Trifluoroacetic Acid Mediated One-Pot Synthesis of Furo-Fused Quinoxalines/Pyrazines

Article abstract of DOI:10.1002/ejoc.201700541

A trifluoroacetic acid promoted step-economical one-pot approach to the synthesis of furo-fused quinoxalines/pyrazines by the reaction of 2,3-dichloroquinoxalines/pyrazines with alkynes is described. The reaction involves a selective in-situ Sonogashira c

Full text of DOI:10.1002/ejoc.201700541

A Journal of
Accepted Article
Title: TFA-Mediated One-Pot Synthesis of Furo-Fused Quinoxalines/
Pyrazines
Authors: Akhilesh Kumar Verma, Kapil Mohan Saini, Sonu Kumar,
Monika Patel, and Rakesh K. Saunthwal
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201700541
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10.1002/ejoc.201700541
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TFA-Mediated One-Pot Synthesis of Furo-Fused Quinoxalines/
Pyrazines
Kapil Mohan Saini,a Sonu Kumar, a Monika Patel, a Rakesh K. Saunthwal a and Akhilesh K. Verma* a
Dedication ((optional))
Abstract: Trifluoroacetic acid (TFA) promoted step-economical one-
pot approach for the synthesis of furo-fused quinoxalines/pyrazines
by the reaction of 2, 3-dichloroquinoxalines/pyrazines with
electronically varied alkyne is described. The reaction shows the
selective in-situ Sonogashira conjoined hydroxylation followed by
metal free 5-endo-dig cyclization. The preliminary experiment
depicted the role of TFA as a source of oxygen for oxyarylation and
isotopic labeling studies supports the proposed mechanistic pathway
goes via activation of alkyne in acidic medium. This methodology
tolerates a various kind of substituents, which proves to be valuable
for structural and biological assessment.
the construction of N-heterocyclic scaffolds have been devel-
oped.[6,7] Literature survey revealed that majority of reported
procedures for the synthesis of furan-fused heterocycles re-
quired substrate with pre-installed hydroxyl group.[8] However the
metal/ligand/additive and oxidant-free protocol via in-situ instal-
lation of hydroxyl group for the synthesis furoquinoxaline and
pyrazine derivatives has not been much explored. In 2007,
Ackermann et. al. demonstrated the synthesis of benzo[b]furan
via anti-Markovnikov hydration of ortho-alkynylhaloarenes with
concomitant O-arylation in presence of Cu-catalyst (Scheme 1,
i).[9] Later, Pal and co-workers[4b] investigated a two-step synthe-
sis of furo[2,3-b]quinoxaline/pyrazine under basic medium
(Scheme 1, ii). A microwave-assisted three component synthe-
sis of furo[2,3-b]quinoxaline derivatives using copper catalyst
has been reported by Narender group in 2014 (Scheme 1, iii).[10]
Subsequently, Keivanloo group designed the multi-step synthe-
sis of iodo substituted furo[2,3-b]quinoxaline using ICl as rea-
gent (Scheme 1, iv).[11]
Introduction
The ubiquity of quinoxaline core in pharmacologically[1] impor-
tant compounds encouraged the interest of organic chemist to
develop an architectural complexity around it. The C-C cross
coupling strategy is an efficient tool for the synthesis of a wide
variety of biologically active fused N- and O-heterocycles.[2] For
instance, some furano-containing nucleosides possess in vitro
antiviral and antileukemic activity (Figure 1i).[3] The furo[2,3-
b]pyrazine and furo[2,3-b]quinoxaline derivatives act as potent
inhibitors of PDE4B and sirtuins. The significance of alkyl chain
at C-2 position of furo[2,3-b]quinoxaline showed considerable
inhibition in the cell growth against cervical cancer (HeLa) cells
(Figure 1 ii and iii).[4] Benthocyanin B control lipid peroxidation
induced by free radicals in rat liver microsomes and also inhibits
rat erythrocyte hemolysis (Figure 1 iv).[5] Owing to the biological
importance of quinoxaline/pyrazine derivatives; functionalization
of these heterocycles using cost-effective methodology from
easily accessible starting materials is an important area of cur-
rent research.
Figure 1. Biologically active furo-fused N-heterocyclic derivatives.
Over the past decade, several synthetic approaches for
a Department of chemistry
University of Delhi, Delhi-110007
E-mail: akverma@acbr.du.ac.in
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
Scheme 1. Designed domino approach for the synthesis of furo-fused N-
heterocycles.
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Pd(OAc)2 was employed at 60 oC for 4 h in DMF under inert
atmosphere (entry 1). Replacement of Pd(OAc)2 with
PdCl2(PPh3)2, resulted the formation of intermediate 3a in
higher yield (entry 2). The reaction of 1a with alkyne 2a using
Recently, our group[12] have also explored the Pd-
catalyzed
hydroarylation
of
2-aryl-3-(aryl/alkylethynyl)
quinoxaline for the synthesis of benzophenazine. In addition to
our existing research on heterocyclic chemistry;[13] herein we
have developed a one-pot approach for the synthesis of highly
functionalized furo[2,3-b]quinoxaline/pyrazine. The reaction
o
PdCl2(PPh3)2 in MeCN at 60 C for 1.5 h provided the coupled
intermediate 3a in 90% yield (entry 3). On performing the C-C
coupling reaction at room temperature, declines the yield of
intermediate 3a (entry 4). After optimizing the regioselective
Sonogashira reaction,[14] we focused our attention towards the
tandem cyclization of 2-chloro-3-(phenylethynyl)quinoxaline (3a).
Inspired from our preliminary results; the sequential one-pot
addition of 2 mL of trifluoroacetic provided the desired product
4a in 65% yield (entry 5). Significant improvement in the yield of
the product 4a was observed on increasing the amount of TFA
from 2 mL to 4 mL (entries 6-7). Further elevation in the amount
of acid, did not affect the yield of the desire product 4a (entry 8).
Lowering the reaction temperature provided the desire product
4a in 79% yield (entry 9). In contrast to TFA, glacial acetic acid
provided the desire product 4a in 35% yield (entry 10). However,
no product was detected when trifluoromethanesulfonic acid and
methanesulfonic acid were employed in the reaction (entries 11
proceeded via
a
Pd/Cu-catalyzed alkynylation of 2,3-
dichloroquinoxaline followed by 5-endo-dig ring closure in
presence of TFA. The present strategy appeared to be attractive
as no external oxidant is required. TFA itself act as a source of
oxygen for oxyarylation and facilitates the activation of alkyne.
The practical utility of one-pot synthesis obviates the tedious
purification of the intermediate as well as reduces the cost and
efforts for the synthesis of furo-fused quinoxaline/pyrazine.
Results and Discussion
To chase the objective of domino synthesis of 5-endo-dig cy-
clization,
we
began
our
investigation
using
2,3-
dichloroquinoxaline 1a and phenylacetylene 2a as a model
substrates with a variety of acids. We established a protocol for
the Pd/Cu induced C-C coupling reaction for the generation of
key intermediate 3a. As shown in Table 1, the mono Sonoga-
shira intermediate 3a was isolated in 60% yield when 5 mol %
and
12).
Table 1. Optimization of Reaction Conditions [a]
Yield (%)[b]
3aa
Entry
Catalyst (mol %)
Solvent (mL)
T oC/time (h)
4a
60
75
90
49
30
10
-
-
1
2
DMF
60/4
Pd(OAc)2
-
-
-
DMF
60/4
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
60/1.5
3
MeCN
4
MeCN
25/4
65
5
MeCN + CF3COOH/2
MeCN + CF3COOH/3
MeCN + CF3COOH/4
MeCN + CF3COOH/5
MeCN + CF3COOH/4
MeCN + CH3COOH/4
MeCN + CF3SO3H/4
MeCN + CH3SO3H/4
60/1.5 + 60/6
60/1.5 + 60/6
60/1.5 + 60/2
60/1.5 + 60/2
60/1.5 + 45/2
60/1.5 + 60/2
60/1.5 + 60/2
60/1.5 + 60/2
69
86
86
79
35
-
6
7
-
8
15
50
82
86
9
10
11
12
-
[a]Unless otherwise noted, all Sonogashira reactions were carried out using 0.5 mmol of 2,3-Dichloroquinoxaline (1a), 0.52
mmol of alkyne (2a), catalyst (5 mol %), CuI (5 mol %), Et3N (2.5 equiv) in 2.0 mL of solvent, under inert atmosphere.
[b]Isolated yield.
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We explored the scope of reaction for the synthesis of furo[2,3-
yields
(entries
7
and
8).
However,
1-ethynyl-4-
b]quinoxaline
by
allowing
highly
substituted
2,3-
(phenoxymethyl)benzene 2i failed to provide the desired product
4i probably due to the low reactivity of alkyne (entry 9). Interest-
ingly, when 2,3-dichloro-6-methylquinoxaline 1b was imple-
mented for tandem cyclization, the desired products 4j-o were
obtained in 83-94% yields (entries 10-15). On increasing the
electron density over quinoxaline moiety 1c, the intriguing cy-
clized products 4p-r were obtained in 82-95% yields (entries 16-
18). The electronically varied chloro- substituted quinoxaline 1d
afforded the yields of the furo-fused products 4s-u in 76-79%
(entries 19-21). The X-ray crystallographic studies of 4b further
elucidated the formation of cyclized product.[15]
dichloroquinoxaline (1a-d) with a variety of electron-neutral,
electron-rich and electron-deficient terminal alkynes 2 in the
presence of trifluoroacetic acid (Table 2). Both electron-neutral
and electron-rich alkynes with 1a afforded the desired products
4a-c in excellent yields (entries 1-3). The bulky substitutent 4-
tBuPh alkyne 2d was also capable in providing the cyclized
product 4d in 86% yield (entry 4). Electron deficient alkynes 2e-f
gave the corresponding product 4e-f in 84 and 80% yields,
respectively (entries 5 and 6).The heterocyclic alkynes 2g-h
were successful in providing the fused products 4g-h in good
Table 2. Synthesis of furoquinoxaline derivative.[a]
S.No
1
Quinoxaline
Alkyne
Product
Yield (%)[b]
2a
2b
4a
4b
86
88
1a
1a
2
3
1a
1a
1a
1a
2c
2d
2e
2f
4c
4d
4e
4f
87
86
84
80
4
5
6
7
8
1a
1a
2g
2h
4g
4h
88
82
9
1a
1b
2i
4i
4j
0[c]
88
10
2c
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11
1b
2j
4k
86
12
13
14
1b
1b
2k
2e
4l
94
86
4m
1b
1b
2g
2h
4n
4o
90
83
15
16
2b
4p
90
1c
1c
17
18
19
2k
2f
2l
4q
4r
95
82
76
1c
4s
1d
1d
20
21
2c
2k
4t
78
79
1d
4u
N1
N2
C5
C9
C21
C12
C16
C13
C14
C7
C8
C4
C6
C1
C10
C11
C18 C19
C17
O1
4k
C15
C3
C2
C20
[a] Sonogashira reactions were carried out using 0.5 mmol of 2,3-Dichloroquinoxaline (1), 0.52 mmol of alkyne (2), PdCl2(PPh3)2 (5 mol %), CuI (5
mol %), Et3N (2.5 equiv) in 2.0 mL of MeCN, under inert atmosphere, After completion of Sonogashira reactions 4 mL trifluoroacetic acid (TFA) was
added. [b] Isolated yield. [c] 2-chloro-3-(3-phenoxyprop-1-yn-1-yl)quinoxaline was obtained. CCDC number of 4b and 4k are 1538954 and 1549438
respectively.
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Encouraged from above results, we further extended the chem-
istry using 2, 3-dichloropyrazine with a variety of terminal al-
kynes (Table 3). The reaction of 2, 3-dichloropyrazine 5 with
electronically varied alkynes 2 afforded the furo-fused pyrazines
(6a-h) in good yields. The X-ray crystallographic studies[15] of 6b
further supported the synthesis of furo-pyrazine.
Table 3. Synthesis of furo-pyrazine derivative
S.No
1
Alkyne
Product
Yield (%)b
70
2a
6a
6b
2
3
2m
68
72
2l
6c
4
5
6
7
8
2b
2c
2k
2j
6d
6e
6f
74
73
76
74
71
6g
6h
2d
[a] Sonogashira reactions were carried out using 0.5 mmol of 2,3-Dichloropyrazine (5), 0.52 mmol of alkyne (2), PdCl2(PPh3)2 (5
mol %), CuI (5 mol %), Et3N (2.5 equiv) in 2.0 mL of MeCN, under inert atmosphere, After completion of Sonogashira reactions 4 mL
trifluoroacetic acid (TFA) was added. [b] Isolated yield. CCDC number of 6b is 1538955.
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In order to propose a mechanistic pathway and role of TFA
in one-pot synthesis of furo-fused N-heterocycles, an array of
preliminary experiments were conducted (Scheme 3). Initially,
we performed the regioselective C-C coupling of 1 and 5 with
electron-releasing (2b, 2k) and electron-deficient alkyne (2e, 2h)
under standard reaction condition provided the key intermediate
3b, 3m, 3o and 11f in good to excellent yields (eq. i, ii). In order
to determine the role of TFA, the isolated intermediates were
further subjected for domino cyclization by the addition of TFA,
afforded the furo-fused quinoxalines (4b, 4m and 4o) and
pyrazine (6f) in 80-91% yields (eq. iii, iv). This suggests that Pd-
catalyst is not involved in the cyclization. The acidic medium
accelerates the formation of furo[2,3-b]quinoxaline/pyrazines. To
gain insights into the reaction mechanism, various isotopic label-
ling experiments were performed. When alkynylquinoxaline 3b
was treated with TFA followed by D2O work up, no deuterium
incorporation was observed in product 4b (eq. v). This imply that
the proton exchange occur in situ within the reaction. When
deuterated TFA was used as a solvent the desired products
12a-b and 13 were obtained in 90, 89 and 79% yields respec-
tively with 99% D at C-3 position (eq. vi, vii). The formation of
deuterated product confirms that the mechanism goes via acid
activation of alkyne.
Scheme 2. Scope of dihalopyridine
As illustrated in Scheme 2, the reactivity of dihalopyridine was
also evaluated, the corresponding uncyclized oxidised product 9
was obtained in 70% yield probably due to the presence of
highly activating alkyne 8 (Scheme 4a). When ketone 9 was
reacted using CuI (10 mol%), L-Proline and K3PO4 in DMF
provided the cyclized product 10 in 62% yield (Scheme 2b).
Based on the control experiments and literature studies,[12]
we proposed a plausible mechanistic hypothesis as described in
Scheme 4. The mechanism was initiated by the Pd-catalyzed
Sonogashira coupling reaction of dihalo compound 1 with termi-
nal alkynes 2 which leads to the formation of alkynyl intermedi-
ate 3, 11. The one-pot addition of TFA generates the species A.
Subsequently, the nucleophilic addition on carbonyl moiety B
develop species C followed by elimination afforded the species
D. Another possibility for the formation of species D is via hy-
drolysis of species B. The acid promoted activation of alkyne
with concomitant 5-endo-dig ring closer provided the desired
cyclized product 4, 6 via formation of species E.
Scheme 4. Plausible Mechanism
Scheme 3. Mechanistic Experiment
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126.1, 100.7. HRMS (ESI): [M+H]+ Calcd for [C16H10N2O]
247.0871; found 247.0868.
Conclusion
In conclusion, we have demonstrated an efficient metal-
free one-pot domino approach for the synthesis of diversely
substituted furo-fused quinoxalines/pyrazines. The strategy
involves the in situ alknylation followed by 5-endo-dig cyclization
in the presence of trifluoroacetic acid. The major role of TFA was
to provide oxygen for oxyarylation and to facilitate the acidic
activation of alkyne for intramolecular cyclization. The prelimi-
nary control experiments validate the mechanistic pathway and
X-ray crystallographic studies further support the designed
chemistry of furo-fused N-heterocycles. We anticipate that this
protocol is useful for the synthesis of N-, O- containing polycyclic
heterocycles which could find further application, in biologically
active compound.
2-(p-Tolyl)furo[2,3-b]quinoxaline (4b): The product was obtained
as a yellow needles, mp: 219–221 C (table 2: 114.5 mg, 88%;
o
Scheme 5: 118.4 mg, 91%); 1H NMR (400 MHz, CDCl3): δ 8.19–
8.16 (m, 1H), 8.13–8.10 (m, 1H), 7.91 (d, J = 8.4 Hz, 2H), 7.76–
7.71 (m, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.22 (s, 1H), 2.43 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 164.3, 154.4, 144.7, 142.2, 141.9,
138.6, 129.9, 128.6, 128.57, 128.2, 126.1, 125.7, 99.9, 21.6.
HRMS (ESI): [M+H]+ Calcd for [C17H12N2O] 261.1028; found
261.1032.
2-(4-Ethylphenyl)furo[2,3-b]quinoxaline (4c): The product was
obtained as a yellow needles, mp: 159–161 oC (119.2 mg, 87%);
1H NMR (400 MHz, CDCl3): δ 8.18–8.15 (m, 1H), 8.12–8.09 (m,
1H), 7.94 (d, J = 8.4 Hz, 2H), 7.75–7.70 (m, 2H), 7.36 (d, J = 8.4
Hz, 2H), 7.22 (s, 1H), 2.72 (q, J = 7.6 Hz, 2H), 1.28 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 164.3, 154.4, 148.2, 144.7,
142.2, 138.6, 128.69, 128.65, 128.62, 128.56, 128.2, 126.2,
125.9, 99.9, 28.9, 15.3. HRMS (ESI): [M+H]+ Calcd for
[C18H14N2O] 275.1184; found 275.1178.
Experimental
General Experimental
All the reactions were performed in an oven-dried Schlenk flask
under inert atmosphere. Column chromatography was per-
formed using silica gel (100-200 Mesh). Thin layer chromatog-
raphy (TLC) was performed on silica gel GF254 plates. Visuali-
zation of spots on TLC plate was accomplished with UV light
(254 nm) and staining over I2 chamber. 1H and 13C NMR spectra
were recorded at 400 and 100 MHz respectively. Thin-layer
chromatography was performed using commercially prepared 60
F254 silica gel plates. All melting points are uncorrected.
2-(4-(tert-butyl)phenyl)furo[2,3-b]quinoxaline (4d): The product
o
was obtained as a brown needles, mp: 226–228 C (129.9 mg,
86%); 1H NMR (400 MHz, CDCl3): δ 8.18–8.15 (m, 1H),8.12–
8.10 (m, 1H),7.97 (d, J = 7.3 Hz, 2H), 7.75–7.70 (m, 2H),7.56 (d,
J = 7.3 Hz, 2H), 7.24 (s, 1H), 1.38 (s, 9H); 13C NMR (100 MHz,
CDCl3): δ 164.3, 155.0, 144.7, 142.2, 138.6, 128.7, 128.62,
128.56, 128.2, 126.1, 126.0, 125.7, 100.0, 35.1, 31.1. HRMS
(ESI): [M+H]+ Calcd for [C20H18N2O] 303.1497; found 303.1487.
General
Procedure
for
the
Synthesis
of
furoquinoxalines/Pyrazine: To a solution of substituted 2,3-
dichloroquinoxaline/pyrazine 1 (0.5 mmol) in MeCN (2 mL), 5
mol% of Pd(PPh3)2Cl2 and CuI were added. The reaction vial
was then sealed and flushed with nitrogen. Then, 2.5 equiv of
Et3N and 0.52 mmol of alkyne 2 were added to the reaction
mixture. The reaction was then stirred at 60 °C until TLC re-
vealed complete conversion of the starting material. After the
completion of the first coupling reaction (monitored by TLC) 4 ml
of TFA was added. The reaction was then stirred at 60 °C until
TLC revealed complete conversion of mono sonogashira inter-
mediate into final product. The reaction mixture was then al-
lowed to cool, was diluted with H2O, and was extracted with
EtOAc (3 × 10 mL). The combined organic layers were dried
over Na2SO4, concentrated under vacuum, and purified by col-
umn chromatography using 100−200 mesh size silica gels (hex-
ane: ethyl acetate) to afford the corresponding product. The
structure and purity of known starting materials (1a, 1b, 1c and
1d) were confirmed by comparison of their physical and spectral
data (1H NMR, 13C NMR and HRMS).[16]
2-(3-Methoxyphenyl)furo[2,3-b]quinoxaline (4e): The product
was obtained as a pale yellow needles, mp: 154–156 C (116.1
o
mg, 84%); 1H NMR (400 MHz, CDCl3): δ 8.16–8.12 (m, 1H),
8.10–8.06 (m, 1H), 7.73–7.68 (m, 2H), 7.57 (d, J = 7.6 Hz, 1H),
7.52–7.51 (m, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.24 (s, 1H),
7.01(dd, J = 8.4 and 2.3 Hz, 1H), 3.87 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 163.7, 160.0, 154.3, 144.5, 142.2, 138.7, 130.2,
129.6, 128.8, 128.7, 128.6, 128.3, 118.7, 117.4, 110.8, 101.0,
55.4. HRMS (ESI): [M+H]+ Calcd for [C17H12N2O2] 277.0979;
found 277.0956.
2-(4-(Trifluoromethyl)phenyl)furo[2,3-b]quinoxaline (4f): The
product was obtained as a pale yellow needles, mp: 233–235 oC
1
(125.6 mg, 80%); H NMR (400 MHz, CDCl3): δ 8.22–8.18 (m,
1H), 8.15–8.13 (m, 3H), 7.82–7.76 (m, 4H), 7.41 (s, 1H); 13C
NMR (100 MHz, CDCl3): δ 161.9, 154.3, 143.9, 142.4, 139.1,
131.7, 129.3, 128.9, 128.7, 128.6, 126.3, 126.18 (q, J = 7.7Hz),
114.1, 102.7. HRMS (ESI): [M+H]+ Calcd for [C17H9F3N2O]
315.0745; found 315.0726.
2-Phenylfuro[2,3-b]quinoxaline (4a): The product was obtained
o
1
as a pale yellow needles, mp: 189–190 C (105.9 mg, 86%); H
NMR (400 MHz, CDCl3): δ 8.10–8.06 (m, 1H), 8.03–8.01 (m, 1H),
7.94–7.92 (m, 2H), 7.67–7.62 (m, 2H), 7.46–7.41 (m, 3H), 7.19
(s, 1H); 13C NMR (100 MHz, CDCl3): δ 163.9, 154.3, 144.5,
142.1, 138.7, 131.2, 129.1, 128.72, 128.67, 128.6, 128.4, 128.3,
2-(Thiophen-3-yl)furo[2,3-b]quinoxaline (4g): The product was
obtained as a yellow needles, mp: 177–179 oC (111.0 mg, 88%);
1H NMR (400 MHz, CDCl3): δ 8.17–8.14 (m, 1H), 8.12–8.06 (m,
2H), 7.74–7.71 (m, 2H), 7.59–7.58 (m, 1H), 7.49–7.48 (m, 1H),
7.07 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 160.1, 154.2, 144.6,
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142.2, 138.6, 130.6, 129.1, 128.6, 128.3, 127.6, 126.2, 125.2,
100.2. HRMS (ESI): [M+H]+ Calcd for [C14H8N2OS]: 253.0436,
found 253.0457.
7.50–7.40 (m, 3H), 6.98 (s, 1H), 2.53 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 159.8, 144.3, 143.7, 142.2, 138.6, 131.0, 130.6 ,
128.1, 127.5, 126.0, 125.2, 100.3, 21.7. HRMS (ESI): [M+H]+
Calcd for [C15H10N2OS] 267.0592; found 267.0588.
2-(Pyridin-2-yl)furo[2,3-b]quinoxaline (4h): The product was
obtained as a green needles, mp: 140–142 oC (101.3 mg, 82%);
1H NMR (400 MHz, CDCl3): δ 8.70 (d, J = 3.8 Hz, 1H), 8.58 (s,
1H), 8.20–8.17 (m, 1H), 8.04–8.0 (m, 2H), 7.85–7.78 (m, 3H),
7.36–7.33 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 153.3, 149.3,
148.2, 140.8, 138.1, 137.1, 131.2, 130.4, 129.3, 128.2, 124.2,
121.8, 114.1. HRMS (ESI): [M+H]+ Calcd for [C15H9N3O]
248.0824; found 248.0836.
6-Methyl-2-(pyridin-2-yl)furo[2,3-b]quinoxaline (4o): The product
was obtained as a green needles, mp: 169–171 oC (Table 2:
108.4 mg, 83%; Scheme 5: 112.4 mg, 86%); 1H NMR (400 MHz,
CDCl3): δ 8.70–8.69 (m, 1H), 8.56 (s, 1H), 8.06–7.99 (m, 1H),
7.94 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.84–7.78 (m, 1H), 7.63–
7.60 (m, 1H), 7.35–7.32 (m, 1H), 2.60 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 153.3, 148.0, 146.4, 142.1, 139.2, 137.8, 132.7,
128.8, 128.1, 127.6, 127.0, 121.7, 114.0, 21.8. HRMS (ESI):
[M+H]+ Calcd for [C16H11N3O] 262.0980; found 262.0962.
2-(4-Ethylphenyl)-6-methylfuro[2,3-b]quinoxaline (4j): The prod-
uct was obtained as a pale yellow needles, mp: 136–138 oC
(126.9 mg, 88%); 1H NMR (400 MHz, CDCl3): δ 8.05–7.98 (m,
1H), 7.95–7.86 (m, 3H), 7.57–7.54 (m, 1H), 7.36 (d, J = 8.4 Hz,
2H), 7.20 (s, 1H), 2.73 (q, J = 7.6 Hz, 2H), 2.61 (s, 3H), 1.29 (t,
J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 163.9, 154.2,
148.0, 144.5, 142.2, 138.5, 130.9, 128.7, 128.1, 127.6, 126.2,
126.1, 100.0, 28.9, 21.7, 15.3. HRMS (ESI): [M+H]+ Calcd for
[C19H16N2O] 289.1341; found 289.1327.
6,7-Dimethyl-2-(p-tolyl)furo[2,3-b]quinoxaline (4p): The product
o
was obtained as a pale yellow needles, mp: 264–266 C (129.8
mg, 90%); 1H NMR (400 MHz, CDCl3): δ 7.91–7.89 (m, 3H), 7.84
(s, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.19 (s, 1H), 2.51 (s, 6H), 2.44
(s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.3, 154.3, 143.7,
141.5, 141.1, 139.2, 138.5, 137.4, 129.8, 127.8, 127.7, 126.0,
100.0, 21.6, 20.4, 20.3. HRMS (ESI): [M+H]+ Calcd for
[C19H16N2O] 289.1341; found 289.1334.
2-(4-Butylphenyl)-6-methylfuro[2,3-b]quinoxaline (4k): The prod-
uct was obtained as a pale yellow needles, mp: 153–155 oC
(136.1 mg, 86%); H NMR (400 MHz, CDCl3): δ 7.99 (d, J = 8.4
Hz, 1H), 7.93 (d, J = 7.6 Hz, 3H), 7.58–7.54 (m, 1H), 7.34 (d, J =
8.4 Hz, 2H), 7.21 (s, 1H), 2.69 (t, J = 7.6 Hz, 2H), 2.62 (s, 3H),
1.67–1.61 (m, 2H), 1.43–1.34 (m, 2H), 0.95 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 163.9, 154.6, 146.8, 144.5, 139.3,
138.5, 130.5, 129.2, 128.1, 127.5, 126.0, 100.0, 35.7, 33.3, 22.3,
21.7, 13.9. HRMS (ESI): [M+H]+ Calcd for [C21H20N2O]
317.1654; found 317.1647.
2-(4-Methoxyphenyl)-6,7-dimethylfuro[2,3-b]quinoxaline
(4q):
1
The product was obtained as a yellow needles, mp: 204–206 oC
1
(144.6 mg, 95%); H NMR (400 MHz, CDCl3): δ 7.97–7.93 (m,
2H), 7.88 (s, 1H), 7.83 (s, 1H), 7.10 (s, 1H), 7.05–7.02 (m, 2H),
3.89 (s, 3H), 2.50 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 163.2,
161.9, 154.3, 143.9, 141.0, 139.0, 138.4, 137.2, 127.7, 127.67,
127.6, 121.3, 114.6, 99.0, 55.5, 20.33, 20.27. HRMS (ESI):
[M+H]+ Calcd for [C19H16N2O2] 305.1290; found 305.1284.
6,7-Dimethyl-2-(4-(trifluoromethyl)phenyl)furo[2,3-b]quinoxaline
(4r): The product was obtained as a yellow needles, mp: 310–
2-(4-Methoxyphenyl)-6-methylfuro[2,3-b]quinoxaline (4l): The
product was obtained as a pale yellow needles, mp: 241–243 oC
(136.5 mg, 94%); H NMR (400 MHz, CDCl3): δ 7.92–7.89 (m,
3H), 7.85 (s, 1H), 7.50–7.46 (m, 1H), 7.06 (s, 1H), 6.98 (d, J =
9.2 Hz, 2H), 3.83 (s, 3H), 2.54 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 162.0, 155.6, 144.7, 142.2, 139.0, 138.5, 136.8, 130.7,
128.1, 127.9, 127.5, 121.2, 114.6, 98.9, 55.5, 21.7. HRMS (ESI):
[M+H]+ Calcd for [C18H14N2O2] 291.1134; found 291.1124.
1
312 oC (140.4 mg, 82%); H NMR (400 MHz, CDCl3): δ 8.13 (d,
1
J = 8.4 Hz, 2H), 7.94 (s, 1H), 7.87 (s, 1H), 7.80 (d, J = 8.4 Hz,
2H), 7.39 (s, 1H), 2.53 (d, J = 1.9 Hz, 6H); 13C NMR (100 MHz,
CF3COOD): δ 172.0, 161.5, 156.9, 149.5, 146.3, 138.8, 135.3,
129.6, 129.0, 128.7, 127.4 (q, J = 7.7 Hz, 1C), 97.9, 20.1, 19.6.
HRMS (ESI): [M+H]+ Calcd for [C19H13F3N2O] 343.1058; found
343.1048.
2-(3-Methoxyphenyl)-6-methylfuro[2,3-b]quinoxaline (4m): The
product was obtained as a off white needles, mp: 167–169 oC
(Table 2: 124.8 mg, 86%; Scheme 5: 129.1 mg, 89%); H NMR
(400 MHz, CDCl3): δ 8.05–7.96 (m, 1H), 7.91–7.85 (m, 1H),
7.59–7.53 (m, 3H), 7.43 (t, J = 7.6 Hz, 1H), 7.25 (s, 1H), 7.03 (d,
J = 7.6 Hz, 1H), 3.91 (s, 3H), 2.60 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 163.2, 159.9, 153.9, 144.1, 142.1, 139.3, 138.5, 136.9,
131.0, 130.0, 127.9, 127.5, 118.5, 117.1, 100.9, 55.3, 21.5.
HRMS (ESI): [M+H]+ Calcd for [C18H14N2O2] 291.1134; found
291.1128.
6,7-Dichloro-2-(m-tolyl)furo[2,3-b]quinoxaline (4s): The product
was obtained as a yellow needles, mp: 255–257 C (124.2 mg,
o
76%); 1H NMR (400 MHz, CF3COOD): δ 8.38 (d, J = 3.1 Hz, 1H),
8.21 (d, J = 3.8 Hz, 1H), 7.95–7.92 (m, 2H), 7.52–7.50 (m, 2H),
7.44 (t, J = 7.6 Hz, 1H), 2.38 (s, 3H); 13C NMR (100 MHz,
CF3COOD): δ 177.8, 158.1, 141.8, 140.9, 138.5, 138.11, 138.08,
137.5, 130.9, 130.6, 129.8, 128.1, 127.0, 126.0, 120.6, 96.4,
20.3. HRMS (ESI): [M+H]+ Calcd for [C17H10Cl2N2O] 329.0248;
found 329.0241.
1
6,7-Dichloro-2-(3-ethylphenyl)furo[2,3-b]quinoxaline (4t): The
product was obtained as a yellow needles, mp: 240–242 oC
(132.9 mg, 78%); H NMR (400 MHz, CF3COOD): δ 8.36–8.35
6-Methyl-2-(thiophen-3-yl)furo[2,3-b]quinoxaline (4n): The prod-
o
1
uct was obtained as a yellow needles, mp: 193–194 C (119.8
mg, 90%); 1H NMR (400 MHz, CDCl3): δ 7.97–7.78 (m, 3H),
(m, 1H), 8.18–8.17 (m, 1H), 8.06–8.04 (m, 2H), 7.45–7.41 (m,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700541
European Journal of Organic Chemistry
FULL PAPER
3H), 2.70 (q, J = 7.6 Hz, 2H), 1.21–1.18 (m, 3H); 13C NMR (100
MHz, CF3COOD): δ 177.9, 158.2, 157.3, 140.7, 138.2, 137.8,
137.1, 130.8, 130.5, 130.1, 128.1, 123.4, 120.5, 95.7, 29.9, 14.0.
HRMS (ESI): [M+H]+ Calcd for [C18H12Cl2N2O] 343.0405; found
343.0392.
6-(4-Methoxyphenyl)furo[2,3-b]pyrazine (6f): The product was
obtained as a yellow needles, mp: 115–117 oC (Table 3: 85.9
mg, 76%; Scheme 5: 90 mg, 80%); H NMR (400 MHz, CDCl3):
δ 8.45 (d, J = 3.1 Hz, 1H), 8.16 (d, J = 2.3 Hz, 1H), 8.0 (d, J =
9.2 Hz, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.08 (s, 1H), 7.02–7.0 (m,
1H), 6.97–6.95 (m, 1H), 3.87 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 161.5, 151.2, 142.4, 142.2, 136.6, 130.7, 127.4, 114.5,
99.4, 55.4. HRMS (ESI): [M+H]+ Calcd for [C13H10N2O2]
227.0821; found 227.0810.
1
6,7-Dichloro-2-(4-methoxyphenyl)furo[2,3-b]quinoxaline
(4u):
The product was obtained as a yellow needles, mp: 278–280 oC
1
(135.3 mg, 79%); H NMR (400 MHz, CF3COOD): δ 8.38–8.37
(m, 1H), 8.19–8.17 (m, 3H), 7.40–7.39 (m, 1H), 7.15 (d, J = 9.2
Hz, 2H), 3.95 (s, 3H); 13C NMR (100 MHz, CF3COOD): δ 177.6,
168.3, 158.4, 140.4, 138.4, 137.4, 136.6, 132.8, 130.7, 128.1,
120.3, 118.7, 94.8, 56.0. HRMS (ESI): [M+H]+Calcd for
[C17H10Cl2N2O] 345.0198; found 345.0169.
6-(4-Butylphenyl)furo[2,3-b]pyrazine (6g): The product was
obtained as a yellow needles, mp: 51–53 oC (93.4 mg, 74%); 1H
NMR (400 MHz, CDCl3): δ 8.46 (d, J = 3.4 Hz, 1H), 8.16 (d, J =
3.1 Hz, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.30–7.27 (m, 2H), 7.14 (s,
1H), 2.65 (t, J = 8.0 Hz, 2H), 1.63–1.57 (m, 2H), 1.40–1.34 (m,
2H), 0.93–0.89 (m, 3H); 13C NMR (100 MHz, CDCl3): δ 160.7,
155.5, 146.0, 141.4, 136.9, 129.1, 125.7, 100.5, 35.6, 33.3, 22.3,
13.9. HRMS (ESI): [M+H]+ Calcd for [C16H16N2O] 253.1341;
found 253.1329.
6-Phenylfuro[2,3-b]pyrazine (6a)3b: The product was obtained as
a off white needles, mp: 99–101 oC (68.7 mg, 70%); 1H NMR
(400 MHz, CDCl3): δ 8.18 (d, J = 2.3 Hz, 1H), 8.16 (d, J = 2.3 Hz,
1H), 7.79–7.76 (m, 1H), 7.31–7.26 (m, 4H), 7.18 (s, 1H); HRMS
(ESI): [M+H]+ Calcd for [C12H8N2O] 197.0715; found 197.0707.
6-(4-(tert-Butyl)phenyl)furo[2,3-b]pyrazine (6h): The product was
obtained as a yellow needles, mp: 79–81 oC (89.6 mg, 71%); 1H
NMR (400 MHz, CDCl3): δ 8.50 (d, J = 3.0 Hz, 1H), 8.20 (d, J =
2.3 Hz, 1H), 7.91–7.89 (m, 2H), 7.55–7.52 (m, 2H), 7.26 (s, 1H),
1.37 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 160.6, 154.2, 142.8,
141.5, 137.0, 128.3, 125.8, 125.5, 100.6, 35.0, 31.1. HRMS
(ESI): [M+H]+ Calcd for [C16H16N2O] 253.1341; found 253.1331.
6-(o-Tolyl)furo[2,3-b]pyrazine (6b): The product was obtained as
o
1
a yellow needles, mp: 81–83 C (71.5 mg, 68%); H NMR (400
MHz, CDCl3): δ 8.50 (d, J = 3.1 Hz, 1H), 8.22 (d, J = 3.1 Hz, 1H),
7.91–7.89 (m, 1H), 7.40–7.27 (m, 3H), 7.11 (s, 1H), 2.61 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 160.3, 155.2, 142.3, 141.5, 137.4,
136.7, 132.0, 130.2, 128.6, 126.4, 105.2, 21.9. HRMS (ESI):
[M+H]+ Calcd for [C13H10N2O] 211.0871; found 211.0864.
2-(2-Chloropyridin-3-yl)-1-(4-ethylphenyl)ethan-1-one (9): The
product was obtained as a pale yellow semi-solid (90.9 mg,
70%); 1H NMR (400 MHz, CDCl3): δ 8.32–8.31 (m, 1H), 7.97 (d,
J = 8.4 Hz, 2H), 7.61–7.59 (m, 1H), 7.32 (d, J = 8.4 Hz, 2H),
7.22–7.20 (m, 1H), 4.41 (s, 2H), 2.72 (q, J = 7.6 Hz, 2H), 1.26 (t,
J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 194.9, 151.6,
150.6, 148.1, 140.4, 133.8, 130.0, 128.4, 128.2, 122.5, 42.4,
28.8, 15.0. HRMS (ESI): [M+H]+ Calcd for [C15H14ClNO]:
260.0842, found 260.0840.
6-(m-Tolyl)furo[2,3-b]pyrazine (6c): The product was obtained
as a yellow needles, mp: 87–89 oC (75.7 mg, 72%); 1H NMR
(400 MHz, CDCl3): δ 8.48 (d, J = 2.7 Hz, 1H), 8.18 (d, J = 2.7 Hz,
1H), 7.75–7.72 (m, 2H), 7.36 (t, J = 7.8 Hz, 1H), 7.25 (d, J = 7.7
Hz, 1H), 7.18 (s, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 160.5, 155.5, 142.5, 141.5, 138.8, 137.2, 131.3, 128.9, 128.6,
126.2, 122.9, 101.1, 21.4. HRMS (ESI): [M+H]+ Calcd for
[C13H10N2O] 211.0871; found 211.0863.
2-(4-Ethylphenyl)furo[2,3-b]pyridine (10): The product was ob-
tained as a off white needles, mp: 130–132 oC (69.22 mg, 62%);
1H NMR (400 MHz, CDCl3): δ 8.26–8.24 (m, 1H), 7.86–7.84 (m,
1H), 7.81 (d, J = 8.4 Hz, 2H), 7.28 (d, J = 7.6 Hz, 2H), 7.19–7.16
(m, 1H), 6.93 (s, 1H), 2.68 (q, J = 7.6 Hz, 2H), 1.25 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 161.8, 155.9, 145.8, 143.5,
129.3, 128.4, 127.1, 125.2, 121.6, 119.4, 99.3, 28.8, 15.4.
HRMS (ESI): [M+H]+ Calcd for [C15H13NO]: 224.1075, found
224.1064.
6-(p-Tolyl)furo[2,3-b]pyrazine (6d): The product was obtained as
o
1
a yellow needles, mp: 84–86 C (77.8 mg, 74%); H NMR (400
MHz, CDCl3): δ 8.48 (dd, J = 8.4 and 3.1 Hz, 2H), 8.31 (d, J =
3.1 Hz, 1H), 8.19 (d, J = 2.3 Hz, 1H), 7.85 (d, J = 8.4 Hz, 2H),
7.17(s, 1H), 2.43 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.6,
155.5, 142.7, 141.4, 137.7, 133.8, 129.8, 129.2, 125.6, 100.5,
21.5. HRMS (ESI): [M+H]+ Calcd for [C13H10N2O] 211.0871;
found 211.0861.
General Procedure for the Synthesis of 2-chloro-3-
(arylethynyl)quinoxaline/Pyrazine: To a solution of substitut-
ed 2,3-dichloroquinoxaline/pyrazine 1 (1.0 mmol) in MeCN (2
mL), 5 mol % of Pd(PPh3)2Cl2 and CuI were added. The reaction
vial was then sealed and flushed with nitrogen. Then, 2.5 equiv
of Et3N and 1.04 mmol of alkyne 2 were added to the reaction
mixture. The reaction was then stirred at 60 °C until TLC re-
vealed complete conversion of the starting material. The reac-
tion mixture was then allowed to cool, was diluted with H2O, and
was extracted with EtOAc (3 × 10 mL). The combined organic
6-(4-Ethylphenyl)furo[2,3-b]pyrazine (6e): The product was
obtained as a yellow needles, mp: 81–83 oC (81.9 mg, 73%); 1H
NMR (400 MHz, CDCl3): δ 8.46 (d, J = 2.7 Hz, 1H), 8.17 (d, J =
3.1 Hz, 1H), 7.85 (d, J = 7.6 Hz, 2H), 7.31 (d, J = 8.4 Hz, 2H),
7.15 (s, 1H), 2.69 (q, J = 6.9 Hz, 2H), 1.25 (t, J = 6.9 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 160.6, 155.5, 142.7, 141.5, 136.8,
129.0, 128.4, 128.2, 125.9, 100.2, 28.8, 15.3. HRMS (ESI):
[M+H]+ Calcd for [C14H12N2O] 225.1028; found 225.1017.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201700541
European Journal of Organic Chemistry
FULL PAPER
1
layers were dried over Na2SO4, concentrated under vacuum,
and purified by column chromatography using 100−200 mesh
size silica gels (hexane: ethyl acetate) to afford the correspond-
ing product. The structure and purity of compounds were con-
(129.6 mg, 89%); H NMR (400 MHz, CDCl3): δ 7.89–7.81 (m,
1H), 7.74–7.69 (m, 1H), 7.40 (t, J = 7.6 Hz, 2H), 7.35 (s, 1H),
7.25 (t, J = 8.4 Hz, 1H), 6.86 (d, J = 8.4 Hz, 1H), 3.75 (s, 3H),
2.44 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.1, 159.9, 153.93,
144.1, 142.2, 139.2, 138.5, 136.9, 130.9, 130.0, 128.0, 127.6,
118.5, 117.1, 100.99–100.93 (m, 1C), 55.3, 21.6. HRMS (ESI):
[M+H]+ Calcd for [C18H13DN2O2] 292.1196; found 292.1186.
firmed by comparison of their physical and spectral data (1
NMR, 13C NMR and HRMS).
H
2-Chloro-3-(p-tolylethynyl)quinoxaline (3b): The product was
obtained as a yellow needles, mp: 179–181 oC (256.4 mg, 92%);
1H NMR (400 MHz, CDCl3): δ 8.10–8.06 (m, 1H), 8.01–7.97 (m,
1H), 7.79–7.74 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.21 (d, J = 8.4
Hz, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 148.0,
140.7, 140.6, 140.2, 138.7, 132.4, 131.2, 130.6, 129.3, 128.8,
128.2, 118.1, 97.7, 85.1, 21.7. HRMS (ESI): [M+H]+ Calcd for
[C17H11ClN2] 279.0689; found 279.0655.
6-(4-Methoxyphenyl)furo[2,3-b]pyrazine-7-d (13): The product
was obtained as a yellow needles, mp: 109–111 oC (89.8 mg,
79%); 1H NMR (400 MHz, CDCl3): δ 8.44 (d, J = 3.1 Hz, 1H),
8.28 (d, J = 2.3 Hz, 1H), 8.0–7.97 (m, 2H), 6.96–6.92 (m, 2H),
3.8 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 163.9, 151.2, 142.3,
142.2, 136.6, 130.7, 127.4, 113.9, 55.5. HRMS (ESI): [M+H]+
Calcd for [C13H9DN2O2] 228.0883; found 228.0876
2-Chloro-3-((3-methoxyphenyl)ethynyl)-6-methylquinoxaline
(3m): The product was obtained as a pale yellow needles, mp:
167–169 oC (271.7 mg, 88%); 1H NMR (400 MHz, CDCl3): δ
7.91–7.68 (m, 2H), 7.53 (d, J = 8.4 Hz, 1H), 7.28–7.25 (m, 2H),
7.15 (s, 1H), 6.95–6.91 (m, 1H), 3.97 (s, 3H), 2.52 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 159.3, 147.0, 141.4, 140.7, 138.7,
138.2, 133.6, 127.60, 127.55, 124.9, 122.2, 122.1, 116.8, 116.7,
96.7, 85.2, 55.3, 21.8. HRMS (ESI): [M+H]+ Calcd for
[C18H13ClN2O]: 309.0795, found 309.0819.
Acknowledgements
The work was supported by DST-SERB. K.M.S., S.K., M.P. and
R.K.S are thankful to CSIR and DST-SERB for fellowship. We
are highly thankful to Dr. Sushil Kumar for solving the crystal
data. We gratefully acknowledge USIC, University of Delhi for
providing the instrumentation facilities.
Keywords: •TFA mediated • Regioselective • Oxyarylation
• Furo[2,3-b]quinoxaline/pyrazine • 5-endo-dig-cyclization.
2-Chloro-6-methyl-3-(pyridin-2-ylethynyl)quinoxaline (3o): The
product was obtained as a yellow needles, mp: 146–148 oC
(243.4 mg, 87%); 1H NMR (400 MHz, CDCl3): δ 8.72 (d, J = 4.6
Hz, 1H), 7.91 (d, J = 8.4 Hz, 1H), 7.87 (s, 1H), 7.78 – 7.71 (m,
2H), 7.65 – 7.62 (m, 1H), 7.38 – 7.34 (m, 1H), 2.60 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 150.5, 141.9, 141.6, 140.8, 139.1,
137.6, 136.3, 134.2, 133.1, 128.2, 127.8, 127.7, 124.1, 94.5,
84.2, 21.9. HRMS (ESI): [M+H]+ Calcd for [C16H10ClN3]
280.0642; found 280.0630.
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10.1002/ejoc.201700541
European Journal of Organic Chemistry
FULL PAPER
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10.1002/ejoc.201700541
European Journal of Organic Chemistry
FULL PAPER
FULL PAPER
Kapil Mohan Saini, Sonu Kumar, Monika
Patel, Rakesh K. Saunthwal and
Akhilesh K. Verma*
Page No. – Page No.
TFA-Mediated One-Pot Synthesis of
Furo-Fused Quinoxalines/ Pyrazines
Abstract: Trifluoroacetic acid (TFA) promoted step-economical one-pot approach for the
synthesis of furo-fused quinoxalines/pyrazines by the reaction of 2, 3-
dichloroquinoxalines/pyrazines with electronically varied alkyne is described. The
reaction shows the selective in-situ Sonogashira conjoined hydroxylation followed by
metal free 5-endo-dig cyclization. The preliminary experiment depicted the role of TFA as
a source of oxygen for oxyarylation and isotopic labeling studies supports the proposed
mechanistic pathway goes via activation of alkyne in acidic medium. This methodology
tolerates a various kind of substituents, which proves to be valuable for structural and
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