 (q, J = 7.1 Hz, 2 H), 3.88 (s, 3 H), 0.92 (t, J
= 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 191.1,
162.3, 161.0, 156.8, 148.5, 140.1, 135.9, 134.8, 130.6, 130.2, 129.1,
129.0, 127.2, 127.0, 121.8, 121.2, 114.1, 113.7, 60.9, 55.3, 13.4 ppm.
HRMS (ESI): calcd. for C27H21Cl2O5 [M + H]+ 495.0761; found
495.0768.
Ethyl
2-(4-Methoxyphenyl)-4-(4-methylbenzoyl)-5-p-tolylfuran-3-
carboxylate (3ie): 2-Acylacrylate 1i (0.5 mmol, 117 mg) and 4-tol-
uoyl chloride (2e, 1.2 mmol, 259 μL) were employed in the typical
procedure to give the product 3ie (186 mg, 82%); white solid; m.p.
132–133 °C. 1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.8 Hz,
2 H), 7.87 (d, J = 7.8 Hz, 2 H), 7.52 (d, J = 7.8 Hz, 2 H), 7.23 (d,
J = 8.0 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 7.00 (d, J = 8.8 Hz, 2
H), 3.96 (q, J = 7.1 Hz, 2 H), 3.87 (s, 3 H), 2.40 (s, 3 H), 2.30 (s,
3 H), 0.89 (t, J = 7.1 Hz, 3 H) ppm. 13C NMR (100 MHz, CDCl3):
δ = 192.3, 162.8, 160.8, 156.0, 149.6, 144.3, 138.7, 135.3, 130.1,
129.5, 129.4, 129.4, 126.2, 125.8, 121.7, 121.4, 114.2, 113.7, 60.7,
55.3, 21.7, 21.3, 13.3 ppm. HRMS (ESI): calcd. for C29H27O5 [M
+ H]+ 455.1853; found 455.1855.
[4] For representative examples of the classical synthesis of furans,
see: a) G. Minetto, L. F. Raveglia, A. Sega, M. Taddei, Eur. J.
Org. Chem. 2005, 70, 5277, and references cited therein; b)
M. A. Calter, C. Zhu, R. J. Lachicotte, Org. Lett. 2002, 4, 209;
c) G. Mross, E. Holtz, P. Langer, J. Org. Chem. 2006, 71, 8045,
and references cited therein. For leading reviews on the synthe-
sis of furans, see: d) X. L. Hou, H. Y. Cheung, T. Y. Hon, P. L.
Kwan, T. H. Lo, S. Y. T. Tong, H. N. C. Wong, Tetrahedron
1998, 54, 1955; e) B. A. Keay, Chem. Soc. Rev. 1999, 28, 209;
f) R. C. D. Brown, Angew. Chem. 2005, 117, 872; Angew. Chem.
Int. Ed. 2005, 44, 850; g) S. F. Kirsch, Org. Biomol. Chem. 2006,
4, 2076.
[5] For reviews, see: a) Ref.[4f,4g]; b) S. Ma, Acc. Chem. Res. 2003,
36, 701. For recent reports, see: c) Z.-P. Zhan, S.-P. Wang, X.-
B. Cai, H.-J. Liu, J.-L. Yu, Y.-Y. Cui, Adv. Synth. Catal. 2007,
349, 2097; d) L.-B. Zhao, Z.-H. Guan, Y. Han, Y.-X. Xie, S.
He, Y.-M. Liang, J. Org. Chem. 2007, 72, 10276; e) A. Sniady,
A. Durham, M. S. Morreale, K. A. Wheeler, R. Dembinski,
Org. Lett. 2007, 9, 1175; f) J. Barluenga, L. Riesgo, R. Vicente,
L. A. Lopez, M. Tomas, J. Am. Chem. Soc. 2008, 130, 13528;
g) J. M. Aurrecoechea, A. Durana, E. Perez, J. Org. Chem.
2008, 73, 3650; h) Y. Li, Z. Yu, J. Org. Chem. 2009, 74, 8904;
i) H. Cao, H. Jiang, W. Yao, X. Liu, Org. Lett. 2009, 11, 1931;
j) H. Cao, H. Jiang, G. Yuan, Z. Chen, C. Qi, H. Huang, Chem.
Eur. J. 2010, 16, 10553; k) H. Cao, H. Jiang, R. Mai, S. Zhu,
C. Qi, Adv. Synth. Catal. 2010, 352, 143; l) Y. Wang, L. Xu, D.
Ma, Chem. Asian J. 2010, 5, 74; m) X. Zhang, Z. Lu, C. Fu,
S. Ma, J. Org. Chem. 2010, 75, 2589; n) W. Liu, H. Jiang, M.
Zhang, C. Qi, J. Org. Chem. 2010, 75, 966; o) J. Yang, C. Wang,
X. Xie, H. Li, E. Li, Y. Li, Org. Biomol. Chem. 2011, 9, 1342;
p) Z. Chen, G. Huang, H. Jiang, H. Huang, X. Pan, J. Org.
Chem. 2011, 76, 1134.
(E)-2-(4-Chlorophenyl)-3-phenyl-5-styrylfuran (3jb): (1E,4E)-1,5-Di-
phenylpenta-1,4-dien-3-one (1j, 0.5 mmol, 118 mg) and 4-chloro-
benzoyl chloride (2b, 0.6 mmol, 77 μL) were employed in the typ-
ical procedure to give the product 3jb (169 mg, 95%); yellow solid;
m.p. 131–132 °C. 1H NMR (400 MHz, CDCl3): δ = 7.49 (d, J =
8.5 Hz, 4 H), 7.33–7.38 (m, 7 H), 7.24 (d, J = 7.0 Hz, 3 H), 7.14
(d, J = 16.2 Hz, 1 H), 6.89 (d, J = 16.2 Hz, 1 H), 6.47 (s, 1 H) ppm.
13C NMR (100 MHz, CDCl3): δ = 152.2, 146.8, 136.9, 133.9, 133.2,
129.4, 128.8, 128.7, 128.6, 128.6, 127.8, 127.7, 127.5, 127.3, 126.4,
125.1, 115.9, 113.1 ppm. HRMS (MALDI): calcd. for C24H17ClO
[M]+ 356.0962; found 356.0968.
tert-Butyl 2-Benzoyl-4-oxo-4-phenylbutanoate (4): Table 1, Entry 8.
1
Yield 34%; m.p. 74–76 °C. H NMR (400 MHz, CDCl3): δ = 8.09
(d, J = 7.5 Hz, 2 H), 8.01 (d, J = 7.5 Hz, 2 H), 7.56–7.62 (m, 2 H),
7.45–7.52 (m, 3 H), 5.04 (dd, J = 7.6, 6.0 Hz, 1 H), 3.79 (dd, J =
18.2, 7.6 Hz, 1 H), 3.67 (dd, J = 18.2, 6.0 Hz, 1 H), 1.35 (s, 9 H)
ppm. 13C NMR (100 MHz, CDCl3): δ = 197.1, 195.2, 168.3, 136.4,
136.2, 133.4, 133.3, 128.9, 128.6, 128.5, 128.2, 82.4, 50.0, 37.9,
27.7 ppm. HRMS (MALDI): calcd. for C21H22O4Na [M + Na]+
361.1410; found 361.1415.
[6] a) C.-K. Jung, J.-C. Wang, M. J. Krische, J. Am. Chem. Soc.
2004, 126, 4118; b) T.-T. Kao, S.-E. Syu, Y.-W. Jhang, W. Lin,
Org. Lett. 2010, 12, 3066; c) K.-W. Chen, S.-E. Syu, Y.-J. Jang,
W. Lin, Org. Biomol. Chem. 2011, 9, 2098; d) S.-E. Syu, Y.-T.
Lee, Y.-J. Jang, W. Lin, Org. Lett. 2011, 13, 2970; e) Y. Wang,
Y.-C. Luo, X.-Q. Hu, P.-F. Xu, Org. Lett. 2011, 13, 5346; f) J.
Hu, Y. Wei, X. Tong, Org. Lett. 2011, 13, 3068.
tert-Butyl 2,5-Diphenylfuran-3-carboxylate (5): Table 1, Entry 9.
Yield 13%; colorless oil. 1H NMR (400 MHz, CDCl3): δ = 8.02 (d,
J = 7.3 Hz, 2 H), 7.73 (d, J = 7.5 Hz, 2 H), 7.38–7.48 (m, 5 H),
7.31 (t, J = 7.4 Hz, 1 H), 7.03 (s, 1 H), 1.56 (s, 9 H) ppm. 13C
[7] a) S. Xu, L. Zhou, S. Zeng, R. Ma, Z. Wang, Z. He, Org. Lett.
2009, 11, 3498; b) S. Xu, L. Zhou, R. Ma, H. Song, Z. He,
8
www.eurjoc.org
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Domino Synthesis of Tetrasubstituted Furans
Org. Lett. 2010, 12, 544; c) S. Xu, W. Zou, G. Wu, H. Song,
Z. He, Org. Lett. 2010, 12, 3556; d) R. Zhou, C. Wang, H.
Song, Z. He, Org. Lett. 2010, 12, 976; e) R. Ma, S. Xu, X.
Tang, G. Wu, Z. He, Tetrahedron 2011, 67, 1053; f) S. Xu, R.
Chen, Z. He, J. Org. Chem. 2011, 76, 7528; g) Z. He, X. Tang,
Z. He, Phosphorus Sulfur Silicon, Relat. Elem. 2008, 183, 1518;
for other closely related papers, see also: h) M. J. Jacobsen,
E. D. Funder, J. R. Cramer, K. V. Gothelf, Org. Lett. 2011, 13,
3418; i) S. N. Khong, Y. S. Tran, O. Kwon, Tetrahedron 2010,
66, 4760.
tuted furan 3jb was still the exclusive product (obtained in 78%
yield).
[10] K. Y. Lee, J. E. Na, M. J. Lee, J. N. Kim, Tetrahedron Lett.
2004, 45, 5977, and references therein.
[11] In another experiment, running the model reaction in water-
containing toluene resulted in an increase in the yield of 4.
[12] D. Comegna, M. DellaGreca, M. R. Iesce, L. Previtera, A. Zar-
relli, S. Zuppolini, Org. Biomol. Chem. 2012, 10, 1219.
[13] N. J. Lawrence, J. P. Crump, A. T. McGown, J. A. Hadfield,
Tetrahedron Lett. 2001, 42, 3939.
[14] Compound 3ea is a known compound, see: T. Eicher, V.
Shaefer, Tetrahedron Lett. 1975, 45, 3919.
[8]
In some cases (Table 1, Entries 1–9) small amounts of byprod-
uct 5 were observed in the 1H NMR spectra of the crude prod-
ucts, and even isolated (in 13% yield) in one case (Entry 9).
[15] Compound 3fa is a known compound, see: D. T. Hsu, C. H.
Lin, J. Org. Chem. 2009, 74, 9180.
[9] Despite benzoyl chloride 2b being used in large excess, such as
Received: July 17, 2012
in a 1j/2b/PBu3/NEt3 molar ratio of 0.5:1.2:0.6:1.8, trisubsti-
Published Online: ᭿
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Date: 10-09-12 10:58:00
Pages: 10
J. Wang, R. Zhou, Z.-R. He, Z. He
FULL PAPER
Flexible Furan Substituent Patterns
J. Wang, R. Zhou, Z.-R. He,
Z. He* ............................................ 1–10
Phosphane-Mediated Domino Synthesis of
Tetrasubstituted Furans from Simple Ter-
minal Activated Olefins
Keywords: Polysubstituted furans / Acti-
vated olefins / Domino reactions / Oxygen
heterocycles / Phosphanes
Simplicity can give rise to flexibility and ef-
ficiency. Convenient and highly efficient
syntheses of tetrasubstituted furans from
simple terminal activated olefins through
phosphane-mediated multiple domino as-
sembly sequences (such as C-acylation/O-
acylation/C-acylation/intramolecular Wit-
tig reaction) have been achieved.
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