Copper(ii) bromide-catalyzed intramolecular decarboxylative functionalization to form a C(sp3)-O bond for the synthesis of furo[3,2-c]coumarins

Article abstract of DOI:10.1039/c4ob02490g

An efficient and eco-friendly copper(ii) bromide-catalyzed intramolecular decarboxylative functionalization to form a C(sp³)-O bond for the synthesis of furo[3,2-c]coumarins has been developed. In this reaction, a copper(ii) bromide-catalyzed intramolecular decarboxylative functionalization of α-carbonyl is successfully realized to generate an α-bromo carbonyl compound as a key intermediate.

Full text of DOI:10.1039/c4ob02490g

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DOI: 10.1039/C4OB02490G
ARTICLE
Copper(II)
Bromide-catalyzed
Intramolecular
Decarboxylative Functionalization to Form C(sp3)–O
Cite this: DOI: 10.1039/x0xx00000x
Bond for the Synthesis of Furo[3,2-c]coumarins
W. L. Zhang,a S. N. Yue,a Y. M. Shen,b H. Y. Hu,c Q.-H. Meng,a H. Wua,* and Y.
Liua,*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
An efficient and eco-friendly copper(II) bromide-catalyzed intramolecular decarboxylative
functionalization to form C(sp3)-O bond for the synthesis of furo[3,2-
c
]coumarins has been
developed. In this reaction, a copper(II) bromide-catalyzed intramolecular decarboxylative
functionalization of -carbonyl is successfully realized to generate an -bromo carbonyl
compound as a key intermediate.
www.rsc.org/
α
α
elegant example of copper(II) bromide-catalyzed intermolecular
dehydrogenative functionalization of α-carbonyl species for the
synthesis of α-amino carbonyl adducts had been reported (Scheme
1).15 In this reaction, copper(II) bromide was employed as catalysis
to transiently render carbonyls electrophilic at the α-position, thereby
enabling the in situ addition of a broad range of nitrogen coupling
partners. Inspired by this work and following our continuing interest
in transition-metal-catalyzed reaction,16 we reported herein a simple
and efficient copper(II) bromide-catalyzed three-component reaction
to synthesize furo[3,2-c]coumarins derivatives. In this reaction, a
copper(II) bromide-catalyzed intramolecular decarboxylative
functionalization of α-carbonyl is successfully realized, which may
be complementary to the limited examples of copper-catalyzed
functionalization of α-carbonyl species with nucleophiles.14,15
Compared with previous synthetic methods for furo[3,2-c]coumarins,
our protocol has a much wider reaction scope and is highly atom-
economic, furnishing the products in excellent yields in an
operationally simple one-pot reaction.
Introduction
Furan is a privileged scaffold in a variety of biologically important
natural products1 and the development of efficient synthetic methods
toward furan derivatives is an important task in modern organic
synthesis.2 As an important class of furan derivatives, furo[3,2-
c]coumarins exhibit important biological activities3 and are found in
many natural products.4 For example, Neo-tranchinlactone, a kind of
furo[3,2-c]coumarin derivative, was isolated from Salvia miltiorrhiza
and showed potent and selective antibreast cancer activity.4e,4f
Consequently, much attention had been attracted for the construction
of furo[3,2-c]coumarin derivatives.
There are several methods for the preparation of furo[3,2-
c]coumarin derivatives. They mainly include: tandem alkylation and
intramolecular aldolization reaction;5 cycloaddition of coumarin
methides with isocyanides;6 cascade addition–cyclization–oxidation
of 3-alkyne-chromone;7 multi-component reaction between α-
chloroketones, aldehydes and 4-hydroxycoumarin;8 Pd-catalyzed
annulation of 3-alkynyl-4-methoxycoumarins with aryl halides;9 Cu-
catalyzed cyclization of 3-alkynylchromone;10 and Ag(I)-catalyzed
cyclization reaction of 4-hydroxycoumarin with olefin.11 Lately, a
two-step reaction was reported for the synthesis of furo[3,2-
c]coumarins in the presence of iodine and stoichiometric amount of
K2S2O8 by heating 3,3'-methylenedicoumarins at 120 ºC in PEG with
limited reaction scope and moderate product yield.12 Although many
efforts have been devoted to this area, it is still highly desirable to
develop more simple and efficient synthetic protocol for the
preparation of furo[3,2-c]coumarins using easily available substrates
under environmental benign conditions.
O
X
O
CuBr2
air
N
+
X
N
H
Scheme
1
CuBr2-catalyzed intermolecular dehydrogenative
functionalization of α-carbonyl species with nucleophile15
Results and discussion
On the other hand, α-functionalization of carbonyl with
nucleophile is an important research field of organic chemistry. The
general protocol to achieve this is using stoichiometric or catalytic
amount of halogen, NBS or NIS to reverse the activity of α-carbon
of carbonyl.13 Recently, copper salt was found to be an effective
catalyst to α-functionalization of carbonyl compounds14 and an
In our initial attempt, we found that in the presence of copper
bromide (1.0 equiv), 4-hydroxycoumarin 1 (2.0 equiv) may react
with benzaldehyde 2a (1.2 equiv) using pyridine (3.0 equiv) as a
base to afford the desired furo[3,2-c]coumarin 4a in 91% yield
(Table 1, entry 1). On the basis of this promising result, we began to
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optimize the reaction conditions using benzaldehyde 2a and 4- and 4m–4o respectively in excellent yields. Multisubstituted
hydroxycoumarin 1 as the model substrates. Firstly, different benzaldehydes 2p–2t reacted equally well to furnish the products
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solvents were screened in the presence of 1.0 equiv of copper(II) 4p–4t in 85–92% yields. In regard to the steric effect of the
bromide and it was found that changing acetonitrile to all the other substituent, ortho-, meta-substituted benDzOalId: e10h.y10d3e9s/Ca4nOdB02m4u9l0tGi-
solvents tested led to only trace amount of product (Table 1, entry 1– substituted benzaldehydes all turned out to be good substrates,
5). Without copper(II) bromide, no product was formed at all (Table indicating that steric hindrance had little effect to this reaction.
1, entry 6). Interestingly, using other copper(II) salt as copper(II) Furthermore, heterocyclic aromatic aldehydes 2u, 2v and aliphatic
chloride, copper(II) triflate or copper(II) acetate to carry out this aldehydes 2w–2y were also tried, and they all led to the desired
reaction in place of copper(II) bromide proved unsuccessful (Table 1, products in good to excellent yields without exception. Except for
entry 7-9). Copper(I) bromide also showed low efficiency in NMR and HRMS data for all the products, the structures of 4c was
mediating this transformtion (Table 1, entry 10). We then optimized further established by X-ray crystallographic analysis (see
the amount of base and found 2.0 equiv of pyridine only led to 65% supporting information).
yield of 4a (Table 1, entry 11). Subsequently, the amount of
copper(II) bromide was tested using acetonitrile as solvent. It was
found that 0.3 equiv CuBr2 was enough in the air, giving the target
Table 2 Reaction of 4-Hydroxycoumarin 1 with Aldehydesa
O
O
product 4a in high yields (Table 1, entries 12–13). When the reaction
was carried out in pure oxygen atmosphere, the amount of CuBr2
could be reduced to 0.1 equiv (Table 1, entry 14). Contrary to this,
stoichiometric amount of CuBr2 was needed to give the product 4a
in high yield when the reaction was undertaken in N2 atmosphere
(Table 1, entry 15). Finally, we screened the reaction temperature
and found that decreasing temperature led to poor yield of the
product (Table 1, entry 16). Therefore, the optimal reaction
conditions are refluxing the mixture of benzaldehyde 2a (1.2 equiv),
10 mol% CuBr2
pyridine
O
O
R
+
RCHO
CH3CN, reflux, O2
O
OH
1
2b-2y
4b 4y
-
O
HO
HO
O
HO
HO
O
HO
O
O
O
O
O
O
O
4-hydroxycoumarin
1 (2.0 equiv), pyridine (3.0 equiv) and
Br
Cl
F
I
copper(II) bromide (0.1 equiv) in an oxygen atmosphere for 12 hours.
O
O
O
O
O
O
O
4e, 93%
HO
4b, 97%
HO
4d
, 95%
HO
4c, 95%
HO
Table 1 Optimization of Reaction Conditionsa
O
O
O
O
O
O
O
O
O
O
O
O
Copper salt
OMe
Me
CN
NO2
+
PhCHO
O
O
O
O
O
O
O
O
Ph
pyridine, solvent
4i, 90%
4h
, 88%
4f, 98%
4g, 93%
O
HO
HO
O
OH
HO
O
HO
O
O
2a
4a
1
O
O
O
O
O
HO
Yield(%)b
Entry Solvent
Copper (equiv)
CuBr2(1.0)
CuBr2(1.0)
CuBr2(1.0)
CuBr2(1.0)
CuBr2(1.0)
none
CuCl2(1.0)
Cu(OTf)2(1.0)
Cu(OAc)2(1.0)
CuBr (1.0)
CuBr2 (1.0)c
CuBr2(0.3)
CuBr2(0.2)
CuBr2(0.1)d
CuBr2(2.0)e
CuBr2(0.1)d
Temp(oC)
reflux
reflux
80
O
O
OCH3
O
O
O
O
Br
O
O
Cl
F
1
2
3
4
5
6
7
8
CH3CN
C6H6
Toluene
DMF
91
4m, 96%
4j, 91%
4k, 90%
4l
, 86%
Trace
Trace
Trac
Trace
0
Trace
0
0
31
65
91
78
HO
O
HO
O
HO
HO
O
O
O
O
O
O
80
O
Br
Cl
C2H5OH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
reflux
50
O
O
O
F
Br
O
O
Cl
O
O
NO2
4q
, 90%
4p
4n, 92%
, 92%
4o
, 97%
HO
HO
O
HO
HO
O
O
O
9
O
O
O
O
O
10
11
12
13
14
15
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
4r, 87%
4u, 88%
4s, 85%
HO
4t, 90%
HO
HO
O
HO
O
O
O
91
88
Trace
O
O
O
S
n-Pr
16
O
O
O
O
O
O
O
O
a
4x
, 92%
4y
, 82%
4v, 86%
4w
, 95%
Heating the mixture of 4-hydroxycoumarin 1 (2.0 mmol) with
benzaldehyde 2a (1.2 mmol), pyridine (3.0 mmol), and copper salt in
a
Refluxing the mixture of 4-hydroxycoumarin 1 (2.0 mmol), with
aldehydes 2b-2y (1.2 mmol), pyridine (3.0 mmol), and CuBr2 (0.1
solvent for 12 h. Isolate yields. 2.0 Equiv of pyridine was used.d
b
c
Heated in O2 atmosphere. e Heated in N2 atmosphere.
mmol) in CH3CN for 12 h in O2 atmosphere.
With the optimized reaction conditions in hand, the substrate
scope was then studied, as shown in Table 2. The electronic effect of
substituent in benzaldehydes was first studied and it turned out that
benzaldehydes with either electron–withdrawing or electron-
donating group on the para- (2b–2i), ortho- (2j–2l) or mata-position
(2m–2o) of the phenyl ring took part in the reaction smoothly under
the optimal conditions, providing the desired products 4b–4i, 4j–4l
In order to expand the substrate scope further, substituted 4-
hydroxycoumarin was applied in this reaction. As we expected, by
refluxing
a mixture of 6-methyl or 6-chloro-substituted 4-
hydroxycoumarin 3 (2.0 mmol) with aromatic aldehydes or aliphatic
aldehyde (1.2 mmol) under the optimal condition, the desired
products 5a–5f were obtained in excellent yield, as shown in Table 3
(For crystallographic structure of 5c, see supporting information).
2 | J. Name., 2012, 00, 1‐3
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ARTICLE
Table 3 Reaction of Substituted 4-Hydroxycoumarin 3 with
On the basis of these experimental results and previous
report,18,19 a plausible mechanism is suggested, as shown in Scheme
3. Initially, intermediate I was formed by sequential reaction of one
Aldehydesa
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O
O
molecule of 4-hydroxycoumarine 1 with beDnOzaI:ld10eh.1y0d39e/C2a4,OfBo0l2lo4w90eGd
by a Michael addition with another 4-hydroxycoumarin in the basic
reaction media. Subsequently, hydrolysis of I generated intermediate
II, which upon decarboxylation and reacting with copper(II)
bromide gave an α-bromo carbonyl III along with copper(I)
bromide. Finally, an intramolecular SN2 reaction in III led to a
primary cyclization product which underwent oxidative
aromatization to give the target product 4a. Copper(II) may be
regenerated via oxidation of copper(I) by oxygen in the presence of
pyridine which may facilitate the oxidation of Cu(I).20
10 mol% CuBr2
pyridine
O
O
+
R
R'
R'
RCHO
R'
CH3CN, reflux, O2
O
OH
3
5a 5e
2
-
O
HO
O
O
O
O
Cl
O
O
CN
Br
O
O
O
O
O
O
O
5a, 90%
5b, 92%
HO
5c, 97%
HO
HO
O
O
O
O
O
O
O
O
O
O
O
O
Cl
O
H2O
O
O
PhCHO
base
Cl
O
O
Br
Cl
base
Cl
OH
O
OH
O
Ph
Ph
O
O
II
I
O
CuBr2
II
O
O
H2O
O
2 CuBr2
5e, 88%
5d, 93% HO
HO
5f
, 86%
HO
CO2 + Br-
a
1/2 O2 + 2HBr
Refluxing the mixture of 6-substituted 4-hydroxycoumarin 3 (2.0
mmol), with aldehydes 2 (1.2 mmol), pyridine (3.0 mmol), and
CuBr2 (0.1 mmol) in CH3CN for 12 h in O2 atmosphere. Isolate
yields.
b
O
O
O
Copper
2 CuBr
Catalytic Cycle
CuBr
O
CuBr
OH
Ph
To gain a better understanding of the reaction mechanism, the
following control experiments were carried out. By refluxing 4-
hydroxycoumarin 1 (2.0 mmol), with benzaldehyde 2a (1.2 mmol)
and pyridine (3.0 mmol) in O2 atmosphere in the presence of
copper(II) chloride (0.1 mmol) and potassium bromide (0.2 mmol),
we also obtained the desired product 4a in excellent yield (Scheme
2a). It was worth noting that using copper(II) chloride along as
catalyst without the aid of potassium bromide could only generate
product 4a in trace amount (see Table 1, entry 10). These results
indicated that the bromide anion (Br-) was crucial in this reaction.
Additionally, it was found that when a typical radical scavenger,
tetramethylpiperidine N-oxide (TEMPO), was added into the
reaction system under the standard condition, the reaction was not
appreciably suppressed, which excluded significant involvement of
any radical intermediate (Scheme 2b). Furthermore, refluxing
III
O
O
O
Br
O
CuBr
OH
Ph
O
O
O
O
O
O
O
Cu2+
Br
SN
2
Ph
Ph
O
oxidative
aromatization
O
O
O
O
OH
Ph
III
OH
OH
4a
Scheme 3 Reaction Mechanism
Conclusions
compound 6 prepared according to previous literature17 with In conclusion, we have developed a simple and efficient method for
copper(II) bromide (0.1 equiv) and pyridine (3.0 equiv) in
acetonitrile for 12 hours in O2 atmosphere also led to product 4a in
excellent yield (Scheme 2c).
the synthesis of furo[3,2-c]coumarin derivatives. This reaction
combines two molecules of 4–hydroxycoumarin with one molecule
of aldehyde in one pot by using a catalytic amount of copper(II)
O
O
10 mol% CuCl2
CHO
20 mmol% KBr
bromide as the catalyst.
intramolecular decarboxylative functionalization of α-carbonyl with
nucleophile is achieved in this reaction process.
A
copper(II) bromide-catalyzed
O
O
+
(a)
pyridine
O
CH3CN, reflux, O2
OH
2a
2a
4a, 90%
1
1
O
HO
Experimental
General
O
O
10 mol% CuBr2
O
O
CHO
1.0 equiv TEMPO
(b)
1
+
pyridine
O
Melting points are uncorrected. H NMR spectra were measured at
CH3CN, reflux, O2
OH
400 MHz with CDCl3 as solvent. The chemical shifts (δ) are
reported in parts per million relative to the residual deuterated
solvent signal, and coupling constants (J) are given in Hertz. 13C
NMR spectra were measured at 100 MHz with CDCl3 as solvent.
General procedure for the synthesis of 4
A mixture of 4-hydroxycoumarin 1 (2.0 mmol), aldehydes 2 (1.2
mmol), pyridine (3.0 mmol), and copper bromide (0.1 mmol) in
acetonitrile (15 ml) was refluxed for 12 h with magnetic stirring
under 1 atm of O2. After the reaction was completed, the solvent was
4a, 82%
O
HO
O
O
OH
O
OH
O
CuBr2 (10 mmol %)
(c)
O
pyridine
CH3CN, reflux, O2
O O
O
6
4a
HO
(92%)
Scheme 2 Control Experiments
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removed under reduced pressure, and the residue was separated by Hz, 2H), 11.56 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 186.6, 164.0,
flash chromatography on a silica gel column with ethyl acetate/ 159.1, 156.8, 154.1, 148.5, 148.0, 137.8, 135.4, 133.4, 132.1, 131.7,
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petroleum ether (1:10) as eluent to give the products 4.
3-Phenyl-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]chromen-4-one
(4a): Yellow solid, yield 347 mg (91%); mp 225─227 C; 1H NMR 428.0769.
131.3, 125.6, 123.7, 122.2, 119.6, 119.2, 118.9, 118.1, 112.0, 110.4;
DOI: 10.1039/C4OB02490G
HMRS m/z [M+H]+ calcd for C24H14NO7: 428.0770; found:
o
(400 MHz, CDCl3) δ 6.74 (td, J = 7.2, 1.2 Hz, 1H), 7.02 (dd, J = 8.8, 4-(2-(2-Hydroxybenzoyl)-4-oxo-4H-furo[3,2-c]chromen-3-yl)
1.2 Hz, 1H), 7.40–7.54 (m, 8H), 7.63–7.67 (m, 1H), 7.73 (dd, J = 8.0, benzonitrile (4g): Yellow solid, yield 380 mg (93%); mp 253─255
1.6 Hz, 1H), 8.03 (dd, J = 8.0, 1.6 Hz, 1H), 11.61 (s, 1H); 13C NMR oC; 1H NMR (400 MHz, CDCl3) δ 6.88 (t, J = 7.6 Hz, 1H), 7.08 (d, J
(100 MHz, CDCl3) δ 187.5, 163.6, 158.9, 157.0, 153.9, 147.3, 137.2, = 8.8 Hz, 1H), 7.47–7.57 (m, 3H), 7. 69–7.75 (m, 5H), 7.86 (dd, J =
133.3, 132.9, 132.4, 130.6, 129.6, 128.5, 125.2, 122.1, 119.2, 119.0, 8.0, 1.6 Hz, 1H), 8.05 (dd, J = 7.6, 1.2 Hz, 1H), 11.55 (s, 1H); 13C
118.7, 117.8, 112.3, 110.5; HMRS m/z [M+H]+ calcd for C24H15O5: NMR (100 MHz, CDCl3) δ 186.4, 163.6, 158.8, 156.5, 153.7, 147.5,
383.0919; found: 383.0925.
3-(4-Fluorophenyl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]chrom-
en-4-one (4b): Yellow solid. yield 388 mg (97%); mp 220─222 C; calcd for C25H14NO5: 408.0872; found: 408.0877.
137.3, 133.0, 132.9, 131.8, 131.7, 131.2, 131.0, 125.2, 121.8, 119.2,
118.7, 118.5, 118.4, 117.6, 113.0, 111.7, 109.9; HMRS m/z [M+H]+
o
1H NMR (400 MHz, CDCl3) δ 6.79 (td, J = 7.6, 1.2 Hz, 1H), 7.03 2-(2-Hydroxybenzoyl)-3-(4-methoxyphenyl)-4H-furo[3,2-c]
(dd, J = 8.4, 0.8 Hz, 1H), 7.10 (t, J = 8.4 Hz, 2H), 7.44–7.56 (m, 5H), chromen-4-one (4h): Yellow solid, yield 362 mg (88%); mp
7.64–7.68 (m, 1H), 7.75 (dd, J = 8.0, 1.6 Hz, 1H), 8.02 (dd, J = 7.6, 168─170 oC; 1H NMR (400 MHz, CDCl3) δ 3.86 (s, 3H), 6.78 (t, J =
1.2 Hz, 1H), 11.59 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 187.1, 7.6 Hz, 1H), 6.94 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 7.45–
1
163.4, 163.3 (d, JC-F = 248 Hz), 158.7, 156.8, 153.7, 147.1, 137.1, 7.53 (m, 5H), 7.66 (t, J = 7.6 Hz, 1H), 7.78 (dd, J = 8.0, 0.8 Hz, 1H),
132.8, 132.5, 132.4, 132.2, 132.1, 125.1, 124.1, 124.0, 121.9, 119.1, 8.04 (d, J = 7.6 Hz, 1H), 11.67 (s, 1H); 13C NMR (100 MHz, CDCl3)
118.7, 118.6, 117.6, 115.4 (d, 2JC-F = 21.8 Hz), 112.0, 110.2; HMRS δ 187.6, 163.5, 160.7, 158.9, 157.1, 153.9, 146.9, 137.0, 133.4, 132.8,
m/z [M+H]+ calcd for C24H14FO5: 401.0825; found: 401.0818.
3-(4-Chlorophenyl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]chrom-
132.4, 132.2, 125.2, 122.1, 120.4, 119.3, 119.0, 118.7, 117.8, 114.0,
112.3, 110.4, 55.6; HMRS m/z [M+H]+ calcd for C25H17O6:
o
en-4-one (4c): Yellow solid, yield 395 mg (95%); mp 206–207 C; 413.1025; found: 413.1022.
1H NMR (400 MHz, CDCl3) δ 6.82 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 2-(2-Hydroxybenzoyl)-3-p-tolyl-4H-furo[3,2-c]chromen-4-one
8.4 Hz, 1H), 7.38–7.52 (m, 7H), 7.66 (t, J = 7.2 Hz, 1H), 7.80 (dd, J (4i): Yellow solid, yield 355 mg (90%); mp 171─172 C; 1H NMR
o
= 8.4, 1.2 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 11.59 (s, 1H); 13C NMR (400 MHz, CDCl3) δ 2.41 (s, 3H), 6.80 (t, J = 8.0, 0.8 Hz, 1H), 7.05
(100 MHz, CDCl3) δ 186.9, 163.4, 158.7, 156.7, 153.7, 147.1, 137.1, (dd, J = 8.4, 0.8 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.46–7.54 (m,
135.6, 132.8, 132.0, 131.7, 128.5, 126.5, 125.0, 121.8, 119.1, 118.7, 5H), 7.67 (s, 1H), 7.81 (dd, J = 8.0, 1.6 Hz, 1H), 8.04 (dd, J = 8.0,
118.6, 117.6, 111.9, 110.1. HMRS m/z [M+H]+ calcd for C24H14ClO5: 1.2 Hz, 1H), 11.66 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 187.2,
417.0530; found: 417.0538.
2-(2-Hydroxybenzoyl)-3-(4-bromophenyl)-4H-furo[3,2-c]chrom-
en-4-one (4d): Yellow solid, yield 436 mg (95%); mp. 222–223 oC; 110.2, 21.5; HMRS m/z [M+H]+ calcd for C25H17O5: 397.1076;
1H NMR (400 MHz, CDCl3) δ 6.82 (td, J = 7.6, 1.2 Hz, 1H), 7.04 found: 397.1084.
163.3, 158.6, 156.7, 153.6, 146.9, 139.4, 136.7, 133.4, 132.5, 132.1,
130.2, 128.9, 125.0, 124.8, 121.8, 118.9, 118.8, 118.4, 117.5, 112.0,
(dd, J = 8.4, 0.8 Hz, 1H), 7.42–7.46 (m, 3H), 7.50–7.56 (m, 4H), 3-(2-Chlorophenyl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]chrom-
o
7.64–7.68 (m, 1H), 7.80 (dd, J = 8.0, 1.6 Hz, 1H), 8.02 (dd, J = 8.0, en-4-one (4j): Yellow solid, yield 377 mg (91%); mp 245–247 C;
1.6 Hz, 1H), 11.57 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 186.9, 1H NMR (400 MHz, CDCl3) δ 6.83 (td, J = 8.0, 0.8 Hz, 1H), 7.01
163.4, 158.7, 156.7, 153.7, 147.1, 137.1, 132.8, 132.1, 132.0, 131.9, (dd, J = 8.4, 0.8 Hz, 1H), 7.31–7.52 (m, 7H), 7.63–7.68 (m, 1H),
131.4, 127.0, 125.0, 123.9, 121.8, 119.1, 118.7, 118.6, 117.6, 111.9, 7.95 (dd, J = 8.0, 1.6 Hz, 1H), 8.05 (dd, J = 7.6, 1.2 Hz, 1H), 11.50
110.0; HMRS m/z [M+H]+ calcd for C24H14BrO5: 461.0025; found: (s, 1H); 13C NMR (100 MHz, CDCl3) δ 186.3, 163.3, 158.5, 156.3,
461.0020.
153.8, 148.1, 137.0, 133.8, 132.8, 131.8, 131.5, 130.6, 130.0, 129.7,
128.4, 126.8, 125.0, 121.9, 119.1, 118.7, 118.5, 117.7, 112.0, 111.2;
2-(2-Hydroxybenzoyl)-3-(4-iodophenyl)-4H-furo[3,2-c]chromen-
4-one (4e): Yellow solid, yield 471 mg (93%); mp 223–224 C; H HMRS m/z [M+H]+ calcd for C24H14ClO5: 417.0530; found:
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NMR (400 MHz, CDCl3) δ 6.83 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 8.4 417.0535.
Hz, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.44 (t, J = 7.6 Hz, 1H), 7.49–7.52 2-(2-Hydroxybenzoyl)-3-(2-bromophenyl)-4H-furo[3,2-c]chrom-
o
(m, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.75 (d, J = 8.0 Hz, 2H), 7.80 (dd, en-4-one (4k): Yellow solid, yield 415 mg (90%); mp 251–252 C;
J = 8.0, 1.2 Hz, 1H), 8.01 (dd, J = 8.0, 1.2 Hz, 1H), 11.58 (s, 1H); 1H NMR (400 MHz, CDCl3) δ 6.84 (td, J = 8.0, 1.2 Hz, 1H), 7.01
13C NMR (100 MHz, CDCl3) δ 186.8, 163.4, 158.6, 156.6, 153.6, (dd, J = 7.6, 0.8 Hz, 1H), 7.26–7.31 (m, 1H), 7.36–7.38 (m, 2H),
147.0, 137.3, 137.0, 132.7, 132.1, 131.9, 131.8, 127.6, 125.0, 121.8, 7.43–7.52 (m, 3H), 7.64–7.69 (m, 2H), 7.99 (dd, J = 8.0, 1.6 Hz, 1H),
119.1, 118.6, 118.5, 117.5, 111.8, 109.9, 95.9; HMRS m/z [M+H]+ 8.05 (dd, J = 8.0, 1.2 Hz, 1H), 11.51 (s, 1H); 13C NMR (100 MHz,
calcd for C24H14IO5: 508.9886; found: 508.9886.
CDCl3) δ 186.1, 163.2, 158.4, 156.2, 153.8, 148.0, 136.9, 132.9,
2-(2-Hydroxybenzoyl)-3-(4-nitrophenyl)-4H-furo[3,2-c]chromen- 132.7, 131.8, 131.7, 131.4, 130.6, 130.4, 127.3, 125.0, 123.7, 121.8,
o
4-one (4f): Yellow solid, yield 419 mg (98%); mp 233─235 C; 1H 119.0, 118.7, 118.4, 117.7, 112.0, 111.1; HMRS m/z [M+H]+ calcd
NMR (400 MHz, CDCl3) δ 6.90 (td, J = 8.0, 0.8 Hz, 1H), 7.08 (dd, J for C24H14BrO5: 461.0025; found: 461.0023.
= 8.0, 0.8 Hz, 1H), 7.49–7.56 (m, 3H), 7.69–7.78 (m, 3H), 7.93 (dd, 2-(2-Hydroxybenzoyl)-3-(2-methoxyphenyl)-4H-furo[3,2-c]
J = 8.4, 1.2 Hz, 1H), 8.06 (dd, J = 8.0, 1.2 Hz, 1H), 8.31 (d, J = 8.8 chromen-4-one (4l): Yellow solid, yield 353 mg (86%); mp 201–
4 | J. Name., 2012, 00, 1‐3
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Organic & Biomolecular Chemistry
ARTICLE
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202 C; H NMR (400 MHz, CDCl3) δ 3.63 (s, 3H), 6.65 (t, J = 8.0 116.1, 115.9, 111.8, 110.5; HMRS m/z [M+H]+ calcd for
Hz, 1H), 6.81 (d, J = 8.0 Hz, 1H), 6.97–7.03 (m, 2H), 7.32–7.50 (m, C24H13BrFO5: 478.9930; found: 478.9939.
View Article Online
DOI: 10.1039/C4OB02490G
5H), 7.62 (t, J = 8.0 Hz, 1H), 7.68 (dd, J = 8.4, 2.0 Hz, 1H), 8.04 (dd, 2-(2-Hydroxybenzoyl)-3-(3,4-dimethoxyphenyl)-4H-furo[3,2-c]
J = 7.6, 1.2 Hz, 1H), 11.52 (s, 1H); 13C NMR (100 MHz, CDCl3) δ chromen-4-one (4r): Yellow solid, yield 384 mg (87%); mp 182–
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187.5, 162.7, 158.6, 156.5, 153.6, 147.6, 136.5, 132.3, 131.9, 131.6, 183 C; H NMR (400 MHz, CDCl3) δ 3.83 (s, 3H), 3.90 (s, 3H),
131.0, 128.1, 124.8, 121.8, 120.5, 118.7, 117.9, 117.7, 117.5, 112.2, 6.73 (td, J = 8.0, 1.2 Hz, 1H), 6.87 (d, J = 7.6 Hz, 1H), 7.02 (d, J =
110.8, 55.1; HMRS m/z [M+H]+ calcd for C25H17O6: 413.1025; 8.4 Hz, 1H), 7.08 (d, J = 2.0 Hz, 1H), 7.14 (dd, J = 8.4, 2.0 Hz, 1H),
found: 413.1022.
3-(3-Fluorophenyl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]chrom-
7.43–7.51 (m, 3H), 7.63–7.69 (m, 2H), 8.03 (dd, J = 7.6, 1.2 Hz, 1H),
11.61 (s, 1H); 13C NMR (100MHz, CDCl3) δ 187.5, 163.1, 158.7,
en-4-one (4m): Yellow solid, yield 384 mg (96%); mp 246–248 oC; 156.8, 153.5, 150.0, 148.4, 146.5, 136.8, 132.8, 132.5, 132.1, 124.8,
1H NMR (400 MHz, CDCl3) δ 6.81 (t, J = 8.0 Hz, 1H), 7.03 (dd, J = 123.6, 121.8, 120.1, 118.9, 118.7, 118.2, 117.4, 113.8, 111.9, 110.7,
7.6, 0.8 Hz, 1H), 7.09–7.14 (m, 1H), 7.28–7.31 (m, 2H), 7.34–7.40 109.9, 55.9, 55.8; HMRS m/z [M+H]+ calcd for C26H19O7: 443.1131;
(m, 1H), 7.42–7.52 (m, 3H), 7.66 (t, J = 8.0 Hz, 1H), 7.78 (dd, J = found: 443.1117.
8.0, 1.6 Hz, 1H), 8.02 (dd, J = 7.6, 1.2 Hz, 1H), 11.58 (s, 1H); 13C 2-(2-Hydroxybenzoyl)-3-(2,3-dimethoxyphenyl)-4H-furo[3,2-c]
NMR (100 MHz, CDCl3) δ 186.9, 163.4, 158.7, 156.6, 153.7, 147.3, chromen-4-one (4s): Yellow solid, yield 375 mg (85%); mp 188–
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137.1, 132.8, 131.9, 130.2, 129.8, 129.7, 126.2, 126.1, 125.0, 121.9, 190 C; H NMR (400 MHz, CDCl3) δ 3.68 (s, 3H), 3.83 (s, 3H),
2
119.1, 118.6, 117.6, 117.5, 117.3, 116.4 (d, JC-F = 21.0 Hz), 111.9, 6.78 (t, J = 8.0 Hz, 1H), 6.96–7.04 (m, 3H), 7.10 (t, J = 8.0 Hz, 1H),
110.1; HMRS m/z [M+H]+ calcd for C24H14FO5: 401.0825; found: 7.40–7.49 (m, 3H), 7.62 (t, J = 8.0 Hz, 1H), 7.83 (dd, J = 8.0, 1.6 Hz,
401.0829.
1H), 8.02 (dd, J = 8.0, 1.6 Hz, 1H), 11.56 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 187.3, 163.4, 158.6, 156.8, 153.9, 152.8, 148.3,
2-(2-Hydroxybenzoyl)-3-(3-bromophenyl)-4H-furo[3,2-c]chrom-
o
en-4-one (4n): Yellow solid, yield 423 mg (92%); mp 194–195 C; 147.0, 136.9, 132.6, 132.1, 128.4, 125.1, 124.0, 123.3, 123.1, 122.0,
1H NMR (400 MHz, CDCl3) δ 6.84 (t, J = 8.0 Hz, 1H), 7.07 (dd, J = 119.1, 119.0, 118.6, 117.8, 114.5, 112.5, 111.2, 61.1, 56.3; HMRS
8.4, 1.2 Hz, 1H), 7.30 (t, J = 8.0 Hz, 1H), 7.46–7.55 (m, 5H), 7.66– m/z [M+H]+ calcd for C26H19O7: 443.1131; found: 443.1123.
7.71 (m, 2H), 7.82 (dd, J = 8.0, 1.6 Hz, 1H), 8.04 (dd, J = 7.6, 1.6 2-(2-Hydroxybenzoyl)-3-(2,3,4-trimethoxyphenyl)-4H-furo[3,2-c]
Hz, 1H), 11.58 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 186.7, 163.4, chromen-4-one (4t): Yellow solid, yield 425 mg (90%); mp
o
158.6, 153.7, 137.1, 133.1, 132.8, 132.4, 131.9, 130.2, 129.7, 128.9, 202─204 C; 1H NMR (400 MHz, CDCl3) δ 3.79 (s, 6H), 3.86 (s,
125.1, 122.1, 121.9, 119.1, 118.7, 118.6, 117.6, 113.2, 111.8, 110.1; 3H), 6.68 (td, J = 8.0, 1.2 Hz, 1H), 6.77 (s, 2H), 7.01 (dd, J = 8.4,
HMRS m/z [M+H]+ calcd for C24H14BrO5: 461.0025; found: 0.8 Hz, 1H), 7.42–7.46 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 7.55 (dd, J
461.0030.
= 8.0, 1.6 Hz, 1H), 7.64 (dd, J = 8.4, 1.2 Hz, 1H), 8.05 (dd, J = 8.0,
2-(2-Hydroxybenzoyl)-3-(3-nitrophenyl)-4H-furo[3,2-c]chromen- 1.6 Hz, 1H), 11.50 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 187.7,
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4-one (4o): Yellow solid, yield 415 mg (97%); mp 213–215 C; H 162.9, 158.9, 158.8, 153.6, 152.8, 146.7, 139.1, 137.0, 132.6, 132.5,
NMR (400 MHz, CDCl3) δ 6.89 (t, J = 8.0 Hz, 1H), 7.05 (dd, J = 8.4, 132.0, 124.9, 122.8, 121.9, 119.0, 118.8, 118.2, 117.4, 111.9, 109.7,
0.8 Hz, 1H), 7.43–7.53 (m, 3H), 7.60–7.71 (m, 2H), 7.89 (dt, J = 7.6, 108.3, 60.8, 56.2; HMRS m/z [M+H]+ calcd for C27H21O8: 473.1236;
1.6 Hz, 1H), 7.94 (dd, J = 8.0, 1.6 Hz, 1H), 8.03 (dd, J = 8.0, 1.6 Hz, found: 473.1236.
1H), 8.28–8.31 (m, 1H), 8.46 (t, J = 2.0 Hz, 1H), 11.51 (s, 1H); 13C 3-(Furan-2-yl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]chromen-4-
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NMR (100 MHz, CDCl3) δ 185.8, 163.3, 158.3, 156.1, 153.4, 147.6, one (4u): Yellow solid, yield 327 mg (88%); mp 252– 254 C; H
147.4, 136.9, 136.0, 132.7, 131.4, 130.7, 129.6, 128.7, 125.2, 124.9, NMR (400 MHz, CDCl3) δ 6.51–6.52 (m, 1H), 6.79 (t, J = 7.6 Hz,
123.7, 121.5, 118.9, 118.5, 118.3, 117.4, 111.4, 109.8; HMRS m/z 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.29 (s, 1H), 7.42 (t, J = 7.2 Hz, 1H),
[M+H]+ calcd for C24H14NO7: 428.0770; found: 428.0761.
7.50–7.64 (m, 5H), 7.98 (d, J = 8.0 Hz, 1H), 11.72 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 189.1, 163.9, 159.6, 157.5, 154.2, 146.3, 144.7,
3-(2,4-Dichlorophenyl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-c]
chromen-4-one (4p): Yellow solid, yield 413 mg (92%); mp 142.9, 137.7, 133.2, 132.6, 125.7, 122.6, 121.0, 120.2, 119.8, 119.2,
244─246 oC; 1H NMR (400 MHz, CDCl3) δ 6.89–6.93 (m, 1H), 7.04 118.1, 116.5, 112.9, 108.8, 100.7; HMRS m/z [M+H]+ calcd for
(dd, J = 8.4, 0.8 Hz, 1H), 7.35 (dd, J = 8.4, 2.4 Hz, 1H), 7.40–7.53 C22H13O6: 373.0712; found: 373.0717.
(m, 5H), 7.65–7.70 (m, 1H), 8.04 (dd, J = 8.0, 1.6 Hz, 2H), 11.52 (s, 2-(2-Hydroxybenzoyl)-3-(thiophen-2-yl)-4H-furo[3,2-c]chromen-
o
1H); 13C NMR (100 MHz, CDCl3) δ 185.7, 163.5, 158.4, 156.1, 4-one (4v): Yellow solid, yield 333 mg (86%); mp 210─212 C; 1H
153.8, 148.3, 137.1, 132.9, 132.5, 132.1, 131.6, 131.2, 130.7, 130.5, NMR (400 MHz, CDCl3) δ 6.80 (t, J = 7.6 Hz, 1H), 7.04–7.10 (m,
129.9, 128.9, 125.1, 121.8, 119.1, 118.7, 117.8, 111.9, 111.0; HMRS 2H), 7.43–7.52 (m, 4H), 7.61–7.65 (m, 2H), 7.72 (d, J = 8.0 Hz, 1H),
m/z [M+H]+ calcd for C24H13Cl2O5: 451.0140; found: 451.0133.
3-(2-Fluoro-4-bromophenyl)-2-(2-hydroxybenzoyl)-4H-furo[3,2-
7.99 (d, J = 7.6 Hz, 1H), 11.64 (s, 1H); 13C NMR (100 MHz, CDCl3)
δ 187.3, 163.3, 158.6, 156.6, 153.5, 146.7, 137.0, 132.6, 132.0, 131.9,
c]chromen-4-one (4q): Yellow solid, yield 430 mg (90%); mp 190– 129.0, 127.5, 127.3, 125.5, 124.9, 121.8, 119.1, 118.9, 118.5, 117.4,
192 oC; 1H NMR (400 MHz, CDCl3) δ 6.90 (t, J = 8.0 Hz, 1H), 7.05 111.8, 109.7; HMRS m/z [M+H]+ calcd for C22H13O5S: 389.0484;
(d, J = 8.4 Hz, 1H), 7.33 (dd, J = 9.2, 1.2 Hz, 1H), 7.39–7.55 (m, found: 389.0493.
5H), 7.66 (td, J = 8.4, 1.2 Hz, 1H), 7.97–8.03 (m, 2H), 11.56 (s, 1H); 2-(2-Hydroxybenzoyl)-4H-furo[3,2-c]chromen-4-one
(4w):
1
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13C NMR (100 MHz, CDCl3) δ 186.1, 163.5, 159.5 (d, JC-F = 252 Yellow solid, yield 291 mg (95%); mp 155─157 C; 1H NMR (400
Hz), 158.6, 156.3, 153.7, 148.0, 137.0, 132.8, 131.6, 127.4, 127.3, MHz, CDCl3) δ 7.02 (td, J = 7.2, 0.8 Hz, 1H), 7.12 (dd, J = 8.4, 0.8
125.4, 125.0, 121.7, 119.4 (d, 2JC-F = 24.9 Hz), 119.1, 118.6, 117.6, Hz, 1H), 7.45 (t, J = 8.0 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.58–7.62
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1‐3 | 5

Organic & Biomolecular Chemistry
Page 6 of 7
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(m, 1H), 7.64–7.68 (m, 1H), 7.83 (s, 1H), 8.08 (dd, J = 7.6, 1.6 Hz, mp 258─260 oC; 1H NMR (400 MHz, CDCl3) δ 2.14 (s, 3H), 2.51 (s,
1H), 8.16 (dd, J = 8.4, 1.6 Hz, 1H), 11.70 (s, 1H); 13C NMR (100 3H), 6.94 (d, J = 8.8 Hz, 1H), 7.30 (dd, J = 8.4, 2.0 Hz, 1H), 7.39–
View Article Online
MHz, CDCl3) δ 185.2, 164.1, 160.5, 157.9, 154.5, 152.7, 137.8, 7.43 (m, 2H), 7.47 (dd, J = 8.4, 2.0 Hz, 1H), 7.63–7.69 (m, 4H), 7.80
DOI: 10.1039/C4OB02490G
133.5, 131.5, 125.8, 122.7, 120.2, 119.6, 118.9, 118.4, 112.6, 112.3; (d, J = 1.2 Hz, 1H), 11.27 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
HMRS m/z [M+H]+ calcd for C18H11O5: 307.0606; found: 307.0604.
2-(2-Hydroxybenzoyl)-3-methyl-4H-furo[3,2-c]chromen-4-one
187.0, 161.8, 159.4, 157.2, 152.3, 147.8, 138.8, 135.6, 134.5, 133.7,
132.2, 132.0, 131.5, 131.1, 128.7, 121.8, 118.8, 118.5, 117.8, 113.3,
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(4x): Yellow solid, yield 294 mg (92%); mp 208–210 C; H NMR 111.8, 110.0, 21.4, 20.7; HMRS m/z [M+H]+ calcd for C27H18NO5:
(400 MHz, CDCl3) δ 2.78 (s, 3H), 7.02 (t, J = 7.6 Hz, 1H), 7.08 (d, J 436.1185; found: 436.1184.
= 8.4 Hz, 1H), 7.42 (t, J = 7.6 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.55 3-(2,4-Dichlorophenyl)-2-(2-hydroxy-5-methylbenzoyl)-8-meth-
(td, J = 8.4, 1.2 Hz, 1H), 7.63 (td, J = 8.4, 0.8 Hz, 1H), 7.95 (dd, J = yl-4H-furo[3,2-c]chromen-4-one (5d): Yellow solid, yield 445 mg
8.0, 1.2 Hz, 1H), 8.26 (dd, J = 8.0, 1.2 Hz, 1H), 12.08 (s, 1H); 13C (93%); mp 138–140 oC; 1H NMR (400 MHz, CDCl3) δ 2.20 (s, 3H),
NMR (100 MHz, CDCl3) δ 186.1, 163.4, 157.6, 157.3, 153.5, 148.1, 2.51 (s, 3H), 6.91 (d, J = 8.4 Hz, 1H), 7.28–7.31 (m, 2H), 7.34 (d, J
136.2, 132.8, 132.2, 131.1, 124.6, 121.4, 118.8, 118.4, 117.3, 111.7, = 1.6 Hz, 1H), 7.39 (dd, J = 8.8, 2.0 Hz, 2H), 7.46 (dd, J = 8.4, 1.6
111.6, 10.7; HMRS m/z [M+H]+ calcd for C19H13O5: 321.0763; Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H), 7.82 (d, J = 0.8 Hz, 1H), 11.18 (s,
found: 321.0763.
1H); 13C NMR (100 MHz, CDCl3) δ 186.0, 161.0, 158.7, 156.3,
2-(2-Hydroxybenzoyl)-3-propyl-4H-furo[3,2-c]chromen-4-one
152.0, 148.0, 138.1, 135.0, 133.8, 132.5, 132.2, 131.3, 130.6, 130.4,
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(4y): Yellow solid, yield 285 mg (82%); mp 201–202 C; H NMR 130.1, 128.2, 128.1, 121.4, 118.2, 118.1, 117.4, 111.5, 110.7, 21.0,
(400 MHz, CDCl3) δ 1.05 (t, J = 7.6 Hz, 3H), 1.77–1.83 (m, 2H), 20.2; HMRS m/z [M+H]+ calcd for C26H17Cl2O5: 479.0453; found:
3.21 (t, J = 7.6 Hz, 2H), 7.02 (td, J = 8.0, 1.2 Hz, 1H), 7.09 (dd, J = 479.0453.
8.4, 1.6 Hz, 1H), 7.41 (td, J = 7.6, 0.8 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2-(2-Hydroxy-5-methylbenzoyl)-8-methyl-4H-furo[3,2-c]chrom-
o
1H), 7.56 (td, J = 8.4, 1.6 Hz, 1H), 7.63 (td, J = 8.4, 1.6 Hz, 1H), en-4-one (5e): Yellow solid, yield 293 mg (88%); mp 196–198 C;
7.95 (dd, J = 8.0, 1.2 Hz, 1H), 8.25 (dd, J = 8.4, 1.6 Hz, 1H), 12.09 1H NMR (400 MHz, CDCl3) δ 2.39 (s, 3H), 2.50 (s, 3H), 7.01 (d, J =
(s, 1H); 13C NMR (100 MHz, CDCl3) δ 186.5, 163.7, 158.0, 157.3, 8.8 Hz, 1H), 7.38–7.47 (m, 3H), 7.77 (s, 1H), 7.85 (dd, J = 8.0, 1.2
153.8, 148.2, 137.7, 136.4, 132.4, 131.5, 124.9, 121.6, 119.2, 119.1, Hz, 2H), 11.46 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 184.2, 160.9,
118.7, 117.6, 112.1, 111.5, 26.4, 23.0, 14.0; HMRS m/z [M+H]+ 159.5, 157.2, 151.6, 151.3, 137.8, 134.8, 133.5, 130.0, 128.4, 121.3,
calcd for C21H17O5: 349.1076; found: 349.1077.
General procedure for the synthesis of 5
118.3, 117.9, 117.8, 117.1, 111.2, 111.1, 20.6, 20.4; HMRS m/z
[M+H]+ calcd for C20H15O5: 335.0919; found: 335.0932.
A mixture of 6-substituted 4-hydroxycoumarin 3 (2.0 mmol), 3-(4-Bromophenyl)-8-chloro-2-(5-chloro-2-hydroxybenzoyl)-4H-
aldehydes 2 (1.2 mmol), pyridine (3.0 mmol), and copper bromide furo[3,2-c]chromen-4-one (5f): Yellow solid, yield 455 mg (86%);
o
1
(0.1 mmol) in acetonitrile (15 ml) was refluxed for 12 h with mp 223–224 C; H NMR (400 MHz, CDCl3) δ 7.00 (d, J = 8.8 Hz,
magnetic stirring under 1 atm of O2. After the reaction was 1H), 7.38–7.48 (m, 4H), 7.55–7.63 (m, 3H), 7.70 (d, J = 2.4 Hz, 1H),
completed, the solvent was removed under reduced pressure, and the 7.99 (d, J = 2.4 Hz, 1H), 11.39 (s, 1H); 13C NMR (100 MHz, CDCl3)
residue was separated by flash chromatography on a silica gel δ 185.6, 161.8, 157.7, 155.9, 152.0, 147.0, 137.0, 133.0, 132.8, 131.8,
column with ethyl acetate/ petroleum ether (1:10) as eluent to give 131.6, 131.0, 130.9, 126.5, 124.4, 124.1, 121.3, 120.2, 119.1, 118.9,
products 5.
112.8, 110.7; HMRS m/z [M+H]+ calcd for C24H12BrCl2O5:
3-(4-Chlorophenyl)-2-(2-hydroxy-5-methylbenzoyl)-8-meth-yl-
4H-furo[3,2-c]chromen-4-one (5a): Yellow solid, yield 398 mg
(90%); mp 223–225 oC; 1H NMR (400 MHz, CDCl3) δ 2.10 (s, 3H),
2.50 (s, 3H), 6.92 (d, J = 7.6 Hz, 1H), 7.26–7.28 (m, 1H), 7.33–7.40
(m, 4H), 7.44–7.47 (m, 3H), 7.81 (d, J = 0.8 Hz, 1H), 11.33 (s, 1H);
13C NMR (100 MHz, CDCl3) δ 187.0, 161.1, 158.9, 156.9, 151.9,
147.0, 138.1, 135.5, 135.0, 133.8, 131.8, 131.7, 131.4, 128.4, 128.2,
126.8, 121.4, 118.1, 118.0, 117.3, 111.6, 109.8, 21.0, 20.2; HMRS
m/z [M+H]+ calcd for C26H18ClO5: 445.0843; found: 445.0844.
3-(4-Bromophenyl)-2-(2-hydroxy-5-methylbenzoyl)-8-methyl-
4H-furo[3,2-c]chromen-4-one (5b): Yellow solid, yield 449 mg
(92%); mp 238─240 oC; 1H NMR (400 MHz, CDCl3) δ 2.10 (s, 3H),
2.50 (s, 3H), 6.92 (d, J = 8.4 Hz, 1H), 7.28 (d, J = 2.0 Hz, 1H), 7.36–
7.40 (m, 4H), 7.44–7.51 (m, 3H), 7.80 (d, J = 2.0 Hz, 1H), 11.32 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 187.1, 161.2, 158.9, 157.0,
151.9, 147.0, 138.2, 135.1, 133.9, 132.0, 131.8, 131.5, 131.4, 128.3,
127.3, 123.9, 121.5, 118.2, 118.1, 117.3, 111.6, 109.8, 21.0, 20.3;
HMRS m/z [M+H]+ calcd for C26H18BrO5: 489.0338; found:
489.0350.
528.9245, found 528.9258.
Acknowledgements
The authors gratefully acknowledge National Natural Science
Foundation of China (NSFC 21172188, 21202101, 21202058), the
Key Project of Natural Science Research of Universities in Jiangsu
Province (14KJA430003), and the Priority Academic Program
Development of Jiangsu Higher Education Institutions (PAPD) for
financial support of this work..
Notes and references
a
Jiangsu Key Laboratory of Green Synthesis for Functional Materials
and School of Chemistry and Chemical Engineering, Jiangsu Normal
University, Xuzhou 221116, Jiangsu, P. R. China; E-mail:
wuhui72@126.com; liu__yun3@sina.com
b
School of Chemistry and Chemical Engineering, Shaoxing University,
Shaoxing, Zhejiang, P. R. China
c
Jiangsu Key Laboratory for Chemistry of Low-Dimensional Materials,
School of Chemistry and Chemical Engineering, Huaiyin Normal
University, Huaian 223300, Jiangsu, P. R. China
4-(2-(2-Hydroxy-5-methylbenzoyl)-8-methyl-4-oxo-4H-furo[3,2-c]
chromen-3-yl)benzonitrile (5c): Yellow solid, yield 421 mg (97%);
The contributions of Zhang and Yue are equal.
6 | J. Name., 2012, 00, 1‐3
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ARTICLE
†
Electronic Supplementary Information (ESI) available: [details of any
11 Y. R. Lee, B. S. Kim and H. C. Wang, Tetrahedron, 1998, 54, 12215.
supplementary information available should be included here]. See
DOI: 10.1039/c000000x/
12 Z. Zeinab, K. Mehdi, R. Ali, F. Alireza, S. Ali, S. Katarzyna, L.
Tadeusz and S. Abbas, Tetrahedron, 2012, 68, 6721. View Article Online
DOI: 10.1039/C4OB02490G
13 For recent examples, see (
T.-P. Loh, Angew. Chem., Int. Ed., 2012, 51, 9105; (
and K. R. Prabhu, Chem.-Eur. J., 2012, 18, 14638; ( ) Y. Wei, S.-X.
a
) J.-S. Tian, K. W. J. Ng, J.-R. and Wong,
1
(
a
) A. R. Katritzky, S. R. Tala, H. Lu, A. V. Vakulenko, Q. Y. Chen,
J. Sivapackiam, K. Pandya, S. B. Jiang and A. K. Debnath, J. Med.
Chem., 2009, 52, 7631; ( ) B. L. Flynn, E. Hamel and M. K. Jung, J.
Med. Chem., 2002, 45, 2670; ( ) L. Racane, V. Tralic-Kulenovic, S.
b
) M. Lamani
c
b
Lin, H.-X. Xue, F.-S. Liang and B.-Z. Zhao, Org. Lett., 2012, 14
,
c
712.
K. Pavelic, I. Ratkaj, P. Peixoto, R. Nhili, S. Depauw, M. P. 14
(
a
) T. Miura, M. Morimoto and M. Murakami, Org. Lett., 2012, 14
5214; (
Chem., Int. Ed., 2012, 51, 11827.
) X. L. Hou, H. Y. Cheung, T. Y. Hon, P. L. 15 R. W. Evans, J. R. Zbieg, S.-L. Zhu, W. Li and D. W. C. MacMillan,
Kwan, T. H. Lo, S. Y. Tong and H. N. C. Wong, Tetrahedron, 1998, J. Am. Chem. Soc., 2013, 135, 16074.
54, 1955; ( ) T. L. Gilchrist, J. Chem. Soc., Perkin Trans. 1, 2001, 16 ) F.-Y. Wang, Y.-M. Shen, H.-Y. Hu, X.-S. Wang, H. Wu and Y.
2491; ( ) M. M. Bandurraga, W. Fenical, S. F. Donovan and J. Liu, J. Org. Chem., 2014, 79, 9556; ( ) J.-W. Sun, H.-Y. Hu, F.-Y.
Clardy, J. Am. Chem. Soc., 1982, 104, 6463; ( ) F. W. Sum, V. S. Wang, H. Wu and Y. Liu, RSC adv., 2014, , 36498; ( ) J.-W. Sun,
F.-Y. Wang, H.-Y. Hu, X.-S. Wang, H. Wu and Y. Liu, J. Org.
Chem., 2014, 79, 3992; ( ) J.-W. Sun, X.-S. Wang and Y. Liu, J.
Org. Chem., 2013, 78, 10560; ( ) Y. Liu, H.-Y. Hu, X.-B. Su, J.-W.
,
Hildebrand, M. H. David-Cordonnier, K. Pavelic and G. Karminski-
b
) N. Matsuda, K. Hirano, T. Satoh and M. Miura, Angew.
Zamola, J. Med. Chem., 2010, 53, 2418; (
Rev., 1986, 86, 795; (
d) B. H. Lipshutz, Chem.
e
f
(a
g
b
h
4
c
Wong, H. E. Largis and R. Malvey, Bioorg. Med. Chem. Lett., 2003,
13, 2191.
d
2
3
For recent reviews of furan synthesis, see: (
H. M. Elwahy, Curr. Org. Synth., 2013, 10, 425; (
and P. Crochet, Adv. Org. Synth., 2013, , 36; ( ) K.-S. Yeung, X.-
a
) M. R. Shaaban and A.
e
b
) V. Cadierno
Sun, C.-S. Cao and Y.-H. Shi, Eur. J. Org. Chem., 2013, 2020; (
Liu and J.-W. Sun, J. Org. Chem., 2012, 77, 1191.
f) Y.
3
c
S. Peng, J. Wu and X.-L. Hou, Prog. Heterocycl. 17 Kidwai, M.; Bansal, V.; Mothsra, P.; Saxena, S.;Somvanshi, R. K.;
Chem., 2012, 24, 205; ( ) X.-L. Hou, X.-S. Peng, K.-S. Yeung and Dey, S.; Singh, T. P. J. Mol. Cat. A: Chem. 2007 268, 76.
H. N. C. Wong, Sci. Synth., 2011, , 261.
) R. D. H. Murray, in The Natural Coumarins, Occurrence,
Chemistry and Biochemistry; Wiley–Inter-science: New York, NY,
1982; ( ) R. L. J. Edelson, Photochem. Photobiol. B, 1991, 10, 165;
) T. Grese, L. D. Pennington, J. P. Sluka, M. D. Adrian, H. W. 19 For copper-catalyzed decarboxylation reaction, see for examples: (a)
d
,
2
18 In ref. 15, CuBr2 was found to be a suitable catalyst while CuCl2
was significantly less effective. On the basis of this, the
transformation was proposed to proceed via a catalytically generated
(
a
b
α-bromo carbonyl species.
(
c
Cole, T. R. Fuson, D. E. Magee, D. L. Phillips, E. R. Rowley, P. K.
Shetler, L. L. Short, M. Venugopalan, N. N. Yang, M. Sato, A. L.
L. J. Goossen, N. Rodríguez, B. Melzer, C. Linder, G. J. Deng and L.
M. Levy, J. Am. Chem. Soc., 2007, 129, 4824; (
Feng and K. Yang, Org. Lett., 2014, 16, 624.
b) Q. L. Song, Q.
Glasebrook and H. U. Bryant, J. Med. Chem., 1998, 41, 1272; (
Zhao and R. D. Brinton, J. Med. Chem., 2005, 48, 3463; (
Wang, K. Nakagawa-Goto, M. Kozuka, H. Tokuda, H. Nishino and
K.-H. Lee, Pharm. Biol., 2006, 44, 116; ( ) L. Piccagli, M. Borgatti,
E. Nicolis, N. Bianchi, I. Mancini, I. Lampronti, D. Vevaldi, F.
d) L.
e
) X.-H. 20 For examples of transition-metal-catalyzed reaction using molecular
oxygen as the oxidant, see: ( ) W.-Q. Wu and H.-F. Jiang, Acc.
Chem. Res., 2012, 45, 1736; ( ) Z.-Z. Shi, C. Zhang, C.-H. Tang and
N. Jiao, Chem. Soc. Rev., 2012, 41, 3381; ( ) A.-Z. Wang, H.-F.
a
f
b
c
Dall’Acqua, G.
.
Cabrini and R. Gambari, Bioorg. Med. Chem., 2010,
Jiang and H.-J. Chen, J. Am. Chem. Soc., 2009, 131, 3846; (
Wang and H.-F. Jiang, J. Am. Chem. Soc., 2008, 130, 5030.
d) A.-Z.
18, 8341.
4
(
a
) M. Misky and J. Jakupovic, Phyochemistry, 1990, 29, 1995; (
R. H. D. Murray, Progr. Chem. Org. Nat. Prod., 1991, 58, 83; ( ) N.
Schuster, C. Christiansen, J. Jakupovic and M. Mungai,
Phytochemistry, 1993, 34, 1179; ( ) D. M. X. Donnelly and G. M.
Boland, Nat. Prod. Rep., 1998, 241; ( ) X. Wang, K. F. Bastow, C.-
M. Sun, Y.-L. Lin, H.-J. Yu, M.-J. Don, T.-S. Wu, S. Nakamura and
K.–H. Lee, J. Med. Chem., 2004, 47, 5816; ( ) X. Wang, K.
b)
c
d
e
f
Nakagawa-Goto, K. F. Bastow, M.-J. Don, Y.-L. Lin, T.-S. Wu and
K.-K. Lee, J. Med. Chem., 2006, 49, 5631.
5
6
F. Risitano, G. Grassi, F. Foti and C. Bilardo, Tetrahedron Lett.,
2001, 42, 3503.
V. Nair, R. S. Menon, A. U. Vinod and S. Viji, Tetrahedron Lett.,
2002, 43, 2293.
7
8
G. Cheng and Y.-H. Hu, Chem. Commun., 2007, 3285.
E. Altieri, M. Cordaro, G. Grassi, F. Risitano and A. Scala,
Tetrahedron, 2010, 66, 9493.
9
G. Raffa, M. Rusch, G. Balme and N. Monteiro, Org. Lett., 2009, 11,
5254.
10 G. Cheng and Y.–H. Hu, J. Org. Chem., 2008, 73, 4732.
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