Copper-Catalyzed Reaction of Secondary Propargylamines with Ethyl Buta-2,3-dienoate for the Synthesis of 1,6-Dihydropyridines

Article abstract of DOI:10.1002/ejoc.201801227

A copper(I) bromide-catalyzed reaction of A³-coupling-derived propargylamines with ethyl buta-2,3-dienoate for the fast assembly of a 1,6-dihydropyridine core is described. The developed protocol was tested on a variety of secondary propargylamines and the possibility of a one-pot synthesis of 1,6-dihydropyridine through the A³-coupling and subsequent ethyl buta-2,3-dienoate incorporation was investigated.

Full text of DOI:10.1002/ejoc.201801227

A Journal of
Accepted Article
Title: Copper-catalyzed reaction of secondary propargylamines with
ethyl buta-2,3-dienoate for the synthesis of 1,6-dihydropyridines
Authors: Chao Liu, Gaigai Wang, Yuqing Wang, Olga P. Pereshivko,
and Vsevolod A. Peshkov
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201801227
Link to VoR: http://dx.doi.org/10.1002/ejoc.201801227
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10.1002/ejoc.201801227
European Journal of Organic Chemistry
COMMUNICATION
Copper-catalyzed reaction of secondary propargylamines with
ethyl buta-2,3-dienoate for the synthesis of 1,6-dihydropyridines
Chao Liu,[a] Gaigai Wang,[a] Yuqing Wang,[a] Olga P. Pereshivko*[a] and Vsevolod A. Peshkov*[a],[b]
Abstract: A copper(I) bromide-catalyzed reaction of A3-coupling-
derived propargylamines with ethyl buta-2,3-dienoate for the fast
assembly of a 1,6-dihydropyridine core is described. The developed
protocol was tested on a variety of secondary propargylamines and
the possibility of a one-pot synthesis of 1,6-dihydropyridine through
the A3-coupling and subsequent ethyl buta-2,3-dienoate
incorporation was investigated.
component coupling of amines, aldehydes and alkynes (A3-
coupling) that has been recently emerged as a major tool for the
generation of various classes of propargylamines.[11]
Consecutively, we have prepared a number of secondary
propargylamines 1 by the copper(I) bromide-catalyzed A3-
coupling of primary amines 8, aldehydes 9 and terminal alkynes
10 (Scheme 2).[12] Next, we attempted to react propargylamine
1a with various electron-deficient alkynes 11a-c aiming to
generate 1,5-enynes 2 (Scheme 3). Using ethyl propiolate (11a)
and diethyl acetylenedicarboxylate (11b), 1,5-enynes 2a and 2b
were obtained in 75% and 98%, respectively. In contrast,
treatment of 1a with ethyl but-2-ynoate (11c) failed to yield the
expected enyne 2c, which could be attributed to a lower
electrophilicity of 11c compared to 11a and 11b. Nevertheless,
both 2a and 2b could be successfully converted into
corresponding dihydropyridines 3a and 3b with the aid of
cationic copper(I) complex [Cu(MeCN)4]PF6 following a modified
Oguri’s protocol (Scheme 3).
Introduction
Propargylic compounds are convenient building blocks for the
generation of a large variety of heterocyclic molecules.[1] For
example, 1,5-enynes 2 derived from propargylamines or amides
1 are known to undergo 6-endo-dig cycloisomerizations into
dihydropyridines (DHPs) 3 under rhodium,[2] gold,[3] silver,[4]
copper[5] and zinc[6] catalysis (Scheme 1). Furthermore, for the
substrates derived from terminal primary propargylamines, the
initially obtained dihydropyridines 3 could be in situ oxidized into
pyridines 4.[4b] Analogously to metal-catalyzed transformations,
electrophile-mediated cyclizations of 2 occur in 6-endo-dig
fashion producing dihydropyridines 4 (Scheme 1).[7,8] In contrast,
base-mediated transformations of 1,5-enynes
2 selectively
deliver isomeric pyrroles 6 or 7 depending on the applied
reaction conditions (Scheme 1).[5a,9,10]
Results and Discussion
Despite that the above procedures collectively cover broad
substrate scope towards divergent products, most of them suffer
from various limitations. In particular, the most common
drawbacks for the reactions leading to dihydropyridines 3
include the necessity to use expensive catalysts as well as
tedious preparation of starting materials that imposes additional
restrictions on the substrate’s substitution pattern. For example,
recent copper-catalyzed protocol of Oguri and coworkers[4a] was
mainly tested for the terminal propargylenamines
2
unsubstituted at the propargylic position. We decided to address
this issue by taking an advantage of a metal-catalyzed three-
[a]
[b]
C. Liu, G. Wang, Y. Wang, Dr. O. P. Pereshivko and Dr. V. A.
Peshkov
College of Chemistry, Chemical Engineering and Materials Science,
Soochow University,
Dushu Lake Campus, Suzhou 215123, P. R. China
E-mails: olga@suda.edu.cn, vsevolod@suda.edu.cn
Dr. V. A. Peshkov
Scheme 1. Cyclizations of 1,5-enynes 2.
Department of Chemistry, School of Science and Technology,
Nazarbayev University,
53 Kabanbay Batyr Ave, Block 7,
Astana 010000, Republic of Kazakhstan
E-mail: vsevolod.peshkov@nu.edu.kz
Scheme 2. Synthesis of starting propargylamines 1.
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201801227
European Journal of Organic Chemistry
COMMUNICATION
Scheme 3. Two-step synthesis of dihydropyridines 3a and 3b based on Oguri’s Cu-catalyzed protocol.
Table 1. Screening the conditions for the reaction of propargylamine 1a and ethyl buta-2,3-dienoate (12)[a]
Entry
X, equiv
Catalyst, mol%
Base
Solvent
Dilution
Temp., °C
Time, h[b]
Conversion
Yield,[c]
%
of 1a,[c]
%
3c
2c
1
1.2
1.2
1.2
1.2
1.2
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
-
-
toluene
toluene
DCM
0.2 M
0.2 M
0.1 M
0.1 M
0.2 M
0.2 M
0.2 M
0.2 M
0.2 M
0.2 M
0.2 M
0.4 M
0.4 M
0.4 M
0.4 M
110
90
rt
40 min
29
-
27
43
59
37
-
2
-
-
40
90
7
3
[Cu(MeCN)4]PF6, 10
[Cu(MeCN)4]PF6, 10
Cu(OTf)2, 15
Cu(OTf)2, 10
AgOTf, 10
CuI, 10
-
2
84
9
4
-
DCM
rt
6
90
30
32
33
38
39
62
45
51
66
74
5
-
toluene
toluene
toluene
toluene
toluene
1.4-dioxane
DMF
110
90
90
90
90
90
90
90
90
90
90
40 min
95
6
-
2
2
2
2
2
2
2
2
2
2
100
81
-
7
-
-
8
-
100
100
100
100
100
100
100
100
33
-
9
CuBr, 10
CuBr, 10
CuBr, 10
CuBr, 10
CuBr, 10
CuBr, 10
-
-
10
11
12
13[d]
14[d]
15[d]
-
-
-
-
-
toluene
toluene
toluene
toluene
-
Et3N
-
Pyridine
Pyridine
78 (76)[e]
3
-
82
[a] All reactions were conducted on 0.2 mmol scale. [b] The reaction time is in hours, unless otherwise indicated. [c] Determined by 1H NMR using 3,4,5-
trimethoxybenzaldehyde as an internal standard. [d] The reactions were conducted in the presence of 1 equiv of base. [e] Isolated yield for a 0.5 mmol scale
reaction is given in parenthesis.
Scheme 4. Stepwise synthesis of dihydropyridine 3c.
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10.1002/ejoc.201801227
European Journal of Organic Chemistry
COMMUNICATION
It is well known, that secondary propargylamines can
undergo additions to a number of heteroallenes allowing to
assemble a variety of heterocycles through the subsequent
heterocyclizations involving triple bond. Using toluene as
reaction media at the temperature of 110 or 90°C,
dihydropyridine 3c was obtained with the yields ranging from
32% to 38% (entries 5-7). Consequently, we have turned our
attention to copper(I) iodide and copper(I) bromide that were
also reported as efficient triple bond activators.[18] While
copper(I) iodide produced a mixture of 2c and 3c (entry 8),
copper(I) bromide delivered dihydropyridine 3c in a 62% yield as
a sole reaction product (entry 9). Changing toluene to other
solvents led to decreased yield of 3c (entries 10 and 11), while
lowering toluene’s volume resulted in a small improvement
(entry 12). Finally, introducing 1 equiv of a mild organic base led
to another substantial upgrade of the reaction outcome allowing
to obtain 3c in up to 76% isolated yield (entries 13 and 14). To
investigate the role of base, we conducted a control experiment
in the absence of copper catalyst (entry 15). This resulted in a
complete conversion of propargylamine 1a into 1,5-enyne 2c
underlying a beneficial influence of base on the addition of 1a to
buta-2,3-dienoate (12).
transition
metal-catalyzed
or
electrophile-mediated
cyclizations.[13-15] Considering this, we decided to investigate an
addition of propargylamine 1a to ethyl buta-2,3-dienoate (12) in
an attempt to overcome the limitation arisen from the inability of
former to react with electron-deficient alkyne 11c (Table 1). We
were pleased to find that buta-2,3-dienoate (12) turned out to be
a stronger electrophile than ethyl but-2-ynoate (11c). However,
reacting 1a with 12 in toluene at 110°C for 40 min resulted in
only a poor conversion of 1a, yielding 1,5-enyne 2c in only 27%
(Table 1, entry 1). Conducting the reaction at 90°C over
extended time of 40 h led to an improved conversion, producing
1,5-enyne 2c along with corresponding dihydropyridine 3c in
43% and 7% yield, respectively (entry 2). Encouraged by this
result, we decided to evaluate the reaction of 1a and 12 in the
presence of various catalysts aiming for the direct synthesis of
dihydropyridine 3c. Initially, we have attempted to utilize cationic
tetrakis(acetonitrile)copper(I) hexafluorophosphate complex.
Carrying out the reactions in DCM at rt delivered dihydropyridine
3c in up to 30% yield albeit in a mixture with uncyclized enyne
2c and unreacted propargylamine 1a (entries 3 and 4). Next, we
decided to evaluate copper(II)[16] and silver(I)[17] triflates that
Interestingly, the copper(I) bromide/pyridine-catalyzed
conditions found above turned out to be unsuitable for the
stepwise synthesis of 3c. When the mixture of 1,5-enyne 2c and
dihydropyridine 3c obtained by the copper(I) iodide-catalyzed
were proved to be promising catalysts in
a number of
Scheme 5. Copper-catalyzed synthesis of dihydropyridines 3 from secondary propargylamines 1 and ethyl buta-2,3-dienoate (12).
Scheme 6. One-pot A3-coupling/ethyl buta-2,3-dienoate addition for the synthesis of dihydropyridines 3.
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10.1002/ejoc.201801227
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COMMUNICATION
NMR (100 MHz) spectra were recorded using a Bruker Avance III HD
reaction (Table 1, entry 8) was resubjected to the copper(I)
bromide-catalyzed protocol in the presence of pyridine base no
full conversion of 2c into 3c could be achieved (Scheme 4,
conditions A). In contrast, treating the same mixture with cationic
1
instrument. The H and 13C chemical shifts are reported relative to TMS
using the residual CDCl3 signal as internal reference. HRMS were
performed on a Bruker micrOTF-Q III.
[Cu(MeCN)4]PF6
catalyst
could
effectively
drive the
General
procedure
for
copper-catalyzed
synthesis
of
cycloisomerization of 2c to completion (Scheme 4, conditions B).
To sum up, our procedure allows to efficiently assemble
dihydropyridines 3 directly from propargylamines 1 through a
one-pot addition to buta-2,3-dienoate (12) and subsequent
cycloisomerization while Oguri’s protocol appears to be a better
choice for accessing 3 from premade 1,5-enynes 2.
dihydropyridines 3 from secondary propargylamines 1 and ethyl
buta-2,3-dienoate (12)
Propargylamine 1 (0.8 mmol) was places in a screw cap vial followed by
addition of toluene (1 mL), ethyl buta-2,3-dienoate 12 (135 mg, 1.2 mmol),
CuBr (11.5, 0.08 mmol), and pyridine (63 mg, 0.8 mmol). The resulting
mixture was flashed with argon, sealed and stirred at 90°C for 2 h. Upon
completion of this time, the mixture was diluted with ethyl acetate and
transferred to the round bottom flask. Then the silica gel was added and
the mixture was concentrated under reduced pressure. Column
chromatography on silica gel using petroleum ether-ethyl acetate
(49:19:1) as eluent provided dihydropyridine 3.
Scheme 5 summarizes the scope of our new copper-
catalyzed protocol for the direct synthesis of 1,6-
dihydropyridines 3 from secondary propargylamines 1 and ethyl
buta-2,3-dienoate (12). Examining the substrates substituted
differently at the propargylic position, it can be concluded that
the aliphatic substituents give slightly better results as compared
to benzylic and aromatic (Scheme 5, products 3c and 3d versus
3e and 3f). As for the nitrogen atom, both alkyl and benzyl
substituted substrates produced dihydropyridines 3d,g,h in
consistently good yields. With regard to the triple bond, both
aromatic and heteroaromatic substituents were well tolerated
allowing to obtain products 3i-p in up to 88% yield. Substrates
bearing electron-deficient aromatic groups on the triple bond
produced dihydropyridines 3j and 3n in moderate yields of 52%
and 62%, respectively. Utilizing aliphatic propargylamine led to
unclean reaction delivering dihydropyridine 3q in a mixture with
unidentified impurities.
Acknowledgements
This work was supported by the start-up fund from Soochow
University (grant Q410900714), National Natural Science
Foundation of China (grant 21650110445), Natural Science
Foundation of Jiangsu Province of China (grants BK20160310
and BK20150317), the Priority Academic Program Development
of Jiangsu Higher Education Institutions (PAPD) and the Project
of Scientific and Technologic Infrastructure of Suzhou (grant
SZS201708).
Finally, we have explored the possibility of merging A3-
coupling and ethyl buta-2,3-dienoate incorporation in a two-step
one-pot process, since both of these transformations are
operated under copper(I) bromide catalysis. As a result of these
efforts, 1,6-dihydropyridines 3d and 3n were prepared in 45%
and 55% yields, starting directly from amines 8, aldehydes 9 and
alkynes 10 with no need in isolating intermediate
propargylamines 1 (Scheme 6).
Keywords: allenes • copper • cyclization • 1,6-dihydropyridines •
propargylamines
[1]
For focused reviews on the synthesis of heterocycles from propargylic
precursors, see: a) W. Jia-Jie, Y. Zhu, Z.-P. Zhan Asian J. Org. Chem.
2012, 1, 108–129; b) K. Lauder, A. Toscani, N. Scalacci, D. Castagnolo
Chem. Rev. 2017, 117, 14091-14200; c) S. Arshadi, E. Vessally, L.
Edjlali, E. Ghorbani-Kalhor, R. Hosseinzadeh-Khanmiri RSC Adv. 2017,
7, 13198–13211; d) B. Zhang, T. Wang Asian J. Org. Chem. 2018, doi:
10.1002/ajoc.201800324.
Conclusions
[2]
[3]
H. Kim, C. Lee J. Am. Chem. Soc. 2006, 128, 6336–6337.
a) E. C. Minnihan, S. L. Colletti, F. D. Toste, H. C. Shen J. Org. Chem.
2007, 72, 6287–6289; b) H. Imase, K. Noguchi, M. Hirano, K. Tanaka
Org. Lett. 2008, 10, 3563–3566; c) S. Undeela, S. T., J. B. Nanubolu, K.
K. Singarapu, R. S. Menon Chem. Commun. 2015, 51, 13748–13751;
d) X. Zhang, X.-M. Xu, L. Zhao, J. You, J. Zhu, M.-X. Wang,
Tetrahedron Lett. 2015, 56, 3898–3901; e) J. Mikušek, P. Matouš, E.
Matoušová, M. Janoušek, J. Kuneš, M. Pour Adv. Synth. Catal. 2016,
358, 2912–2922; f) K. Goutham, V. Kadiyala, B. Sridhar, G. V.
Karunakar Org. Biomol. Chem. 2017, 15, 7813-7818.
In summary, we have elaborated a copper-catalyzed protocol for
the synthesis of 1,6-dihydropyridines that involves the addition of
secondary propargylamines to ethyl buta-2,3-dienoate and
subsequent cycloisomerization of resulting 1,5-enynes. This
novel process is complementary to the known syntheses of
pyridine derivatives from either premade 1,5-enynes[2,3,4a,5,7,8] or
from those that are generated in situ from propargylamines and
electron-deficient alkynes.[4b,6]
[4]
[5]
a) M. A. P. Martins, M. Rossatto, C. P. Frizzo, E. Scapin, L. Buriol, N.
Zanatta, H. G. Bonacorso Tetrahedron Lett. 2013, 54, 847–849; b) T. A.
Nizami, R. Hua Tetrahedron 2017, 73, 6080–6084.
a) S. Cacchi, G. Fabrizi, E. Filisti Org. Lett. 2008, 10, 2629–2632; b) H.
Mizoguchi, R. Watanabe, S. Minami, H. Oikawaa, H. Oguri Org. Biomol.
Chem. 2015, 13, 5955–5963.
Experimental Section
General remarks
[6]
[7]
S. A. Shehzadi, C. M. L. Vande Velde, A. Saeed, K. A. Tehrani Org.
Biomol. Chem. 2018, 16, 3241–3247.
Unless otherwise specified, the starting materials and solvents were
purchased from commercial sources and used as received. Melting
points were measured using INESA WRR apparatus. Infrared (FT-IR)
spectra were recorded neat on a Bruker Vertex 70. 1H (400 MHz), 13C
X. Xin, D. Wang, F. Wu, X. Li, B. Wan J. Org. Chem. 2013, 78,
4065−4074.
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[8]
[9]
For the synthesis of pyridines through the one-pot iodocyclization /
oxidation, see: S. Karabiyikoglu, Y. Kelgokmen, M. Zora Tetrahedron
2015, 71, 4324–4333.
Org. Chem. 2017, 1063–1069; c) O. P. Pereshivko, V. A. Peshkov, A. A.
Peshkov, J. Jacobs, L. Van Meervelt, E. V. Van der Eycken Org.
Biomol. Chem. 2014, 12, 1741–1750.
a) X. Xin, D. Wang, X. Li, B. Wan Angew. Chem. Int. Ed. 2012, 51,
1693–1697; b) J. Weng, Y. Chen, B. Yue, M. Xu, H. Jin Eur. J. Org.
Chem. 2015, 3164–3170.
[15] For recent examples from other groups, see: a) K.-H. Kwon, C. M.
Serrano, M. Koch, L. R. Barrows, R. E. Looper Org. Lett. 2014, 16,
6048–6051; b) P. Fedoseev, N. Sharma, R. Khunt, D. S. Ermolat’ev, E.
V. Van der Eycken RSC Adv. 2016, 6, 75202–75206; c) B. Xu, B. Peng,
B. Cai, S. Wang, X. Wang, X. Lv Adv. Synth. Catal. 2016, 358, 653–
660; d) A. Ranjan, A. S. Deore, S. G. Yerande, D. H. Dethe Eur. J. Org.
Chem. 2017, 4130–4139; e) N. Scalacci, C. Pelloja, M. Radi, D.
Castagnolo Synlett 2016, 1883–1887; f) A. La-Venia, N. S. Medran, V.
Krchňák, S. A. Testero ACS Comb. Sci. 2016, 18, 482–489; g) S.
Huang, Y. Shao, R. Liu, X. Zhou Tetrahedron 2015, 71, 4219–4226; h)
B.-B. Cheng, B. Yu, C.-W. Hu RSC Adv. 2016, 6, 87179–87187; i) T.
Ishida, R. Kobayashi, T. Yamada Org. Lett. 2014, 16, 2430–2433; j) F.
Inagaki, K. Maeda, K. Nakazawa, C. Mukai, Eur. J. Org. Chem. 2018,
2972–2976.
[10] In certain cases, metal-catalyzed transformations of 1,5-enynes 2 also
produce pyrroles 6 or 7, see ref.[4b] and A. Saito, T. Konishi, Y.
Hanzawa Org. Lett. 2010, 12, 372–374.
[11] For reviews, see: a) W.-J. Yoo, L. Zhao, C.-J. Li Aldrichimica Acta 2011,
44, 43–51; b) L. Zani, C. Bolm Chem. Commun. 2006, 4263–4275; c)
C.-J. Li Acc. Chem. Res. 2010, 43, 581–590; d) V. V. Kouznetsov, L. Y.
Vargas Méndez Synthesis 2008, 491–506; e) V. A. Peshkov, O. P.
Pereshivko, E. V. Van der Eycken Chem. Soc. Rev. 2012, 41, 3790–
3807.
[12] For the synthesis of secondary propargylamines through the A3-
coupling, see: a) J. B. Bariwal, D. S. Ermolat'ev, E. V. Van der Eycken
Chem. Eur. J. 2010, 16, 3281–3284; b) Y. Lu, T. C. Johnstone, B. A.
Arndtsen J. Am. Chem. Soc. 2009, 131, 11284–11285; c) S. A.
Shehzadi, A. Saeed, F. Lemière, B. U. W. Maes, K. Abbaspour Tehrani
Eur. J. Org. Chem. 2018, 78–88.
[16] a) N. Sakai, N. Uchida, T. Konakahara Tetrahedron Lett. 2008, 49,
3437–3440; b) D. Chernyak, N. Chernyak, V. Gevorgyan Adv. Synth.
Catal. 2010, 352, 961–966.
[17] a) V. A. Peshkov, O. P. Pereshivko, S. Sharma, T. Meganathan, V. S.
Parmar, D. S. Ermolat’ev, E. V. Van der Eycken J. Org. Chem. 2011,
76, 5867–5872; b) O. P. Pereshivko, V. A. Peshkov, J. Jacobs, L. Van
Meervelt, E. V. Van der Eycken Adv. Synth. Catal. 2013, 355, 781–789;
c) X. Zhou, Z. Jiang, L. Xue, P. Lu, Y. Wang Eur. J. Org. Chem. 2015,
5789–5797.
[13] For reviews, see: a) V. A. Peshkov, O. P. Pereshivko, A. A. Nechaev, A.
A. Peshkov, E. V. Van der Eycken Chem. Soc. Rev. 2018, 47, 3861–
3898; b) S. Arshadi, E. Vessally, M. Sobati, A. Hosseinian, A.
Bekhradnia J. CO2 Util. 2017, 19, 120–129; c) Z. Zhang, J.-H. Ye, D.-S.
Wu,
Y.-Q.
Zhou,
D.-G.
Yu
Chem.
Asian
J.
2018,
10.1002/asia.201800672.
[18] a) N. T. Patil, V. S. Raut J. Org. Chem. 2010, 75, 6961–6964; b) Y.
Ohta, H. Chiba, S. Oishi, N. Fujii, H. Ohno J. Org. Chem. 2009, 74,
7052–7058.
[14] For recent examples from our group, see: a) G. Wang, C. Liu, B. Li, Y.
Wang, K. Van Hecke, E. V. Van der Eycken, O. P. Pereshivko, V. A.
Peshkov Tetrahedron 2017, 73, 6372–6380; b) A. A. Nechaev, A. A.
Peshkov, K. Van Hecke, V. A. Peshkov, E. V. Van der Eycken Eur. J.
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COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
1,6-Dihydropyridines
Chao Liu, Gaigai Wang, Yuqing Wang,
Olga P. Pereshivko,* Vsevolod A.
Peshkov*
Page No. – Page No.
Copper-catalyzed reaction of
secondary propargylamines with ethyl
buta-2,3-dienoate for the synthesis of
1,6-dihydropyridines
A copper(I) bromide-catalysed reaction of A3-coupling-derived propargylamines with
ethyl buta-2,3-dienoate for the fast assembly of a 1,6-dihydropyridine core is
described. The possibility of a one-pot synthesis of 1,6-dihydropyridine through the
A3-coupling and subsequent ethyl buta-2,3-dienoate incorporation was investigated.
This article is protected by copyright. All rights reserved.