Synthesis of multisubstituted furans via Cu(i)-catalyzed annulation of ketones with alkynoate under ligand- and additive-free conditions

Article abstract of DOI:10.1039/c5ra23058f

A facile and efficient annulation strategy for the synthesis of multisubstituted furan derivatives has been achieved under mild conditions. The developed transformation via C(sp³)-H bond functionalization catalyzed by copper(i) salts using benz

Full text of DOI:10.1039/c5ra23058f

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Synthesis of multisubstituted furans via Cu(I)-
catalyzed annulation of ketones with alkynoate
Cite this: RSC Adv., 2016, 6, 5436
under ligand- and additive-free conditions†
Zaigang Luo, Yuyu Fang,a Yu Zhao,a Peng Liu,b Xuemei Xu,a Chengtao Feng,a
a
*
a
a
*
Zhong Li and Jie He
A facile and efficient annulation strategy for the synthesis of multisubstituted furan derivatives has been
achieved under mild conditions. The developed transformation via C(sp3)–H bond functionalization
catalyzed by copper(I) salts using benzoyl peroxide as an external oxidant possess some obvious
advantages. This ligand- and additive-free cyclization protocol offers an environmentally friendly and
efficient access to biologically important scaffolds from readily available substrates.
Received 3rd November 2015
Accepted 5th January 2016
DOI: 10.1039/c5ra23058f
www.rsc.org/advances
conditions and low conversions. As a consequence, the devel-
opment of a new synthetic route to synthesize furan derivatives
Introduction
from simple and commercially available starting materials is
still desirable.
Multisubstituted furans represent an important class of ve
membered heterocycles ubiquitous in natural products, phar-
maceuticals, and agrochemicals as well as act as useful inter-
mediates in organic synthesis.1 Hence, the development of
efficient methods for their preparation has been an important
research orientation in organic chemistry. The classical
approaches such as Paal–Knorr synthesis2 and Feist–Benary
synthesis3 have already been established for the assembly of
multisubstituted furans. The Paal–Knorr method relies on acid
catalyzed intramolecular cyclization of 1,4-dicarbonyl
compounds and Feist–Benary method represents one of rst
approaches for the intermolecular annulation of 1,3-dicarbonyl
compounds and a-halogen ketones.
In the past few decades, transition-metal-catalyzed
approaches to the synthesis of furan derivatives have been
developed, such as Pd-catalyzed cyclization of 2,3-allenoic acids
in the presence of allenes,4 Pd-catalyzed cyclization of alky-
nylbenziodoxolones and imine derivatives of acetophenone,5
Au-catalyzed cycloisomerizations of bromoallenyl ketones,6
Co-catalyzed cyclization of alkynes and a-diazocarbonyls,7
Ag-catalyzed cycloisomerizations of phenyl and tert-butyl
alkynyl ketones utilizing [3,3] acyloxy migration,8 successive
Ru-catalyzed dimerization of terminal alkynes and Cu(II)-cata-
lyzed cyclization of 1,3-dienyl ethers9 and so forth. However, the
synthetic potential of these strategies is still suffer from limi-
tations like the requirement of functionalized precursors, harsh
Despite the recent advances with these transition metal
catalysts, copper catalyzed synthesis of furans is highly attrac-
tive. Because copper salts are inexpensive and possess low
toxicity. Recently, copper catalyzed C–H functionalization
reactions to the construction of heterocycles have been
successfully developed.10 In 2010, Jiang' group demonstrated
the synthesis of furans from alkynoates and 1,3-dicarbonyl
compounds through Sn(II)- and Cu(I)-involved addition/
oxidative cyclization (Scheme 1a).11 Subsequently, they re-
ported a novel and convenient one-pot Cu(I)-catalyzed approach
for the preparation of 2-carbonyl furans via (2-furyl)carbene
complexes.12 Very recently, Antonchick and Manna described
the rst copper-catalyzed annulation of acetophenone deriva-
tives and an alkyl acetylenedicarboxylate with a broad reaction
scope (Scheme 1b).13 This reaction provides a useful method for
the synthesis of multisubstituted furans from readily available
acetophenones and electron-decient alkynes via Cu(I)-cata-
lyzed direct C(sp3)–H bond functionalization under radical
reaction conditions, which are generally difficult to access from
other conventional methods. However, this reaction was pro-
ceeded in the presence of a ligand such as 2,20-bipyridine, and
the ligand was essential for the catalytic activity of the copper(I)
salt. Moreover, the substrate scope is limited to the electron-
poor arylmethyl ketones. Hence, copper catalyzed C(sp3)–H
functionalization reactions between arylmethyl ketones and
alkynoate to the construction of furans is still lled with
challenges.
aCollege of Chemical Engineering, AnHui University of Science & Technology, Huainan
232001, P. R. China. E-mail: luozi139@163.com; aust_jhe@163.com
bGuang Zhou Institutes of Biomedicine and Health, Chinese Academy of Sciences,
Guangzhou 510530, China
Herein we present a facile and efficient Cu(I)-catalyzed
annulation of simple and readily available ketones with alky-
noate under mild conditions (Scheme 1c). Comparing to the
research work of Antonchick and Manna's,14 the advantages of
† Electronic supplementary information (ESI) available: NMR Spectra for products
3. See DOI: 10.1039/c5ra23058f
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Table 1 Optimization of the reaction conditionsa
Entry Catalyst (eq.)
Oxidant (eq.) Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
—
CuCl(0.2)
CuBr(0.2)
CuI2(0.2)
Air
O2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
n.r.
5
H2O2(2)
TBHP(2)
DTBP(2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
13
15
26
90
22
16
37
70
54
56
50
85
55
52
83
54
9
10
11
12
13
14
15
16
17
Scheme 1 Synthesis of furan from ketone and alkynoate.
CuCl2$2H2O (0.2) BPO(2)
CuBr2(0.2)
CuCO3(0.2)
CuI(0.3)
CuI(0.1)
CuI(0.1)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
CuI(0.2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
BPO(1)
BPO(1)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
BPO(2)
our current study are clear, such as ligand- and additive-free,
high yield, large-scale processes and broad substrate scope
(well suitable for both nonactivated arylmethyl ketones with
electron-donating or electron-withdrawing groups and 1,3- 18
dicarbonyl compounds with an activated methylene group).
19
CH3CN : H2O(1 : 1) 68
20
21
22
DMSO
CH3OH
DCE
DMA
CH3CN
CH3CN
52
32
34
48
n.r.
28
Results and discussion
23
24c
25d
Initially, acetophenone 1a and dimethyl acetylenedicarboxylate
(DMAD) 2a were chosen as the model substrates to optimize the
reaction conditions, including the catalyst, oxidant, solvent,
and temperature under ambient air. As described in Table 1, six
oxidants, air, O2, H2O2, tert-butyl hydroperoxide (TBHP), di-tert-
butyl peroxideꢀ(DTBP) and benzoyl peroxide (BPO) were inves-
tigated at 100 C in 2 mL of CH3CN using CuI as the catalyst,
a
Reaction conditions: 1a (0.5 mmol), 2a (1 mmol), solvent (2 mL), 100 ꢀC,
10 h. Isolated yield. c 90 ꢀC. d 110 ꢀC, n.r. – no reaction.
b
Having established the reaction conditions, various aryl-
and BPO was found to be the most effective oxidant (90%) methyl ketones were examined in the cyclization with DMAD
(entries 1–6). When the reaction was carried out without CuI, (Table 2). To our delight, aryl methyl ketones with electron-
a signicant decrease of the yield was observed (entry 7). donating substituents (p-OMe) or electron-withdrawing
Changing the counterion of copper salt, such as CuCl and substituents (p-NO2, m-NO2, o-NO2, p-CF3), as well as the para-,
CuBr (entries 8–9), or replacing Cu(I) with Cu(II), such as CuI2, ortho- and meta-substituted groups both gave the desired prod-
CuCl2$2H2O, CuBr2, CuCO3, led to inferior results (entries ucts in good yields (3ab–3af), showing no obvious electronic
10–13). Variations in the loading of CuI and BPO did not provide effect in this reaction. While electron-rich aryl methyl ketones
an improvement in yield of product 3aa (entries 14–17). Aer- were not well tolerated under reported conditions.13 The para-
ward, the solvents, including CH3CN, DMF, CH3CN/H2O (1 : 1), and meta-substituted halogen atoms such as chlorine and uo-
DMSO, CH3OH, 1,2-dichloroethane (DCE) and N,N-dimethyla- rine were well tolerated, affording the corresponding products in
cetamide (DMA) were tested using CuI as the catalyst and BPO 82%, 78% and 80% isolated yields, respectively (3ag–3ai).
as the oxidant at 100 ꢀC, and CH3CN provided the highest yield Notably, 2-acetonaphthone 1j is also a suitable substrate for this
(enꢀtries 6, 18–23). Finally, when the temperature was dropped to reaction, which reacted smoothly to give the expected annula-
90 C, the target product was not be found (entry 24), and the tion products in good yields (3aj, 83%). Interestingly, benzoyla-
yield dramatically decreased when the temperature was elevated cetonitrile 1k undergoes the annulation and the desired product
to 110 ꢀC (entry 25). Aer the optimization process for catalyst, 3ak was isolated with 70% yield under the reaction conditions.
oxidant, solvent, and temperature, the multisubstituted furans However, when R2 was an electron-donating group, such as
3 were synthesized under our standard conditions: 0.2 equiv. methyl or ethyl, the corresponding product 3al and 3am could
of CuI as the catalyst, 2 equiv. of BPO as the oxidant, and CH3CN not be obtained. Obviously, a-position of acetophenones bearing
ꢀ
as the solvent under air atmosphere at 100 C.
an electron-withdrawing group can afford the desired products
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Table 2 Copper catalyzed synthesis of furansa
sterically hindered groups were cyclized in higher yields than
those with sterically hindered groups or sterically hindered
substrate.
Aerward, the application of our present protocol for cycli-
zation of 1,3-dicarbonyl compound and b-ketoester with DMAD,
including acetylacetone 1o and ethyl acetoacetate 1p, were
explored (Scheme 2). Gratifyingly, the target furan derivatives
3ao and 3ap were isolated in 89% and 85% yields, respectively.
In terms of the NMR spectra and related literature,11,15 the
structure of 3ap was conrmed, and there was no evidence
indicating that the regioisomer of 3ap existed. Obviously, this
developed transformation via C(sp3)–H functionalization cata-
lyzed by copper(I) salts using benzoyl peroxide as an external
oxidant is well suitable for both nonactivated arylmethyl
ketones with electron-donating or electron-withdrawing groups
and 1,3-dicarbonyl compounds with an activated methylene
group.
Gram-scale applications for the present method were also
explored. As shown in Scheme 3, the proposed reaction of 1a
and 2a was investigated under the standard conditions, which
could give 2.44 g of 3aa in 86% yield without any signicant loss
of reactive efficiency. Thus, this simple, ligand- and additive-
free protocol could be extended as an efficient and practical
method to construct various potentially bioactive multi-
substituted furan derivatives.
To gain further insight into the reaction mechanism, we
added the radical scavenger 2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) to the model reaction system. While the product (3aa)
was not obtained, which indicated that a free radical pathway
might be involved. The mechanism of the copper catalyzed furan
synthesis has been proposed by previous related literature.10,13
One common process is the CuII/CuI catalytic cycle initiated via
one-electron oxidation by CuII (single electron transfer, SET)
(Scheme 4). The combination of one- and two-electron processes
Scheme 2 Synthesis of furan from 1,3-dicarbonyl compounds and
alkynoate.
a
Reaction conditions: arylmethyl ketones 1 (0.5 mmol), 2 (1 mmol),
CH3CN (2 mL). Isolated yield.
smoothly. It is also worth noting that the reaction was insensi-
tive to the sterically hindered substrate 2-phenyl acetophenone
1n and the corresponding product 3an was obtained in 81%
isolated yield. In addition, the presence of ethyl groups in ace-
tylenedicarboxylate, diethyl acetylenedicarboxylate 2b, also
allowed the synthesis of the corresponding furan derivatives
(3ba–3bc). Generally speaking, aryl methyl ketones without Scheme 3 Synthesis of 3aa in a Gram scale.
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General methods for preparing compounds 3
A 25 mL Schlenk tube was charged with various ketone (1) (0.5
mmol), alkynoate (2) (1 mmol), CuI (0.1 mmol), BPO (1 mmol) and
CH3CN (2 mL). The tube was sealed, and then the mixture was
stirred under air at 100 ꢀC for 10 h. Aer cooling, the solvent was
diluted with water (5 mL) and extracted with dichloromethane (3 ꢁ
4 mL). The combined organic layers were dried over anhydrous
Na2SO4 and concentrated by a rotary evaporator, and the residue
was puried by column chromatography on silica gel (petroleum
ether/ethyl acetate 4 : 1) to provide the desired products (3).
Dimethyl 5-phenylfuran-2,3-dicarboxylate (3aa). Yellow
solid, m.p. 99–101 ꢀC. 1H NMR (400 MHz, CDCl3) d: 8.20 (d, 2H,
J ¼ 8.0 Hz, ArH), 7.68 (d, 1H, J ¼ 8.0 Hz, ArH), 7.54 (m, 2H, ArH),
6.83 (s, 1H, CH]C), 3.90 (s, 3H, OCH3), 3.76 (s, 3H, OCH3); 13
C
NMR (100 MHz, CDCl3) d: 163.8, 163.2, 161.7, 147.0, 134.1,
130.5, 128.7, 128.2, 117.2, 53.3, 52.1; MS (ESI) m/z: 286.8
[M + Na]+, 550.9 [2M + Na]+; HRMS m/z: calcd for C14H12NaO5
[M + Na]+, 283.0577; found, 283.0579.
Scheme 4 Plausible reaction mechanism.
Dimethyl 5-(4-methoxyphenyl)furan-2,3-dicarboxylate (3ab).
was also proposed to occur via a CuI/CuII/CuIII catalytic cycle, in
which the key step is the formation of an organocopperIII
intermediate (Scheme 4). In addition, the plausible mechanism
of cyclization of 1,3-dicarbonyl compound and b-ketoester with
alkynoate is similar to the related literature.15
1
ꢀ
White solid, m.p. 64–66 C. H NMR (400 MHz, CDCl3) d: 7.99
(d, 2H, J ¼ 4.0 Hz, ArH), 6.99 (d, 2H, J ¼ 8.0 Hz, ArH), 6.83 (s, 1H,
CH]C), 3.92 (s, 3H, OCH3), 3.91 (s, 3H, ArOCH3), 3.77 (s, 3H,
OCH3); 13C NMR (100 MHz, CDCl3) d: 165.0, 134.0, 130.6, 130.5,
128.7, 117.2, 113.7, 55.5, 53.3, 52.1, 26.3; MS (ESI) m/z: 312.9
[M + Na]+, 603.0 [2M + Na]+; HRMS m/z: calcd for C15H14NaO6
[M + Na]+, 313.0683; found, 313.0687.
Dimethyl 5-(4-nitrophenyl)furan-2,3-dicarboxylate (3ac).
Conclusions
1
ꢀ
Yellow solid, m.p. 82–84 C. H NMR (400 MHz, CDCl3) d: 8.19
(t, 2H, J ¼ 4.0 Hz, ArH), 7.55 (t, 2H, J ¼ 6.0 Hz, ArH), 6.83 (s, 1H,
CH]C), 3.91 (s, 3H, OCH3), 3.76 (s, 3H, OCH3); 13C NMR (100
MHz, CDCl3) d: 163.8, 163.2, 161.8, 147.0, 134.0, 130.5, 128.7,
128.2, 117.2, 53.3, 52.1; MS (ESI) m/z: 304.1 [M ꢂ H]ꢂ; HRMS
m/z: calcd for C14H11NNaO7 [M + Na]+, 328.0428; found, 328.0430.
Dimethyl 5-(3-nitrophenyl)furan-2,3-dicarboxylate (3ad).
In conclusion, we have disclosed the annulation method of
ketones with alkynoate catalyzed by CuI. The developed reaction
is highly practical, because diverse, easily available starting
materials can be used without preliminary functionalization.
Also, this undecorated cyclization protocol is characterized by
mild conditions, inexpensive catalyst, wide substrate scope and
large-scale processes, as well as no any ligand and additive,
allowing an environmentally and efficient access to biologically
important scaffolds.
1
ꢀ
Yellow solid, m.p. 68–72 C. H NMR (400 MHz, CDCl3) d: 8.18
(s, 1H, ArH), 7.69 (t, 1H, J ¼ 6.0 Hz, ArH), 7.55 (t, 2H, J ¼ 6.0 Hz,
ArH), 6.83 (s, 1H, CH]C), 3.91 (s, 3H, OCH3), 3.76 (s, 3H, OCH3);
13C NMR (100 MHz, CDCl3) d: 164.0, 163.2, 162.0, 147.0, 134.0,
130.5, 128.7, 128.2, 117.2, 53.3, 52.1; MS (ESI) m/z: 304.1
[M ꢂ H]ꢂ; HRMS m/z: calcd for C14H11NNaO7 [M + Na]+,
328.0428; found, 328.0431.
Experimental
Unless otherwise noted, all materials were obtained from
commercial suppliers and dried and puried by standard
procedures. The melting point was measured on a SGW X-4
monocular microscope melting point apparatus with ther-
mometer unadjusted. 1H NMR and 13C NMR spectra were
acquired on a Bruker Avance III 400 MHz spectrometer with
CDCl3 as the solvent and tetramethylsilane (TMS) as the
internal standard. The chemical shis were reported in d (ppm).
Mass spectra (MS) data were obtained using Esquire 6000 Mass
Spectrometer. HRMS were obtained by ESI on a TOF mass
analyzer. Column chromatography was performed with silica
gel (200–300 mesh, Qingdao Haiyang Chemical Co., Ltd, China).
Petroleum ether used for column-chromatography has a boiling
Dimethyl 5-(2-nitrophenyl)furan-2,3-dicarboxylate (3ae).
1
ꢀ
Yellow solid, m.p. 78–80 C. H NMR (400 MHz, CDCl3) d: 8.18
(d, 2H, J ¼ 8.0 Hz, ArH), 7.67 (d, 1H, J ¼ 4.0 Hz, ArH), 7.54 (t, 2H,
J ¼ 6.0 Hz, ArH), 6.83 (s, 1H, CH]C), 3.90 (s, 3H, OCH3), 3.76 (s,
3H, OCH3); 13C NMR (100 MHz, CDCl3) d:164.0, 163.2, 161.7,
147.0, 134.0, 130.5, 128.7, 128.3, 117.2, 53.3, 52.1; MS (ESI) m/z:
304.1 [M ꢂ H]ꢂ; HRMS m/z: calcd for C14H11NNaO7 [M + Na]+,
328.0428; found, 328.0429.
Dimethyl 5-(4-(triuoromethyl)phenyl)furan-2,3-dicarboxylate
1
ꢀ
(3af). White solid, m.p. 55–58 C. H NMR (400 MHz, CDCl3) d:
8.05 (d, 2H, J ¼ 4.4 Hz, ArH), 7.39 (m, 2H, ArH), 6.71 (s, 1H, CH]C),
3.77 (s, 3H, OCH3), 3.63 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3)
d: 163.8, 163.3, 161.8, 147.0, 134.1, 133.9, 130.5, 130.2, 129.4, 128.7,
128.5, 124.8, 117.5, 53.3, 52.2; HRMS m/z: calcd for C15H11F3NaO5
[M + Na]+, 351.0456; found, 351.0450.
ꢀ
range of 60–90 C.
Caution! Organic peroxides can be severe re and explosion
hazards.
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Hz, OCH2CH3), 1.32 (t, 3H, J ¼ 6.8 Hz, OCH2CH3), 1.18 (t, 3H, J ¼
7.2 Hz, OCH2CH3); 13C NMR (100 MHz, CDCl3) d: 163.8, 163.3,
161.8, 147.0, 134.1, 133.8, 130.5, 130.2, 128.7, 128.5, 124.4,
117.2, 53.3, 52.2, 14.6, 14.4; HRMS m/z: calcd for C17H15F3NaO5
[M + Na]+, 379.0769; found, 379.0765.
Dimethyl 5-(4-chlorophenyl)furan-2,3-dicarboxylate (3ag).
White oil. 1H NMR (400 MHz, CDCl3) d: 8.20 (m, 2H, ArH), 7.54
(t, 2H, J ¼ 6.0 Hz, ArH), 6.83 (s, 1H, CH]C), 3.90 (s, 3H, OCH3),
3.76 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) d: 163.8, 163.2,
161.8, 147.0, 134.1, 130.5, 128.7, 128.2, 117.2, 53.3, 52.1; MS
(ESI) m/z: 316.9 [M + Na]+, 611.0 [2M + Na]+; HRMS m/z: calcd for
Diethyl
4-cyano-5-phenylfuran-2,3-dicarboxylate
(3bc).
Yellow oil. 1H NMR (400 MHz, CDCl3) d: 8.08 (m, 2H, ArH), 7.55
(m, 1H, ArH), 7.40 (m, 2H, ArH), 4.25 (q, 2H, J ¼ 6.4 Hz,
OCH2CH3), 4.10 (q, 2H, J ¼ 6.8 Hz, OCH2CH3), 1.24 (t, 3H, J ¼ 6.4
Hz, OCH2CH3), 1.10 (t, 3H, J ¼ 6.8 Hz, OCH2CH3); 13C NMR (100
MHz, CDCl3) d: 163.8, 162.9, 161.2, 146.9, 134.0, 133.8, 130.5,
130.2, 129.3, 128.6, 128.5, 117.5, 106.0, 62.6, 61.2, 14.0, 13.9;
HRMS m/z: calcd for C17H16NO5 [M + H]+, 314.1028; found,
314.1021.
C
14H11ClNaO5 [M + Na]+, 317.0187; found, 317.0190.
Dimethyl 5-(3-chlorophenyl)furan-2,3-dicarboxylate (3ah).
Yellow oil. 1H NMR (400 MHz, CDCl3) d: 8.15 (d, 2H, J ¼ 4.4 Hz,
ArH), 7.64 (t, 1H, J ¼ 4.8 Hz, ArH), 7.50 (d, 1H, J ¼ 4.4 Hz, ArH),
6.79 (s, 1H, CH]C), 3.86 (s, 3H, OCH3), 3.72 (s, 3H, OCH3); 13
C
NMR (100 MHz, CDCl3) d: 162.9, 161.5, 161.2, 146.9, 134.0,
130.5, 128.6, 128.3, 117.5, 62.6, 61.2; HRMS m/z: calcd for
C
14H11ClNaO5 [M + Na]+, 317.0193; found, 317.0190.
Dimethyl 4-acetyl-5-methylfuran-2,3-dicarboxylate (3ao).15
White solid, m.p. 114–116 ꢀC. 1H NMR (400 MHz, CDCl3) d: 4.02
(s, 3H, OCH3), 3.95 (s, 3H, OCH3), 2.72 (s, 3H, ArCH3), 2.45
(s, 3H, COCH3); 13C NMR (100 MHz, CDCl3) d: 191.7, 164.2,
160.9, 157.7, 139.2, 125.5, 122.5, 53.2, 52.5, 29.4, 14.9; MS (ESI)
m/z: 262.8 [M + Na]+, 503.0 [2M + Na]+.
Trimethyl 5-methylfuran-2,3,4-tricarboxylate (3ap).15 White
solid, m.p. 131–133 ꢀC. 1H NMR (400 MHz, CDCl3) d: 4.34 (q, 2H,
J ¼ 4.0 Hz, OCH2CH3), 3.99 (s, 3H, OCH3), 3.94 (s, 3H, OCH3), 2.71
(s, 3H, Ar-CH3), 1.38 (t, 3H, J ¼ 4.0 Hz, OCH2CH3); 13C NMR (100
MHz, CDCl3) d: 163.6, 162.3, 157.7, 138.9, 133.7, 130.2, 128.5, 61.1,
52.9, 52.5, 14.1; MS (ESI) m/z: 280.9 [M + Na]+, 539.0 [2M + Na]+.
Dimethyl 5-(4-uorophenyl)furan-2,3-dicarboxylate (3ai).
White oil. 1H NMR (400 MHz, CDCl3) d: 8.18 (d, 2H, J ¼ 4.0 Hz,
ArH), 6.99 (d, 2H, J ¼ 8.0 Hz, ArH), 6.83 (s, 1H, CH]C), 3.92 (s,
3H, OCH3), 3.77 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) d:
164.0, 163.2, 161.8, 147.0, 134.1, 130.5, 128.7, 128.2, 117.2, 52.3,
52.1; MS (ESI) m/z: 300.9 [M + Na]+, 579.1 [2M + Na]+; HRMS m/z:
calcd for C14H11FNaO5 [M + Na]+, 301.0483; found, 301.0485.
Dimethyl 5-(naphthalen-2-yl)furan-2,3-dicarboxylate (3aj).
Brown solid. m.p. 123–126 ꢀC. 1H NMR (400 MHz, CDCl3) d: 8.16
(m, 2H, ArH), 7.66 (m, 2H, ArH), 7.53 (m, 3H, ArH), 6.84 (s, 1H,
CH]C), 3.91 (s, 3H, OCH3), 3.77 (s, 3H, OCH3); 13C NMR (100
MHz, CDCl3) d: 163.8, 163.3, 161.8, 147.0, 134.1, 133.8, 130.5,
130.2, 128.7, 128.5, 117.2, 53.3, 52.2; MS (ESI) m/z: 332.8
[M + Na]+, 642.9 [2M + Na]+; HRMS m/z: calcd for C18H14NaO5
[M + Na]+, 333.0733; found, 333.0735.
Acknowledgements
The authors gratefully acknowledge the nancial support from
the National Natural Science Foundation of China (21102003)
and Scientic Research Foundation for the Introduction of
Talent of Anhui University of Science & Technology.
Dimethyl 4-cyano-5-phenylfuran-2,3-dicarboxylate (3ak).
1
ꢀ
Yellow solid, m.p. 57–60 C. H NMR (400 MHz, CDCl3) d: 8.15
(d, 2H, J ¼ 4.8 Hz, ArH), 7.64 (m, 1H, ArH), 7.50 (m, 2H, ArH),
3.86 (s, 3H, OCH3), 3.72 (s, 3H, OCH3); 13C NMR (100 MHz,
CDCl3) d: 163.8, 163.0, 161.3, 146.9, 134.0, 133.8, 130.5, 130.2,
129.3, 128.6, 128.5, 117.5, 106.0, 62.6, 61.2; HRMS m/z: calcd for
Notes and references
C
15H12NO5 [M + H]+, 286.0715; found, 286.0711.
Dimethyl 4,5-diphenylfuran-2,3-dicarboxylate (3an).16 Brown
1 (a) X. L. Hou, H. Y. Cheung, T. Y. Hon, P. L. Kwan, T. H. Lo,
S. Y. Tong and H. N. C. Wong, Tetrahedron, 1998, 54, 1955; (b)
B. H. Lipshutz, Chem. Rev., 1986, 86, 795; (c) M. Ghosh,
S. Mishra, K. Monir and A. Hajra, Org. Biomol. Chem., 2015,
13, 309.
1
oil. H NMR (400 MHz, CDCl3) d: 8.17 (d, 4H, J ¼ 4.0 Hz, ArH),
7.65 (m, 2H, ArH), 7.51 (m, 4H, ArH), 6.84 (s, 1H, CH]C), 3.95
(s, 3H, OCH3), 3.88 (s, 3H, OCH3); 13C NMR (100 MHz, CDCl3) d:
171.9, 163.8, 163.3, 161.8, 147.0, 134.1, 133.8, 130.5, 130.2,
128.7, 128.5, 117.2, 53.3, 52.2; MS (ESI) m/z: 360.9 [M + Na]+,
699.0 [2M + Na]+.
2 (a) L. Knorr, Ber. Dtsch. Chem. Ges., 1884, 17, 2863; (b) C. Paal,
Ber. Dtsch. Chem. Ges., 1884, 17, 2756.
3 (a) E. Benary, Ber. Dtsch. Chem. Ges., 1911, 44, 489; (b)
F. Feist, Ber. Dtsch. Chem. Ges., 1902, 35, 1537.
4 Z. H. Gu, X. K. Wang, W. Shu and S. G. Ma, J. Am. Chem. Soc.,
2007, 129, 10948.
5 B. L. Lu, J. L. Wu and N. Yoshikai, J. Am. Chem. Soc., 2014,
136, 11598.
6 Y. Z. i. Xia, A. S. Dudnik, V. Gevorgyan and Y. H. Li, J. Am.
Chem. Soc., 2008, 130, 6940.
7 X. Cui, X. Xu, L. Wojtas, M. M. Kim and X. P. Zhang, J. Am.
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Diethyl 5-(2-chlorophenyl)furan-2,3-dicarboxylate (3ba).
Yellow oil. 1H NMR (400 MHz, CDCl3) d: 8.16 (d, 2H, J ¼ 4.8 Hz,
ArH), 7.62 (d, 1H, J ¼ 4.0 Hz, ArH), 7.50 (t, 1H, J ¼ 4.8 Hz, ArH),
6.77 (s, 1H, CH]C), 4.32 (q, 2H, J ¼ 6.8 Hz, OCH2CH3), 4.18 (q,
2H, J ¼ 6.8 Hz, OCH2CH3), 1.32 (t, 3H, J ¼ 6.8 Hz, OCH2CH3),
1.18 (t, 3H, J ¼ 6.8 Hz, OCH2CH3); 13C NMR (100 MHz, CDCl3) d:
163.8, 163.0, 161.2, 146.9, 134.0, 130.5, 128.6, 128.3, 117.5, 62.6,
61.2, 14.0; HRMS m/z: calcd for C16H15ClNaO5 [M + Na]+,
345.0506; found, 345.0501.
Diethyl 5-(4-(triuoromethyl)phenyl)furan-2,3-dicarboxylate
1
ꢀ
8 A. W. Sromek, A. V. Kel'in and V. Gevorgyan, Angew. Chem.,
Int. Ed., 2004, 43, 2280.
9 M. Zhang, H. F. Jiang, H. Neumann, M. Beller and
P. H. Dixneuf, Angew. Chem., Int. Ed., 2009, 48, 1681.
(3bb). Yellow solid, m.p. 51–53 C. H NMR (400 MHz, CDCl3)
d: 8.15 (d, 2H, J ¼ 4.0 Hz, ArH), 7.50 (m, 2H, ArH), 6.77 (s, 1H,
CH]C), 4.32 (q, 2H, J ¼ 6.8 Hz, OCH2CH3), 4.18 (q, 2H, J ¼ 7.2
5440 | RSC Adv., 2016, 6, 5436–5441
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This journal is © The Royal Society of Chemistry 2016
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