Decarboxylative Arylation of α,β-Unsaturated Carboxylic Acids Using Aryl Triazenes by Copper/Ionic Liquid Combination in PEG-400

Article abstract of DOI:10.1002/ejoc.201800930

A practical method for the construction of stilbene derivatives has been developed via catalytic cross-coupling of cinnamic acids with aryl triazenes. The methodology offers high stereoselectivity and is endowed with broad substrate scope, high yield, and significant functional group tolerance.

Full text of DOI:10.1002/ejoc.201800930

A Journal of
Accepted Article
Title: Decarboxylative Arylation of α,β-Unsaturated Carboxylic Acids
using Aryl Triazenes by Copper/Ionic Liquid Combination in
PEG-400
Authors: Saurabh Kumar, Anand Kumar Pandey, Rahul Singh, and
Krishna Nand Singh
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201800930
Link to VoR: http://dx.doi.org/10.1002/ejoc.201800930
Supported by

10.1002/ejoc.201800930
European Journal of Organic Chemistry
COMMUNICATION
Decarboxylative Arylation of α,β-Unsaturated Carboxylic Acids
using Aryl Triazenes by Copper/Ionic Liquid Combination in PEG-
400
Saurabh Kumar,[a] Anand Kumar Pandey,[a] Rahul Singh[a] and Krishna Nand Singh[a],*
handle, render the carboxylic acids a valuable starting material
in organic transformations.[13]
Abstract: A practical method for the construction of stilbene
derivatives has been developed via catalytic cross-coupling of
cinnamic acids with aryl triazenes. The methodology offers high
stereoselectivity, and is endowed with broad substrate scope, high
yield, and significant functional group tolerance.
Aryl triazenes have been recently employed for certain cross
coupling reactions owing to their identical acceptability to the
corresponding arenediazonium salts, and are known to have
rather better stability under ambient conditions lending them an
edge over the later.[14]
Introduction
Stilbenes are widely explored motifs present in natural products,
pharmaceuticals and biological systems.[1] They also serve as
valuable synthetic intermediates for the preparation of many
useful organic molecules owing to their propensity to participate
in cycloaddition,[2] cyclopropanation,[3] and epoxidation
reactions.[4] Therefore, the synthesis and functionalization of
stilbenes has perpetually attracted a great deal of interest of
organic chemists.
The Wittig reaction, Julia olefination and Peterson reaction
employing phosphonium salts or organometallic starting
materials are amongst the most prominent and extensively used
synthetic approaches to achieve diverse alkene derivatives.
Alternatively, the semihydrogenation of alkynes may also be
utilized to accomplish stilbene derivatives.[5] The transition-
metal-catalyzed Heck-type reaction is another powerful way for
preparing stilbene derivatives using alkenes,[6] nitroalkenes,[7]
vinyl halides,[8] vinylic ethers,[9] boronic acids,[10] and cinnamic
acids.[11] Some notable recent advances for their synthesis are
outlined in Scheme 1. Despite considerable progress over the
years, the existing methods still suffer from certain drawbacks,
such as use of expensive materials, harsh conditions, and
requirement for an inert conditions. Thus from the above
perspective, there stands enough scope for further exploration
and necessity to develop new and useful protocols to simplify
the synthesis of stilbene motifs.
Decarboxylative cross-coupling reactions have attained the
repute of a proficient strategy for the creation of a variety of C–C
and C–heteroatom bonds, owing to their prospective use in step-
economic, environmentally benign, and regio- and stereo-
selective synthesis.[12] Also the ready commercial availability,
ample structural diversity apart from easy preparation via a
range of well established protocols, and ease to store and
Scheme 1. Synthesis of stilbene derivatives.
Ionic liquids have been identified as potential alternative reaction
medium, and are endowed with green features like non-volatility,
non-flammability, thermal stability and recyclability.15 Brønsted
acidic ionic liquid (BAIL)-promoted synthetic protocols have
drawn major industrial and academic interest with adjustable
acidity, easy recyclability and their dual role as catalyst as well
as reaction medium.16 Accordingly some acidic ILs (Figure 1)
have been prepared and subjected to the studies undertaken.
In order to avoid the hazards associated with the commonly
used organic solvents, organic chemists have always been
tempted to accomplish the synthesis in environmentally benign
solvents with lower volatility and less toxicity. Polyethylene
glycol (PEG) is one of the most desirable reaction media to
overcome the concerns of organic solvents, as it is thermally
stable, easily recoverable and nontoxic, thereby reassuring the
synthetic protocols.[17]
[a]
Saurabh Kumar, Anand Kumar Pandey, Dr. Rahul Singh and Prof.
Dr. Krishna Nand Singh*
Department of Chemistry (Centre of Advanced Study)
Institute of Science
Banaras Hindu University, Varanasi 221005,
India
E-mail: knsinghbhu@yahoo.co.in;
knsingh@bhu.ac.in
Our group has recently explored the scope of decarboxylative
strategy for the synthesis of vinyl sulfones, N-acylated indoles,
2-substituted benzothiazoles, thioamides and α,β-epoxy ketones,
using easily accessible α,β-unsaturated carboxylic acids as
functional surrogate to the corresponding alkenes as well as
alkynes.[18]
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201800930
European Journal of Organic Chemistry
COMMUNICATION
Table 1. Optimization of reaction conditions.[a]
N
N
COOH
catalyst
solvent
N
3a
1a
2a
Entry
Catalyst
Promoter
Solvent
Yield(%)[b]
(20 mol %)
1.
2.
-
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
IL1
…..
IL2
IL3
IL4
IL5
IL6
IL7
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
Toluene
DCE
0
0
NiCl2.6H2O
FeCl3
3.
0
4.
CoCl2.6H2O
CuI
0
5.
28
22
25
39
27
58
63
68
15
35
40
12
76
82
86
76
0
6.
CuBr
Figure 1. Acidic ionic liquids (AILs) examined.
7.
CuCl
8.
CuBr2
In order to further explore the scope of decarboxylative strategy,
we envisaged and realized a stereoselective synthesis of
stilbenes through decarboxylative aryation using cinnamic acids
and aryl triazene as vinyl and aryl surrogates respectively in an
environmentally benign medium (Scheme 1).
9.
Cu2O
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
CuCl2.2H2O
Cu(OAc)2
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Cu(OAc)2.H2O
Results and Discussion
DMSO
To begin with, a model reaction employing cinnamic acid (1a)
and 1-(p-tolyldiazenyl)pyrrolidine (2a) was screened thoroughly
by varying different parameters such as catalyst, acidic ionic
liquid, solvent, temperature, and time (Table 1). The initial
reaction conditions using equimolar quantities of both the
reactants and 1-methylimidazolium hydrogen sulfate (IL1)
without a catalyst in acetonitrile at 70 °C for 24 h failed to yield
the desired product. After that, different transition metal catalysts
(20 mol%) viz., NiCl2.6H2O, FeCl3, CoCl2.6H2O and CuI were
added to screen their catalytic efficacy (entries 2–5), which
revealed CuI as the only hit to afford 28 % product yield. Then
were used some other copper salts such as CuCl, CuBr, CuBr2,
Cu2O and CuCl2.2H2O (entries 6–10), but yet no significant
observation was made. However to our utmost delight, the use
of Cu(OAc)2 and Cu(OAc)2.H2O enhanced the yield considerably
to 63 % and 68 % respectively (entries 11 & 12). Maintaining
other parameters of the entry 12 intact, the effect of different
solvents was afterward examined (entries 13-20). Markedly high
product yields were observed with MeOH, EtOH, PEG-400 and
PEG-600, with PEG-400 as the top one (entry 19). Notably, the
reaction could not succeed in the absence of the acidic ionic
liquid (entry 21) demonstrating the inevitability of the acidic ionic
liquid.
DMF
MeOH
EtOH
PEG-400
PEG-600
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
42
66
15
60
40
trace
[a]Using 1 (1.0 mmol), 2 (1.0 mmol), catalyst (20 mol%), ionic liquid (1 equiv.),
solvent (1 mL) in open vessel at 70 °C for 24 h.
[b]Isolated yield after flash column chromatography.
Pyrrolidine was also replaced by different secondary amines
viz. piperidine, morpholine and diethyl amine, and the resulting
triazenes were subsequently allowed to undergo the reaction
with cinnamic acid. However, pyrrolidine remained to be the best
choice to afford the maximum yield of the product (Scheme 2).
Other acidic ionic liquids IL2, IL3, IL4, IL5, IL6 and IL7,
when tried, could not provide the product in appreciable yields
(entries 22-27). The catalyst loading required was also studied,
which disclosed that an increase in the concentration upto 40
mol% could not bring about any sizable lead, while lowering the
concentration to 10% lowered the product yield considerably.
Thus the best set of reaction conditions (entry 19)
comprised of 20 mol% of Cu(OAc)2.H2O assisted by IL1 in PEG
400 at 70 °C under open atmosphere.
Scheme 2. Reaction of different triazene derivatives with cinnamic acids.
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10.1002/ejoc.201800930
European Journal of Organic Chemistry
COMMUNICATION
With the established conditions in hand, the versatility of the
reaction was examined using a variety of cinnamic acids and
aryl triazenes with different substitution patterns. The outcome is
given in Table 2. Both the reacting partners containing different
electron-withdrawing as well as electron-donating substituent
participated nicely in the reaction and offered the desired
products 3a–3x in reasonably good to high yields. Aryl triazenes
containing electron rich substituent in particular provided higher
yields. A number of substituent viz., CH3, Cl, F, OMe, NO2, CF3,
CN, and COOMe were well tolerated during the course of
reaction. o-Chlorocinnamic acid afforded somewhat low product
yield (3d, 71%) perhaps due to steric reason. The reaction was
also extended to a heteroaromatic (E)-3-(thiophen-2-yl)acrylic
acid to afford the products 3k and 3l. 1-(Naphthalen-1-
yldiazenyl)pyrrolidine also underwent the reaction smoothly to
give the product 3s in fairly high yield.
intermediacy of the arenediazonium cation during the course of
reaction.
Scheme 3. Control experiments.
Based on the existing literature,[19–22] control experiments
and isolation of products, a plausible mechanism is outlined in
Figure 2. The reaction is assumed to proceed via a copper
carboxylate intermediate I, which undergoes decarboxylation to
provide the organo-copper intermediate II. Ionic liquid (IL1)-
assisted generation of the arenediazonium cation (4) from aryl
triazene (2) finally couples with the intermediate II to give the
intermediate III and sets the stage for the reductive elimination,
which regenerates the catalytic copper acetate by aerial
oxidation of Cu(I) species to Cu(II) along with the final product 3.
Table 2. Scope and versatility of the reaction.[a,b]
Figure 2. Plausible reaction mechanism.
Conclusions
In conclusion, a practical approach involving decarboxylative
arylation of cinnamic acids using aryl triazenes has been
developed to accomplish the synthesis of synthetically and
biologically important stilbenes by copper/Ionic Liquid
combination in PEG-400. The method is versatile and offers high
yield, broad substrate scope and good functional group
tolerance.
[a]Using 1 (1.0 mmol), 2 (1.0 mmol), Cu(OAc)2·H2O (20 mol%), IL1 (1 equiv.),
PEG-400 (1mL) in open vessel at 70 °C for 24 h. [b]Isolated yield after flash
column chromatography.
Experimental Section
A mixture of cinnamic acid (1, 1.0 mmol), aryl triazene (2, 1.0 mmol),
Cu(OAc)2.H2O (20 mol%), IL1 (1.0 equiv.) and PEG-400, placed in a 10–
mL borosilicate vial, was stirred under open atmosphere at 70° C for 24 h.
After completion of the reaction (monitored through TLC), the mixture
was worked–up using water–ethyl acetate. The organic phase was dried
over anhydrous Na2SO4, filtered and concentrated under reduced
pressure. The resulting crude product was finally purified by Flash
chromatography using n–hexane and ethyl acetate as eluent.
To get an insight into the reaction mechanism, a number of
control experiments were carried out (Scheme 3). The model
reaction between 1a and 2a under the standard conditions
remained almost unaffected in the presence of radical
scavengers like TEMPO and BHT, thereby excluding the
possibility of a radical pathway. The reaction of a representative
diazonium
salt
namely
p-methoxybenzenediazonium
tetrafluoroborate (4a) instead of aryl triazene, with 1a, also gave
rise to the corresponding product (3r, 79%), suggesting an
Acknowledgements
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10.1002/ejoc.201800930
European Journal of Organic Chemistry
COMMUNICATION
(c) T. Hostier, Z. Neouchy, V. Ferey, D. G. Pardo, J. Cossy Org.
Lett. 2018, 20, 1815.
We are thankful to the CSIR, New Delhi (Project No.
02(0258)/16/EMR-II) for financial assistance, and for SRF to SK.
[10] V. Gauchot, A.-L. Lee, Chem. Commun. 2016, 52, 10163.
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Ding, X. He, J. Wu, Org. Biomol. Chem. 2009, 7, 863.
Conflict of interest
The authors declare no conflict of interest.
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Keywords: Decarboxylative coupling • Stilbenes • Aryl triazenes
• Copper catalysis • Ionic Liquid
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Entry for the Table of Contents
Layout 2:
COMMUNICATION
Saurabh Kumar, Anand Kumar Pandey,
Rahul Singh and Krishna Nand Singh*
Page No. – Page No.
Decarboxylative Arylation of α,β-
Unsaturated Carboxylic Acids using
Aryl Triazenes by Copper/Ionic Liquid
Combination in PEG-400
Decarboxylative Arylation
Decarboxylative Arylation: A practical approach involving decarboxylative arylation of cinnamic acids using aryl triazenes has been
developed to accomplish the synthesis of stilbenes. The method employs easily accessible starting materials, and is endowed with
broad substrate scope and functional group tolerance.
This article is protected by copyright. All rights reserved.