Palladium-catalyzed domino protodecarboxylation/oxidative Heck reaction: Regioselective arylation of coumarin-3-carboxylic acids

Article abstract of DOI:10.1016/j.tet.2013.10.089

A protocol for straightforward and step-economical synthesis of neoflavones from coumarin-3-carboxylic acids is developed. This approach enables controlled protodecarboxylation/regioselective C-H arylation of coumain-3-carboxylic acids in one-pot using a

Full text of DOI:10.1016/j.tet.2013.10.089

Tetrahedron 69 (2013) 11164e11168
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed domino protodecarboxylation/oxidative Heck
reaction: regioselective arylation of coumarin-3-carboxylic acids
,
Mehdi Khoobi a, Fatemeh Molaverdi b, Masoumeh Alipour b, Farnaz Jafarpour b
*
,
,
Alireza Foroumadi a, Abbas Shafiee a
*
a Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran
14176, Iran
b School of Chemistry, College of Science, University of Tehran, PO Box 14155-6455, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 12 August 2013
Received in revised form 17 October 2013
Accepted 28 October 2013
Available online 1 November 2013
A
protocol for straightforward and step-economical synthesis of neoflavones from coumarin-3-
carboxylic acids is developed. This approach enables controlled protodecarboxylation/regioselective
CeH arylation of coumain-3-carboxylic acids in one-pot using a monometallic catalytic system. A wide
variety of electron-donating and -withdrawing substituents on both coumarins and arylboronic acid are
tolerated under the reaction conditions and 4-aryl coumarins are constructed in high yields.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Domino reaction
Neoflavone
Oxidative Heck reaction
Palladium
Protodecarboxylation
1. Introduction
Calophyllum coumarins, such as calophyllolide II are reported to
have anti-coagulant, anti-tuberculosis, anti-inflammatory, and
The regioselective synthesis of arylcoumarins has become in-
creasingly important, because of their presence in a variety of
natural products and their diverse pharmacological and biological
properties.1 For instance, neoflavones (4-aryl coumarins) of type I
show relevant cytotoxic and antitubulin activities (Fig. 1).2 Also
anti-arthritis activities (Fig. 1).3
Among various methods reported for construction of these
privileged structural motifs, transition-metal-catalyzed cross-cou-
pling reactions of coumarin frameworks activated at the C-4 posi-
tion are among the most important.4 Very recently, we and others
have developed more efficient palladium-catalyzed CeH func-
tionalization reactions for direct arylation of coumarins at C-4 via
oxidative addition of arylboronic acids and arenes to coumarins.5
On the other hand, the convenient ring-closure reactions for con-
struction of coumarins6 leaves behind a surplus carboxylate group
at C-3, which should be removed before arylation of coumarins.
One might therefore expect that decarboxylative arylation of these
scaffolds would find significant utility in organic synthesis. The
documented combination of CeH functionalization of aromatic
carboxylic acids with a concomitant decarboxylation is limited
exclusively to arenes.7 The direct CeH arylation of ortho-
substituted heteroarene carboxylic acids with a subsequent re-
moval of the carboxylate group by in situ protodecarboxylation
however remains largely unexplored.8
In this context, we have demonstrated an efficient palladium-
catalyzed arylation of coumarin-3-carboxylic acids with iodoar-
enes (Scheme 1, Path a).9 In this work, C-3 arylation proceeded
regioselectively, and 4-arylated coumarins were not detected. In
this paper, we set out to explore C-4 arylation of these heteroarene
Fig. 1. 4-Aryl coumarins with biological activities.
* Corresponding authors. Tel.: þ98 21 61112480; fax: þ98 21 66495291 (F.J.); tel.:
þ98 21 66406757; fax: þ98 21 66461178 (A.S.); e-mail addresses: jafarpur@
khayam.ut.ac.ir (F. Jafarpour), ashafiee@ams.ac.ir (A. Shafiee).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.10.089

M. Khoobi et al. / Tetrahedron 69 (2013) 11164e11168
11165
carboxylic acids using arylboronic acids in place of iodoarenes
(Scheme 1, Path b). This transformation could be achieved by a two-
step sequence involving protodecarboxylation of coumarin-3-
carboxylic acid10 and subsequent oxidative cross-coupling with
arylboronic acid coupling partners11 using the same catalytic sys-
tem. The reaction features attractive synthetic attributes, such as
protodecarboxylation/direct arylation in one-pot, regioselective
functionalization, tolerance of a wide variety of functional groups
and mild reaction conditions without the requisite for addition of
Ag salts or acids for protodecarboxylation.
place of PdCl2, established Pd(OAc)2 as the most effective catalyst
for promoting the cross-coupling reaction where, desired 4-
phenylcoumarin 3a was obtained in 80% yield (entries 3e5). Fur-
ther optimizations, which included screening ligands and the ad-
dition of bases, did not give any satisfactory results (entries 6e9).
No biaryl product was observed in the absence of the oxidant, and
the oxidant’s properties were critical to the cross-coupling effi-
ciency, evidenced by the observation that replacing O2 with
Na2S2O8 dramatically diminished the yield (entry 10). Finally,
a solvent screen was performed; DMF was replaced with solvents,
such as 1,4-dioxane, amyl alcohol, n-butanol and H2O, but the de-
sired product was obtained in lower yields (entries 11e13).
We were pleased to see that under the optimized reaction
conditions a tandem protodecarboxylation/CeH arylation reaction
occurred, leading to the exclusive formation of C-4 arylated product
despite the presence of the carboxylic acid group at the C-3 posi-
tion. 3-Arylcoumarin was not observed and regioselective efficient
C-4 arylation of coumarin was accompanied with CO2 extrusion/
protonation at C-3 in 80% yield. It is also noteworthy that proto-
decarboxylation was accomplished in the absence of silver salts or
catalytic amounts of acids in lower temperature compared with the
previous protodecarboxylation reactions.10
With the optimized reaction conditions in hand, we next stud-
ied the scope and limitations of the protodecarboxylation cross-
coupling procedure with various substituted coumarins and aryl-
boronic acids (Table 2). The results showed that various electron-
donating and electron-withdrawing substituents including alkyl,
halo, methoxy and nitro groups were tolerated under the optimized
reaction conditions. To our delight, the C-4 functionalization and
protodecarboxylation of coumarins with p-fluoro and -bromophe-
nylboronic acids were accomplished in 80% and 65% yields, re-
spectively (3b and 3c). With alkyl substituted boronic acids and
coumarins, 4-aryl coumarins 3def were also obtained in high
yields. It is noteworthy that coumarins containing relatively labile
CeBr bonds were tolerated under the reaction conditions, offering
an opportunity for further arylation or alkenylation reactions at C-6
Scheme 1. Regioselectivity in arylation of coumarin-3-carboxylic acids.
2. Results and discussion
We initially focused on the cross-coupling of coumarin 1a and
phenylboronic acid 2a as test substrates to explore the prospect of
the proposed palladium-catalyzed direct arylation reaction. Negli-
gible activity was observed applying our previous reaction condi-
tions for decarboxylative arylation of coumarin-3-carboxylic acids
(Table 1, entry 1). Next we examined protodecarboxylation/aryla-
tion reaction of coumarin using a catalytic system comprising
PdCl2/phen, and gratifyingly 4-phenylcoumarin 3a was obtained
albeit in a 15% yield (entry 2). Using other palladium sources in
and facilitating synthesis of
p-electron extended coumarins. The
cross-coupling reaction of 6-bromocoumarin with unsubstituted
and p-chloro substituted arylboronic acids proceeded successfully,
affording the desired products 3h and 3i in yields exceeding 70%.
Next it was desirable to extend the scope of this regioselective
arylation reaction to construct methoxy neoflavones as the pres-
ence of methoxyphenyl moieties in these compounds, increase
their potent antileishmanial activity.1c In this context, 7-methoxy
coumarin was reacted with phenylboronic acid and, gratifyingly,
C-4 arylated coumarin 3g was obtained in high yield. Regioselective
C-4 arylation of 6-nitrocoumarins, which is not feasible in direct
arylation reactions with simple arenes, were also proceeded
smoothly to give desired products 3jel in good to high yields. Direct
arylation of coumarin with 2,4-difluorophenyl boronic acid, how-
ever, was not successful. Further investigations showed that p-
methoxy substituted boronic acid was also amenable to this ary-
lation reaction and the related product 3n was obtained in satis-
factory yield. 3,5-Dimethylphenylboronic acid and a sterically
hindered boronic acid with an o-methyl substituent also afforded
the desired 4-aryl coumarins 3o and 3p in good to moderate yields.
We also investigated the reaction scope with electron-deficient
boronic acids with a nitro substituent. Unfortunately, the corre-
sponding arylated coumarin 3r was not observed.
Table 1
Screening of the reaction conditions for domino CeH arylation and decarboxylation
of 1aa
Entry
Catalyst
Ligand
Base
Solvent
Yield (%)b
1
2
3
4
5
6
7
8
PdCl2
PdCl2
d
Ag2CO3
d
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
1,4-Dioxane
Amyl alcohol
H2O
0
Phen
Phen
Phen
Phen
Dmphen
Bpy
Phen
Phen
Phen
Phen
Phen
Phen
15
30
14
80c
Trace
30
0
Pd(acac)2
Pd(PPh3)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
d
d
d
d
d
Cs2CO3
K2CO3
d
9
0
10
11
12
13
20d
15
20
12
d
d
This process is likely to proceed via
a tandem proto-
d
decarboxylation/arylation, as depicted in Scheme 2. A palladium-
catalyzed controlled protodecarboxylation at C-3 is followed by
a regioselective oxidative Heck reaction at C-4 (Scheme 2). When
coumarin-3-carboxylic acid was submitted to the reaction condi-
tions in the absence of arylboronic acid, protodecarboxylated cou-
marin was isolated in 46% yield. Also beside the desired 4-aryl
a
All reactions were run under the following conditions: phenylboronic acid
(2 equiv), catalyst (10 mol %), ligand (20 mol %), base (2 equiv), O2 (balloon pressure)
in solvent (0.3 M) were heated in a sealed tube at 100 ꢀC for 24 h.
b
Isolated yields.
Optimized reaction conditions.
Na2S2O8 was used as oxidant.
c
d

11166
M. Khoobi et al. / Tetrahedron 69 (2013) 11164e11168
coumarin, coumarin was observed during the reaction. When the
reaction of coumarin-3-carboxylic acid 1a and phenylboronic acid
2a was interrupted at different time intervals of 4, 8 and 12 h, the
protodecarboxylated coumarin was obtained in 24%, 38% and 10%
yields, respectively. The results show an initial formation of pro-
todecarboxylated coumarin in the course of reaction, which is then
consumed to afford the desired arylated coumarin.
Scheme 3. Direct arylation of coumarin at C-4.
Table 2
Scope of domino protodecarboxylation/oxidative Heck reaction of coumarinsa
3. Summary and conclusions
In summary, we have developed a monometallic catalyst for effi-
cient, regioselective and step-economical domino proto-
decarboxylation/arylation of coumarin-3-carboxylic acids. No base or
co-catalyst was required for protodecarboxylation and O2 was suc-
cessfully utilized as the sole oxidant for the oxidative Heck coupling.
Protodecarboxylation of a wide range of coumarin-3-carboxylic acids
regardless of their substitution pattern was proceeded smoothly and
followed by direct arylation with a wide range of arylboronic acids.
This protocol provided a new route to neoflavone backbones, which
are privileged motifs in many biologically active compounds. Ex-
pansion of the derived methodology to heterocycles and their sub-
sequent functionalizations are under investigation.
4. Experimental section
4.1. General remarks
Scheme 2. Plausible reaction mechanism.
Anhydrous solvents were systematically used. DMF and amyl
alcohol were distilled under nitrogen from CaH2 and immediately
ꢀ
Furthermore, the reaction of coumarin and phenylboronic acid
under the optimized reaction condition afforded the desired 4-aryl
coumarin in 82% isolated yield (Scheme 3).
used or stored under 4 A molecular sieves. 1,4-Dioxane was
ꢀ
refluxed over Na and benzophenone, distilled and stored over 4 A
molecular sieves in the dark. Other reagents, palladium catalysts

M. Khoobi et al. / Tetrahedron 69 (2013) 11164e11168
11167
and ligands were commercially available and used as received.
These reactions were carried out in an oil bath using microwave
vials (2e5 mL). 1H and 13C NMR spectra were recorded at room
temperature on 500 MHz spectrometers using CDCl3 as the NMR
42e44 ꢀC (Ref.141e44 ꢀC); vmax 1737 cmꢁ1
;
dH (500 MHz, CDCl3) 1.35
(3H, t, J 7.5 Hz, CH2eCH3), 2.35 (3H, s, CH3), 2.77 (2H, q, J 7.5 Hz,
CH2eCH3), 6.35 (1H, s, ]CH), 7.30e7.31 (2H, d, J 8.3 Hz, Ph), 7.35e7.40
(5H, m, Ph); dC (125 MHz, CDCl3) 15.3, 20.9, 28.4, 114.8, 117.0, 118.7,
126.7, 127.3, 128.5, 128.6, 132.7, 133.6, 146.0, 152.3, 155.7, 161.1.
solvent. 1H NMR spectra are referenced to tetramethylsilane and 13
C
NMR spectra are referenced from the solvent central peak. Chem-
ical shifts are given in parts per million. IR is reported as charac-
teristic bands (cmꢁ1) in their maximal intensity.
4.2.7. 7-Methoxy-4-phenyl-2H-chromen-2-one (3g). Operation as
above with 7-methoxy-2-oxo-2H-chromene-3-carboxylic acid
(0.1 mmol), phenylboronic acid (0.2 mmol, 2 equiv), compound 3g
was obtained as white solid (0.018 g, 70%), mp 116e118 ꢀC (Ref. 5a
4.2. Synthesis of 4-aryl coumarins
114e116 ꢀC); vmax 1734 cmꢁ1
; dH (500 MHz, CDCl3) 3.89 (3H, s,
4.2.1. 4-Phenyl-2H-chromen-2-one (3a). A vial equipped with a stir
bar was charged with coumarin-3-carboxylic acid (0.1 mmol),
phenylboronic acid (0.2 mmol, 2 equiv), Pd(OAc)2 (10 mol %),
phenanthroline (20 mol %). DMF (0.3 M) was added and the vial
was capped and degassed. The resulting mixture was heated under
O2 (balloon pressure) in an oil bath at 100 ꢀC for 24 h, cooled then
filtered through a short plug of silica. Purification of the crude
product by flash column chromatography (10% EtOAc/hexane)
afforded the corresponding product 3a as white solid (0.018 g, 80%),
OCH3), 6.23 (1H, s, ]CH), 6.81 (1H, dd, J 8.9, 2.4 Hz, Ph), 6.90 (1H, d,
J 2.4 Hz, Ph), 7.39 (1H, d, J 8.9 Hz, Ph), 7.43e7.45 (2H, m, Ph),
7.51e7.53 (3H, m, Ph); dC (125 MHz, CDCl3) 55.8, 101.1, 111.8, 112.3,
127.9, 128.3, 128.8, 129.6, 130.9, 132.3, 135.6, 155.8, 161.2, 162.8.
4.2.8. 6-Bromo-4-phenyl-2H-chromen-2-one (3h). Operation as
above with 6-bromo-2-oxo-2H-chromene-3-carboxylic acid
(0.1 mmol), phenylboronic acid (0.2 mmol, 2 equiv), compound 3h
was obtained as white solid (0.023 g, 77%), mp 163e165 ꢀC (Ref. 13
mp 79e81 ꢀC (Ref. 4g 74e76 ꢀC); vmax 1765 cmꢁ1
;
dH (500 MHz,
161e163 ꢀC); vmax 1727 cmꢁ1
; dH (500 MHz, CDCl3) 6.42 (1H, s, ]
CDCl3) 6.40 (1H, s, ]CH), 7.26 (1H, t, J 7.5 Hz, Ph), 7.42e7.57 (8H, m,
Ph); dC (125 MHz, CDCl3) 115.1,117.3,124.2,126.9,128.4,128.9,129.7,
130.9, 131.9, 135.2, 154.2, 155.7, 160.8.
CH), 7.31 (1H, d, J 8.5 Hz, Ph), 7.45e7.57 (6H, m, Ph), 7.65 (1H, d, J
8.5 Hz, Ph); dC (125 MHz, CDCl3) 116.1, 117.1, 119.0, 120.6, 126.8,
128.4, 128.7, 129.1, 130.0, 134.4, 134.8, 153.1, 154.5, 160.1.
4.2.2. 4-(4-Fluorophenyl)-2H-chromen-2-one (3b). Operation as
above with coumarin-3-carboxylic acid (0.1 mmol), (4-
fluorophenyl)boronic acid (0.2 mmol, 2 equiv), compound 3b was
obtained as white solid (0.019 g, 80%), mp 154e156 ꢀC (Ref. 12
4.2.9. 6-Bromo-4-(4-chlorophenyl)-2H-chromen-2-one
(3i). Operation as above with 6-bromo-2-oxo-2H-chromene-3-
carboxylic acid (0.1 mmol), (4-chlorophenyl)boronic acid (0.2 mmol,
2 equiv), compound 3i was obtained as white solid (0.025 g, 74%), mp
156e157 ꢀC); vmax 1732 cmꢁ1
;
dH (500 MHz, CDCl3) 6.38 (1H, s, ]
207e209 ꢀC; vmax 1732 cmꢁ1
; dH (500 MHz, CDCl3) 6.40 (1H, s, ]CH),
CH), 7.24e7.27 (4H, m, Ph), 7.42e7.46 (3H, m, Ph), 7.58 (1H, t, J
7.3 Hz, Ph); dC (125 MHz, CDCl3) 115.6,116.4,117.7,119.2,124.6,127.1,
130.6, 130.7, 132.4, 146.7, 154.5, 154.7, 160.9.
7.32 (1H, d, J 8.7 Hz, Ph), 7.40 (2H, d, J 7.5 Hz, Ph), 7.54e7.57 (3H, m,
Ph), 7.67 (1H, dd, J 8.8, 2.2 Hz, Ph); dC (125 MHz, CDCl3) 160.6, 154.6,
153.3, 136.1, 134.7, 130.2, 129.2, 128.5, 126.8, 123.5, 119.2, 117.2, 115.1.
C15H8BrClO2 (335.58): calcd C, 53.69; H, 2.40; found C, 53.97; H, 2.51.
4.2.3. 4-(4-Bromophenyl)-6-methyl-2H-chromen-2-one
(3c). Operation as above with 6-methyl-2-oxo-2H-chromene-3-
carboxylic acid (0.1 mmol), (4-bromophenyl)boronic acid
(0.2 mmol, 2 equiv), compound 3c was obtained as white solid
(0.020 g, 65%), mp 105e106 ꢀC (Ref. 5a 104e106 ꢀC); vmax
4.2.10. 6-Nitro-4-phenyl-2H-chromen-2-one (3j). Operation as above
with 6-nitro-2-oxo-2H-chromene-3-carboxylic acid (0.1 mmol),
phenylboronic acid (0.2 mmol, 2 equiv), compound 3j was obtained
as white solid (0.019 g, 70%), mp 208e210 ꢀC (Ref. 5a 208e210 ꢀC);
1725 cmꢁ1
;
dH (500 MHz, CDCl3) 2.35 (3H, s, CH3), 6.34 (1H, s, ]CH),
vmax 1327, 1511, 1729 cmꢁ1
; dH (500 MHz, CDCl3) 6.53 (1H, s, ]CH),
7.19 (1H, s, Ph), 7.31e7.39 (4H, m, Ph), 7.68 (2H, d, J 8.1 Hz, Ph); dC
(125 MHz, CDCl3) 20.4, 114.8, 116.7, 117.8, 123.5, 125.8, 129.5, 130.6,
132.6, 133.5, 133.7, 151.8, 153.9, 160.2.
7.47e7.49 (3H, m, Ph), 7.54e7.56 (2H, m, Ph), 7.60 (1H, dd, J 7.2,
2.2 Hz, Ph), 8.42e8.44 (2H, m, Ph); dC (125 MHz, CDCl3) 116.7, 118.5,
123.0, 126.7, 128.2, 129.4, 130.5, 133.7, 143.9, 154.6, 157.7, 158.0.
4.2.4. 4-(p-Tolyl)-2H-chromen-2-one (3d). Operation as above with
coumarin-3-carboxylic acid (0.1 mmol), p-tolylboronic acid
(0.2 mmol, 2 equiv), compound 3d was obtained as white solid
4.2.11. 6-Nitro-4-(p-tolyl)-2H-chromen-2-one (3k). Operation as
above
with
6-nitro-2-oxo-2H-chromene-3-carboxylic
acid
(0.1 mmol), p-tolylboronic acid (0.2 mmol, 2 equiv), compound 3k
(0.017 g, 70%), mp 81e83 ꢀC (Ref. 5a 79e81 ꢀC); vmax 1745 cmꢁ1
; dH
was obtained as white solid (0.021 g, 75%), mp 215e217 ꢀC (Ref. 5a
(500 MHz, CDCl3) 2.46 (3H, s, CH3), 6.38 (1H, s, ]CH), 7.24 (1H, t, J
7.8 Hz, Ph), 7.33e7.37 (4H, m, Ph), 7.42 (1H, d, J 7.8 Hz, Ph),
7.53e7.57 (2H, m, Ph); dC (125 MHz, CDCl3) 21.3, 114.8, 117.3, 119.0,
124.1, 127.0, 128.4, 129.5, 131.8, 132.3, 139.9, 154.2, 155.7, 160.8.
214e216 ꢀC); vmax 1338, 1516, 1731 cmꢁ1
; dH (500 MHz, CDCl3) 2.48
(3H, s, CH3), 6.50 (1H, s, ]CH), 7.35e7.40 (4H, m, Ph), 7.53 (1H, d, J
8.9 Hz, Ph), 8.42 (1H, dd, J 8.9, 2.7 Hz, Ph), 8.47 (1H, d, J 2.7 Hz, Ph);
dC (125 MHz, CDCl3) 21.4,116.3,118.4,119.4,123.1,126.6,128.2,130.1,
130.8, 140.9, 143.9, 154.7, 157.7, 159.0.
4.2.5. 4-(4-Ethylphenyl)-2H-chromen-2-one (3e).5a Operation as
above with coumarin-3-carboxylic acid (0.1 mmol), (4-ethylphenyl)
boronic acid (0.2 mmol, 2 equiv), compound 3e was obtained as an
4. 2.12. 4-(4-Ethylphenyl)-6-nitro-2H-chromen-2-one
(3l).5a Operation as above with 6-nitro-2-oxo-2H-chromene-3-
carboxylic acid (0.1 mmol), 4-ethylphenylboronic acid (0.2 mmol,
2 equiv), compound 3l was obtained as an oil (0.019 g, 65%); vmax
oil (0.018 g, 70%); vmax 1724 cmꢁ1
; dH (500 MHz, CDCl3) 1.30 (3H, t, J
7.6 Hz, CH3), 2.77 (2H, q, J 7.6 Hz, CH2), 6.38 (1H, s, ]CH), 7.24 (1H, dt,
J 8.4, 1.2 Hz, Ph), 7.35e7.41 (4H, m, Ph), 7.42 (1H, d, J 8.4 Hz, Ph),
7.54e7.57 (2H, m, Ph); dC (125 MHz, CDCl3) 15.4, 28.7, 114.9, 117.3,
119.0, 124.0, 127.0, 128.3, 128.5, 131.8, 132.5, 146.2, 154.2, 155.7, 160.9.
1337, 1505, 1730 cmꢁ1
; dH (500 MHz, CDCl3) 1.33 (3H, t, J 7.6 Hz,
CH3), 2.80 (2H, q, J 7.6 Hz, CH2), 6.51 (1H, s, ]CH), 7.39e7.44 (4H, m,
Ph), 7.54 (1H, d, J 9.0 Hz, Ph), 8.42 (1H, dd, J 9.0, 2.6 Hz, Ph), 8.49 (1H,
d, J 2.6 Hz, Ph); dC (125 MHz, CDCl3) 15.3, 28.7, 116.3, 118.4, 119.4,
123.1, 126.5, 128.3, 128.9, 131.0, 143.9, 147.1, 154.7, 157.7, 159.0.
4. 2 . 6 . 4-(4-Ethylphenyl)-6-methyl-2H-chromen-2-one
(3f).5a Operation as above with 6-methyl-2-oxo-2H-chromene-3-
carboxylic acid (0.1 mmol), (4-ethylphenyl)boronic acid (0.2 mmol,
2 equiv), compound 3f was obtained as white solid (0.017 g, 65%), mp
4.2.13. 4-(4-Methoxyphenyl)-2H-chromen-2-one (3n). Operation as
above with 2H-chromene-3-carboxylic acid (0.1 mmol), 4-

11168
M. Khoobi et al. / Tetrahedron 69 (2013) 11164e11168
Chem. 2010, 3945e3955; (h) Oh, S.; Jang, H. J.; Ko, S. K.; Ko, Y.; Park, S. B. J. Comb.
Chem. 2010, 12, 548e558; (i) Rieke, R. D.; Kim, S.-H. Tetrahedron Lett. 2011, 52,
3094e3096; (j) Wong, P. Y.; Chow, W. K.; Chung, K. H.; So, C. M.; Lau, C. P.;
Kwong, F. Y. Chem. Commun. 2011, 8328e8330; (k) Xing, C.-H.; Lee, J.-R.; Tang,
Z.-Y.; Zheng, J. R.; Hu, Q.-S. Adv. Synth. Catal. 2011, 353, 2051e2059.
5. (a) Khoobi, M.; Alipour, M.; Zarei, S.; Jafarpour, F.; Shafiee, A. Chem. Commun.
2012, 2985e2987; (b) Li, Y.; Qi, Z.; Wang, H.; Fu, X.; Duan, C. J. Org. Chem. 2012,
77, 2053e2057; (c) Min, M.; Hong, S. Chem. Commun. 2012, 9613e9615.
6. For selected recent examples see: (a) Scott, J. L.; Raston, C. L. Green. Chem. 2000,
2, 245e247; (b) Maggi, R.; Bigi, F.; Carloni, S.; Mazzacani, A.; Sartori, G. Green.
Chem. 2001, 3, 173e174; (c) Song, A.; Wang, X.; Lam, K. S. Tetrahedron Lett. 2003,
44, 1755e1758; (d) Lepore, S. D.; He, Y. J. Org. Chem. 2003, 68, 8261e8263; (e)
Ranu, B. C.; Jana, R. Eur. J. Org. Chem. 2006, 3767e3770; (f) Heravi, M. M.;
Sadjadi, S.; Oskooie, H. A.; Hekmat Shoar, R.; Bamoharram, F. Catal. Commun.
2008, 9, 470e474; (g) Bardajee, G. R.; Jafarpour, F.; Afsari, H. S. Cent. Eur. J. Chem.
2010, 8, 370e374.
methoxyphenylboronic acid (0.2 mmol, 2 equiv), compound 3n was
obtained as white solid (0.015 g, 58%), mp 127e128 ꢀC (Ref. 5b
128e129 ꢀC); dH (500 MHz, CDCl3) 3.91 (3H, s, CH3), 6.36 (1H, s,
]CH), 7.00e7.09 (2H, m, Ph), 7.22e7.29 (1H, m, Ph), 7.38e7.47 (3H,
m, Ph), 7.52e7.61 (2H, m, Ph); dC (125 MHz, CDCl3) 55.7, 114.4, 114.8,
117.6, 119.4, 124.3, 127.3, 127.6, 130.2, 132.0, 154.5, 155.5, 161.1, 161.2.
4.2.14. 4-(3,5-Dimethylphenyl)-2H-chromen-2-one (3o). Operation
as above with 2H-chromene-3-carboxylic acid (0.1 mmol), (3,5-
dimethylphenyl)boronic acid (0.2 mmol, 2 equiv), compound 3o
was obtained as white solid (0.017 g, 68%), mp 136e139 ꢀC (Ref. 5b
138e140 ꢀC); dH (500 MHz, CDCl3) 2.39 (6H, s, 2CH3), 6.33 (1H, s, ]
CH), 7.04e7.05 (2H, m, Ph), 7.14e7.15 (1H, m, Ph), 7.20e7.24 (1H, m,
Ph), 7.37 (1H, d, J 8.2 Hz, Ph), 7.51e7.55 (2H, m, Ph); dC (125 MHz,
CDCl3) 21.4, 115.0, 117.3, 119.2, 124.2, 126.2, 127.4, 131.4, 132.0, 135.2,
138.8, 154.3, 156.1, 161.0.
7. (a) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett. 2010, 12, 5776e5779;
(b) Cornella, J.; Righi, M.; Larrosa, I. Angew. Chem., Int. Ed. 2011, 50, 9429e9432;
(c) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2011, 76,
3024e3033; (d) Bhadra, S.; Dzik, W. I.; Gooßen, L. J. Angew. Chem., Int. Ed. 2013,
52, 2959e2962.
8. For oxidative vinylation/decarboxylation of heteroarene carboxylic acids see:
(a) Maehara, A.; Tsurugi, H.; Satoh, T.; Miura, M. Org. Lett. 2008, 10, 1159e1162.
9. Jafarpour, F.; Zarei, S.; Olia, M. B. A.; Jalalimanesh, N.; Rahiminejadan, S. J. Org.
Chem. 2013, 78, 2957e2964.
4.2.15. 4-(o-Tolyl)-2H-chromen-2-one (3p). Operation as above
with 2H-chromene-3-carboxylic acid (0.1 mmol), o-tolylboronic
acid (0.2 mmol, 2 equiv), compound 3p was obtained as white solid
(0.011 g, 45%), mp 97e99 ꢀC (Ref. 5b 98e99 ꢀC); dH (500 MHz,
CDCl3) 2.16 (3H, s, CH3), 6.31 (1H, s, ]CH), 7.06e7.08 (1H, m, Ph),
7.16e7.19 (2H, m, Ph), 7.30e7.39 (2H, m, Ph), 7.40e7.42 (2H, m, Ph),
7.51e7.55 (1H, m, Ph); dC (125 MHz, CDCl3) 20.0, 115.8, 117.2, 119.5,
124.4, 126.3, 127.2, 128.6, 129.4, 130.7, 132.1, 134.9, 135.4, 154.0,
156.3, 161.0.
10. Recent examples of protodecarboxylation of (hetero)arene carboxylic acids: (a)
Dickstein, J. S.; Mulrooney, C. A.; O’Brien, E. M.; Morgan, B. J.; Kozlowski, M. C.
Org. Lett. 2007, 9, 2441e2444; (b) Gooßen, L. J.; Thiel, W. R.; Rodríguez, N.;
Linder, C.; Melzer, B. Adv. Synth. Catal. 2007, 349, 2241e2246; (c) Goossen, L. J.;
Manjolinho, F.; Khan, B. A.; Rodríguez, N. J. Org. Chem. 2009, 74, 2620e2623; (d)
Sharma, A.; Kumar, R.; Sharma, N.; Kumar, V.; Sinha, A. K. Adv. Synth. Catal.
2008, 350, 2910e2920; (e) Gooßen, L. J.; Linder, C.; Rodríguez, N.; Lange, P. P.;
Fromm, A. Chem. Commun. 2009, 7173e7175; (f) Cornella, J.; Sanchez, C.; Ba-
nawa, D.; Larrosa, I. Chem. Commun. 2009, 7176e7178; (g) Lu, P.; Sanchez, C.;
Cornella, J.; Larrosa, I. Org. Lett. 2009, 11, 5710e5713; (h) Gooßen, L. J.;
Rodríguez, N.; Linder, C.; Lange, P. P.; Fromm, A. ChemCatChem 2010, 2,
430e442; (i) Zhang, Y.; Jamison, T. F.; Patel, S.; Mainolfi, N. Org. Lett. 2011, 13,
280e283; (j) Cornella, J.; Larrosa, I. Synthesis 2012, 44, 653e676; (k) Tilstam, U.
Org. Process Res. Dev. 2012, 16, 1449e1454; (l) Seo, S.; Taylor, J. B.; Greaney, M. F.
Chem. Commun. 2012, 8270e8272; (m) Jouanno, L.-A.; Sabot, C.; Renard, P.-Y. J.
Org. Chem. 2012, 77, 8549e8555; (n) Dickstein, J. S.; Curto, J. M.; Gutierrez, O.;
Mulrooney, C. A.; Kozlowski, M. C. J. Org. Chem. 2013, 78, 4744e4761 Proto-
decarboxylation of coumarins: (o) Adams, R.; Mathieu, J. J. Am. Chem. Soc. 1948,
70, 2120e2122; (p) Adams, R.; Bockstahler, T. E. J. Am. Chem. Soc. 1952, 74,
5346e5348; (q) Cramer, F.; Windel, H. Chem. Ber. 1956, 89, 354e365; (r)
Worden, L. R.; Kaufman, K. D.; Weis, J. A.; Schaaf, T. K. J. Org. Chem. 1969, 34,
2311e2313; (s) Kawata, H.; Ichikawa, S.; Kumagai, T.; Niizuma, S. Tetrahedron
Lett. 2002, 43, 5161e5163; (t) Posakony, J.; Hirao, M.; Stevens, S.; Simon, J. A.;
Bedalov, A. J. Med. Chem. 2004, 47, 2635e2644; (u) Jafarpour, F.; Jalalimanesh,
N.; Olia, M. B. A.; Kashani, A. O. Tetrahedron 2010, 66, 9508e9511.
Acknowledgements
We gratefully acknowledge the financial support of the Phar-
maceutical Science Research Center, Iranian National Elites Foun-
dation (INEF), Iran National Science Foundation (INSF) and the
University of Tehran.
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.10.089.
11. For reviews on direct arylation reactions with boronic acids see: (a) Sun, C.-L.;
Li, B.-J.; Shi, Z.-J. Chem. Commun. 2010, 677e685; (b) Liu, C.; Zhang, H.; Shi, W.;
Lei, A. Chem. Rev. 2011, 111, 1780e1824 For some recent examples of palladium-
catalyzed direct arylation reactions with aryl boron reagents see: (c) Wei, Y.;
Kan, J.; Wang, M.; Su, W.; Hong, M. Org. Lett. 2009, 11, 3346e3349; (d) Sun, C.-L.;
Liu, N.; Li, B.-J.; Yu, D.-G.; Wang, Y.; Shi, Z.-J. Org. Lett. 2010, 12, 184e187; (e)
Nishikata, T.; Abela, A. R.; Huang, S.; Lipshutz, B. H. J. Am. Chem. Soc. 2010, 132,
4978e4979; (f) Liu, B.; Qin, X.; Li, K.; Li, X.; Guo, Q.; Lan, J.; You, J. Chem.dEur. J.
2010, 16, 11836e11839; (g) Kirchberg, S.; Tani, S.; Ueda, K.; Yamaguchi, J.; Studer,
A.; Itami, K. Angew. Chem., Int. Ed. 2011, 50, 2387e2391; (h) Romero-Revilla, J.
A.; Garcia-Rubia, A.; Arrayas, R. G.; Fernandez-Ibanez, M. A.; Carretero, J. C. J.
Org. Chem. 2011, 76, 9525e9530; (i) Mochida, K.; Kawasumi, K.; Segawa, Y.;
Itami, K. J. Am. Chem. Soc. 2011, 133, 10716e10719; (j) Engle, K. M.; Thuy-Boun,
P. S.; Dang, M.; Yu, J.-Q. J. Am. Chem. Soc. 2011, 133, 18183e18193; (k) Kim, Y. W.;
Niphakis, M. J.; Georg, G. I. J. Org. Chem. 2012, 77, 9496e9503; (l) Kawasumi, K.;
Mochida, K.; Kajino, T.; Segawa, Y.; Itami, K. Org. Lett. 2012, 14, 418e421; (m)
Chu, J.-H.; Wu, C.-C.; Chang, D.-H.; Lee, Y.-M.; Wu, M.-J. Organometallics 2013,
32, 272e282; (n) Yamaguchi, K.; Kondo, H.; Yamaguchi, J.; Itami, K. Chem. Sci.
2013, 4, 3753e3757.
References and notes
1. (a) Argotte-Ramos, R.; Ramírez-Avila, G.; Rodriguez-Gutierrez, M. C.; Ovilla-
Munoz, M.; Lanz-Mendoza, H.; Rodriguez, M. H.; Gonzalez-Cortazar, M.; Al-
varez, L. J. Nat. Prod. 2006, 69, 1442e1444; (b) Matos, M. J.; Vina, D.; Quezada, E.;
~
Picciau, C.; Delogu, G.; Orallo, F.; Santana, L.; Uriarte, E. Bioorg. Med. Chem. Lett.
2009, 19, 3268e3270; (c) Pierson, J.-T.; Dumetre, A.; Hutter, S.; Delmas, F.; Laget,
M.; Finet, J.-P.; Azas, N.; Combes, S. Eur. J. Med. Chem. 2010, 45, 864e869; (d)
Sun, J.; Ding, W. X.; Zhang, K. Y.; Zou, Y. Chin. Chem. Lett. 2011, 22, 667e670; (e)
Wu, S.-F.; Chang, F.-R.; Wang, S.-Y.; Hwang, T.-L.; Lee, C.-L.; Chen, S.-L.; Wu, C.-
C.; Wu, Y.-C. J. Nat. Prod. 2011, 74, 989e996; (f) Sun, J.; Ding, W.-X.; Hong, X.-P.;
Zhang, K.-Y.; Zou, Y. Chem. Nat. Compd. 2012, 48, 16e22.
2. Combes, S.; Barbier, P.; Douillard, S.; McLeer-Florin, A.; Bourgarel-Rey, V.;
Pierson, J.-T.; Fedorov, A. Y.; Finet, J.-P.; Boutonnat, J.; Peyrot, V. J. Med. Chem.
2011, 54, 3153e3162.
3. Ma, T.; Wang, L.; Cheng, G. F.; Liu, G. Acta Pharm. Sin. 2010, 45, 1265e1269.
4. For some recent examples see: (a) Wu, J.; Zhang, L.; Xia, H.-G. Tetrahedron Lett.
2006, 47, 1525e1528; (b) Zhang, L.; Meng, T.; Fan, R.; Wu, J. J. Org. Chem. 2007,
72 7279e7276; (c) Kuroda, J.-I.; Inamoto, K.; Hiroya, K.; Doi, T. Eur. J. Org. Chem.
2009, 2251e2261; (d) Luo, Y.; Wu, J. Tetrahedron Lett. 2009, 50, 2103e2105; (e)
Xu, L.; Li, B.-J.; Wu, Z.-H.; Lu, X.-Y.; Guan, B.-T.; Wang, B.-Q.; Zhao, K.-Q. Org. Lett.
2010, 12, 884e887; (f) Gao, W.; Luo, Y.; Ding, Q.; Peng, Y.; Wu, J. Tetrahedron
Lett. 2010, 51, 136e138; (g) Rao, M. L. N.; Venkatesh, V.; Jadhav, D. N. Eur. J. Org.
12. (a) Wu, J.; Yang, Z. J. Org. Chem. 2001, 66, 7875e7878; (b) Wu, J.; Zhang, L.; Gao,
K. Eur. J. Org. Chem. 2006, 5260e5263.
13. (a) Shi, Z.; He, C. J. Org. Chem. 2004, 69, 3669e3671; (b) Wu, L.-Q.; Yang, C.-G.;
Wu, Y.-F.; Yang, L.-M. J. Chin. Chem. Soc. 2009, 56, 606e608.