Direct C-3 alkylation of coumarins via decarboxylative coupling with carboxylic acids

Article abstract of DOI:10.1039/c8nj06410e

A new method for selective C-3 alkylation of coumarins using carboxylic acids as alkyl sources is reported. This process offers a practical method for the facile construction of 3-alkyl coumarins with a broad substrate scope. The reaction works under metal-free and aqueous media and both cyclic and acyclic aliphatic carboxylic acids participate in this radical C-C cross coupling reaction.

Full text of DOI:10.1039/c8nj06410e

View Article Online
View Journal
NJC
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: F. Jafarpour, M.
Darvishmolla, N. azaddoost and F. Mohaghegh, New J. Chem., 2019, DOI: 10.1039/C8NJ06410E.
Volume 40 Number
1
January 2016 Pages 1–846
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
NJC
New Journal of Chemistry
www.rsc.org/njc
A journal for new directions in chemistry
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
rsc.li/njc

Please do not adjust margins
New Journal of Chemistry
Page 1 of 6
View Article Online
DOI: 10.1039/C8NJ06410E
1
2
3
4
5
6
7
8
9
Journal Name
COMMUNICATION
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Direct C-3 Alkylation of Coumarins via Decarboxylative Coupling
with Carboxylic Acids
Received 00th January 20xx,
Accepted 00th January 20xx
Farnaz Jafarpour,* Masoumeh Darvishmolla, Narges Azaddoost and Farid Mohaghegh
DOI: 10.1039/x0xx00000x
www.rsc.org/
A new method for selective C-3 alkylation of coumarins using
carboxylic acids as alkyl sources is reported. This process offers a
practical method for the facile construction of 3-alkyl coumarins
with a broad substrate scope. The reaction works under metal-
free and aqueous media and both cyclic and acyclic aliphatic
carboxylic acids participate in this radical C-C cross coupling
reaction.
In the past decades, sustainable chemistry as a tremendous
challenge has fascinated chemists to develop facile, efficient
and environmentally friendly protocols. Among various
approaches toward the green chemistry, a great emphasis was
placed on protocols which avoid or minimize the use of
transition metals in organic synthesis.1
Direct C-H functionalization of heteroaromatic scaffolds has
become a valuable tool in organic chemistry for the synthesis
of biologically active molecules. Alkylation of heteroarenes as
one of the most impressive C-C bond-forming reactions
provides convenient access to pharmaceutically active
compounds. Direct C−H alkylation of heteroaromatic scaffolds
by alkyl radicals has been brought to the spotlight
consequently, bringing about the substantial development of
this type of reactions over the past few years. The seminal
work regarding direct C−H alkylaꢀon of heteroarenes is often
known as ‘Minisci’ reaction in which carboxylic acids are used
Scheme 1. Previous reports on direct alkylation of heteroarenes
2
as alkylating reagent. Henceforward, several protocols have
been evolved using a variety of alkylating agents (Scheme 1).3-8
Coumarins, significant compounds ubiquitous in plants, are
well-known due to their wide array of pharmacological and
9
optical properties. In particular, 3-Alkyl-substituted coumarins
are tremendously important molecules because of the
occurrence of these structural motifs in a vast range of highly
potent drug candidates, many of which have been used in
cancer chemotherapy and also as anticoagulants (Scheme 2).10
Scheme 2. Biologically active 3-alkyl coumarin derivatives
School of Chemistry, College of Science, University of Tehran, P.O. Box 14155-
6
455, Tehran, Iran. E-mail: jafarpur@khayam.ut.ac.ir.
Electronic Supplementary Information (ESI) available: Experimental procedures
and characterization data. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 2 of 6
View Article Online
DOI: 10.1039/C8NJ06410E
COMMUNICATION
Journal Name
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Table 1. Screening optimal conditionsa
Entry
Oxidant
Base
Solvent
DMSO
DMF
Yield%a
1
2
3
4
5
K
K
K
K
K
2
2
2
2
2
2
2
2
S
S
S
S
S
2
2
2
2
2
2
2
2
O
O
O
O
O
8
8
8
8
8
8
8
8
K
K
K
K
K
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
25
trace
0
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
DCE
Scheme 3. Strategies for decarboxylative alkylation of coumarin at C-3
ACN
0
toluene
PhCl
0
As a result, the development of new and effective strategies
on regioselective C-3-alkylation of coumarins is highly desired.
Thus far, several developments have been achieved for the
synthesis of C-3 alkylated coumarins using various transition
metal catalysts, including Cu, Fe and Co. For instance in 2014
6
K
K
K
K
K
S
S
S
S
S
O
O
O
O
O
K
K
K
K
K
CO
CO
CO
CO
CO
0
7
H
2
O
45
8
DMSO/H
DMF/H O (1/1)
DCE/H O (1/1)
PhCl/H
2
O (1/1)
0
9
10
2
2
2
2
8
8
2
2
3
3
2
0
2
trace
Duan and co-workers described
a
copper catalyzed
1
1
1
1
2
3
K
K
2
S
2
2
O
8
8
K
K
K
K
K
K
K
K
2
2
2
2
2
2
2
2
CO
CO
CO
CO
CO
CO
CO
CO
3
3
3
3
3
3
3
3
2
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
O (1/1)
0
regioselective benzylation of coumarins at C-3.11 In other
efforts the copper-catalyzed and also the iron-catalyzed C-3-
2
S
O
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
ACN/H
2
55
30
0
(NH
4
)
2
S
O
2 8
2
2
2
2
2
2
2
2
2
2
alkylation of coumarins with the use of cycloalkyl ethers and
cycloalkanes were demonstrated.12 Moreover, Du et. al. have
14
TBHP
DTBP
BQ
recently disclosed
coumarins with alkyl ethers.1
a
cobalt-catalyzed C-3-alkylation of 15
0
3
16
0
Despite the importance of these contributions unfortunately,
all these methods are restricted to transition metals and the
substrate scope is rather limited and works only with
cycloalkanes/ethers and benzyl groups. We have also recently
reported a metal-free cross dehydrogenative coupling of
coumarins and ethers where, the substrate scope for direct
alkylation was limited and a single example of cyclohexane was
disclosed.1
1
1
1
2
2
2
7
8
9
0
1
2
DDQ
—
0
0
K
K
K
K
S
2 2
S
2 2
S
2 2
S
2 2
O
8
O
8
O
8
O
8
NaOAc
DABCO
NaHCO
LiOAc
43
0
3
50
35
4
23
K S O
KOAc
—
ACN/H O (1/1)
42
2
2
8
2
Carboxylic acids owing to their attractive features such as low 24
K
S
2 2
O
8
ACN/H O (1/1)
2
ACN/H O (1/5)
2
Trace
74
2
5
K
S
2 2
O
8
K
2
CO
3
cost, high stability and easy availability, represent valuable
starting materials in synthetic organic chemistry. Given that,
transition metal catalyzed decarboxylative couplings have
been an important and very attractive research point of
organic synthesis in recent years.15
Following our interest in direct functionalization of halides,19 (hetero)arenes20 and organoboron reagents21 to the
coumarins16 herein, we disclose
transition-metal-free best of our knowledge a transition metal-free decarboxylative
a
Reaction conditions: Coumarin 1a (0.2 mmol), pivalic acid 2a (2 equiv), oxidant
(2 equiv), base (2 equiv), solvent (0.6 ml) were heated in a sealed tube at 120˚C
for 2 h.
a
alkylation of coumarins with carboxylic acids through a direct cross-coupling of arene carboxylic acids and (hetero)arenes is
decarboxylative cross-coupling process. This protocol features not precedented.
good yields and high regioselectivities, is water compatible, At the outset, decarboxylative alkylation of coumarin 1a
and has environmentally friendly conditions excluding any employing pivalic acid 2a was chosen as a benchmark reaction
toxic metals and could open a route for direct instalment of for the optimization of the reaction conditions and different
alkyl groups at C-3 of coumarins. Moreover, this protocol oxidants, bases and solvents were screened (Table 1). The
affords an unprecedented approach for chain alkylation of reaction of coumarin and pivalic acid in the presence of K S O
2
2 8
coumarins using primary alkyl carboxylic acids under metal- as oxidant and K CO as base in various solvents at 120˚C, was
2
3
free conditions. The only report in this area is limited to Jin’s explored and fortunately the desired product was detected in
and Sun’s work reported very recently, and could provide 25% yield in DMSO (entries 1-6). Fortunately, conducting the
alkylated coumarins only under Ir-catalyzed photocatalytic reaction in water, increased the yield of the desired product to
decarboxylative reaction using TFA as an additive (Scheme 3).17 45% (entry 7). According to the low solubility of the substrates
Some progress in direct arylation of coumarins through an in water, co-solvents (v/v: 1/1) were chosen and the best
unprecedented metal-free decarboxylative functionalization of result was obtained in ACN/H O (entries 8-12). Inferior results
arene carboxylic acids is also achieved. Although, there are were obtained when various oxidants including (NH ) S O ,
many reports on transition metal catalyzed decarboxylative DTBP, TBHP, BQ and DDQ were employed (entries 13-17). The
coupling of arene carboxylic acids with alkenes,18 aryl
2
4
2 2 8
reaction did not proceed in the lack of the oxidant, suggesting
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 3 of 6
New Journal of Chemistry
Please do not adjust margins
View Article Online
DOI: 10.1039/C8NJ06410E
Journal Name
COMMUNICATION
1
2
3
4
5
6
7
8
9
its crucial importance for this type of transformation (entry has been evidenced however, that cyclopropyl carboxylic acids
8). A screening of various bases was also performed and are traditionally unproductive alkylating coupling partners in
among the bases surveyed, K CO proved to be the best Minisci reactions due to the ring-opening of cyclopropyl
entries 19-23). Due to the great environmental concerns of radicals in the course of the reaction.23 Fortunately,
1
2
3
(
solvents and to improve the sustainability of this cyclopropylation reaction of coumarin proceeded smoothly
transformation, the water content was gradually increased and under the presented reaction conditions to afford the desired
gratefully a 74% of the desired product was obtained in 2h in product 3d in 67% isolated yield. Furthermore, more
2
H O/ACN with 84% of water content (v/v: 5/1) (entry 25). challenging linear carboxylic acids producing primary radicals
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Applied reaction condition is appreciated due to water participated well in this alkylation process. Gratifyingly, acetic
compatibility of the reaction, and toxic metal- and waste-free acid was used successfully and furnished the desired 3-methyl
production of alkyl coumarins in short reaction times.
coumarin 3i in moderate yield considering the high reactivity
Having established the optimized reaction conditions, the of methyl radical. There are several reports which highlight the
substrate scope was evaluated (Table 2). Using aliphatic importance of methyl groups in biologically active molecules.
carboxylic acids including primary, secondary and tertiary Instalment of methyl groups have proved to improve
carboxylic acids in the current approach, a variety of properties of drug candidates and physical properties of
coumarins with linear and branched alkyl groups at C-3 were molecules.24
obtained in good to high yields (3a
hexyl analogues were also obtained in 51%, 67% and 65% with respect to coumarins. Methyl and methoxy substituted
yields, respectively (3e 3g). Cyclopropanes as a common part coumarins led to the desired products in yields exceeding 70%.
of many pharmaceuticals22 provide distinct structural and Gratifyingly, 4-substituted coumarin furnished the desired
-3c). Cyclobutyl, pentyl and Moreover, the scope of the methodology was investigated
-
electronic properties when installed on heteroaryl scaffolds. It
product 3p in 55% isolated yield despite of steric
encumbrance. To our delight, bromo and chloro-substituted
coumarins were also found to be suitable for these
transformations, which provide useful components for further
transformations through traditional cross-coupling reactions
Table 2. Scope of the alkylation of coumarins with aliphatic carboxylic acidsa.
(
3m, 3l and 3v). Alkylation of the π–extended coumarin with
interesting photophysical and biological properties25 also
proceeded smoothly to afford the desired 3-alkylated adduct
3
u
in 57% isolated yield.
Pleasingly, alkylation of coumarins at C-3 was also achieved via
metal-free double decarboxylative cross-coupling of
a
coumarin-3-carboxylic acids and aliphatic acids (Table 3). This
transformation removes the surplus carboxylate group left
behind as a result of the common synthetic routes26 in the
course of the reaction and protodecarboxylation27 is not pre-
requisite. This transition-metal-free one step sequence was
possible using the optimized reaction conditions and a
comparable yield of the desired products were obtained.
Table 3. Scope of alkylation of coumarin-3-carboxylic acids with aliphatic acidsa
aAll reactions were run under the optimized reaction conditions.
aAll reactions were run under the optimized reaction conditions.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
New Journal of Chemistry
Page 4 of 6
View Article Online
DOI: 10.1039/C8NJ06410E
COMMUNICATION
Journal Name
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
would be owing to extremely high polarity of water, strong
hydrogen bonding ability, here with carbonyl group of
R
H
+
K S O
8
coumarin, and lack of easily transferable hydrogen via a radical
process.32
2
2
R
K CO
2
3
O
O HO2C
O
O
H2O/ACN (5/1)
20 °C
CO2
4b, R = 4-Me, 53%
Scheme 4. Decarboxylative coupling of arene carboxylic acids and coumarin.
1a
4a, R = H, 40%
1
Conclusions
In conclusion, we have developed an efficient and practical
decarboxylative alkylation of coumarins in an environmental
benign manner. This protocol works with a wide spectrum of
readily available aliphatic cyclic and acyclic acids and
coumarin(-3-carboxylic acid)s affording interesting 3-
alkylcoumarins that serve as the key intermediates in the
synthesis of drug candidates. Furthermore, this protocol
featured simple instalment of primary alkyl groups at C-3 of
coumarins which remains a formidable challenge. This simple
procedure which proceeds in aqueous solvent mixtures could
serve as an alternative approach towards construction of 3-
alkyl coumarins.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
We acknowledge the financial support from University of
Tehran.
Conflicts of interest
There are no conflicts of interest to declare.
Scheme 5. Plausible Mechanism for C-3 Alkylation of Coumarin
Previous efforts directed towards functionalization of these
scaffolds excluding metals however, provided only
esterification products or C-4 functionalization of coumarins
with subsequent reduction of the double bond to build up 3,4-
dihydrocoumarins.28
References
1
For some reviews see: (a) C.-L. Sun and Z.-J. Shi, Chem. Rev.,
2014, 114, 9219. (b) S. Roscales and A. G. Csaky, Chem. Soc.
Rev., 2014, 43, 8215.
F. Minisci, R. Bernardi, F. Bertini, R. Galli and M.
Perchinummo, Tetrahedron, 1971, 27, 3575.
Fortunately, some aromatic carboxylic acids were also
favoured in this system and afforded the corresponding
products (Scheme 4).
2
3
4
5
6
O. Yamazaki, H. Togo, S. Matsubayashi and M. Yokoyama,
Tetrahedron Lett., 1988, 39, 1921.
To get insight to the mechanism of this reaction, 2,2,6,6-
tetramethylpiperidyl-1-oxyl (TEMPO) (2.0 equiv.) as a radical
scavenger was added into the model reaction mixture of
coumarin and pivalic acid and the reaction was fully
suppressed. This effect may suggest a radical mechanism for
the process. A plausible radical mechanism is accordingly
outlined in Scheme 4 based on the control experiment and
previous literature. Initially, the thermal decomposition of
G. Molander, V. Colombel and V. Braz, Org. Lett., 2011, 13
,
1852.
R.-J. Tang, L. Kang and L. Yang, Adv. Synth. Catal., 2015, 357
,
2055.
Y. Fujiwara, J. A. Dixon, F. O Hara, E. Daa Funder, D. D. Dixon,
R. A. Rodriguez, R. D. Baxter, B. Herl´e, N. Sach, M. R. Collins,
Y. Ishihara and P. S. Baran, Nature, 2012, 492, 95.
7
8
J. Jin and D. W. C. MacMillan, Nature, 2015, 525, 87.
D. A. Dirocco, K. Dykstra, S. Krska, P. Vachal, D. V. Conway
and M. Tudge, Angew. Chem., Int. Ed., 2014, 53, 4802.
(a) M. J. Matos, S. Vazquez- Rodriguez, L. Santana, E. Uriarte,
C. Fuentes-Edfuf, Y. Santos, and A. Munoz-Crego, Molecules,
2013, 18, 1394; (b) D. Olmedo, R. Sancho, L. M. Bedoya, J. L.
Lopez-Perez, E. Del Olmo, E. Munoz, J. Alcami, M. P. Gupta
and A. S. Feliciano, Molecules, 2012, 17, 9245; (c) G.-Y. Liu, F.
Dai, X.-Y. Cao, Y.-F. Kang, L.-M. Hu, J.-J. Tang, X.-Z. Li, Y. Li, X.-
L. Jin and B. Zhou, Bioorg. Med. Chem. Lett., 2011, 21, 6420;
(d) M. Roussaki, C. A. Kontogiorgis, D. Hadjipavlou-Litina, S.
2
−
S
2
O
8
with an estimated standard redox potential of 2.01 V in
9
aqueous solution, affords sulfate radical anion.29 Hydrogen-
atom transfer between the carboxylic acid and the sulfate
radical anion, generates the carboxyl radical which quickly
undergoes decarboxylation to provide the corresponding alkyl
radical.30 Then the alkyl radical adds to the double bond of the
substrate 1a
intermediate IV. Finally, further oxidation of IV by another
sulfate radical produces the corresponding carbocation
,31
, which affords the most stable radical
Hamilakis and A. Detsi, Bioorg. Med. Chem. Lett., 2010, 20
3889; (e) C. H. Chang, H. C. Cheng, Y. J. Lu, K. C. Tien, H. W.
Lin, C. L. Lin, C. J. Yang and C. C. Wu, Org. Electron., 2010, 11
247; (f) M. T. Lee, C. K. Yen, W. P. Yang, H. H. Chen, C. H.
Liao, C. H. Tsai and C. H. Chen, Org. Lett., 2004, , 1241; (g) S.
,
V
and deprotonation/decarboxylation of intermediate
basic conditions regenerates a double bond leading to 3a
V
under
.
,
6
Furthermore, considering the results of radical reactions in
aqueous media, the origin of the favorable solvent effect
A. Swanson, G. M. Wallraff, J. P. Chen, W. J. Zhang, L. D.
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 6
New Journal of Chemistry
Please do not adjust margins
View Article Online
DOI: 10.1039/C8NJ06410E
Journal Name
COMMUNICATION
1
2
3
4
5
6
7
8
9
Bozano, K. R. Carter, J. R. Salem, R. Villa and J. C. Scott,
Chem. Mater., 2003, 15, 2305.
2009, 11, 5506; (f) C. Wang, I. Piel, F. Glorius, J. Am. Chem.
Soc., 2009, 131, 4194.
1
0 (a) C. Kontogiorgis, A. Detsi and D. Hadjipavlou-Litina, Expert 21 C. Feng and T.-P. Loh, Chem. Commun., 2010, 46, 4779.
Opin. Ther. Pat., 2012, 22, 437; (b) A. Kathuria, S. Jalal, R. 22 (a) A. Gagnon, M. St-Onge, K. Little, M. Duplessis and F.
Tiwari, A. Nasrolahi-Shirazi, Sh. Gupta, Sh. Kumar, K. Parang
and S. K. Sharma, Chem. Biol. Interfaces., 2011, , 279.
11 S.-L. Zhou, L.-N. Guo and X.-H. Duan, Eur. J. Org. Chem.,
014, 8094.
Barabe, J. Am. Chem. Soc., 2007, 129, 44; (b) P. Pevarello, M.
G. Brasca, P. Orsini, G. Traquandi, A. Longo, M. Nesi, F. Orzi,
C. Piutti, P. Sansonna, M. Varasi, A. Cameron, A. Vulpetti, F.
Roletto, R. Alzani, M. Ciomei, C. Albanese, W. Pastori, A.
Marsiglio, E. Pesenti, F. Fiorentini, J. R. Bischoff and C.
1
2
1
2 (a) C. Wang, X. Mi, Q. Li, Y. Li, M. Huang, J. Zhang and Y. Wu,
Tetrahedron, 2015, 71, 6689; (b) A. Banerjee, S. K. Santra, N.
Mercurio, J. Med. Chem., 2005, 48, 2944; (c) L. A.
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Khatun, W. Ali and B. K. Patel, Chem. Commun., 2015, 51
15422; (c) B. Niu, W. Zhao, Y. Ding, Z. Bian, C. U. Pittman Jr.,
A. Zhou and H. Ge, J. Org. Chem., 2015, 80, 7251.
,
Wessjohann, W. Brandt and T. Thiemann, Chem. Rev., 2003,
103, 1625; (d) H. Maag, J. T. Nelson, J. L. R. Steiner and E. J.
Prisbe, J. Med. Chem., 1994, 37, 431.
1
3 L. Dian, H. Zhao, D. Zhang-Negrerie and Y. Du, Adv. Synth. 23 D. j. Mann and W. L. Hase, J. Am. Chem. Soc., 2002, 124
Catal., 2016, 358, 2422. 3208.
14 (a) F. Jafarpour and M. Darvishmolla, Org. Biomol. Chem., 24 For methylation effects in Medicinal Chemistry see: (a) C. S.
,
2
018, 16
,
3396; For more examples on radical
Leung, S. S. F. Leung, J. Tirado-Rives and W. L. Jorgensen, J.
Med. Chem., 2012, 55, 4489; (b) E. J. Barreiro, A. E.
Kümmerle and C. A. M. Fraga, Chem. Rev., 2011, 111, 5215;
For some recent examples on methylations see: (c) X. Y.
Chen and E. J. Sorensen, J. Am. Chem. Soc., 2018, 140, 2789;
functionalization of coumarins see: (b) G. A. Russell, B. H.
Kim and S. V. Kulkarni, J. Org. Chem., 1989, 54, 3768; (c) H.
Wang, S.-L. Zhou, L.-N. Guo, X.-H. Duan, Tetrahedron, 2015,
71, 630.
1
1
5 For reviews on decarboxylative cross-coupling reactions, see:
(d) N. Zhu, J. Zhao and H. Bao, Chem. Sci., 2017, 8, 2081; (e)
(
a) T. Zhang, N.-X. Wang and Y. Xing, J. Org. Chem., 2018, 83
,
Z. Liu, Z. Yang, X. Yu, H. Zhang, B. Yu, Y. Zhao and Z. Liu, Org.
Lett., 2017, 19, 5228; (f) T. Kubo and N. Chatani, Org. Lett.,
2016, 18, 1698; (g) Y. Zhang, J. Feng and C.-J. Li, J. Am. Chem.
Soc., 2008, 130, 2900.
7
559; (b) Y. Wei, M. Zhang and W. Su, Chem. Rev., 2017, 117
,
8864; (c) I. Larrosa and J. Cornella, Synthesis, 2012, 44, 653;
(d) W. I. Dzik, P. P. Lange and L. J. Goossen, Chem. Sci., 2012,
3, 2671; (e) N. Rodriguez and L. J. Goossen, Chem. Soc. Rev., 25 M. Tasior, D. Kim, S. Singha, M. Krzeszewski, K. H. Ahn and D.
2
011, 40, 5030. T. Gryko, J. Mater. Chem. C., 2015, , 1421.
3
6 (a) M. Golshani, M. Khoobi, N. Jalalimanesh, F. Jafarpour and 26 For some recent examples see: (a) W.-Y. Pan, Y.-M. Xiao, H.-
A. Ariafard, Chem. Commun., 2017, 53, 10676; (b) F.
Jafarpour and M. Abbasnia, J. Org. Chem., 2016, 81, 11982;
Q. Xiong and C.-W. Lü, Res. Chem. Intermed., 2016, 42, 7057;
(b) G. Brahmachari, ACS Sustainable Chem. Eng., 2015, 3,
2350.
(c) F. Jafarpour, H. Hazrati, N. Mohasselyazdi, M. Khoobi and
A. Shafiee, Chem. Commun., 2013, 49, 10935; (d) F. 27 For some recent examples on protodecarboxylation of
Jafarpour, M. B. A. Olia and H. Hazrati, Adv. Synth. Catal.,
2013, 355, 3407; (e) F. Jafarpour, S. Zarei, M. B. A. Olia, N.
coumarins-3-carboxylic acids see: (a) M. Li, J. L. Peterson and
J. M. Hoover, Org. Lett., 2017, 19, 638; (b) Z. Li, Z. Fu, H.
Zhang, J. Long, Y. Song and H. Cai, New J. Chem., 2016, 40,
3014.
Jalalimanesh and S. Rahiminejadan, J. Org. Chem., 2013, 78
957.
7 C. Jin, Z. Yan, B. Sun and J. Yang, Org. Lett., 2019, 21, 2064.
,
2
1
28 (a) Y. Zheng, J. Mao, G. Rong and X. Xu., Chem. Commun.,
2015, 51, 8837; (b) L. Xu, Z. Shao, L. Wang and J. Xiao, Org.
Lett., 2014, 16, 796; (c) Z. Shao, L. Xu, L. Wang, H. Wei and J.
Xiao, Org. Biomol. Chem., 2014, 12, 2185; (d) L. Chen, E. Shi,
Z. Liu, S. Chen, W. Wei, H. Li, K. Xu and X. Wan, Chem. Eur. J.,
2011, 17, 4085;
18 (a) J. Zhou, G. Wu, M. Zhang, X. Jie and W. Su, Chem. Eur. J.,
2
2
012, 18, 8032; (b) Z. Sun, J. Zhang and P. Zhao, Org. Lett.,
010, 12, 992; (c) M. Zhang, J. Zhou, J. Kan, M. Wang, W. Su
and M. Hong, Chem. Commun., 2010, 46, 5455; (d) Z. Fu, S.
Huang, W. Su and M. Hong, Org. Lett., 2010, 12, 4992; (e) S.-
L. Zhang, Y. Fu, R. Shang, Q.-X. Guo and L. Liu, J. Am. Chem. 29 (a) L. W. Matzek and K. E. Carter, Chemosphere, 2016, 151
Soc., 2010, 132, 638; (f) P. Hu, J. Kan, W. Su and M. Hong,
Org. Lett., 2009, 11, 2341; (g) Z. Sun and P. Zhao, Angew.
Chem. Int. Ed., 2009, 48, 6726; (h) D. Tanaka, S. P. Romeril
,
178; (b) I. M. Kolthoff, E. J. Meehan and E. M. Carr, J. Am.
Chem. Soc., 1953, 75, 1439; (c) F. Minisci and A. Citterio, Acc.
Chem. Res., 1983, 16, 27.
and A. G. Myers, J. Am. Chem. Soc., 2005, 127, 10323; (i) A. 30 (a) R. A. Garza-Sanchez, A. Tlahuext-Aca, G. Tavakoli and F.
G. Myers, D. Tanaka and M. R. Mannion, J. Am. Chem. Soc., Glorius, ACS Catal., 2017, , 4057; (b) R. E. Huie and C. L. J.
002, 124, 11250.
7
2
Clifton, Phys. Chem., 1990, 94, 8561; (c) S. N. Rustgi and P.
Riesz, Int. J. Radiat. Biol., 1978, 34, 301; (d) O.P. Chawla and
R. W. Fessenden, J. Phys. Chem., 1975, 79, 2693.
1
9 (a) R. Shang, D.-S. Ji, L. Chu, Y. Fu and L. Liu, Angew. Chem.
Int. Ed., 2011, 50, 4470; (b) R. Shang, Z.-W. Yang, Y. Wang, S.-
L. Zhang and L. Liu, J. Am. Chem. Soc., 2010, 132, 14391; (c) 31 (b) S. Mandal, T. Bera, G. Dubey, J. Saha and J. K. Laha, ACS
C. Feng and T. Loh, Chem. Commun., 2010, 46, 4779; (d) R. Catal., 2018, , 5085.
Shang, Y. Fu, J.-B. Li, S.-L. Zhang, Q.-X. Guo and L. Liu, J. Am. 32 (a) P. Xie, J. Wang, Y. Liu, J. Fan, X. Wo, W. Fu, Z. Sun and T.-
Chem. Soc., 2009, 131, 5738; (e) R. Shang, Y. Fu, Y. Wang, Q.
Xu, H.-Z. Yu and L. Liu, Angew. Chem. Int. Ed., 2009, 48, 9350;
(f) M. Miyasaka, A. Fukushima, T. Satoh, K. Hirano and M.
Miura, Chem. Eur. J., 2009, 15, 3674; (g) L. J. Gooßen, N.
Rodriguez, B. Melzer, C. Linder, G. Deng and L. M. Levy, J.
Am. Chem. Soc., 2007, 129, 4824; (h) L. J. Gooßen, G. Deng
and L. M. Levy, Science, 2006, 313, 662.
8
P. Loh, Nature Commun., 2018,
Shinokubo and K. Oshima, Synlett, 2002,
9
, 1321; (b) H. Yorimitsu, H.
, 674.
5
2
0 (a) P. Hu, M. Zhang, X. Jie and W. Su, Angew. Chem. Int. Ed.,
2
012, 51, 227; (b) H. Zhao, Y. Wei, J. Xu, J. Kan, W. Su and M.
Hong, J. Org. Chem., 2011, 76, 882; (c) F. Zhang and M. F.
Greaney, Angew. Chem. Int. Ed., 2010, 49, 2768; (d) J. Zhou,
P. Hu, M. Zhang, S. Huang, M. Wang and W. Su, Chem. Eur. J.,
2
010, 16, 5876; (e) J. Cornella, P. Lu and I. Larrosa, Org. Lett.,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

New Journal of Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/C8NJ06410E
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Graphical Abstract:
Direct C-3 Alkylation of Coumarins via Decarboxylative
Coupling with Carboxylic Acids
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Farnaz Jafarpour,* Masoumeh Darvishmolla, Narges Azaddoost and Farid Mohaghegh
A metal-free direct alkylation of coumarins using carboxylic acids in aqueous media with
a broad substrate scope is devised.
H
R
K S O
8
2
2
Ar
+
R-CO2H
Ar
K CO
2
3
O
O
O
O
H O/ACN (5:1)
2
R = methyl, primary, secondary and
No transition metals
Water compatible
Regioselective
tertiary alkyl groups