New insight into anionic cyclizations of alkynyl- and ortho- dialkynylarenes: A specific reactivity of 3-alkynyl-2-chloro- and 2,3-dialkynylquinoxalines and related compounds toward CH-acids' carbanions

Article abstract of DOI:10.1016/j.tet.2011.11.018

The reactivity of 3-alkynyl-2-chloroquinoxalines, 2,3- dialkynylquinoxalines, and some related pyrazine derivatives toward carbanions of the CH-acids (malononitrile, ethyl cyanoacetate, diethyl malonate, 1,3-dimethylbarbituric acid) has been studied. Most

Full text of DOI:10.1016/j.tet.2011.11.018

Tetrahedron 68 (2012) 488e498
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Tetrahedron
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New insight into anionic cyclizations of alkynyl- and ortho-dialkynylarenes:
a specific reactivity of 3-alkynyl-2-chloro- and 2,3-dialkynylquinoxalines and
related compounds toward CH-acids’ carbanions
*
Anna V. Gulevskaya , Huong T.L. Nguyen, Alexander S. Tyaglivy, Alexander F. Pozharskii
Department of Organic Chemistry, Southern Federal University, Zorge 7, Rostov-on-Don 344090, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 8 August 2011
Received in revised form 17 October 2011
Accepted 7 November 2011
Available online 15 November 2011
The reactivity of 3-alkynyl-2-chloroquinoxalines, 2,3-dialkynylquinoxalines, and some related pyrazine
derivatives toward carbanions of the CH-acids (malononitrile, ethyl cyanoacetate, diethyl malonate, 1,3-
dimethylbarbituric acid) has been studied. Most of the observed reactions proceeded as tandem or
cascade cyclizations yielding polynuclear heterocyclic compounds. The process starts with the addition
of a nucleophile to an alkyne triple bond. Depending on the nature of the used C-nucleophile, the thus
formed anionic adduct underwent further cyclization via (i) intramolecular nucleophilic substitution of
the chlorine atom, (ii) intramolecular acylation of the ring nitrogen atom by the ester side chain or (iii)
intramolecular nucleophilic attack on the second C^C bond. Reactions of 3-alkynyl-2-chloro- and 2,3-
dialkynylpyrazines with 1,3-dimethylbarbituric acid in the presence of t-BuOK were accompanied by
recyclization of the 1,3-dimethylbarbituric acid moiety.
Keywords:
Alkynes
Enediynes
Anionic cyclizations
Quinoxalines
Pteridines
Ó 2011 Elsevier Ltd. All rights reserved.
Pyrido[2,3-b]pyrazines
1. Introduction
Alkynes find ever-increasing use in synthetic organic chemis-
try.1 Cyclizations of alkynes possessing a nucleophilic site in prox-
imity to the triple bond have been shown to be extremely effective
for synthesis of a wide variety of carbo- and heterocycles.2 Nor-
mally, such transformations require a catalyst (base, transition
metal complex or electrophile) and proceed according to Scheme 1.
One prominent group of alkynes are enediynes, because of the
presence this moiety in naturally occurring antibiotics (enediyne
antibiotics).3 It is supposed that the antitumor activity of these
natural products is based on the Bergman cyclization4 involving the
formation of benzenoid diradical intermediates (Scheme 2), which
are able to cleave DNA and to rupture the protein structure via
oxidative cleavage of the peptide bond.
Typically, the Bergman cyclization is induced thermally or
photochemically. However, several other cyclizations of enediynes
promoted by metals,5 radicals,6 electrophiles,5a,b,7 transition metal
complexes,8 organometallics5a,b or other anionic nucleophiles9
have been reported. Most of these initiators (electrophiles,
metals, radicals, transition metal complexes) promote 5-exo-dig
carbocyclization of enediyne and the fulvene ring formation
(Scheme 3, A). In the contrast, nucleophilic attack on the enediyne
Scheme 1.
substrate leads to 6-endo-dig carbocyclization (cycloaromatization)
(Scheme 3, B). The only exception is butyllithium,5a,b whose in-
teraction with 1,2-bis(phenylethynyl)benzene yields benzofulvene
derivative (Scheme 3, C)y. In the presence of a base10a,b or transition
metal complex,10ceh enediynes bearing a nucleophilic group at the
alkyne terminus or at the position ortho to the alkynyl substituent
have been shown enter cascade cyclizations (Scheme 3, D).
y
* Corresponding author. Tel.: þ7 863 297 5146; fax: þ7 863 297 5151; e-mail
To the best of our knowledge, no other C-nucleophiles have been studied in
addresses: agulevskaya@sfedu.ru, anvasgul@gmail.com (A.V. Gulevskaya).
such cyclizations.
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.018

A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
489
2. Results and discussion
Starting 3-chloro-2-(phenylethynyl)quinoxaline 1,12 2,3-bis(al-
kynyl)quinoxalines 2a,b,11d 6-chloro-1,3-dimethyl-7-(phenylethy-
nyl)pteridine-2,4(1H,3H)-dione 3,11b 1,3-dimethyl-6,7-bis(p-tolyle-
thynyl)pteridine-2,4(1H,3H)-dione 4, and 2,3-bis(p-tolylethynyl)
pyrido[2,3-b]pyrazine 5 (Fig. 1) were synthesized by the Sonoga-
shira coupling in accordance with a common procedure.
Scheme 2.
However, only acyclic enediynes and ortho-dialkynylbenzenes were
tested as substrates in the above cyclizations.
Fig. 1. Substrates under investigation.
The reaction of 2-chloro-3-(phenylethynyl)quinoxaline 1 with
malononitrile/t-BuOK in dry THF led to substitution (SNAr) of the
chlorine atom by the acidic residue and gave compound 6 in 37%
yield (Scheme 5). The latter was not cyclized into cyclo-
pentaquinoxaline 7 even on the prolonged heating with t-BuOK in
DMSO.
Treatment of 1 with ethyl cyanoacetate under the same condi-
tions gave a mixture of compounds 8 and 9 (Scheme 6). The major
product was obtained in 22% yield and its structure was assigned as
8. Compound 9, which is analog of 6, was isolated in 7% yield only.
The methylidene tautomeric form of 8 and 9 is likely stabilized by
intramolecular hydrogen bonding of the NeH/O type. It was
confirmed by the combination of spectral methods, e.g., 1H NMR
Scheme 3.
Recently, we have reported several nucleophilic cyclizations of
7-alkynyl-6-chloro- and 6,7-dialkynyl derivatives of 1,3-
dimethylpteridine-2,4(1H,3H)-dione promoted by N- and S-nucle-
ophiles.11 It has been found that their reactivity toward nucleo-
philes differs from that of acyclic alkynes and enediynes as well as
(
dNH¼13.5e14.3 ppm, CDCl3).
A plausible mechanism for the formation of pyridoquinoxaline 8
is shown in Scheme 7. It likely starts from the addition of ethyl
cyanoacetate carbanion to the triple bond of 1 to give a vinylic in-
alkynyl- and ortho-dialkynylbenzenes. Due to the high p-deficiency
of the azine ring, alkynyl- and ortho-dialkynylpteridines react easily
even with neutral nucleophiles (e.g., alkylamines). The thus formed
addition product undergoes unprompted or base-induced hetero-
cyclization with direct participation of the added nucleophile
(Scheme 4).
termediate 10, which rearranges into
a more stable 1-
azapentadienyl anion 11. Subsequent intramolecular nucleophilic
attack of the ring nitrogen atom on the side chain carbonyl provides
chloropyridoquinoxaline 12. Finally, the chlorine atom of 12 is
replaced by the ethyl cyanoacetate residue affording compound 8.
Another reaction pathway via initial formation of 9 and subsequent
addition of the nucleophile to the C^C bond is less probable be-
cause of the steric reasons.
Heating of compound 1 with diethyl malonate and t-BuOK in
THF led to the annulation of the cyclopentadiene ring to the parent
heterocyclic system (Scheme 8). The structure of a sole reaction
product 13 was unambiguously determined by single-crystal X-ray
analysis (Fig. 2). When treated with the diethyl malonate/t-BuOK/
THF system, 6-chloro-1,3-dimethyl-7-(phenylethynyl)pteridine-
2,4(1H,3H)-dione 3 showed the same reactivity producing cyclo-
pentapteridine 14 in 54% yield.
Scheme 4.
In principle, two pathways are possible for this tandem carboan-
nulation:(i)nucleophilicsubstitutionof thechlorineatomof1 or3 by
the CH-acid residue followed by the cyclopentadiene ring closure, or
(ii) initial addition of a nucleophile to the C^C bond of 1 or 3 with
a consecutive intramolecular replacement of the chlorine atom. The
last one seems to be a more probable due to the formation of the
vinylic intermediate with favorable for the cyclization geometry. In
the case of pteridine 3, a low mobility of the chlorine atom11b is an
additional argument in the favor of the second sequence.
The revealed specificity in the reactivity of alkynylpteridines
encouraged us to continue our study and turned attention on other
heterocyclic substrates and nucleophiles. Herein, we present re-
actions of 3-alkynyl-2-chloro- and 2,3-dialkynylquinoxalines and
other fused pyrazines with carbanions of the CH-acids (malononi-
trile, ethyl cyanoacetate, diethyl malonate, 1,3-dimethylbarbituric
acid) and discuss some newfound tandem and cascade anionic
cyclizations.

490
A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
t
Scheme 5.
It should be noted that a number of routes leading to the an-
nulation of a cyclopentadiene ring to alkynes have been described.
The most general methods are: (i) transition metal-catalyzed,13
phase transfer-catalyzed14 or electrophile-promoted15 intra-
molecular cyclization of alkynylarenes bearing a carbon side chain
with carbanion-stabilizing groups [e.g., CH(CO2Et)2] in close prox-
imity to the alkynyl substituent, and (ii) transition metal-catalyzed
coupling of internal alkynes with arylhalides possessing a C-nu-
cleophilic center at the position ortho to the halogen sub-
stituent.13b,16 To the best of our knowledge, there has been no
report on the tandem 5-endo-dig carbocyclization of 2-alkynyl
arylhalide involving addition of a carbanion to the C^C bond fol-
lowed by intramolecular nucleophilic substitution of halogen.
The reaction of 2-chloro-3-(phenylethynyl)quinoxaline 1 with
1,3-dimethylbarbituric acid in the t-BuOK/DMSO system proceeded
rather unexpectedly. Taking into account results of the preceding
cyclization, we supposed to obtain a spirocyclic compound 15
(Scheme 9). However, the only isolated product was 2-methyl-4-
Scheme 6.
phenyl-2,6,10b-triazaacephenathrylene-1,3(2H,10bH)-dione
16.
Unfortunately, no single-crystal of 16 suitable for X-ray diffraction
study was obtained. The structural assignment, apart from ele-
mental analysis, was based on the following evidence. The mass
spectrum of 16 included a peak of the molecular ion (Mþ m/z 327),
which was the most intense. Two characteristic bands of the amide
Scheme 7.
Scheme 8.
Fig. 2. ORTEP plots for X-ray crystal structure of 13.

A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
491
carbonyl stretching vibration at 1644 and 1667 cmꢀ1 were regis-
9H)-tetraone 17 in 62% yield (Schemes 9 and 10). The structure 17 was
tered in the IR spectrum. The 1H NMR spectrum of 16 revealed
provedbya combination of UV,IR,1Hand13CNMRmeasurements.The
a three-proton singlet at
tons, a one-proton singlet at
d
3.85 ppm attributed to the NeMe pro-
6.65 ppm belonging to the H(5)
chemical shifts of its N(2)eMe and H(5) protons (d 3.8 and 6.7 ppm,
d
respectively) are similar to those of 16. The IR and 13C NMR spectra
indicated the absence of the C^C bond in this molecule. Three upfield
proton and signals of nine aromatic protons. The proposed struc-
ture 16 was also confirmed by the 13C NMR data showed a total of
signals of sp3 carbons were observed at
d
28.8, 28.9, and 29.8 ppm. The
eighteen signals. Among them, only one upfield peak at
(sp3 C) and two peaks of the amide carbonyl carbons at
161.7 ppm were observed.
d
29.4 ppm
159.7 and
amide carbonyl carbons appeared themselves as downfield peaks at
d
d 158.7, 160.0, 161.1, and 161.2 ppm. The mass spectrum of 17 showed
an intensive peak of the molecular ion (Mþ m/z 389).
The observed difference in the reactivity of 2-chloro-3-(phenyl-
ethynyl)quinoxaline 1 toward CH-acids can not be simply connected
with the difference in their CH-acidity20 or nucleophilicity of the
correspondingcarbanions(Fig. 3). Evidently, anucleophilecanattack
any of two electrophilic centers in the molecule 1: either ring C(2)
atom or alkyne C(b) atom. However, nucleophilic attack on the C(2)
atom is sterically more hindered. Indeed, only the smallest malo-
nonitrile anion is able to replace the chlorine atom of 1. In contrast,
bulkieranionsofdiethylmalonateor1,3-dimethylbarbituricacidadd
to the triple bond. When reacted with ethyl cyanoacetate, compound
1 demonstrates reactivity of both types.
We further explored the reactivity of 2,3-dialkynylpyrazines 2,
Scheme 9.
We have assumed that during the reaction course a primarily
formed spirocyclic compound 15 could undergo recyclization ac-
companied by the elimination of methylisocyanate molecule. The
mechanism shown in Scheme 10 has been proposed for this cas-
cade process. At first, 1,3-dimethylbarbituric acid carbanion adds to
the triple bond of 1 to form intermediate 18. The last one undergoes
spirocyclization into 15 via intramolecular nucleophilic sub-
stitution reaction. Then a tert-butoxide ion promotes the pyrimi-
dine ring opening to give carbamate intermediate 19, which loses
a methylisocyanate molecule. The resulted anion 20 is converted
into 16. The ability of 5,5-disubstituted and spirobarbituric acids to
undergo a ring contraction (alkoxide ion-catalyzed17 or nucleo-
phile-induced18) is known. Nucleophilic reactions of potassium
tert-butoxide have been also reported.19
Fig. 3. Acidity in DMSO of the used CH-acids.
4, and 5 toward C-nucleophiles. When 2,3-bis(phenylethynyl)qui-
noxaline 2a was heated with the malononitrile/t-BuOK/THF system,
nucleophilic addition to one or both triple bonds of 2a yielding
compounds 21 and 22 was observed (Scheme 11). The methylidene
tautomeric forms of 21 and 22 were deduced from their spectro-
scopic data as well as their deep color (red to purple) testifying the
presence of a long conjugated chain.
Scheme 10.
Scheme 11.
To investigate the scope of the above cyclization, 6-chloro-1,3-
dimethyl-7-(phenylethynyl)pteridine-2,4(1H,3H)-dione 3 was then
studied as a substrate. Treatmentof 3 with 1,3-dimethylbarbituric acid
and t-BuOK in DMSO solution afforded 2,7,9-trimethyl-4-phenyl-1H-
2,6,7,9,10b-pentaazaacephenanthrylene-1,3,8,10(2H,7H,
The use of cyanoacetic and malonic esters carbanions as nu-
cleophiles, led to the annulation of two pyridine rings to the parent
heterocyclic system 2a providing polynuclear compounds 23a and

492
A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
Table 1
23b, respectively (Scheme 11). The mechanism of this cyclization is
likely to be similar to that outlined in Scheme 7. The cyclization
products 23a and 23b are yellow-orange crystals. Their mass
spectra revealed peaks of the corresponding molecular ions. The IR
Comparison of spectral data for 24a, 24b, 29, and 30
24a
24b
29
30
IR (cmꢀ1
)
1673 (C]O)
1651e1677
(C]O)
1716 (C]O)
3338 (NeH)
1676 (C]O)
1667 (C]O)
spectrum of 23a showed absorption of the amide carbonyl (
n
1680 cmꢀ1) and the C^N bond ( 2221 cmꢀ1). In the IR spectrum of
n
1713 (C]O)
1712 (C]O)
1683 (C]O)
1708 (C]O)
1724 (C]O)
3:33
3:52
3.63
6.67 [H(50)]
7.56 [H(6)]
23b two characteristic bands of the carbonyl stretching vibration at
1662 and 1740 cmꢀ1 were registered. The 1H NMR spectra of 23a,b
indicated their symmetrical structure showing three pairs of the
magnetically equivalent aromatic protons [H(6) and H(9), H(7) and
H(8), H(1) and H(14)]. This was also supported by their 13C NMR
ꢀ
1H NMR
(ppm)
d
2.63 [NHMe]
3.42 [Me(10)]
d
½NeMeꢂ
3.38 [Me(10)]
6.70 [H(50)]
7.62 [H(3)]
3.34 [Me(10)]
6.69 [H(50)]
7.66 [H(6)]
7.48 [H(3)]
26.8 [NHMe]
28.0 [Me(10)]
65.5 [C(1)]
163.8 [C]O]
164.6 [C]O]
168.4 [C]O]
13C NMR
(ppm)
d
spectra. For example, two carbonyl (
aromatic and two aliphatic ( 14.2 and 62.2 ppm) signals were
observed in the spectrum of 23b.
d 159.5 and 165.7 ppm), eleven
27.6 [Me(10)]
65.3 [C(1)]
27.6 [Me(10)]
65.3 [C(8)]
d
Again, it was difficult to predict a result of the reaction of 2,3-
bis(phenylethynyl)quinoxaline 2a with 1,3-dimethylbarbituric
acid. Heating of 2a and 1,3-dimethylbarbituric acid with potas-
sium tert-butoxide in DMSO gave a spirocyclic product 24a in 44%
yield (Scheme 12). Its structure was unambiguously secured by X-
ray crystal structure analysis (Fig. 4). Interestingly, the same re-
action of 2b provided carboxamide 24b in 49% yield. Compounds
24a and 24b showed similar spectroscopic properties (Table 1), in
particular, chemical shifts of the H(3) and Me(1) protons as well as
the C(1), Me(1) and the carbonyl carbons. The IR and NMR spectra
of 24b included the corresponding signals of the carboxamide
function. The structural assignment of 24b was also supported by
mass spectrometry (Mþ m/z 514) and elemental analysis.
165.1 [C]O]
169.4 [C]O]
164.7 [C]O]
169.0 [C]O]
ring opening by the tert-butoxide to give 26. Evidently, this step is
similar to the transformation of 15 into 19 outlined in Scheme 10. A
proton transfer and subsequent spirocyclization yield spiro[cyclo-
penta[b]quinoxaline-1,30-pyridine] 28. Further development of the
process depends on the substituent R at the alkyne termini. When
R¼p-Tol, the reaction is stopped. When R¼Ph, compound 28 loses
methylisocyanate molecule to produce 24a. This difference in the
reactivity of 24a and 24b is not clear. Probably, it may be caused by
the higher stability of 24b under this particular reaction conditions
due to its lesser solubility in DMSO.
Under the same reaction conditions, ortho-dialkynyl derivatives
of pteridine 4 and pyrido[2,3-b]pyrazine 5 underwent similar
transformation to yield spirocyclic products 29 and 30, respectively
(Scheme 14). In both cases an initial nucleophilic attack was di-
rected on the more electron-deficient alkynyl group of the starting
molecule (7-alkynyl of 411b,d and 3-alkynyl of 521). The structural
assignments for compounds 29 and 30 were based on comparison
of their spectroscopic data with those of compounds 24 and ele-
mental analysis. As it follows from Table 1, a close similarity in the
1H, 13C chemical shifts as well as in the C]O stretching vibration,
was observed for 29, 30, and 24. Peaks of the molecular ions were
also registered in the mass spectra of 29 and 30.
Scheme 12.
As it was indicated in the introduction, nucleophilic attack on
the enediyne substrate commonly results in 6-endo-dig carbocyc-
lization (see, Scheme 3). The only exception is the butyllithium,
whose interaction with 1,2-bis(phenylethynyl)benzene yields the
benzofulvene derivative.5a,b Our cascade cyclization of ortho-dia-
lkynylpyrazines 2, 4, and 5 into spiropyridines 24, 29, and 30 also
includes a carbanion-promoted annulation of the fulvene ring to
the parent heterocycle as a key step. At the same time, when 2,3-
bis(phenylethynyl)quinoxaline 2a was allowed to react with
butyllithium in THF at ꢀ16 to ꢀ13 ꢁC, both acetylenic bonds
remained unchanged and the process led to the formation of the
1,2-adduct 32, that is typically for ordinary azines (Scheme 15).
Presumably, the nucleophilic attack on the position 2 of the pyr-
azine ring was assisted here by the pre-coordination of the Liþ ion
to the aza group as shown in the structure 31.
3. Conclusion
Fig. 4. ORTEP plots for X-ray crystal structure of 24a.
In summary, we have found that alkynyl azines and alkynyl
carboarenes differ essentially in their reactivity toward nucleo-
philes. It can be explained by the electron-withdrawing nature of
the ring heteroatoms, which activate the C^C triple bonds and
some other reaction centers as electrophiles. In addition, the aza
group itself can participate as a nucleophile in subsequent cycli-
zation reactions. Most of the tested reactions of 3-alkynyl-2-chloro-
A plausible mechanism for the formation of 24 is depicted in
Scheme 13. First, 1,3-dimethylbarbituric acid carbanion adds to one
of the triple bonds of 2 triggering a cyclopentadiene ring closure
with participation of the second C^C bond (5-exo-dig carbocycli-
zation). Thus formed intermediate 25 undergoes the pyrimidine

A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
493
Scheme 13.
and 2,3-dialkynyl derivatives of fused pyrazines with the CH-acids
carbanions start with the addition of a nucleophile across the more
electrophilic carbonecarbon triple bond. Further processes de-
velop, resulting in a tandem or cascade cyclization ultimately
yielding polynuclear heterocyclic compounds.
Some novel anionic cascade cyclizations of 3-alkynyl-2-chloro-
and 2,3-dialkynylpyrazines providing derivatives of new hetero-
cyclic systems have been found. Among these findings are those
promoted by the malonic ester carbanion conversion of 3-chloro-2-
alkynylpyrazines into diethyl 2-phenyl-1H-cylopenta[b]pyrazine-
1,1-dicarboxilates, and initiated by the 1,3-dimethylbarbituric acid
carbanions transformations of 3-chloro-2-alkynylpyrazines and
2,3-dialkynylpyrazines into triazaphenanthrylenes and spiro
[cyclopenta[b]pyrazine-1,30-pyridine], respectively.
4. Experimental
4.1. General
Scheme 14.
Proton (1H) nuclear magnetic resonance (NMR) spectra were
recorded on a Bruker DPX-250 (250 MHz) spectrometer. 13C NMR
spectra were recorded on Bruker DPX-250 (62.9 MHz) spectrome-
ter. 1H and 13C NMR chemical shifts are in parts per million relative
to Me4Si. Coupling constants are in hertz. The IR spectra were
recorded on a Varian Excalibur 3100 FT-IR spectrometer using
Nujol. Ultraviolet absorption (UV) spectra were registered on a Cary
50 Probe spectrophotometer with CHCl3 as a solvent. Mass spectra
were measured on a Finnigan MAT INCOS 50 spectrometer. CHN
analysis was accomplished by combustion analysis (Dumas and
Pregl method). Melting points were determined in glass capillaries
using a PTP device and are uncorrected. Flash column chromatog-
raphy was performed on silica gel and Al2O3 (IIIeIV activity,
Brockman). All commercial reagents (1-alkynes, palladium cata-
lysts, DMSO, THF) were purchased from Acros and Aldrich.
Scheme 15.

494
A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
4.2. X-ray structure determination
145.8, 150.8, 159.5; IR, cmꢀ1: 1669 and 1714 (C]O), 2195 and 2210
(C^C); MS m/z: 420 ([M]þ, 62), 405 (6), 340 (11), 230 (100), 215
(13),140 (14),115 (8), 81 (5). Anal. Calcd for C26H20N4O2: C, 74.27; H,
4.79; N, 13.33. Found: C, 74.09; H, 4.94; N, 13.21.
Crystallographic data for 13: at 100 K crystals of C23H20N2O4 are
monoclinic, space group C c, a¼ꢁ12.543(3), b¼20.155(6), c¼7.639(2)
3
ꢀ
ꢀ
A,
a
¼90ꢁ,
b
¼95.014(5)ꢁ,
g
¼90 , V¼1923.8(9) A , Z¼4, M¼388.41,
dcalcd¼1.341 g cmꢀ3
,
m
(Mo
Ka
)¼0.093 mmꢀ1
,
F(000)¼816. In-
4.3.2. Synthesis of 2,3-bis(p-tolylethynyl)pyrido[2,3-b]pyrazine 5.
CuI (6.00 mg, 0.03 mmol), PdCl2(PPh3)2 (30.0 mg, 0.04 mmol), and
i-Pr2NH (2 mL) were added to 2,3-dichloropyrido[2,3-b]pyrazine21
(240 mg, 1.20 mmol) in dry DMSO (4 mL) under a slow stream of
argon. After 20 min stirring under argon, p-tolylacetylene (348 mg,
3.00 mmol) in i-Pr2NH (2 mL) was added drop wise for 25 min.
Stirring was continued for 6 h at room temperature. The reaction
mixture was then filtered and solids over the filter were rinsed with
hexane (5 mL) giving 5. This crude product 5 was purified by flash
column chromatography on silica gel (3ꢃ30 cm) with CHCl3 as the
eluent. The yield was 346 mg. The filtrate was evaporated to dry-
ness under reduced pressure. The residue was mixed with silica gel
and purified by flash column chromatography on silica gel
(2ꢃ20 cm) with CHCl3 as the eluent. The yellowish fraction Rf
(CHCl3) 0.3 gave 25.0 mg of 5. Compound 5 was obtained in 86%
total yield (371 mg) as pale yellow crystals, mp 219e221 ꢁC
tensities of 9010 reflections were measured with a Bruker APEX II
CCD area detector at 100 K and 5417 independent reflections
(Rint¼0.0317) were used in further refinement. The structures were
solved by direct method and refined by the full-matrix least squares
against F2 in the anisotropiceisotropic approximation. Hydrogen
atoms were located from the Fourier synthesis and refined in the
isotropic approximation. The refinement converged to wR2¼0.0842
and GOF¼0.997 for all independent reflections [R1¼0.0416 was
calculated against F for observed 4280 reflections with I>2s(I)].
Crystallographic data for 24a: at 100 K crystals of C28H19N3O2
are monoclinic, space group P 21/n, a¼10.7543(3), b¼17.0084(6),
ꢀ
c¼12.3208(4) A,
a
¼90ꢁ,
b
¼110.6380(10)ꢁ,
g
¼90ꢁ, V¼2109.01(13)
A , Z¼4, M¼429.46, dcalcd¼1.353 g cmꢀ3
,
m
(Mo K
a
)¼0.087 mmꢀ1
,
3
ꢀ
F(000)¼896. Intensities of 24,951 reflections were measured with
a Bruker APEX II CCD area detector at 100 K and 5602 independent
reflections (Rint¼0.0228) were used in further refinement. The
structures were solved by direct method and refined by the full-
matrix least squares against F2 in the anisotropic-isotropic ap-
proximation. Hydrogen atoms were located from the Fourier syn-
thesis and refined in the isotropic approximation. The refinement
converged to wR2¼0.1001 and GOF¼1.015 for all independent re-
flections [R1¼0.0436 was calculated against F for observed 4861
(decomp., EtOH); 1H NMR (CDCl3, 250 MHz)
d ppm: 2.39 (br s, 6H,
2Me), 7.20 (m, 4H, p-Tol), 7.59 (m, 4H, p-Tol), 7.67 (dd, J¼8.4, 4.3 Hz,
1H, H(7)), 8.38 (dd, J¼8.4, 1.9 Hz, 1H, H(8)), 9.13 (dd, J¼4.3, 1.9 Hz,
1H, H(6)); 13C NMR (CDCl3, 62.9 MHz)
d ppm: 22.1, 86.5, 86.7, 97.9,
98.6, 118.6, 118.8, 126.0, 129.8, 132.8, 132.9, 136.5, 137.9, 141.0, 141.1,
142.5, 144.5, 149.3, 155.1; IR, cmꢀ1: 2207 (C^C). MS m/z: 359 ([M]þ,
30), 344 (33), 217 (49), 203 (15), 190 (30), 179 (30), 164 (11), 140
(100), 141 (52), 89 (14), 77 (64), 65 (13). Anal. Calcd for C25H17N3: C,
83.54; H, 4.77; N, 11.69. Found: C, 83.71; H, 4.56; N, 11.54.
reflections with I>2s(I)].
All calculations were performed using SHELXLe97 on an IBM PC
AT. Atomic coordinates, bond lengths, bond angles, and thermal
parameters have been deposited at the Cambridge Crystallographic
Data Centre (CCDC) and allocated the deposition number CCDC
836379 (13) and CCDC 836384 (24a).
4.4. Synthesis of 2-(3-(phenylethynyl)quinoxalin-2(1H)-
ylidene)malononitrile 6
Malononitrile (39.6 mg, 0.60 mmol) and t-BuOK (112 mg,
1.00 mmol) in dry THF (5 mL) was stirred at room temperature for
10 min. To this mixture 2-chloro-3-(phenylethynyl)quinoxaline 1
(133 mg, 0.50 mmol) was added by portions. Stirring was continued
for 6 h at reflux. The reaction mixture was then treated with one
drop of acetic acid and evaporated to dryness under reduced
pressure. The residue was purified by flash column chromatogra-
phy on silica gel (3.5ꢃ10 cm) using CH2Cl2/EtOH (100:1, v/v) as the
eluent. The first fraction recovered was 1 (33.0 mg). The orange
fraction with Rf (CH2Cl2/EtOH, 100:1, v/v) 0.1 gave 6. Crystallization
from CH2Cl2/EtOH (100:1) yielded compound 6 (54.0 mg, 37%) as
orange needles, decomp.>200 ꢁC; 1H NMR (DMSO-d6, 250 MHz)
4.3. Synthesis of the starting compounds
Starting 3-chloro-2-(phenylethynyl)quinoxaline 1,12 2,3-bis
(alkynyl)quinoxalines 2a,b,11d 6-chloro-1,3-dimethyl-7-(phenyl-
ethynyl)pteridine-2,4(1H,3H)-dione 311b were synthesized in ac-
cordance with known procedures.
4.3.1. Synthesis of 1,3-dimethyl-6,7-bis(p-tolylethynyl)pteridine-
2,4(1H,3H)-dione 4. CuI (19.0 mg, 0.10 mmol), PdCl2(PPh3)2
(21.0 mg, 0.03 mmol), and Et3N (1 mL) were added to 6,7-dichloro-
1,3-dimethylpteridine-2,4(1H,3H)-dione22 (261 mg, 1.00 mmol) in
dry DMSO (3 mL) under a slow stream of argon. After 20 min stir-
ring under argon, p-tolylacetylene (145 mg, 1.25 mmol) in Et3N
(0.5 mL) was added drop wise. For 10 min yellow solids were pre-
cipitated. Stirring was continued for 1 h at room temperature. The
mixture was then heated to 80 ꢁC and p-tolylacetylene (145 mg,
1.25 mmol) in Et3N (0.5 mL) was added drop wise. After 2.5 h stir-
ring at 80 ꢁC, the mixture was allowed to cool down overnight. The
reaction mixture was then filtered and solids over the filter were
rinsed with methanol (5 mL) giving product 4 (121 mg). The filtrate
was evaporated to dryness under reduced pressure. The residue
was mixed with silica gel and purified by flash column chroma-
tography on silica gel (3ꢃ30 cm) with CHCl3 as the eluent. The
yellow fraction with Rf (CHCl3) 0.1 gave an additional amount of 4.
After crystallization from EtOH compound 4 was obtained in 33%
total yield (141 mg) as yellow crystals, mp 225e228 ꢁC; 1H NMR
d
ppm: 7.29 (ddd, J¼8.2, 6.0, 2.2 Hz, 1H), 7.42e7.52 (m, 5H), 7.66 (d,
J¼7.9 Hz, 1H), 7.75e7.83 (m, 2H); 13C NMR (DMSO-d6, 62.9 MHz)
d
ppm: 89.0, 95.2, 122.7, 124.0, 125.1, 126.1, 128.7, 129.5, 130.4, 131.1,
132.5, 133.8, 137.7, 141.9, 155.8; IR, cmꢀ1: 2153 and 2195 (C^C),
3000e3500 (NeH ass.); UVevis, lmax (log ), nm: 244 (4.38), 258
3
(4.60), 316 (4.44), 361 (4.23), 449 (4.21), 472 (4.22), end absorption
up to 536 nm; MS m/z: 294 ([M]þ, 100), 267 (8), 243 (6), 229 (37),
218 (6), 147 (12), 139 (7), 134 (5), 127 (15), 102 (60), 88 (8), 76 (37).
Anal. Calcd for C19H10N4: C, 77.54; H, 3.42; N, 19.04. Found: C, 77.36;
H, 3.26; N, 18.93.
4.5. Reaction of 2-chloro-3-(phenylethynyl)quinoxaline 1 with
ethyl cyanoacetate
The reaction of 1 with ethyl cyanoacetate (66.0 mg, 0.062 mL,
0.60 mmol) was carried out in a similar to Section 4.4 way. The
evaporated reaction mixture was purified by flash column chro-
matography on silica gel (2ꢃ40 cm) using CH2Cl2/EtOH (100:1, v/v)
as the eluent. The first fraction recovered was 1 (27.0 mg). The or-
ange fraction with Rf 0.6 gave a mixture of 8 and 9.
(CDCl3, 250 MHz)
d ppm: 2.38 (s, 3H, Me), 2.40 (s, 3H, Me), 3.53 (s,
3H, NeMe), 3.72 (s, 3H, NeMe), 7.16e7.22 (m, 4H, p-Tol), 7.51 (d,
J¼8.2 Hz, 2H, p-Tol), 7.56 (d, J¼8.1 Hz, 2H, p-Tol); 13C NMR (CDCl3,
62.9 MHz) d ppm: 22.1, 22.2, 29.5, 30.0, 85.5, 86.6, 96.9, 101.1, 118.3,
119.0, 125.3, 129.8, 129.9, 132.5, 132.9, 137.6, 140.6, 141.7, 144.6,

A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
495
The mixture of 8 and 9 was separated by additional flash column
chromatography on Al2O3 (2ꢃ30 cm) with CH2Cl2/EtOH (100:1, v/v)
as the eluent. The first orange fraction with Rf (CH2Cl2/EtOH, 100:1,
v/v) 0.6 gave 9, which was then crystallized from heptane. Com-
pound 8 was isolated from the next orange fraction with Rf (CH2Cl2/
EtOH, 100:1, v/v) 0.2 and subsequently crystallized from CH2Cl2/
EtOH (100:1, v/v).
temperature for 10 min. To this mixture 6-chloro-1,3-dimethyl-7-
(phenylethynyl)pteridine-2,4(1H,3H)-dione 3 (326 mg, 1.00 mmol)
was added by portions. Stirring was continued for 4 h at reflux.
The reaction mixture was then treated with NH4Cl saturated
aqueous solution (5 mL) and extracted with CHCl3 (3ꢃ10 mL). The
extract was dried over CaCl2. The solvent was subsequently re-
moved under reduced pressure. The residue was crystallized from
i-PrOH yielding compound 14 (243 mg, 54%) as pale yellow crys-
4.5.1. (Z)-Ethyl 2-cyano-2-(9-cyano-10-oxo-8-phenyl-5H-pyrido[1,2-
a]quinoxalin-6(10H)-ylidene)acetate 8. Compound 8 was obtained
in 22% yield (44.0 mg) as orange needles, mp 218e220 ꢁC; 1H NMR
tals, mp 225e228 ꢁC; 1H NMR (CDCl3, 250 MHz)
d ppm: 1.10 (t,
J¼7.1 Hz, 6H, 2Me), 3.54 (s, 3H, NeMe), 3.76 (s, 3H, NeMe),
4.08e4.29 (m, 4H, 2CH2), 7.42e7.48 (m, 3H), 7.53 (s, 1H, H(8)),
7.74e7.81 (m, 2H); IR, cmꢀ1: 1673, 1717, and 1761 (C]O); UVevis,
(CDCl3, 250 MHz)
d
ppm: 1.40 (t, J¼7.2 Hz, 3H, Me), 4.38 (q, J¼7.2 Hz,
2H, CH2), 7.20e7.25 (m, 1H), 7.28e7.35 (m, 1H), 7.39e7.45 (m, 1H),
7.56e7.58 (m, 3H), 7.83e7.87 (m, 2H), 8.34 (s, 1H, H(7)), 9.31 (d,
J¼8.7 Hz, 1H, H(1)), 13.54 (br s, 1H, NH); 13C NMR (CDCl3, 62.9 MHz)
lmax (log ), nm: 318 (4.09), 380 (4.53), end absorption up to
3
430 nm; MS m/z: 450 ([M]þ, 11), 332 (96), 321 (22), 306 (14), 247
(23), 220 (62), 192 (12), 178 (20), 164 (12), 29 (100). Anal. Calcd for
C23H22N4O6: C, 61.33; H, 4.92; N, 12.44. Found: C, 61.15; H, 5.07; N,
12.24.
d
ppm: 14.6, 62.8, 71.9, 106.5, 111.5, 115.3, 117.9, 118.5, 121.6, 125.0,
126.1,126.7,129.1,129.3,129.9,132.2,133.8,134.3,150.8,156.5,160.7,
169.9; IR, cmꢀ1: 1648 and 1662 (C]O), 2206 (C^N), 3000e3500
(NeH ass.); UVevis, lmax (log
3 ), nm: 242 (4.23), 260 (4.25), 327
4.8. Synthesis of 2-methyl-4-phenyl-2,6,10b-triaza-acephenath
(4.14), 422 (4.10), 485 sh (3.75), end absorption up to 529 nm; MS m/
z: 408 ([M]þ, 46), 362 (100), 334 (39), 305 (31), 280 (17), 269 (7), 253
(5), 235 (14), 209 (6), 169 (7), 153 (11), 140 (33), 127 (8), 113 (16), 102
(33), 88 (9), 77 (49). Anal. Calcd for C24H16N4O3: C, 70.58; H, 3.95; N,
13.72. Found: C, 70.78; H, 4.11; N, 13.67.
rylene-1,3(2H,10bH)-dione 16
1,3-Dimethylbarbituric acid (93.6 mg, 0.60 mmol) and t-BuOK
(112 mg, 1.00 mmol) in dry DMSO (5 mL) was stirred at room
temperature for 20 min. To this mixture 3-chloro-2-(phenyl-
ethynyl)quinoxaline 1 (133 mg, 0.50 mmol) was added by portions.
Stirring was continued for 5 h at 70 ꢁC. The reaction mixture was
allowed to cool down overnight and then filtered. Solids over the
filter were rinsed subsequently with DMSO (1 mL) and i-PrOH
(1 mL) yielding 16. Crystallization from EtOH gave 16 (120 mg, 73%)
as yellowish crystals, mp 262e264 ꢁC; 1H NMR (CDCl3, 250 MHz)
4.5.2. (Z)-Ethyl 2-cyano-2-(3-(phenylethynyl)quinoxalin-2(1H)-yli-
dene)acetate 9. Compound 9 was obtained in 7% yield (12.0 mg) as
orange needles, mp 167e169 ꢁC; 1H NMR (CDCl3, 250 MHz)
d ppm:
1.40 (t, J¼7.1 Hz, 3H, Me), 4.35 (q, J¼7.1 Hz, 2H, CH2), 7.25e7.60 (m,
6H), 7.80e7.88 (m, 3H), 14.35 (br s, 1H, NH); IR, cmꢀ1: 1663 (C]O),
2196 (C^N), 2222 (C^C), 3000e3500 (NeH ass.); UVevis, lmax
d
ppm: 3.85 (s, 3H, Me), 6.65 (s, 1H, H(5)), 7.54e7.58 (m, 3H),
7.67e7.75 (m, 2H), 7.93e7.97 (m, 2H), 8.01e8.09 (m, 2H); 13C NMR
(CDCl3, 62.9 MHz) ppm: 29.4, 96.1, 101.2, 114.7, 126.6, 128.8, 129.1,
129.5, 130.7, 131.7, 135.1, 137.7, 139.8, 142.1, 149.6, 152.5, 159.7, 161.7;
IR, cmꢀ1: 1644 and 1667 (C]O); UVevis, lmax (log
), nm: 242
(log ), nm: 246 (4.59), 257 (4.55), 321 (4.52), 434 (4.22), end ab-
3
sorption up to 531 nm; MS m/z: 341 ([M]þ, 52), 312 (6), 296 (24),
282 (9), 269 ([MꢀCO2Et]þ,100), 255 (7), 241 (23), 229 (10), 218 (10),
203 (7), 176 (7), 165 (7), 148 (7), 140 (69), 134 (7), 127 (21), 114 (28),
102 (33), 88 (14), 76 (51). Anal. Calcd for C21H15N3O2: C, 73.89; H,
4.43; N, 12.31. Found: C, 74.03; H, 4.24; N, 12.15.
d
3
(4.76), 244 (4.78), 254 (4.85), 373 (4.72), end absorption up to
450 nm; MS m/z: 327 ([M]þ, 100), 298 (9), 285 (6), 270 (16), 256 (7),
243 (5), 229 (11), 164 (7), 154 (12), 140 (28), 128 (11), 114 (12), 102
(12), 90 (15), 77 (5). Anal. Calcd for C20H13N3O2: C, 73.38; H, 4.00; N,
12.84. Found: C, 73.58; H, 3.92; N, 13.03.
4.6. Synthesis of diethyl 2-phenyl-1H-cyclopenta[b]
quinoxaline-1,1-dicarboxylate 13
The reaction of 1 with diethyl malonate (96.0 mg, 0.091 mL,
0.60 mmol) was carried out for 4 h in accordance with procedure
describedinSection4.4. Evaporatedreaction mixturewaspurifiedby
flash column chromatography on silica gel (2ꢃ30 cm) using CHCl3/
CCl4 (5:1, v/v)astheeluent. The firstyellowishfractionrecoveredwas
1 (35.0 mg). The yellow fraction with Rf (CHCl3/CCl4, 5:1, v/v) 0.1 was
separated from the column and product 13 was eluted with i-PrOH.
Crystallization from heptane gave 13 in 52% yield (100 mg) as yellow
4.9. Synthesis of 2,7,9-trimethyl-4-phenyl-1H-2,6,7,9,10b-
pentaazaacephenanthrylene-1,3,8,10(2H,7H,9H)-tetraone 17
1,3-Dimethylbarbituric acid (93.6 mg, 0.60 mmol) and t-BuOK
(112 mg, 1.00 mmol) in dry DMSO (5 mL) was stirred at room
temperature for 20 min. To this mixture 6-chloro-1,3-dimethyl-7-
(phenylethynyl)pteridine-2,4(1H,3H)-dione 3 (163 mg, 0.50 mmol)
was added by portions. Stirring was continued for 12 h at 70 ꢁC. The
reaction mixture was allowed to cool down overnight and then
filtered. Solids over the filter were rinsed consequently with DMSO
(1 mL) and i-PrOH (1 mL) yielding 17 (86.0 mg). The filtrate was
evaporated to dryness under reduced pressure. The residue was
purified by flash column chromatography on silica gel (3.5ꢃ15 cm)
using CH2Cl2/EtOH (100:1, v/v) as the eluent. The yellow fraction
with Rf (CH2Cl2/EtOH, 100:1, v/v) 0.1 was separated from the col-
umn and product 17 (41.0 mg) was eluted with acetone. Compound
17 was obtained in 62% total yield (121 mg) as yellow needles, mp
313e315 ꢁC (decomp., acetonitrile); 1H NMR (CDCl3, 250 MHz)
crystals, mp 121e123 ꢁC; 1H NMR (CDCl3, 250 MHz)
d ppm: 1.03 (t,
J¼7.1 Hz, 6H, 2Me), 4.04e4.26 (m, 4H, 2CH2), 7.41e7.45 (m, 3H), 7.63
(s, 1H, H(3)), 7.65e7.78 (m, 4H), 8.07 (dd, J¼8.2, 1.6 Hz, 1H), 8.17 (dd,
J¼7.9, 1.9 Hz, 1H); 13C NMR (CDCl3, 62.9 MHz)
d ppm: 14.1, 63.0, 69.1,
128.1,129.0,129.2,129.3,130.2,130.3,130.5,130.6,132.8,140.7,143.1,
154.4, 157.2, 157.6, 166.2; IR, cmꢀ1: 1730 and 1770 (C]O); UVevis,
lmax (log ), nm: 290 (4.25), 360 (4.19), 375 (4.22), 405 (4.08), 425
3
(4.11), end absorption up to 470 nm; MS m/z: 388 ([M]þ, 24), 287 (6),
270 (100), 259 (26), 243 (38), 229 (11), 214 (16),152 (6),140 (33),129
(12),115 (54),102 (36), 88 (20), 77 (41). Anal. Calcd for C23H20N2O4: C,
71.12; H, 5.19; N, 7.21. Found: C, 70.91; H, 5.36; N, 7.28.
d
ppm: 3.52 (s, 3H, Me), 3.57 (s, 3H, Me), 3.81 (s, 3H, Me), 6.67 (s,1H,
H(5)), 7.45e7.59 (m, 3H), 7.75e7.83 (m, 2H); 13C NMR (pyridineeD5,
62.9 MHz) ppm: 28.8, 28.9, 29.8, 96.4, 115.3, 119.1, 128.8, 129.6,
130.0, 130.7, 140.8, 147.6, 148.4, 151.1, 158.7, 160.0, 161.1, 161.2; IR,
4.7. Synthesis of diethyl 1,3-dimethyl-2,4-dioxo-7-phenyl-3,4-
dihydro-1H-cyclopenta[g]pteridine-6,6(2H)-dicarboxylate 14
d
cmꢀ1: 1667e1671 and 1711 (C]O); UVevis, lmax (log
), nm: 404
3
Diethyl malonate (240 mg, 0.23 mL, 1.50 mmol) and t-BuOK
(336 mg, 3.00 mmol) in dry THF (5 mL) was stirred at room
(4.34), end absorption up to 430 nm; MS m/z: 390 ([Mþ1]þ, 9), 389
([M]þ, 47), 388 (7), 361 (2), 277 (18), 209 (19), 166 (8), 152 (7), 140

496
A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
(53), 127 (6), 113 (11), 107 (5), 77 (8), 67 (100). Anal. Calcd for
C20H15N5O4: C, 61.69; H, 3.88; N, 17.99. Found: C, 61.88; H, 4.05; N,
18.10.
(29),113 (38),102 (18), 88 (11), 77 (100). Anal. Calcd for C30H16N4O2:
C, 77.58; H, 3.47; N, 12.06. Found: C, 77.51; H, 3.65; N, 11.91.
4.12. Synthesis of diethyl 4,11-dioxo-2,13-diphenyl-4,11-
4.10. Reaction of 2,3-bis(phenylethynyl)quinoxaline 2a with
malonodinitrile
dihydrodipyrido[1,2-a:20,10-c]quinoxaline-3,12-dicarboxylate 23b
The reaction of 2a with diethyl malonate (80.0 mg, 0.076 mL,
0.50 mmol) was carried out in accordance with procedure de-
scribed in Section 4.10. The evaporated reaction mixture was pu-
rified by flash column chromatography on silica gel (2.5ꢃ30 cm)
using CH2Cl2/EtOAc (5:1, v/v) as the eluent. The first fraction re-
covered was 2a (33.0 mg). The bright yellow fraction with Rf
(CH2Cl2/EtOAc, 5:1, v/v) 0.2 gave 23b. The crude product was
crystallized from acetonitrile yielding 23b (79.0 mg, 28%) as bright
yellow crystals, mp 265e267 ꢁC (lit.12 263e265 ꢁC); 1H NMR (CDCl3,
Malononitrile (33.0 mg, 0.50 mmol) and t-BuOK (56.0 mg,
0.50 mmol) in dry THF (5 mL) was stirred at room temperature for
10 min. To this mixture 2,3-bis(phenylethynyl)quinoxaline 2a
(165 mg, 0.50 mmol) was added by portions. Stirring was contin-
ued for 5 h at reflux. The reaction mixture was then treated with
one drop of acetic acid and evaporated to dryness under reduced
pressure. The residue was purified by flash column chromatogra-
phy on silica gel (2ꢃ35 cm) using CH2Cl2/EtOAc (5:1, v/v) as the
eluent. The first fraction recovered was 2a (42.0 mg). The
raspberry-colored fraction with Rf (CH2Cl2/EtOAc, 5:1, v/v) 0.7 gave
21. The deep raspberry-colored fraction with Rf (CH2Cl2/EtOAc, 5:1,
v/v) 0.1 gave 22. Both products were crystallized from i-PrOH.
250 MHz)
2CH2), 7.02 (s, 2H, H(1) and H(14)), 7.34e7.40 (m, 2H), 7.43e7.48 (m,
10H), 8.83e8.89 (m, 2H); 13C NMR (CDCl3, 62.9 MHz)
ppm: 14.2,
d
ppm: 1.09 (t, J¼7.2 Hz, 6H, 2Me), 4.20 (q, J¼7.2 Hz, 4H,
d
62.2, 106.7, 121.2, 126.3, 126.9, 127.7, 127.9, 129.3, 130.2, 136.6, 136.9,
149.2, 159.5, 165.7; IR, cmꢀ1: 1662 and 1740 (C]O); UVevis, lmax
4.10.1. (Z)-2-(1-Phenyl-2-(3-(phenylethynyl)quinoxalin-2(1H)-yli-
dene)ethylidene)malononitrile 21. Compound 21 was obtained in
34% yield (68.0 mg) as red needles, mp 188e190 ꢁC; 1H NMR
(log ), nm: 284 (3.14), 308 (3.00), 416 (3.07), end absorption up to
3
481 nm; MS m/z: 558 ([M]þ, 100), 530 (31), 513 (16), 502 (23), 458
(16), 430(11), 402 (12), 355 (7), 177 (12), 140 (11), 129 (55), 115 (11),
102 (16), 77 (50). Anal. Calcd for C34H26N2O6: C, 73.11; H, 4.69; N,
5.02. Found: C, 73.31; H, 4.59; N, 4.84.
(CDCl3, 250 MHz)
d ppm: 7.08 (s, 1H, Hvinyl), 7.35e7.64 (m, 10H),
7.65e7.72 (m, 2H), 7.82 (dd, J¼7.6, 2.0 Hz, 1H), 8.32 (br s, 1H, NH),
9.66 (dd, J¼8.3, 1.5 Hz, 1H); 13C NMR (CDCl3, 62.9 MHz)
d ppm: 85.0,
96.4, 101.3, 106.0, 117.0, 120.0, 121.0, 127.9, 128.1, 128.3, 129.1, 129.6,
130.1, 130.2, 130.8, 131.2, 132.8, 136.0, 136.8, 138.2, 143.1, 153.4; IR,
4.13. Synthesis of 10-methyl-2,40-diphenyl-10H-spiro
[cyclopenta[b]quinoxaline-1,30-pyridine]-20,60-dione 24a
cmꢀ1: 2206 (C^N and C^C), 3312 (NeH); UVevis, lmax (log
), nm:
3
256 (4.42), 294 (4.15), 364 (4.20), 520 (3.75), end absorption up to
600 nm; MS m/z: 396 ([M]þ, 57), 395 ([Mꢀ1]þ, 100), 370 (7), 198
(9), 183 (6), 176 (6), 165 (8), 151 (6), 140 (23), 127 (43), 113 (16), 102
(57), 88 (13), 77 (96). Anal. Calcd for C27H16N4: C, 81.80; H, 4.07; N,
14.13. Found: C, 81.67; H, 3.86; N, 14.29.
1,3-Dimethylbarbituric acid (93.6 mg, 0.60 mmol) and t-BuOK
(112 mg, 1.00 mmol) in dry DMSO (5 mL) was stirred at room
temperature for 20 min. To this mixture 2,3-bis(phenylethynyl)
quinoxaline 2a (165 mg, 0.50 mmol) was added by portions. Stir-
ring was continued for 8 h at 70 ꢁC. The reaction mixture was then
treated with one drop of acetic acid and evaporated to dryness
under reduced pressure. The residue was purified by flash column
chromatography on silica gel (3.5ꢃ20 cm) using CHCl3 as the elu-
ent. The first fraction recovered was 2a (42.0 mg). The yellow
fraction with Rf (CHCl3) 0.1 was separated from the column and
product 24a was eluted with CHCl3. The crude product was crys-
tallized from acetonitrile yielding 24a (94.0 mg, 44%) as off-white
4.10.2. 2,20-(2Z,20Z)-2,20-(Quinoxaline-2,3(1H,4H)-diylidene)bis(1-
phenylethane-2,1-diylidene)dimalononitrile 22. Compound 22 was
obtained in 9% yield (21.0 mg) as purple needles, mp 293e296 ꢁC
(decomp.); 1H NMR (CDCl3, 250 MHz)
d
ppm: 6.55 (s, 2H, Hvinyl),
7.26e7.33 (m, 2H), 7.47e7.67 (m, 12H), 8.51 (br s, 2H, NH); 13C NMR
(CD3CO2D, 62.9 MHz) ppm: 100.9, 113.1, 115.7, 121.6, 128.1, 129.5,
129.7, 131.4, 133.1, 133.7, 139.9, 155.7, 160.4; IR, cmꢀ1: 2201 (C^N),
d
crystals, mp 244e247 ꢁC; 1H NMR (CDCl3, 250 MHz)
d ppm: 3.38
3316 (NeH); UVevis, lmax (log
3
), nm: 302 (4.24), 336 (4.21), 504
(s, 3H, NeMe), 6.54 (d, J¼7.6 Hz, 2H), 6.70 (s, 1H, H(50)), 6.92e6.98
(m, 2H), 7.08e7.14 (m, 1H), 7.32e7.50 (m, 5H), 7.62 (s, 1H, H(3)),
7.66e7.78 (m, 2H), 8.06 (d, J¼7.9 Hz, 2H); 13C NMR (CDCl3,
(4.23), end absorption up to 624 nm; MS m/z: 462 ([M]þ, 100), 438
(5), 436 (18), 435 (34), 320 (5), 281 (5), 149 (16), 140 (12), 103 (5),
102 (14), 101 (36), 82 (17), 75 (7), 76 (10). Anal. Calcd for C30H18N6:
C, 77.91; H, 3.92; N, 18.17. Found: C, 78.13; H, 3.72; N, 18.35.
62.9 MHz)
d ppm: 27.6, 65.3, 124.1, 127.0, 127.4, 128.6, 129.5, 129.6,
129.7, 129.9, 130.0, 130.8, 131.3, 132.9, 135.4, 140.5, 143.2, 154.4,
155.9, 158.4, 159.9, 165.1, 169.4; IR, cmꢀ1: 1673 and 1713 (C]O);
4.11. Synthesis of 4,11-dioxo-2,13-diphenyl-4,11-dihydrodipyrido
UVevis, lmax (log ), nm: 263 (4.30), 266 (4.29), 292 (4.36), 362
3
[1,2-a:20,10-c]quinoxaline-3,12-dicarbonitrile 23a
(4.46), 380 nm (4.48); MS m/z: 429 ([M]þ, 2), 372 (11), 343 (21), 267
(18), 240 (34), 215 (39), 186 (39), 172 (98), 170 (98), 139 (52), 113
(56), 102 (88), 89 (30), 77 (100). Anal. Calcd for C28H19N3O2: C,
78.31; H, 4.46; N, 9.78. Found: C, 78.47; H, 4.59; N, 9.92.
The reaction of 2a with ethyl cyanoacetate (56.6 mg, 0.053 mL,
0.50 mmol) was carried out in accordance with procedure de-
scribed in Section 4.10. The evaporated reaction mixture was pu-
rified by flash column chromatography on silica gel (2ꢃ35 cm)
using CH2Cl2/Et2O (15:1, v/v) as the eluent. The first fraction re-
covered was 2a (35.0 mg). The orange fraction with Rf (CH2Cl2/Et2O,
15:1, v/v) 0.6 gave 23a. The crude product was crystallized from
acetonitrile yielding 23a (60.0 mg, 26%) as orange crystals,
4.14. Synthesis of N,10-dimethyl-20,60-dioxo-2,40-di(p-tolyl)-
20,60-dihydro-10H-spiro[cyclopenta[b]quinoxaline-1,30-
pyridine]-50-carboxamide 24b
The reaction of 2b (179 mg, 0.50 mmol) with 1,3-
dimethylbarbituric acid was carried out in accordance with pro-
cedure described in Section 4.13. The evaporated reaction mixture
was purified by flash column chromatography on silica gel
(2.5ꢃ30 cm) using CH2Cl2/Et2O (15:1, v/v) as the eluent. The first
fraction recovered was 2b (58.0 mg). The yellow fraction with Rf
(CH2Cl2/Et2O, 15:1, v/v) 0.1 was separated from the column and
product 24b was eluted with CHCl3. The crude product was
324e326 ꢁC (decomp.); 1H NMR (DMSO-d6, 250 MHz)
d ppm:
7.50e7.54 (m, 2H), 7.62e7.64 (m, 6H), 7.78e7.82 (m, 4H), 8.00 (s,
2H, H(1) and H(14)), 8.64e8.68 (m, 2H); 13C NMR (DMSO-d6,
62.9 MHz)
129.7, 131.9, 135.5, 139.9, 158.3, 160.2; IR, cmꢀ1: 1659 (C]O), 2221
(C^N); UVevis, lmax (log ), nm: 332 (3.13), 446 (3.29), end ab-
sorption up to 520 nm; MS m/z: 464 ([M]þ, 3), 408 (5), 140 (43), 127
d ppm: 104.3, 108.8, 116.6, 121.6, 126.9, 128.3, 129.5,
3

A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
497
crystallized from heptane yielding 24b (125 mg, 49%) as yellowish
crystals, mp 217e220 ꢁC (decomp.); 1H NMR (CDCl3, 250 MHz)
(30), 89 (17), 78 (19). Anal. Calcd for C29H22N4O2: C, 75.97; H, 4.84;
N, 12.22. Found: C, 76.11; H, 5.01; N, 12.32.
d
ppm: 2.12 (s, 3H, Me), 2.39 (s, 3H, Me), 2.63 (d, J¼4.9 Hz, 3H,
NHeMe), 3.42 (s, 3H, N(10)eMe), 5.90e5.92 (m, 1H, NH), 6.27 (d,
J¼7.9 Hz, 2H, p-Tol), 6.70 (d, J¼7.9 Hz, 2H, p-Tol), 7.25 (d, J¼7.9 Hz,
2H, p-Tol), 7.39 (d, J¼7.9 Hz, 2H, p-Tol), 7.48 (s, 1H, H(3)), 7.70e7.82
(m, 2H, H(6) and H(7)), 8.02e8.08 (m, 2H, H(5) and H(8)); 13C NMR
4.17. Synthesis of 2-butyl-2,3-bis(phenylethynyl)-1,2-
dihydroquinoxaline 32
To a stirred solution of 2,3-bis(phenylethynyl)quinoxaline 2a
(165 mg, 0.50 mmol) in dry THF (5 mL) at ꢀ16 ꢁC under argon,
n-BuLi (1.6 M solution in hexane, 0.375 mL, 0.60 mmol) was added
gradually. Stirring was continued for 4 h at ꢀ18 to ꢀ16 ꢁC under
argon. The reaction mixture was then treated with one drop of
acetic acid and evaporated to dryness under reduced pressure. The
residue was purified by flash column chromatography on silica gel
(3ꢃ30 cm) using CH2Cl2 as the eluent. The first fraction recovered
was 2a (21.0 mg). The orange fraction with Rf (CH2Cl2) 0.3 gave 32.
Crystallization from heptane yielded compound 32 (45.0 mg, 23%)
(CDCl3, 62.9 MHz)
d ppm: 21.5, 21.9, 26.9, 28.0, 65.5, 127.0, 127.1,
129.0, 129.4, 129.5, 129.8, 129. 9, 130.0, 130.3, 130.6, 130.9, 132.3,
139.6, 140.3, 141.5, 143.4, 152.4, 155.8, 158.9, 159.5, 163.8, 164.6,
168.4; IR, cmꢀ1: 1651e1677 and 1716 (C]O), 3338 (NeH); UVevis,
lmax (log ), nm: 308 (4.43), 370 (4.57), 386 (4.59); MS m/z: 514
3
([M]þ, 100), 456 (62), 427 (70), 399 (25), 394 (26), 371 (42), 359
(19), 356 (53), 341 (29), 284 (48), 279 (23), 265 (20), 257 (54), 255
(61), 241 (35), 229 (43), 214 (22), 200 (15), 178 (42), 143 (25), 115
(28), 91 (25), 58 (77). Anal. Calcd for C32H26N4O3: C, 74.69; H, 5.09;
N, 10.89. Found: C, 74.88; H, 4.91; N, 11.02.
as orange crystals, mp 94e96 ꢁC; 1H NMR (CDCl3, 250 MHz)
d ppm:
0.94 (t, J¼7.2 Hz, 3H, Me), 1.34e1.49 (m, 2H, (CH2)2CH2Me),
1.52e1.80 (m, 2H, CH2CH2CH2Me), 2.01e2.13 (m, 1H, CH2C3H7),
2.19e2.31 (m, 1H, CH2C3H7), 4.32 (s, 1H, NH), 6.59e6.63 (m, 1H),
6.76e6.82 (m, 1H), 7.03e7.10 (m, 1H, Ph), 7.24e7.40 (m, 9H),
4.15. Synthesis of 1,10,3-trimethyl-40,7-di(p-tolyl)-10H-spiro
[cyclopenta[g]pteridine-8,30-pyridine]-2,20,4,60(1H,3H)-
tetraone 29
7.53e7.58 (m, 2H); 13C NMR (CDCl3, 62.9 MHz)
d ppm: 14.4, 23.2,
The reaction of 4 (210 mg, 0.50 mmol) with 1,3-dimethyl-
barbituric acid was carried out for 10 h in accordance with pro-
cedure described in Section 4.13. The evaporated reaction mixture
was purified by flash column chromatography on silica gel
(3ꢃ30 cm) using CH2Cl2/EtOH (100:1, v/v) as the eluent. The yel-
low fraction with Rf (CH2Cl2/EtOH, 100:1, v/v) 0.2 gave 29. The
crude product was crystallized from i-PrOH yielding 29 (39.0 mg,
15%) as yellow crystals, mp 297e300 ꢁC; 1H NMR (CDCl3,
26.5, 39.9, 55.1, 86.7, 87.3, 89.3, 93.8, 114.4, 119.9, 122.2, 122.8, 128.7,
128.9, 129.0, 129.9, 132.2, 132.8, 135.7, 145.8; IR, cmꢀ1: 2205 (C^C),
3215 (NeH); UVevis, lmax (log ), nm: 272 (4.18), 312 (4.04), 392
3
(3.67), end absorption up to 476 nm; MS m/z: 388 ([M]þ, 3), 332
(32), 331 (100, [MꢀC4H9]þ), 330 (9), 329 (11), 202 (6), 165 (11), 127
(10), 115 (5), 102 (10), 77 (17). Anal. Calcd for C28H24N2: C, 86.56; H,
6.23; N, 7.21. Found: C, 86.36; H, 6.35; N, 7.00.
250 MHz)
d ppm: 2.17 (s, 3H, Me), 2.34 (s, 3H, Me), 3.33 (s, 3H,
Acknowledgements
NeMe), 3.52 (s, 3H, NeMe), 3.63 (s, 3H, NeMe), 6.56 (d, J¼8.2 Hz,
2H, p-Tol), 6.67 (s, 1H, H(50)), 6.83 (d, J¼8.2 Hz, 2H, p-Tol), 7.16 (d,
J¼8.2 Hz, 2H, p-Tol), 7.34 (d, J¼8.2 Hz, 2H, p-Tol), 7.56 (s, 1H, H(6));
We gratefully acknowledge the Russian Foundation for Basic
Research for financial support of this research (grant No 11-03-
00079-a). We also thank Zoya Starikova, Anna Tkachuk and Oleg
Burov for assistance.
IR, cmꢀ1: 1667, 1683, 1708 and 1724 (C]O); UVevis, lmax (log
),
3
nm: 332 (4.17), 398 (4.04), end absorption up to 447 nm; MS m/z:
519 ([M]þ, 100), 462 (47), 434 (29), 346 (16), 334 (14), 322 (26),
307 (16), 293 (16), 278 (23), 264 (20), 217 (15), 189 (16), 175 (43),
166 (21), 159 (24), 146 (29), 132 (31), 119 (82), 115 (39), 91 (78), 83
(50). Anal. Calcd for C30H25N5O4: C, 69.35; H, 4.85; N, 13.48. Found:
C, 69.30; H, 5.07; N, 13.31.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2011.11.018.
4.16. Synthesis of 10-methyl-40,7-di(p-tolyl)-10H-spiro
References and notes
[cyclopenta[e]pyrido[3,2-b]pyrazine-8,30-pyridine]-20,60-dione 30
ꢁ
1. For review, see: Chinchilla, R.; Najera, C. Chem. Rev. 2007, 107, 874e922.
The reaction of 5 (179 mg, 0.50 mmol) with 1,3-dimethyl-
barbituric acid was carried out in accordance with procedure de-
scribed in Section 4.13. The evaporated reaction mixture was pu-
rified by flash column chromatography on silica gel (2.5ꢃ30 cm)
using CH2Cl2/Et2O (15:1, v/v) as the eluent. The first fraction re-
covered was 5 (50.0 mg). The yellow fraction with Rf (CH2Cl2/Et2O,
15:1, v/v) 0.1 gave 30. The crude product was crystallized from
heptane yielding 30 (55.0 mg, 24%) as off-white crystals, mp
2. For review, see: (a) Sakamoto, T.; Kondo, Y.; Yamanaka, H. Heterocycles 1988, 27,
2225e2249; (b) Larock, R. C. Pure Appl. Chem. 1999, 71, 1435e1442; (c) Li, J. J.;
Gribble, G. W. Palladium in Heterocyclic Chemistry. A Guide for the Synthetic
Chemist. Tetrahedron Organic Chemistry Series; Pergamon: Amsterdam, 2002;
€
Vol. 20; p 413; (d) Soderberg, B. C. G. Coord. Chem. Rev. 2002, 224, 171e243; (e)
Cacchi, S.; Fabrizi, G.; Parisi, L. M. Heterocycles 2002, 58, 667e682; (f) Zeni, G.;
Larock, R. C. Chem. Rev. 2004, 104, 2285e2309.
3. For review, see: (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed. Engl. 1991,
30, 1387e1530; (b) Wenk, H. H.; Winkler, M.; Sander, W. Angew. Chem., Int. Ed.
2003, 42, 502e528; (c) Basak, A.; Mandal, S.; Beg, S. S. Chem. Rev. 2003, 103,
4077e4094; (d) Rawat, D. S.; Zaleski, J. M. Synlett 2004, 0393e0421; (e) Kar, M.;
Basak, A. Chem. Rev. 2007, 107, 2861e2890.
207e210 ꢁC (decomp.); 1H NMR (CDCl3, 250 MHz)
d ppm: 2.12 (s,
3H, Me), 2.37 (s, 3H, Me), 3.34 (s, 3H, NeMe), 6.55 (d, J¼8.0 Hz, 2H,
p-Tol), 6.69 (s, 1H, H(50)), 6.76 (d, J¼8.0 Hz, 2H, p-Tol), 7.20 (d,
J¼8.0 Hz, 2H, p-Tol), 7.45 (d, J¼8.0 Hz, 2H, p-Tol), 7.66 (s, 1H, H(6)),
7.69 (dd, J¼8.2, 4.1 Hz, 1H, H(3)), 8.38 (dd, J¼8.2, 1.9 Hz, 1H, H(4)),
4. Jones, R. R.; Bergman, R. G. J. Am. Chem. Soc. 1972, 94, 660e661.
5. (a) Whitlock, H. W.; Sandvick, P. E.; Overman, L. E.; Reichardt, P. B. J. Org. Chem.
1969, 34, 879e886; (b) Whitlock, H. W.; Sandvick, P. E. J. Am. Chem. Soc. 1966,
88, 4525e4526; (c) Bradshaw, J. D.; Solooki, D.; Tessier, C. A.; Youngs, W. J. J. Am.
Chem. Soc. 1994, 116, 3177e3179.
8.97 (dd, J¼4.1, 1.9 Hz, 1H, H(2)); 13C NMR (CDCl3, 62.9 MHz)
d ppm:
€
6. (a) Kohig, B.; Pitsch, W.; Klein, M.; Vasold, R.; Prall, M.; Schreiner, P. R. J. Org.
Chem. 2001, 66, 1742e1746; (b) Scott, J. L.; Parkin, S. R.; Anthony, J. E. Synlett
2004, 0161e0164; (c) Kovalenko, S. V.; Peabody, S.; Manoharan, M.; Clark, R. J.;
Alabugin, I. V. Org. Lett. 2004, 6, 2457e2460; (d) Peabody, S. W.; Breiner, B.;
Kovalenko, S. V.; Patil, S.; Alabugin, I. V. Org. Biomol. Chem. 2005, 3, 218e221.
7. (a) Zhou, Q.; Carroll, P. J.; Swager, T. M. J. Org. Chem. 1994, 59, 1294e1301; (b)
Schreiner, P. R.; Prall, M.; Lutz, V. Angew. Chem., Int. Ed. 2003, 42, 5757e5760.
8. Lee, C.-Y.; Wu, M.-Y. Eur. J. Org. Chem. 2007, 3463e3467.
21.5, 21.9, 27.6, 65.3, 124.2, 125.9, 127.0, 127.5, 129.3, 129.7, 130.0,
130.6, 132.3, 138.3, 138.7, 140.2, 142.0, 149.6, 152.3, 153.7, 157.8,
159.9, 163.8, 164.7, 169.0; IR, cmꢀ1: 1676 and 1712 (C]O); UVevis,
lmax (log ), nm: 284 (4.29), 316 (4.30), 374 (4.57), end absorption
3
up to 410 nm; MS m/z: 458 ([M]þ, 12), 400 (30), 372 (23), 357 (26),
343 (10), 229 (11), 201 (36), 187 (21), 178 (100), 172 (83), 165 (22),
152 (10), 140 (11), 127 (13), 119 (17), 115 (34), 103 (12), 100 (10), 91
9. (a) Sugiyama, H.; Yamashita, K.; Nishi, M.; Saito, I. Tetrahedron Lett. 1992, 33,
515e518; (b) Magnus, P.; Eisenbeis, S. A. J. Am. Chem. Soc. 1993, 115,

498
A.V. Gulevskaya et al. / Tetrahedron 68 (2012) 488e498
12627e12628; (c) Wu, M.-J.; Lin, C.-F.; Chen, S.-H. Org. Lett. 1999, 1, 767e768;
(d) Wu, M.-J.; Lin, C.-F.; Lu, W.-D. J. Org. Chem. 2002, 67, 5907e5912; (e) Chen,
Z.-Y.; Wu, M.-J. Org. Lett. 2005, 7, 475e477.
13. (a) Guo, L.-N.; Duan, X.-H.; Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. J. Org. Chem. 2006, 71,
3325e3327; (b) Zang, D.; Liu, Z.; Yum, E. K.; Larock, R. C. J. Org. Chem. 2007, 72,
251e262; (c) Guo, L.-N.; Duan, X.-H.; Bi, H.-P.; Liu, X.-Y.; Liang, Y.-M. J. Org.
Chem. 2007, 72, 1538e1540.
14. Hu, J.; Wu, L.-Y.; Wang, X.-C.; Hu, Y.-Y.; Niu, Y.-N.; Liu, X.-Y.; Yang, S.; Liang, Y.-M.
Adv. Synth. Catal. 2010, 352, 351e356.
15. Khan, Z. A.; Wirth, T. Org. Lett. 2009, 11, 229e231.
10. (a) Lee, C.-Y.; Lin, C.-F.; Lee, J.-L.; Chiu, C.-C.; Lu, W.-D.; Wu, M.-J. J. Org. Chem.
2004, 69, 2106e2110; (b) Wu, M.-J.; Lee, C.-Y.; Lin, C.-F. Angew. Chem., Int. Ed.
2002, 41, 4077e4079; (c) Taduri, B. P.; Odedra, A.; Lung, C.-Y.; Liu, R.-S. Synthesis
2007, 2050e2054; (d) Chang, W.-R.; Lo, Y.-H.; Lee, C.-Y.; Wu, M.-J. Adv. Synth.
Catal. 2008, 350, 1248e1252; (e) Chen, C.-C.; Chin, L.-Y.; Yang, S.-C.; Wu, M.-J.
Org. Lett. 2010, 12, 5652e5655; (f) Hirano, K.; Inaba, Y.; Watanabe, T.; Oishi, S.;
Fujii, N.; Ohno, H. Adv. Synth. Catal. 2010, 352, 368e372; (g) Hirano, K.; Inaba, Y.;
Takahashi, N.; Shimano, M.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2011, 76,
1212e1227; (h) Miki, K.; Kuge, H.; Umeda, R.; Sonoda, M.; Tobe, Y. Synth.
Commun. 2011, 41, 1077e1087.
11. (a) Gulevskaya, A. V.; Dang, V. S.; Pozharskii, A. F. Russ. Chem. Bull. 2003, 52,
1403e1410; (b) Dang, V. S.; Gulevskaya, A. V.; Pozharskii, A. F.; Kotelevskaya, R.
V. Chem. Heterocycl. Comp. 2005, 41, 124e135; (c) Gulevskaya, A. V.; Dang, V. S.;
Pozharskii, A. F. J. Heterocycl. Chem. 2005, 42, 413e419; (d) Gulevskaya, A. V.;
Dang, V. S.; Tyaglivy, A. S.; Pozharskii, A. F.; Kazheva, O. N.; Chekhlov, A. N.;
Dyachenko, O. A. Tetrahedron 2010, 66, 146e151.
16. Zang, D.; Yum, E. K.; Liu, Z.; Larock, R. C. Org. Lett. 2005, 7, 4963e4966.
_
€
17. (a) Meusel, M.; Ambrozak, A.; Hecker, T. K.; Gutschow, M. J. Org. Chem. 2002, 68,
_
€
4684e4692; (b) Ambrozak, A.; Gutschow, M. J. Heterocycl. Chem. 2006, 43,
807e811.
18. Krasnov, K. A.; Kartsev, V. G.; Khrustalev, V. N. Heterocycles 2007, 71, 13e18.
19. Astruc, D.; Djankovitch, L.; Aranzaes, J. R. ARKIVOC 2006, iv, 173e188.
20. Bordwell pKa Table (Acidity in DMSO)(http://www.chem.wisc.edu/areas/reich/
pkatable/).
ꢁ
21. Unciti-Broceta, A.; Pineda-de-las-Infantas, M. J.; Díaz-Mochon, J. J.; Ro-
magnoli, R.; Baraldi, P. G.; Gallo, M. F.; Espinosa, F. J. Org. Chem. 2005, 70,
2878e2880.
22. (a) Heckel, A.; Pfleiderer, W. Helv. Chim. Acta 1986, 69, 708e717; (b) Blike, F. F.;
Godt, H. C. J. Am. Chem. Soc. 1954, 76, 2798e2800.
12. Ames, D. E.; Brohi, M. I. J. Chem. Soc., Perkin Trans. 2 1980, 1384e1389.