Consecutive Three-Component Coupling-Addition Synthesis of β-Amino Enoates and 3-Hydroxypyrazoles via Ethyl 3-Arylpropiolates

Article abstract of DOI:10.1002/ejoc.202000823

Two consecutive three-component syntheses furnishing β-amino enoates or 3-hydroxypyrazoles based upon the Sonogashira alkynylation of aryl iodides and ethyl propiolate were established in mostly excellent yields. The ethyl 3-arylpropiolate intermediates are Michael systems which are suited for concatenation with conjugate addition or cyclocondensation giving access to libraries of 21 different β-amino enoates and 17 different 3-hydroxypyrazoles. The rotational barrier of β-pyrrolidino enoates was assessed by studying the coalescence of pyrrolidinyl protons in VT-NMR spectra of electronically different substituted derivatives showing that the electronic substituent effect on the aryl group does not affect the height of the rotational barrier. This indicates that the substituents are essentially oriented orthogonally to the plane of the β-pyrrolidino enoates.

Full text of DOI:10.1002/ejoc.202000823

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Consecutive Three-component Coupling-Addition Synthesis
of β‑Amino Enoates and 3-Hydroxypyrazoles via Ethyl
3‑Arylpropiolates
Authors: Jonas Niedballa, Guido J. Reiss, and Thomas J. J. Müller
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
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content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000823
Link to VoR: https://doi.org/10.1002/ejoc.202000823
01/2020

10.1002/ejoc.202000823
European Journal of Organic Chemistry
COMMUNICATION
Consecutive Three-component Coupling-Addition Synthesis of
-Amino Enoates and 3-Hydroxypyrazoles via Ethyl
3-Arylpropiolates
Jonas Niedballa,[a] Guido J. Reiss,[b] and Thomas J. J. Müller*[a]
Dedication ((optional))
Abstract: Two consecutive three-component syntheses furnishing
-amino enoates or 3-hydroxypyrazoles based upon the Sonogashira
alkynylation of aryl iodides and ethyl propiolate were established in
mostly excellent yields. The ethyl 3-arylpropiolate intermediates are
Michael systems and excellently suited for concatenation with
conjugate addition or cyclocondensation giving access to libraries of
21 different -amino enoates and 17 different 3-hydroxypyrazoles.
The rotational barrier of -pyrrolidino enoates was assessed by
studying the coalescence of pyrrolidinyl protons in VT-NMR spectra
of electronically different substituted derivatives showing that the
electronic substituent effect on the aryl group does not affect the
height of the rotational barrier. This indicates that the substituents are
essentially oriented orthogonally to the plane of the -pyrrolidino
enoates.
an entry to consecutive multicomponent syntheses of many
classes of privileged heterocycles.[4] Furthermore, this concept
was successfully expanded to the synthesis of functional
chromophores.[5]
Substituted 3-hydroxypyrazoles rank as a prominent structural
motif in heterocyclic chemistry; particularly as important
constituents of biologically active compounds.[6] Especially
syntheses of these structures are interesting due to their
analgesic, anti-pyretic and anti-inflammatory effects. Also
pesticides based upon this structural motif have been shown to
be effective in agrochemical crop protection.[7] Beyond application
in life sciences 3-hydroxypyrazoles and the tautomeric
pyrazolones, as pyrazoles, receive considerable attention as
ligand substructures in coordination and supramolecular
chemistry.[8]
Likewise, -amino enoates are particularly interesting structural
motifs which can transformed by enantioselective reduction to -
amino acid derivatives.[9] The latter are important chiral building
blocks[10] with considerable interest in pharmaceutical
chemistry.[11] Besides their biological activity,[12] e.g. as
neuropsychotropic agents,[13] they also found application as
organocatalysts in asymmetric synthesis.[14] -Enamino acid
derivatives in their own right were readily transformed into 2-
pyridones by aza-annulation with acroyl chloride derivatives.[15]
The classic approach to 3-hydroxy pyrazoles[16] and -amino
enoates[17] relies on (cyclo)condensation of -ketoesters and
hydrazines. However, carbonyl condensations often require
activation of the carbonyl group, which can be circumvented by
replacing 1,3-diketones with alkynones as their synthetic
equivalents,[4] now reacting as Michael systems. Propiolates are
likewise synthetic equivalents of -ketoesters. Indeed, a concise
two step sequence of 3-hydroxypyrazoles was applied to
synthesize secretase inhibitors to suppress or possibly reverse
the progression of Alzheimer's disease.[18]
Introduction
Multicomponent reactions (MCR) are
a reactivity based
concept,[1] where more than two bonds are formed from more than
two compounds in a one-pot reaction. This implies a plethora of
advantages in sustainability and selectivity, whereby these
reactions appear to be impeccable for the construction of
structures with high diversity, in particular, biologically active
molecules.[2] The vast majority of these compounds are
heterocycles and, therefore, highly efficient and efficacious
concise syntheses, such as MCR, are highly demanded.
Transition metal catalyzed processes promise a particularly
attractive entry to MCR synthesis of heterocycles with selective
transformations and tolerance of various reactive and decorative
functionalities,[3] in particular for biologically interesting uracil
analogues.[3b] In recent years we have developed and explored
the concept of catalytic generation of alkynoyl intermediates as
Previously, we reported a copper-catalyzed carboxylation of
terminal alkynes furnishing methyl 3-aryl propiolates as
intermediates, which were transformed in sense of a consecutive
one-pot synthesis into 3-hydroxy pyrazoles by concluding Michael
addition-cyclocondensation (Scheme 1A).[19] Also just recently,
we reported a straightforward and highly efficient access to ethyl
3-aryl propiolates by Sonogashira coupling of aryl iodides and
ethyl propiolate as a three-carbon building block and coupling
partner.[20] It has to be emphasized that ethyl propiolate is far from
being a seemingly simple substrate in catalytic alkynylations due
to its sluggish reaction with aryl halides,[21] its volatility, and its
inherent propensity to undergo oligomerization under basic
conditions. Here, we communicate the conception of consecutive
three-component syntheses of 3-hydroxy pyrazoles and -amino
[a]
M. Sc. Jonas Niedballa, Prof. Dr. T. J. J. Müller
Department Institut für Organische Chemie und Makromolekulare
Chemie
Heinrich-Heine-Universität Düsseldorf
Universitätsstraße 1, D-40225 Düsseldorf, Germany
E-mail: ThomasJJ.Mueller@uni-duesseldorf.de
Homepage: www.orgchem.hhu.de
[b]
Dr. Guido J. Reiss
Institut für Anorganische Chemie und Strukturchemie, Heinrich-
Heine-Universität Düsseldorf, Universitätsstraße 1, D-40225
Düsseldorf, Germany
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000823
European Journal of Organic Chemistry
COMMUNICATION
enoates by virtue of catalytically generated ethyl 3-aryl
propiolates in a one-pot fashion (Scheme 1B).
sense of
a
consecutive three-component coupling-Michael
addition sequence starting from aryl iodides 1, ethyl propiolate (2),
and amines 4 to give after flash chromatography 21 examples of
the -amino enoates 5 in 33-96% yield (Scheme 3).
Table 1. Optimization of consecutive three-component coupling-Michael
addition synthesis of ethyl -pyrrolidino 3-aryl enoates 5a and 5b.
Entry
Aryl iodide 1
Pyrrolidine
4 [equivs]
1.5
-Amino enoate 5
1
2
3
4
5
1a (aryl = Ph)
5a (aryl = Ph, 84%)
5a (89%)
1a
1.1
1a
1.0
5a (86%)
1b (aryl = p-NCC6H4)
1.5
5b (aryl = p-NCC6H4, 63%)
5b (64%)
Scheme 1. One-pot synthesis of 3-hydroxypyrazoles via carboxylative
alkynylation[19] and one-pot sequences to 3-hydroxypyrazoles and -amino
enoates via ethyl propiolation of aryl iodides.
1b
1.0
The structure of all compounds were unambiguously assigned by
1H and 13C NMR spectroscopy and mass spectrometry, the
elemental composition was determined by HRMS or combustion
analyses.
Results and Discussion
The Michael addition of secondary amines to ethyl 3-aryl
propiolates forming -amino 3-aryl enoates is known,[22] however,
to the best of our knowledge a diversity-oriented consecutive one-
pot process starting from aryl halides and alkyl propiolate has
never been reported. Therefore, we set out to optimize the
reported Sonogashira coupling of aryl iodides (1) and ethyl
propiolate (2)[20] in DME as a solvent. Iodo benzene (1a) was
chosen as a model substrate to give phenyl propiolate 3a
(Scheme 2, for details, see Supp Inf chpt. 2).
From product formation and analyses, it can be seen that aryl
substituents stemming from the aryl iodides 1 span the full scope
from electron-poor (5b, 5n, 5q) to electron rich (5c, 5k). In
addition, meta- (5d) and ortho-substitution (5l, 5o, 5p) are
accessible as well as heteroaromatic derivatives (5m). A slight
steric effect of ortho-substituents becomes apparent, as the
methyl group (5l, 39%) tends to hamper the Michael addition in
the adjacent -position of the 3-aryl propiolate in comparison to
methoxy (5o, 78%), and chloro (5p, 67%) under otherwise
identical conditions for the process and workup.
Also the amines 4 can be varied in a broad range. Secondary
cyclic amines, such as pyrrolidine, piperidine and azepane allow
accessing derivatives with 5-, 6- and 7-membered rings (5a, 5f,
5h). Morpholine (5e) as well as methyl L-prolinate (5i, 5j) can be
applied as well. While using methanol as a co-solvent in the
Michael addition, the ethyl ester transesterifies to the methyl ester
in large parts. Moreover, a mixture of E/Z isomers is obtained.
Using ethanol in the Michael step, the methyl ester is mainly
transesterified (5i). However, omitting ethanol as a co-solvent
allows maintaining the introduced ester in place (5j). Primary
amines can be introduced in slightly lower yields (5s, 5t, 5u).
Finally, also piperazine takes part in twofold Michael addition
resulting in a symmetrically substituted piperazine with two 3-aryl
enoate moieties (5r).
At room temperature the signals of the pyrrolidine protons of the
β-amino enoates 5a-d, 5k-q coalesce, indicating restricted
intramolecular motion. In a VT 1H NMR study with several
compounds 5 bearing electronically diverse substituents in p-
position of the aryl groups the signals of the pyrrolidine -protons
coincide at approximately T = 308 K, whereas the protons at the
-position coalesce at about T = 303 K. At higher temperature,
only two signals are observed for all pyrrolidine protons. At lower
temperature, the signals split and the protons are no longer
isochronous. The rate constants kc and Gibbs free enthalpies of
Scheme 2. Optimized Sonogashira coupling of iodo benzene (1a) and ethyl
propiolate (2) to give ethyl 3-phenyl propiolate (3a).
At higher concentration of iodo benzene (1a) and ethyl propiolate
(2) the reaction time could be lowered from 20 to 12 h and resulted
in an increase of yield for 86 to 99%. An excess of ethyl propiolate
and potassium carbonate is indispensable.
With the optimized Sonogashira step in hand we set out to
optimize the consecutive three-component coupling-Michael
addition synthesis of ethyl -amino 3-aryl enoates 5 using
iodobenzene (1a) and p-cyano-iodobenzene (1b) as aryl iodide
substrates and pyrrolidine (4a) as a secondary amine (Table 1).
As already shown for the three-component formation of
enaminones[23] also this Michael addition can be conducted on an
equistoichiometric level between Michael system and nucleophile.
These conditions are well-suited to probe the methodological
scope of this novel one-pot synthesis of -amino enoates in the
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10.1002/ejoc.202000823
European Journal of Organic Chemistry
COMMUNICATION
activation Gcǂ can be calculated from the obtained VT spectra
(Table 2, for details, see Supp Inf).[24] The electronic nature of the
para-substituent of the aryl group does not influence the
coalescence temperature. Therefore, an orthogonal arrangement
of the aryl substituent with the β-amino enoate indicates that the
coalescence phenomenon reflects the rotational barrier of
pyrrolidinyl ring. These findings are in good agreement with
calculations of pyrrolidine derivates, such as a 13C NMR study of
N-nitrosopyrrolidine,[25] the coalescence temperature of a rigid
pyrrolidine enoate[26] and dynamic NMR studies of three N-
benzoyl pyrrolidines.[27]
Scheme 3 Consecutive three-component synthesis of -amino enoates 5 (amethyl L-prolinate (4f) was employed and transesterified to the ethyl ester derivative 5i;
bmethyl L-prolinate (4f) was employed and ethanol was omitted as a cosolvent in the Michael addition step to give 5j)
Table 2 Rate constants kc and Gibbs free enthalpies of activation Gcǂ
determined from coalescence of pyrrolidine - and -protons.
literature reported synthesis, where the first step (Negishi
coupling of the in situ prepared chlorozinc ethyl propiolate with an
iodo arene) proceeds in 51% yield and the second
cyclocondensation step with ethyl hydrazine furnishes the 3-
hydroxypyrazole in 93%, gives a combined yield for the two steps
of 48%.[18] Our novel one-pot process furnishes the title
compounds generally in overall higher yield. Assuming three new
bonds being formed in this one-pot process the average yield per
bond forming step (coupling, Michael addition, cyclizing
condensation) accounts to 78-98%.
Electronically diverse substitution on the aryl iodide 1 is broadly
tolerated as for the one-pot synthesis of -amino enoates 5 as
seen from the overall good yield of the 3-hydroxypyrazoles 7. In
contrast to -amino enoates 5 ortho-substituted aryl derivatives 7
are uneventfully formed. The variation of the alkyl hydrazines 6
often gives lower yields. However, ortho-fluorobenzyl-hydrazine
is successfully employed also to give a very good yield of
compound 7o. It is noteworthy mentioning that aryl hydrazines
cannot be successfully implemented in this novel sequence.
The structure of all compounds were unambiguously assigned by
1H and 13C NMR spectroscopy and mass spectrometry, the
elemental composition was determined by HRMS and
combustion analyses. All compounds give single sets of signals
Entry
Compound 5
-protons
Gc1
-protons
ǂ
ǂ
(aryl)
kc1
kc2
Gc2
[s-1]
[kcal/mol]
(kJ/mol)
14.32
[s-1]
[kcal/mol]
(kJ/mol)
14.36
1
2
3
4
5a (Ph)
306
278
300
286
426
499
362
415
(59.73)
14.38
(59.91)
14.27
5b (p-NCC6H4)
5c (p-MeOC6H4)
5n (p-BrC6H4)
(59.97)
14.33
(59.51)
14.47
(59.78)
14.36
(60.33)
14.38
(59.90)
(59.98)
Besides successful concatenation of Michael addition and
Sonogashira coupling we also expanded the concept to the
formation of 3-hydroxypyrazoles in the sense of a consecutive
three-component coupling-cyclocondensation sequence starting
from aryl iodides 1, ethyl propiolate (2), and alkyl hydrazines 6 to
give after flash chromatography 17 examples of the 1-alkyl-5-aryl-
3-hydroxypyrazoles 7 in 48-95% yield (Scheme 4). The related
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10.1002/ejoc.202000823
European Journal of Organic Chemistry
COMMUNICATION
in the NMR spectra and the 3-hydroxyl tautomer can be
unambiguously assigned by NOESY. In addition, the structure
was corroborated by a crystal structure of compound 7j (Figure
1).[28] There is no annular tautomer, neither in solution nor in the
solid state. In the crystal structure of 7j O-H···N hydrogen bond
connect adjacent molecules to dimers (see dashed blue lines in
Figure 1, top). The hydrogen-bonded dimers are further linked to
neigboring moieties via stacking interactions (Figure 1,
bottom). The centroid-to-centroid distance (dashed black lines) of
the 4-fluorophenyl groups amounts to 3.77 Å, featuring a parallel
orientation, similarly for 1H-pyrazolyl moieties a centroid-to-
centroid distance of 3.68 Å is found.
Scheme 4 Consecutive three-component synthesis of -amino enoates 5 (amethyl L-prolinate (4f) was employed and transesterified to the ethyl ester derivative 5i;
bmethyl L-prolinate (4f) was employed and ethanol was omitted as a cosolvent in the Michael addition step to give 5j).
hydrogen bonds, dashed black lines between centroids indicate stacking
interactions (bottom).
The para-substituted examples (7a, 7b, 7c, 7h, 7m) were
investigated with regard on their photophysical properties. In
contrast to many pyrazoles upon UV excitation 3-hydroxy
pyrazoles neither emit in solution nor the solid state,
presumably, due to deactivation by H-bonding of the hydroxy
substituent.
Conclusions
In summary, we have developed two novel consecutive three-
component processes taking advantage of the straightforward
Sonogashira synthesis of ethyl 3-aryl propiolates, interesting
Michael acceptors. Indeed, -amino enoates and 3-
hydroxypyrazoles can be obtained in a one-pot fashion starting
from aryl iodides, ethyl propiolate, and amines or alkyl
hydrazines in good yield and with high tolerance of functional
groups. Further studies exploring the potential of this one-pot
approach to other heterocyclic targets and derivatives are
Figure 1 The molecular structure of 7j (view along c-axis, top). Hydrogen
bonds are shown as dashed lines and ellipsoids are drawn at the 50%
probability level. Packing diagram of 7j; blue dashed lines mark classical
currently underway.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000823
European Journal of Organic Chemistry
COMMUNICATION
Experimental Section
Keywords: Cross-coupling • Heterocycles • Michael addition •
Multicomponent reactions • Sonogashira coupling
Typical procedure for the synthesis of compound 5b with 4-iodo
benzonitrile (1b)
[1]
[2]
T. J. J. Müller, ed., Science of Synthesis Series, Georg Thieme Verlag
Pd(PPh3)Cl2 (7.0 mg, 10 mol, 2.0 mol%) and CuI (3.8 mg, 20 mol,
4.0 mol%) were placed in a Schlenk tube with magnetic stir bar. After
three purge-thaw cycles with nitrogen DME (0.9 mL) was added and
the reaction mixture stirred at room temp for 10 min. Then, potassium
carbonate (138 mg, 1.0 mmol, 2.0 equivs) and 4-iodobenzonitrile (1b)
(114 mg, 0.50 mmol) were added and the reaction mixture was heated
to 40 °C. Ethyl propiolate (2) (98 mg, 1.0 mmol, 2.0 equivs) dissolved
in DME (0.6 mL) was added by syringe pump to the reaction mixture
over a period of 12 h. After complete addition, the reaction was stirred
at 40 °C for 1 h. Then, ethanol (1.5 mL) and pyrrolidine (4a) (36 mg,
0.50 mmol, 1.0 equiv) were added and the mixture stirred at 100 °C for
16 h. After cooling to room temp, 3.0 mL acetone was added and the
solvents were removed under reduced pressure. The crude product
was adsorbed on Celite® and purified by flash chromatography on silica
gel (n-hexane/ethyl acetate 3:1) to afford 5b (86 mg, 0.32 mmol, 64 %
yield) as a colorless solid, Mp 139 °C. 1H NMR (CDCl3, 300 MHz): 
1.08 (t, J = 7.1 Hz, 3 H), 1.85-1.99 (m, 4 H), 2.92-3.32 (m, 4 H), 3.90 (q,
J = 7.1 Hz, 2 H), 4.71 (s, 1 H), 7.32-7.37 (m, 2 H), 7.67-7.73 (m, 2 H).
13C NMR (CDCl3, 75 MHz):  13.4 (CH3), 24.2 (CH2), 47.4 (CH2),
57.5 (CH2), 84.9 (CH), 111.0 (Cquat), 117.7 (Cquat), 127.5 (CH), 131.1
(CH), 141.6 (Cquat), 157.6 (Cquat), 166.7 (Cquat). EI-MS (m/z (%)): 270
(33) [M+], 242 [C14H14N2O2+] (17), 241 [C14H13N2O2+] (100), 225
[C14H13N2O+] (44), 198 [C13H14N2+] (37), 197 [C13H13N2+] (78), 169
[C9H15NO2+] (17), 156 (32), 128 [C9H6N+] (35), 70 [C4H8N+] (83). Anal.
calcd. for C16H18N2O2 (270.3): C, 71.09; H, 6.71; N, 10.36; Found:C,
70.95; H, 6.55; N, 10.15.
KG, Stuttgart, 2014, 5–27.
For recent reviews and editorials on the relevance of multicomponent
reactions in the synthesis of biologically active molecules, see e.g. a)
D. Insuasty, J. Castillo, D. Becerra, H. Rojas, R. Abonia, Molecules
2020, 25, 505. b) C. Cimarelli, Molecules 2019, 24, 2372; c) J. G.
Rudick, S. Shaabani, A. Dömling, Front. Chem. 2020, 7, 918. d) T. J.
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Perrone, M. Capua, A. Salomone, L. Troisi, J. Org. Chem. 2015, 80,
8189-8197.
For reviews on the catalytic generation of alkynoyl intermediates and
their application in consecutive multicomponent syntheses of
heterocycles, see e.g. a) T. J. J. Müller, Top. Heterocycl. Chem. 2010,
25, 25–94; b) C. F. Gers-Panther, T. J. J. Müller, Adv. Heterocycl.
Chem. 2016, 120, 67–98.
For reviews on fluorophore syntheses by metal catalysis-initiated
consecutive multicomponent syntheses, see e.g. a) L. Levi, T. J. J.
Müller, Eur. J. Org. Chem. 2016, 2907–2918; b) T. J. J. Müller, Drug
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S. Bourrain, M. Ridgill, I. Collins, Synlett 2004, 795–798.
a) F. Giornal, S. Pazenok, L. Rodefeld, N. Lui,J-P. Vors, F. R. Leroux,
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Typical procedure for the synthesis of compound 7b with 4-
iodobenzonitrile (1b)
Pd(PPh3)Cl2 (7.0 mg, 10 mol, 2.0 mol%) and CuI (3.8 mg, 20 mol,
4.0 mol%) were placed in a Schlenk tube. After three purge-thaw cycles
with nitrogen DME (0.9 mL) was added and the reaction mixture stirred
at room temp for 10 min. Then, potassium carbonate (138 mg, 1.0 mmol,
2.0 equivs) and 4-iodobenzonitrile (1b) (114 mg, 0.50 mmol) were
added and the reaction mixture was heated to 40 °C. Ethyl propiolate
(2) (98 mg, 1.0 mmol, 2.0 equivs) dissolved in DME (0.6 mL) was added
by syringe pump to the reaction mixture over a period of 12 h. After
complete addition, the reaction was stirred at 40 °C for 1 h. Then,
ethanol (1.5 mL) and methyl hydrazine (6a) (23 mg, 0.50 mmol, 1.0
equiv) were added and the mixture stirred at 100 °C for 16 h. After
cooling to room temp, 3.0 mL acetone was added and the solvents were
removed under reduced pressure. The crude was adsorbed on Celite®
and purified by flash chromatography on silica gel (n-hexane/ethyl
acetate 3:1) to afford 7b (78 mg, 0.39 mmol, 78 % yield) as a colorless
solid, Mp 254 °C (dec.).1H NMR (DMSO-d6, 300 MHz):  3.66 (s, 3 H),
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5.77 (s, 1 H), 7.68-7.73 (m, 2 H), 7.91-7.96 (m, 2 H), 9.80 (s, 1 H). 13
C
NMR (DMSO-d6, 75 MHz):  37.1 (CH3), 91.5 (CH), 110.6 (Cquat), 118.6
(Cquat), 128.9 (CH), 132.6 (CH), 134.7 (Cquat), 141.8 (Cquat), 160.0 (Cquat).
EI-MS (m/z (%)): 199 (100) [M+], 198 (48) 43 (10) [CH3N2+]. Anal. calcd.
for C11H9N3O (199.2): C, 66.32; H, 4.55; N, 21.09. Found: C, 66.45; H,
4.64; N, 20.07.
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Acknowledgments
[28] Crystallographic data (excluding structure factors) for the structures
reported in this paper have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication nos.
CCDC-1979471 (7j) and CCDC-1979472 (7e). Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
The authors cordially thank the Fonds der Chemischen
Industrie for support and B. Sc. Saskia Klein for the
experimental assistance.
Cambridge CB2 1EZ, UK (Fax:
+ 44-1223/336-033; E-mail:
deposit@ccdc.cam.ac.ukDOI: 10.1002/ejoc.200800444).
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10.1002/ejoc.202000823
European Journal of Organic Chemistry
COMMUNICATION
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COMMUNICATION
Two consecutive three-component
syntheses furnishing -amino enoates
or 3-hydroxypyrazoles in a one-pot
fashion based upon the Sonogashira
alkynylation of aryl iodides and ethyl
propiolate were established in mostly
excellent yields.
Multicomponent reactions*
Jonas Niedballa, Guido J. Reiss, and
Thomas J. J. Müller*
Page No. – Page No.
Consecutive Three-component
Coupling-Addition Synthesis of
-Amino Enoates and 3-
Hydroxypyrazoles via Ethyl
3-Arylpropiolates
This article is protected by copyright. All rights reserved.