A rapid approach for the copper, amine, and ligand-free Sonogashira coupling of 4-methyl-7-nonafluorobutylsulfonyloxy coumarins under microwave irradiation

Article abstract of DOI:10.1016/j.tetlet.2014.02.094

A rapid, efficient, and reliable access for the synthesis of an assortment of 4-methyl-7-alkyl/aryl/heteroaryl alkynyl coumarins has been developed by the copper, amine, and ligand-free Sonogashira cross-coupling reaction of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin with various terminal alkynes under microwave irradiation. In the presence of a suitable catalyst, base, and solvent, the coupling reaction proceeded smoothly to give the diaryl alkynes in satisfactory to exceptional yields. Nonaflates coupled more efficiently than the corresponding triflates which yielded the detriflated product as well as the hydrolyzed product as competing side products along with the required product. The utilization of TBAF·3H₂O as a mild base as well as a solvating agent was the key for success of the reaction.

Full text of DOI:10.1016/j.tetlet.2014.02.094

Tetrahedron Letters 55 (2014) 2355–2361
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Tetrahedron Letters
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A rapid approach for the copper, amine, and ligand-free Sonogashira
coupling of 4-methyl-7-nonafluorobutylsulfonyloxy coumarins
under microwave irradiation
b
c
M. Nibin Joy a, Yadav D. Bodke a, , K. K. Abdul Khader , Ayyiliyath M. Sajith
⇑
a Department of P.G. Studies and Research in Industrial Chemistry, Kuvempu University, Jnana Sahyadri, Shankaraghatta, Shimoga 577451, Karnataka, India
b Post Graduate and Research Department of Chemistry, Jamal Mohamed College, Bharathidasan University, Tiruchirapalli, India
c Organic Chemistry Division, School of Chemical Sciences, Kasaragod Govt. College, Kannur University, Kannur, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A rapid, efficient, and reliable access for the synthesis of an assortment of 4-methyl-7-alkyl/aryl/hetero-
aryl alkynyl coumarins has been developed by the copper, amine, and ligand-free Sonogashira cross-cou-
pling reaction of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin with various terminal alkynes under
microwave irradiation. In the presence of a suitable catalyst, base, and solvent, the coupling reaction pro-
ceeded smoothly to give the diaryl alkynes in satisfactory to exceptional yields. Nonaflates coupled more
efficiently than the corresponding triflates which yielded the detriflated product as well as the hydro-
lyzed product as competing side products along with the required product. The utilization of TBAFÁ3H2O
as a mild base as well as a solvating agent was the key for success of the reaction.
Received 19 December 2013
Revised 24 February 2014
Accepted 24 February 2014
Available online 12 March 2014
Keywords:
Coumarin
Nonaflate
Sonogashira coupling
Microwave
Ó 2014 Elsevier Ltd. All rights reserved.
The palladium catalyzed cross-coupling reaction between or-
ganic halides or triflates and various nucleophiles has emerged as
one of the foremost methods for the creation of carbon–carbon
and carbon–heteroatom bonds under mild conditions.1 Among
these, the Sonogashira coupling reaction between organic ha-
lides/pseudo halides and terminal alkynes in the presence of a cop-
per cocatalyst with various amines as solvents or cosolvents has
found widespread use in pharmaceutical industries.2 The reaction
provides an efficient pathway to a range of pharmaceuticals, natu-
ral products, polymers etc. and hence has considerably extended
its scope in recent times.3 The role of copper in these reactions is
to assist the coupling reaction by the in situ generation of copper
acetylide which facilitates the transmetallation step in the catalytic
cycle.4 Nevertheless, it can also induce a Glaser-type oxidative
homocoupling to yield a diyne as side-product.5 Moreover, amines
possess a characteristic pungent and irritating smell and hence are
difficult to handle. In order to overcome these limitations, several
modified methodologies such as Cu-free and Cu as well as
amine-free reactions were reported recently.6
Nowadays, the microwave assisted organic synthesis (MAOS) has
indisputably become important in drug discovery laboratories
due often to higher reaction rates, selectivity, and product yields
as compared to standard thermal conditions.8 The time-consuming
transition metal catalyzed cross-coupling reactions will be com-
pleted in minutes with excellent reproducibility and lesser side
reactions under microwave irradiation.9 In particular, the advanta-
ges (short reaction times and high yield) of utilizing microwave
irradiation for the Sonogashira cross-coupling reactions have been
well documented in literature hitherto.10
Coumarins are an important group of benzopyrones found in
green plants either in free or combined state and display a broad
spectrum biological properties.11 The various therapeutic applica-
tions of coumarin derivatives include photo chemotherapy, anti-
tumor therapy, and anti-HIV therapy.12 Coumarins are also active
as anti-bacterial,13,14 anti-inflammatory,15 and anti-viral agents16
and are known to be lipid lowering agents with moderate triglyc-
eride lowering activity.17 The coumarin nucleus is present within
the chemical structure of pharmaceutical drugs such as warfarin,
acenocoumarol, carbochromen etc. and in antibiotics such as novo-
biocin, clorobiocin, and coumermycin A1.18 Moreover, the diverse
applications of coumarins in various fields of chemistry such as
luminescence, laser technologies, and liquid crystalline materials
have been extensively reported in the literature.19 7-Substituted
coumarins are an important group of coumarin derivatives which
shows various bioactive applications.20 4-Methyl-7-substituted
Conjugated alkynes are potentially useful intermediates in the
synthesis of a variety of heterocycles like indoles, azaindoles, ben-
zofurans etc. and hence the investigation of novel and facile meth-
ods for their synthesis is still an area of greater importance.7
⇑
Corresponding author. Tel.: +91 08282 256228; fax: +91 08282 256262.
E-mail address: ydbodke@gmail.com (Y.D. Bodke).
http://dx.doi.org/10.1016/j.tetlet.2014.02.094
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2356
M. N. Joy et al. / Tetrahedron Letters 55 (2014) 2355–2361
coumarins are reported to have diverse applications in the field of
medicinal chemistry such as Monoamine Oxidase Inhibitory Po-
tency and DNA binding capacity.21 Owing to these varied applica-
tions, the investigation of novel methods for the facile and efficient
synthesis of pharmacologically relevant coumarin derivatives has
been the aim of many researchers for the past two decades.22
As a continuation of our ongoing research program in the syn-
thesis of biologically active molecules,23 we were interested in syn-
thesizing some C-7 substituted coumarins which may possess
significant biological activities. On continuation of our ongoing re-
search on palladium catalyzed cross-coupling reactions,24 we
planned to apply the copper, amine, and ligand-free Sonogashira
coupling reaction for the synthesis of various coumarin analogues.
The instability of coumarin nuclei in basic as well as prolonged
heating conditions has been extensively reported in the litera-
ture.22e,25 Moreover, the transition metal catalyzed cross-coupling
reactions usually take hours or days for completion by classical
heating which is too long for medicinal chemistry programs.26
These observations stimulated us to utilize the microwave irradia-
tion for the synthesis of various substituted coumarins in view of
the fact that the reactions could complete within minutes as
compared to conventional heating methodologies. In this letter,
we report a facile and efficient protocol for the synthesis of a vari-
ety of 4-methyl-7-alkyl/aryl/heteroaryl alkynyl coumarins utilizing
the palladium catalyzed cross-coupling of 4-methyl-7-nonaf-
luorobutylsulfonyloxy coumarins with various terminal acetylenes
under microwave irradiation.
The parent coumarin compound 2 was synthesized using the
modified Pechmann cyclization reaction (Scheme 1) in which res-
orcinol 1 was treated with ethyl acetoacetate in 1-butyl-3-methyl-
imidazolium chloroaluminate at 30 °C for 20 min.27 The obtained
hydroxy coumarin 2 was then converted to corresponding triflate
3a by treating it with trifluoromethane sulfonic anhydride in
dichloromethane (DCM) and pyridine at À10 °C for 2 h. The inter-
mediate thus obtained was then subjected to Sonogashira coupling
with the intention of synthesizing an array of novel 4-methyl-7-al-
kyl/aryl/heteroaryl alkynyl coumarins of significant pharmacologi-
cal relevance (Scheme 2).
alysts in combination with various bases and solvents were inves-
tigated at 120 °C at 110 W and the reaction was carried out in a
microwave oven for 30 min. (Table 1). Unfortunately, we could
not obtain the required product in acceptable yield in any of the
explored conditions and the detriflated product 5 as well as the
hydrolyzed product 2 was obtained as competing side products.
The use of various catalysts like Pd(dppf)Cl2, Pd(dppf)CH2Cl2,
PdCl2(CH3CN)2, Pd2(dba)3 etc. was found to be ineffective (Table 1,
entries 1–4). Changing the solvent from toluene to various polar
co-ordinating solvents such as N,N-dimethylacetamide, (DMA),
N,N-dimethylformamide (DMF), and N-methyl-2-pyrrolidone
(NMP) too was unsuccessful. Even though we could see the forma-
tion of product in considerably better yield when PdCl2(PCy3)2 was
used as a catalyst and hydrated tetrabutyl ammonium fluoride
(TBAFÁ3H2O) as a base in DMA, the detriflated product 5 prevailed
as a major competitor (Table 1, entry 7). But more importantly, the
hydrolysis of triflate was suppressed to a greater extent. The utili-
zation of strong bases like NaOH and t-BuOH caused the substan-
tial cleavage of the lactone ring (Table 1, entries 8 and 9).
Neither increasing the reaction times nor the stoichiometric ratio
of reagents and base were instrumental (Table 1, entries 12 and
13). The triflate proved to be inert and unstable in the reaction con-
ditions which could be attributed to the unstable nature of inter-
mediate Pd(II) complex that is expected to form during its
preliminary oxidative addition to Pd(0).28
In order to circumvent the issues related to instability and
saponification of the triflate, we decided to optimize the reaction
conditions with corresponding nonaflates. The synthesis of 4-
methyl-7-nonafluorobutylsulfonyloxy coumarin intermediate 3b
was achieved by the reaction of hydroxy intermediate 2 with nona-
fluorobutane sulfonic anhydride in the presence of pyridine as base
at À10 °C for 1 h. (Scheme 3). Nonaflates are reported to be more
stable than corresponding triflates and are considered as a practi-
cal alternative to triflates.29 The strong electron-withdrawing
property of the perfluorinated alkyl chain in combination with
the SO2 group dramatically enhances the reactivity of nonaflates
and hence is a perfect tool for creating a good leaving group.30
Moreover, it has been well documented that the nonaflates are less
prone to O–S bond cleavage than the corresponding triflates which
apparently causes the hydrolysis.31 Owing to these observations,
we treated the nonaflate 3b with phenyl acetylene in different cat-
We started our initial screening by coupling the triflate 3a with
phenyl acetylene since the formation of product could be easily
identified by TLC and LC–MS (Scheme 2). A series of palladium cat-
TfO
O
O
HO
O
O
HO
OH
Tf2O, -10oC
Pyridine
[bmim]Cl.2AlCl3
CH3COCH2COOEt
1
2
3a
Scheme 1. Synthesis of 4-methyl-7-trifluoromethylsulfonyloxy coumarin intermediate.
TfO
O
O
O
O
O
O
HO
O
O
Catalyst/Ligand
Solvent/120oC
Base
5
4a
2
3a
Major
Traces
Major
O
O
S
F
OTf =
O
F
F
Scheme 2. Sonogashira coupling of 4-methyl-7-trifluoromethylsulfonyloxy coumarin intermediate with phenyl acetylene.

M. N. Joy et al. / Tetrahedron Letters 55 (2014) 2355–2361
2357
Table 1
Effect of various ligands and bases on the coupling of triflate 3a with phenyl acetylene
Entry
Catalyst
Base
Solvent
Yield 5 (%)
Yield 2 (%)
Yield 4a (%)
1
2
3
4
5
Pd2(dba)3
Cs2CO3
K3PO4
Toluene
DMF
NMP
Toluene
DMA
DMF
65
62
57
Traces
35
22
26
30
Traces
23
Nil
Nil
Traces
Nil
25
Pd(dppf)CH2Cl2
Pd(dppf)Cl2
PdCl2(CH3CN)2
PdCl2(PCy3)2
Pd2(OAc)2
TBAFÁ3H2O
K3PO4
Cs2CO3
Cs2CO3
6
40
35
15
7
8
9
10
11
12
13
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
TBAFÁ3H2O
DMA
40
Traces
Nil
Nil
Traces
Traces
Traces
Traces
45
NaOtBu
Dioxane
Dioxane
DMF
NMP
DMA
Nil
Nil
38
32
30
Nil
Nil
37
NaOH
TBAFÁ3H2O
TBAFÁ3H2O
TBAFÁ3H2O
TBAFÁ3H2O
40
50a
35b
DMA
40
Reaction conditions: 4-methyl-7-trifluoromethylsulfonyloxy coumarin 3a (1 mmol), phenyl acetylene (1.3 mmol), catalyst (5 mol %), base (2 mmol), solvent, microwave
irradiated at 110 W at 120 °C for 30 min.
a
1.5 mmol of phenyl acetylene and 3 mmol of base used.
Reaction carried out for 1 h.
b
R
R
HO
O
O
NfO
O
O
O
O
O
O
Nf2O, -10oC
Pyridine
PdCl2(PCy3)2
DMA/100oC
TBAF.3H2O
5
4a-o
2
3b
Traces
Major
F
F
F
F
F
HO
O
O
R=Alkyl/Aryl/Heteroaryl
O
O
O
S
ONf =
F
F
F
F
2
Traces
Scheme 3. Synthesis of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin intermediate and its Sonogashira coupling with various terminal acetylenes.
Table 2
Effect of various ligands and bases on the coupling of nonaflate 3b with phenyl acetylene
Entry
Catalyst
Base
Solvent
Yield 5 (%)
Yield 2 (%)
Yield 4a (%)
1
2
3
4
5
6
7
8
Pd(dppf)CH2Cl2
Pd(dppf)Cl2
Pd(OAc)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
PdCl2(PCy3)2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
TBAFÁ3H2O
TBAFÁ3H2O
TBAFÁ3H2O
TBAFÁ3H2O
Toluene
Dioxane
DMF
DMA
NMP
DMF
DMA
DMA
Traces
Nil
25
76
20
35
Traces
Traces
Traces
Traces
25
Traces
28
45
70
Traces
Traces
Traces
Traces
Traces
Traces
58
80
98a
Reaction conditions: 4-methyl-7-nonafluorobutylsulfonyloxy coumarin 3b (1 mmol), phenyl acetylene (1.3 mmol), catalyst (5 mol %), base (2 mmol), solvent, microwave
irradiated at 110 W at 120 °C for 30 min.
a
3 mmol of TBAFÁ3H2O used and reaction carried out at 100 °C.
alysts, bases, and solvents and the reaction was carried out in a
microwave oven at 120 °C at 110 W for 30 min (Table 2).
Table 3
Effect of various bases on Sonogashira cross-coupling reaction
Gratifyingly, we could not see the denonaflated product in any
of these conditions and a slight improvement in the coupled yield
was noticed. We observed that the reaction conditions and nature
of the catalyst have a significant effect on this coupling reaction.
The catalyst PdCl2(PCy3)2 was found to be essential for better con-
versions and polar solvents like DMF, NMP, and DMA were prom-
ising. To our delight, we could see the product in better yield when
Cs2CO3 was used as a base with the catalyst in DMA, but still the
hydrolysis persisted as a major challenge (Table 2, entry 4). Fortu-
nately, we could see the product in an acceptable yield when
TBAFÁ3H2O (2 equiv) was used as a base in DMA which significantly
reduced the hydrolysis of the nonaflate (Table 2, entry 7). Finally,
Entry
Base
Yielda (%)
1
2
3
4
5
6
7
8
K2CO3
15
25
17
Traces
40
43
58
95
NaHCO3
Na2CO3
NaOH
Cs2CO3
K3PO4
CsF
TBAFÁ3H2O
Reaction conditions: 4-methyl-7-nonafluorobutylsulfonyloxy coumarin 3b
(1 mmol), phenyl acetylene (1.3 mmol), PdCl2(PCy3)2 (5 mol %), base (3 mmol),
DMA, microwave irradiated at 110 W at 100 °C for 30 min.
a
Isolated yield.

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M. N. Joy et al. / Tetrahedron Letters 55 (2014) 2355–2361
Table 4
Sonogashira coupling of the nonaflate intermediate 3b with various terminal acetylenes
Entry
Nonaflate (3)
Alkynes (2)
Product (4a–p)
Time (min)
25
Yielda (%)
O
O
1
3b
95
2a
4a
O
F
O
2
3
4
5
6
7
3b
3b
3b
3b
3b
3b
27
33
30
25
20
18
80
77
82
88
91
90
2b
F
4b
O
O
NO2
O
2c
O2N
4c
CN
O
2d
NC
4d
O
O
2e
4e
O
OH
NH2
O
O
2f
2g
2h
HO
H2N
O
4f
4g
4h
O
O
O
O
8
9
3b
3b
3b
3b
22
30
25
30
85
76
81
75
O
N
N
N
O
2i
N
4i
O
O
10
11
2j
N
4j
O
O
2k
N
4k

M. N. Joy et al. / Tetrahedron Letters 55 (2014) 2355–2361
2359
Table 4 (continued)
Entry
Nonaflate (3)
Alkynes (2)
Product (4a–p)
Time (min)
26
Yielda (%)
O
O
O
O
12
13
14
15
3b
92
90
93
87
2l
4l
N
N
3b
3b
3b
23
25
25
2m
OH
4m
O
O
HO
2n
4n
OH
O
O
HO
2o
4o
Reaction conditions: 4-methyl-7-nonafluorobutylsulfonyloxy coumarin 3b (1 mmol), phenyl acetylene (1.3 mmol), PdCl2(PCy3)2 (5 mol %), TBAFÁ3H2O (3 mmol), DMA,
microwave irradiated at 110 W at 100 °C.
a
Isolated yield.
PdCl2(PCy3)2
2Cl
Pd(PCy3)2
PCy3
Nf
O
R
O
O
O
O
P
Pd(0)
2
9
1
R
Pd
Nf
O
O
3
O
O
Pd
O
8
B
a
s
e
.
O
Pd
N
Nf
R
f
O
H
7
B
R
a
s
e
O
5
6
4
O
Scheme 4. Proposed mechanism of the coupling reaction.
the addition of one more equivalent of TBAFÁ3H2O and reducing
the reaction temperature to 100 °C furnished the required diaryl
acetylene 4a in 98% yield (Table 2, entry 8).
Our subsequent efforts were to study the effect of base on the
reaction system. Keeping this in mind, we continued the coupling
reaction with a variety of bases by maintaining all the other

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M. N. Joy et al. / Tetrahedron Letters 55 (2014) 2355–2361
parameters constant (Table 3). Although various bases like CsF, Cs2-
References and notes
CO3, and K3PO4 showed the mass of the coupled product, TBAFÁ3H2-
1. (a) Loidreau, K.; Levacher, V.; Besson, T. Tetrahedron Lett. 2013, 54, 1160–1163;
(b) Reddy, A. G. K.; Satyanarayana, G. Tetrahedron 2012, 68, 8003–8010; (c)
Takeuchi, M.; Tuihiji, T.; Nishimura, J. J. Org. Chem. 1993, 58, 7388; (d) Sugiura,
H.; Nigorikowa, Y.; Saiki, Y.; Nakamura, K.; Yamaguchi, M. J. Am. Chem. Soc.
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Chem. Soc. 2004, 126, 9186–9187.
2. (a) Sonogashira, K.; Yatake, T.; Tohda, Y.; Takahashi, S.; Hagihara, N. J. Chem.
Soc., Chem. Commun. 1977, 291; (b) Takahashi, S.; Kuroyama, Y.; Sonogashira,
K.; Hagihara, N. Synthesis 1980, 627; (c) Doucet, H.; Hierso, J. C. Angew. Chem.,
Int. Ed. 2007, 46, 834–871; (d) Petricci, E.; Radi, M.; Corelli, F.; Botta, M.
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O
proved to be superior which completely suppressed the
hydrolysis of the nonaflate (Table 3, entries 5–8). The mild basicity
of TBAFÁ3H2O which could facilitate the abstraction of proton from
the most acidic center of the alkyne and its increase in solvation in
the reaction medium when its stoichiometric ratio was increased
could be the plausible reasons for this superiority.32 Similarly,
enhancing the reactivity of the catalytic system by forming a
monoligated species was proved to be vital for the supremacy of
PdCl2(PCy3)2 to other catalysts in this coupling reaction which is
in agreement with our previous observations.24a
With the optimized condition in hands, our next attention was
to evaluate the generality of the developed protocol. A series of ste-
rically and electronically diverse terminal acetylenes were coupled
with the nonaflate 3b and our results are summarized in Table 4.
All the alkynes gave the diaryl alkynes in satisfactory to excellent
yields. Unsurprisingly, electron rich acetylenes gave exceptional
yields of the coupled product whereas electron deficient alkynes
gave slightly lesser yields which could be rationalized by the fact
that the presence of electron withdrawing groups considerably re-
duced the nucleophilicity of acetylenic proton (Table 4, entries 2–
8). Sterically crowded acetylenes procured the coupled product in
slightly lesser yields even after continuing the reaction to 1 h (Ta-
ble 4, entries 9–11).
The plausible mechanism of the copper, ligand, and amine-free
coupling reaction of nonaflate with alkyne has been proposed
(Scheme 4). In the first step, a coordinatively unsaturated Pd(0)
catalytic species is formed in the reaction medium. The subsequent
steps involve the oxidative addition of Pd(0) to the nonaflate spe-
cies to form the Pd(II) oxidative adduct complex 3 and the com-
plexation of alkyne with Pd(II) species thereby increasing the
acidity of alkyne hydrogen which enables the deprotonation with
the base to yield 8. Finally, it undergoes reductive elimination to
form the coupled product and completes the catalytic cycle.
In summary, we have achieved a concise, facile, and efficient
protocol for the copper, amine, and ligand-free Sonogashira
coupling of 4-methyl-7-nonafluorobutylsulfonyloxy coumarins
by the generation of a Pd/PCy3 catalyst system in the presence
of TBAFÁ3H2O under microwave irradiation.33 The nonaflates
proved to be superior than corresponding triflates in terms of
reactivity and resistivity to hydrolysis. The use of hydrated
TBAF as a mild base and as a solvating agent which signifi-
cantly suppressed the nonaflate hydrolysis broadened the sub-
strate scope of this coupling reaction. This method provided
an efficient pathway to a variety of pharmacologically relevant
coumarins and could be further extended for the coupling of
other densely functionalized heterocycles in future. The biolog-
ical screening and the structure activity relationship studies of
the newly synthesized molecules will be done in due course
and will be communicated shortly.
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Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
02.094.

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33. A representative example of the nonaflate and 4-tolyl acetylene is taken. To a
solution of 4-methyl-7-nonafluorobutylsulfonyloxy coumarin (3b, 1 equiv) in
DMA, were added PdCl2(PCy3)2 (5 mol %). The solution was purged with
nitrogen and stirred at room temperature for 10 min, at which time 4-tolyl
acetylene (1.3 equiv) and TBAFÁ3H2O (3 equiv) were added. The reaction
solution was purged again with nitrogen and then placed in the microwave and
heated for 20–30 min at 100 °C at 110 W. When TLC and LC–MS showed full
consumption of starting materials, the reaction mixture was diluted with ethyl
acetate, separated the ethyl acetate layer, given water wash, brine wash and
was dried over anhydrous sodium sulfate and distilled under reduced pressure
to get the crude material. The crude product was purified by column
chromatography (10–40% hexane/EtOAc) to isolate the 4-methyl-7-(2-p-
tolylethynyl)-2H-chromen-2-one (4e) in 88% yield. mp: 80–82 °C; 1H NMR
(400 MHz, CDCl3): d 2.47, d, J = 1.56 Hz, 3H, CH3; d 6.38, s,1H, ArH; d 7.34–7.37,
dd, J1 = 1.24 Hz, J2 = 7.72 Hz, 2H, ArH; d 7.53–7.57, m, 3H, ArH; d 7.71–7.74, dd,
J1 = 2.08 Hz, J2 = 8.28 Hz, 2H, ArH; 13C NMR: d 23.2, CH3; d 26.5, CH3; d 95.2, d
114.3, d 121.5, d 122.6, d 124.1, d 127.2, d 128.3, d 130.8 (2 peaks), d 134.1, d
140.2, d 152.0, d 154.9, d 163.1, CO; LC–MS: Calculated 274.3, Observed 275.3.