Synthesis and properties of new heterocyclic betaines: 4-Aryl-5-(methoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ides

Article abstract of DOI:10.1016/j.tet.2018.03.071

New heterocyclic betaines, 4-aryl-5-(alkoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ides, were synthesized in good yields by the reaction of alkyl 2H-azirine-2-carboxylates with 2-methoxy-2-oxo-1-(pyridin-1-ium-1-yl)ethan-1-ides, gen

Full text of DOI:10.1016/j.tet.2018.03.071

Accepted Manuscript
Synthesis and properties of new heterocyclic betaines: 4-Aryl-5-(methoxycarbonyl)-2-
oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ides
Liya D. Funt, Mikhail S. Novikov, Galina L. Starova, Alexander F. Khlebnikov
PII:
S0040-4020(18)30354-5
10.1016/j.tet.2018.03.071
TET 29411
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 5 March 2018
Revised Date: 26 March 2018
Accepted Date: 29 March 2018
Please cite this article as: Funt LD, Novikov MS, Starova GL, Khlebnikov AF, Synthesis and properties
of new heterocyclic betaines: 4-Aryl-5-(methoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-
pyrrol-3-ides, Tetrahedron (2018), doi: 10.1016/j.tet.2018.03.071.
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ACCEPTED MANUSCRIPT
Synthesis and Properties of New Heterocyclic Betaines: 4-Aryl-5-
(methoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ides
Liya D. Funt, Mikhail S. Novikov, Galina L. Starova, Alexander F. Khlebnikov*
Saint Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab., St. Petersburg,
199034 Russia
Corresponding author. E-mail address: a.khlebnikov@spbu.ru (A.F. Khlebnikov).
Abstract: New heterocyclic betaines, 4-aryl-5-(alkoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-
2,3-dihydro-1H-pyrrol-3-ides, were synthesized in good yields by the reaction of alkyl 2H-
azirine-2-carboxylates with 2-methoxy-2-oxo-1-(pyridin-1-ium-1-yl)ethan-1-ides, generated
from the corresponding pyridinium salts. The betaines exist as the NH-tautomers both in solution
and in the solid state. Two molecules of the betaine form a dimer by hydrogen bonds of the type
N-H···O in solid state. According to TD DFT calculations the long-wave absorption band in
betaines mainly corresponds to the intramolecular charge transfer between the negatively
charged pyrrole unit and the positively charged pyridinium group. The blue shift of the long-
wave absorption in protic solvents was adequately described in terms of H-complex formation
with the nucleophilic centre of the molecular skeleton.
Keywords: heterocyclic betaines, azirines, pyridinium ylides, solvatochromism
1. Introduction
Heterocyclic betaines, whose unique properties, mainly due to their dipolar character, are
of interest for both fundamental and practical reasons.1 They are applied as starting materials for
heterocyclic synthesis and the development of new materials and drugs.1 In particular properties
of pyridinium N-phenolate betaine dyes, such as solvatochromism, thermochromism,
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piezochromism, halochromism and perichromism are used to study the properties of solvents and
solutions as well as their characterization.2 One more important recently recognized aspect of
betaine chemistry is the possibility of a tautomeric equilibrium with N-heterocyclic carbenes
(NHC) and therefore some betaines can be used for the generation of NHC.1d, 3 Although more
than a century has passed since the discovery of the first heterocyclic betaine,4 a great need still
remains to find new types of these zwitterionic molecules. The diversity of betaine structures
provides an opportunity to achieve practically useful properties, as well as gain a deeper insight
into the relationship between the properties and structure of zwitterionic compounds, which is
necessary for developing the principles for their purposeful design.
Pyridinium ylides are versatile building blocks in heterocyclic synthesis.5 Earlier we
discovered the reaction of 2H‐azirines with N-phenacylpyridinium ylides, which gave
1‐(1H‐pyrrol‐3‐yl)pyridinium salts.6 The reaction was successfully extended to N-phenacyl-
imidazolium3e,7 and N-phenacyl-1,2,4-triazolium ylides3d,f affording the corresponding pyrrolyl-
imidazole/triazole dyads. With the intention of broadening the scope of applicability of the
reaction, we decided to vary the type of a substituent in the pyridinium ylide by changing it from
benzoyl to alkoxycarbonyl. This would provide a route for the preparation of hardly accessible
derivatives of 2-alkoxypyrroles 4 by the route shown in Scheme 1.
Scheme 1. Probable route for the synthesis of 2-alkoxypyrroles 4
2. Results and discussion
Preliminary experiments revealed, however, that ylide 2a (R = Me, R1 = H) does not react
with 3-phenyl-2H-azirine at room temperature, and gives a complex mixture of unidentified
products at higher temperatures. Similar ambiguous results were obtained when 2,3-diphenyl-
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2H-azirine was used. We suggested that the presence of an electron-acceptor substituent in the
azirine ring may improve the selectivity of the reaction because of increased electrophilicity
toward nucleophile 2 and due to stabilization of the pyrrole ring. More electrophilic azirines
were, therefore, tested. The reaction of 1-(2-methoxy-2-oxoethyl)pyridin-1-ium chloride 1a with
methyl 3-phenyl-2H-azirine-2-carboxylate 3a in the presence of triethylamine as a base (ca.1
1
equiv), leads, according to H NMR and HRMS data, to the pyrrole-type product 5a (NH-
tautomer) or 5’a (NH-tautomer) in 77% yield (Scheme 2). The use of a 2- or 3-fold excess of
triethylamine does not affect the yield. The isolation of the precipitated product consists simply
of filtering off and washing, making acetonitrile the solvent of choice due to the lower solubility
of the product in this solvent.
Scheme 2. Reaction of azirine 3a with pyridinium salt 1a
1
An analysis of HSQC H-15N NMR spectra makes it possible to distinguish between
tautomers 5a and 5’a (See the Supporting information). The pyrrole-type nitrogen, with chemical
shift of 137.7 ppm, has an intensive cross-peak with the proton at 9.67 ppm. Consequently this
proton is connected to the pyrrole-type nitrogen. According to the DFT calculations at the
B3LYP/6-31G+(d,p) level with the PCM model for DMSO at 298 K, the tautomer 5a in solution
in DMSO is much more stable than tautomer 5’a (by 12.2 kcal/mol). Thus, the reaction of 2-
methoxy-2-oxo-1-(pyridin-1-ium-1-yl)ethan-1-ide 2a with methyl 3-phenyl-2H-azirine-2-
carboxylate 3a provides an access to the new type of betaines 5. To obtain more information
about the structure of the zwitterionic molecule 5a a single crystal was grown from CDCl3 by
slow evaporation of the solvent and studied by single crystal X-ray analysis (Figure 1).
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Fig. 1. Molecular structure of 5a (a), and solid-state packing of H-bonded dimer (b), showing
H···O-contacts.
Compound 5a crystallizes in a monoclinic space group P21/c with four molecules in the
unit cell. The solid-state structure of 5a displays different types of short intermolecular contacts.
Two molecules of the compound form a dimer by hydrogen bonds of the type N-H···O, to which
the CDCl3 molecules are bound by hydrogen bonds of the type С-Н···O. Experimental and
calculated selected bond lengths of molecules 5a, 5’a are listed in Table 1. Computed at the
B3LYP/6-31G+(d,p) level bond lengths of molecules 5a fit well with the XRD bond lengths, and
especially good correspondence is found for the calculated values of the H-bonded dimer of 5a.
Meanwhile, there is a big discrepancy between the computed O1-C1 and N1-C1 bond lengths of
molecules 5a’ and the corresponding XRD bond lengths. Thus, the product of the reaction of 2-
methoxy-2-oxo-1-(pyridin-1-ium-1-yl)ethan-1-ide 2a with methyl 3-phenyl-2H-azirine-2-
carboxylate 3a exists as the NH-tautomer 5a both in solution and in the solid state.
Table 1. Experimental and calculated selected bond lengths of molecules 5a, 5’a.
Bond
5a (XRD) 5aa/ꢀb
5’aa/ꢀb
H-bonded
dimer of 5aa/ꢀb
1.274(3)
1.425(4)
1.421(4)
1.389(4)
1.399(3)
1.368(4)
1.247/-0.027 1.368/0.094
1.269/-0.006
1.445/0.020
1.430/0.009
1.392/0.003
O1-C1
C1-C2
C8-C2
C8-C15
N1-C15
N1-C1
1.459/0.034
1.431/0.010
1.392/0.003
1.426/0.001
1.434/0.013
1.404/0.015
1.396/-0.003 1.390/-0.009 1.396/-0.003
1.380/0.012 1.309/-0.059 1.368/0.000
a Bond lengths computed at the B3LYP/6-31G+(d,p) level.
b ꢀ – difference between the XRD and computed bond length.
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To evaluate the scope of the reaction substituted alkyl azirinecarboxylates 3a-f were
reacted
with pyridinium chlorides 1a-c, 4-(N,N-dimethylamino)-1-(2-methoxy-2-
oxoethyl)pyridin-1-ium chloride 1d, and 1-(2-methoxy-2-oxoethyl)quinolin-1-ium 1e and 2-(2-
methoxy-2-oxoethyl)isoquinolin-1-ium 1f chlorides. However, we failed to isolate betaines
containing N,N-dimethylaminopyridine (from 1d), quinoline (from 1e) and isoquinoline (from
1f) moieties and changing the heterocycle from pyridine to imidazole was also not successful.
Meanwhile betaines 5a-h with electron-donating (MeO), electron-withdrawing (NO2) and
halogen (Br) substituents in the phenyl ring were prepared in good yields. ortho-Substituents,
both in the phenyl and the pyridine rings, do not influence dramatically the yield of the products
(Table 1).
Table 1. Synthesis of betaines 5a-h
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Having decided to evaluate the reactivity of azirines with the opposite location of the aryl
and methoxycarbonyl substituents, we synthesized azirine 3g and reacted it with salt 1a under
the standard conditions. However, instead of the betaine product 5i, the product 6 of formal
dimerization of carbene 7 was unexpectedly isolated in 18% yield (Scheme 3). According to the
DFT calculations at the B3LYP/6-31G+(d,p) level with the PCM model for MeCN at 298 K, the
E-isomer of 6 is more stable than the Z-isomer by 4.4 kcal/mol.
Scheme 3. Reaction of pyridinium salt 1a with methyl 2-(4-chlorophenyl)-2H-azirine-3-
carboxylate 3g
The proposed mechanism of the formation of betaine 5a (Scheme 4) involves generation
of pyridinium ylide 2a, nucleophilic attack of the latter on the C=N bond of the protonated
azirine (3a-H+) with the formation of aziridine intermediate 8a followed by dehydrohalogenation
of 8a to aziridinyl-substituted pyridinium ylide 9a. A rearrangement of 9a to betaine 10a,
followed by an elimination of MeOH leads to betaine 5a.
CO2Me
Ph
Ph
CO2Me
Cl
3a
N
Et3NH+Cl-
Cl
N
O
Et3N
H
N
O
OMe
O
3a-H+
N
1a
OMe
2a
2a
O
N
O
Cl
H
N
N
Et3N
OMe
NH
10a
5a
OMe
OMe
-Et3NH+Cl-
Ph
Ph
MeO2C
Ph
MeO2C
NH
NH
MeO2C
9a
8a
H
H
H
Scheme 4. Proposed mechanism of formation of betaines 5
6

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All new compounds were characterized by 1H, 13C NMR and HRMS methods. Betaines 5
and dimer 6 are non-hygroscopic, air-unstable high-melting intensively colored crystalline
solids, which fade when kept in air for a long time, probably due to the formation of a carbonate
(vide infra). Substances 5a-h and 6 possess poor solubility in dichloromethane, methanol,
dimethyl sulfoxide and very poor solubility in acetonitrile and water. Betaines 5 are weak bases
and reaction with hydrochloric or hydrobromic acids was accompanied by tarring of the reaction
mixture, but the reaction with aq HBF4 led quantitatively to hydroxypyrrole 11a (Scheme 5).
Ph
MeO2C
N
Ph
MeO2C
N
MeOH
rt
BF4
HBF4
O
OH
11a, 99%
N
H
N
H
5a
Scheme 5. Synthesis of 1-(2-hydroxy-5-(methoxycarbonyl)-4-phenyl-1H-pyrrol-3-yl)pyridin-1-
ium tetrafluoroborate 11a
1
Compound 11a was characterized by spectroscopic methods (1H, 13C, HSQC H-13C,
1
HMBC H-13C NMR and HRMS). Its structure was also confirmed by single crystal X-ray
analysis (Fig. 2).
Fig. 2. Molecular structure of 11a (a), and solid-state packing of 11a (b), showing H···O- and
H···F-contacts.
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Salt 11a crystallizes in a monoclinic space group P21/c with four molecules in the unit
cell. The solid-state structure of 11a displays different types of short intermolecular contacts. 1-
(2-Hydroxy-5-(methoxycarbonyl)-4-phenyl-1H-pyrrol-3-yl)pyridin-1-ium ions interacting with
each other through hydrogen bonds of the N-H···O type and with water molecules (via a
hydrogen bond of the С-Н···O type) form one of the layers that is interleaved by the ‒BF4 layers
that have contact both with the pyridin-1-ium ions and with water molecules through hydrogen
contacts of the type O-H···F.
The selective hydrogenation of the pyridinio-substituents in some cases allows them to be
considered as synthetic equivalents of the pyrrolidin-1-yl substituents.6a,b We tried to carry out
this reaction for betaines 5 under heterogeneous hydrogenation conditions. It turned out that they
can be hydrogenated in methanol at atmospheric pressure of H2 in the presence of Adams’
catalyst either to 1,3-dihydro-2H-pyrrol-2-ones 12, or to pyrrolidin-2-ones 13 (Scheme 6).
Scheme 6. Catalytic hydrogenation of betaines 5
In the case of betaine 5a it was possible to obtain both reduction products, 1,3-dihydro-2H-
pyrrol-2-one 12a and pyrrolidin-2-one 13a. The second product was obtained by use of an
additional portion of catalyst and stirring for another 24 h. Betaine 5b, however, was reduced
immediately to pyrrolidin-2-one 13b. Betaine 5c gave only the first step reduction product 12c.
Nitro-substituted compound 3d gave a mixture of compounds, 12d and the amino-substituted
product by reduction of the nitro-group in 12d (30:70 ratio, 33% overall yield). Betaines 5e-g
gave unstable products which could not be obtained as individual compounds. Betaine 5h after 5
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days of stirring in an atmosphere of hydrogen gave 13h and the product of hydrogenation of one
of the phenyl ring (68:32 ratio, 70% overall yield). Unfortunately, we were unable to find
conditions for the chromatographic separation of these mixtures. It has to be noted that
substances 13a and 13b have 3 stereogenic centers, but they were obtained as a single
diastereomer, which has all-cis-configuration. This was confirmed by single crystal X-ray
analysis of 13a (Fig. 3).
Fig. 3. Molecular structure of 13a
The UV spectra of solutions of compounds 5 are characterized by a long-wave absorption
band (Table 2), which is responsible for the color of these compounds (from purple to dark-
brown). The position of this band is hardly affected by changing the solvent. Compounds 5a,c,d
show a hypsochromic shift by about 30–40 nm on changing the solvent from polar aprotic
acetonitrile to a polar protic solvent such as water or methanol. To elucidate the nature of the
long-wave absorption band and the solvent effect on the band position, the geometry of 5a,c,d
was optimized at the B3LYP/6-31+g(d,p) level with PCM model for the corresponding solvent
and then single point calculations at the TD-DFT B3LYP/6-31+G(d,p)/PCM and SMD,
M062X/6-31+G(d,p)/PCM and SMD, CAM-B3LYP/6-31+G(d,p)/SMD level of theory were
performed (Table 2). For details of the computations see Supporting information. The best fit
between the experimental and calculated wave length for compounds 5a,c,d (the long-wave
band) is observed for the TD-DFT B3LYP/6-31+G(d,p) level with SMD solvation model (ꢀ12-
14 nm for MeCN, ꢀ10-63 nm for H2O, ꢀ25 nm for MeOH; Table 2). The TD-DFT B3LYP/6-
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31+G(d,p)/SMD calculation results demonstrate that the long-wave absorption of the compounds
5a,c mainly arises from HOMO to LUMO transitions (coefficient of the wave function >0.7)
(Fig. 4). For compound 5d the HOMO to LUMO transition has an oscillator strength of only
0.03 and was not observed, whereas the observed long-wave absorption correspond to the
HOMO to LUMO+1 transition (f = 0.23, coefficient of the wave function >0.7). Thus, the long-
wave absorption of compounds 5a,c,d is mainly corresponding to the intramolecular charge
transfer excitation between the negatively charged pyrrole unit and the positively charged
pyridinium group. The second possibility for the compound 5d charge transfer from the
negatively charged pyrrole unit (LUMO) to the positively charged nitro-substituted phenyl group
(HOMO) has a too low intensity.
Table 2. Data of experimental absorption spectra and calculated by TD-DFT long
wavelengths and oscillator strengths of compounds 5a,c,d.
solvent absorbance,
B3LYP/6- B3LYP/6- M062X/6- M062X/6- CAM-B3LYP/6-
5
λmax, nm (ε, 10−3 31+G(d,p) 31+G(d,p) 31+G(d,p) 31+G(d,p) 31+G(d,p)
·M−1 cm−1)
PCM
SMD
PCM
SMD
SMD
λ max (nm), f (HOMO→LUMO transition)
MeCN 330 (8.4), 515
(8.9)
535/0.237 527/0.246
533/0.233 493/0.246
539/0.228 531/0.237
440/0.335 432/0.348 430/0.345
437/0.330 403/0.369 401/0.367
441/0.329 434/0.340 432/0.338
a
H2O
288 (21.5), 359
(15.5), 475 (6.0)
a
c
MeCN 329 (11.8), 517
(9.9)
MeOH 318 (12.3), 476
(5.5)
539/0.227 501/0.238
538/0.223 497/0.234
441/0.327 408/0.363 406/0.361
441/0.323 404/0.361 402/0.359
c
c
H2O
320 (14.7), 436
(4.9)
MeCN 320 (17.8), 513
(9.2)
722/0.035 741/0.034
533/0.221a 525/0.228a 426/0.068a 423/0.141a 420/0.134a
447/0.291 447/0.224 445/0.232
d
d
H2O
355 (19.3), 482
(5.1)
723/0.034 721/0.034
532/0.217a 492/0.227a 425/0.076a 396/0.211a 395/0.209a
446/0.276 430/0.172 428/0.177
a HOMO→LUMO+1.
10

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Fig. 4. Contour surface plots of the frontier orbital of compounds 5a,c,d (isovalue is 0.02 a.u.)
Since the betaines 5 are of a basic nature (vide supra), we assumed that complexes with a
hydrogen bond can be formed in proton solvents (water, methanol), and accepting this to be true
we can obtain a better agreement between the experimental and calculated maxima of the long-
wave bands. Indeed, as can be seen from Table 3, the calculated data for such complexes
correspond better to the experimental spectra. Thus, the formation of H-complexes 5-HOR leads
to the blue shift of the calculated absorption. This is mainly due to the higher ground state
stabilization upon H-complex formation compared to the first exited state (Fig. 5).
Table 3 Data of experimental absorption spectra and calculated by TD-DFT B3LYP/6-
31+G(d,p)/PCM and SMDa
exp. λmax, nm
compound
solvent
calcd, λmax, nm
(PCM/SMD)
533/493
521/484
538/497
525/487
539/501
528/492
532/492
5a
5a-H2O
5c
5c-H2O
5c
5c-MeOH
5d
H2O
475
436
476
482
H2O
MeOH
H2O
519/482
5d-H2O
a Geometry of 5a,c,d was optimised at the B3LYP/6-31+g(d,p) level with PCM model for the
corresponding solvent
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Fig. 5. Energies of frontier MO of 5a,c,d and their complexes with ROH
Titration of an aprotic acetonitrile solution of 5с with water (Fig. 6) shows clear cut
isosbestic points in the absorption spectra that is indicative of a chemical equilibrium between
the solvated (with water) and unsolvated forms of 5с.
Fig. 6. Titration of the solution of 5с in MeCN (1.54·10-4 mol/l) with water at rt
3. Conclusion
New heterocyclic betaines, 4-aryl-5-(alkoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-
dihydro-1H-pyrrol-3-ides, were synthesized in good yields by reaction of alkyl 2H-azirine-2-
carboxylates with 2-methoxy-2-oxo-1-(pyridin-1-ium-1-yl)ethan-1-ides, generated from the
corresponding pyridinium salts. The betaines exist as the NH-tautomers both in solution and in
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the solid state. In the solid state two molecules of the betaine form the dimer by hydrogen bonds
of the type N-H···O. Catalytic reduction of betaines 5 in methanol in H2 at the atmospheric
pressure in the presence of Adams’ catalyst give either 1,3-dihydro-2H-pyrrol-2-ones 12 or
pyrrolidin-2-ones 13. The long-wave absorption of the betaines corresponds, according to the TD
DFT calculations, to the intramolecular charge transfer excitation between the negatively
charged pyrrole unit and the positively charged pyridinium group. The blue shift of the long-
wave absorption in protic solvents was adequately described in terms of H-complex formation
with the nucleophilic centre of the molecular skeleton.
4. Experimental section
4.1. General Information and Methods
Melting points were determined on a capillary melting point apparatus Stuart® SMP30.
1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded in CDCl3, DMSO-d6 or
methanole-d4 with Bruker AVANCE III 400 spectrometer. Chemical shifts (δ) are reported in
1
parts per million downfield from tetramethylsilane (TMS δ 0.00). H NMR spectra were
calibrated according to the residual peak of CHCl3 (7.26 ppm), DMSO-d6 (2.50 ppm) or
13
13
methanole-d4 (3.31 ppm). C{1H} and C DEPT-135 were calibrated according to the peak of
CDCl3 (77.00 ppm), DMSO-d6 (39.51 ppm) or methanole-d4. Mass spectra were recorded on a
Bruker maXis HRMS-ESI-QTOF, electrospray ionization, positive mode. Thin-layer
chromatography (TLC) was conducted on aluminum sheets with 0.2 mm silica gel (fluorescent
indicator, Macherey-Nagel) and Macherey-Nagel Silica 60 M was used for column
chromatography. Suitable crystals of 5a, 11a, 13a were selected and studied on an Xcalibur, Eos
diffractometer, SuperNova, Single source at offset/far, HyPix3000 diffractometer and
SuperNova, Dual, Cu at zero, Atlas diffractometer. The crystal was kept at 100(2) K during data
collection. Using Olex2,8 the structure was solved with the Superflip9a-c structure solution
programme using Charge Flipping (for 5a and 13a) or with the ShelXS10 structure solution
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program using Direct Methods (for 11a) and refined with the ShelXL11 refinement package using
Least Squares minimisation. Crystallographic data for structures 5a, 11a, 13a have been
deposited with the Cambridge Crystallographic Data Centre (CCDC 1819078, 1816088,
1586949, respectively). Compounds 1a-c12 and 3a-d,13a 3e,13b and 3g13c were prepared by the
reported procedures.
4.2. Calculation details
All calculations were performed by using the Gaussian 16 suite of quantum chemical
programmes14 at Resource Centre "Computer Centre of Saint Petersburg State University".
Geometry optimizations of molecules were performed with the B3LYP density functional
method15 and 6-31+G(d,p) basis set using PCM solvent model.16 Stationary points on the
respective potential-energy surfaces were characterized at the same level of theory by evaluating
the corresponding Hessian indices. The absorption spectra were investigated for the optimized
DFT/B3LYP/6-31+G(d,p)/PCM geometry with time dependent density function theory (TD-
DFT)17 using B3LYP15, CAM-B3LYP18 and M062X19 functionals and 6-31+G(d,p) basis set
with PCM16 or SMD20 solvent models.
4.3. 3-(2,4-Dimethoxyphenyl)isoxazol-5(4H)-one
Hydroxylamine hydrochloride (827 mg, 1.19 mmol, 3 equiv) was added to a
heterogeneous mixture of ethyl 3-(2,4-dimethoxyphenyl)-3-oxopropanoate (1 g, 3.97 mmol, 1
equiv) and 10 mL of water and the resulting mixture was kept at 100 °С for 5 min. Then
approximately 20 mL of ethanol (till homogenization) was added and the solution was heated at
reflux for 1 h, cooled, the precipitate formed was filtered off, washed with cold mixture of
ethanol and water (1:1) and dried to obtain pure product. Colorless solid, 470 mg (54%), mp
158-160 °С. Product (in DMSO) is a mixture of tautomers: 3-(2,4-dimethoxyphenyl)isoxazol-
1
5(4H)-one and 3-(2,4-dimethoxyphenyl)isoxazol-5-ol at 1:2 ratio. H NMR (DMSO-d6): δ 3.84
(s, 6H), 3.89 (s, 3H), 4.19 (s, 1H), 5.55 (s, 1H), 6.51-6.83 (m, 3H), 7.41-7.61 (m, 1H), 7.62-7.74
(m, 0.5H), 12.27 (s, 1H). 13С NMR (DMSO-d6): δ 37.2 (CH2), 55.6 (CH3), 55.8 (CH3), 55.9
14

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(CH3), 84.2 (CH), 98.8 (CH), 106.2 (CH), 106.4 (CH), 107.3 (C), 109.1 (C), 129.1 (CH), 129.6
(CH), 158.9 (C), 159.3 (C), 161.4 (C), 162.6 (C), 163.3 (C), 163.5 (C), 172.0 (C), 176.7 (C).
+
HRMS (ESI) m/z: 222.0761 calcd for C11H12NO4 [M + H]+, found 222.0764.
4.4. 3-(2,4-Dimethoxyphenyl)-5-methoxyisoxazole
A suspension of 3-(2,4-dimethoxyphenyl)isoxazol-5-ol (0.6 g, 2.71 mmol, 1 equiv) in 10
mL of diethyl ether was cooled with ice bath and a solution of diazomethane (obtained from 0.84
g of 1-methyl-1-nitrosourea and 1.52 g of potassium hydroxide) in 30 mL of diethyl ether was
added dropwise. The resulting mixture was stirred at rt for 1 h and quenched with acetic acid.
The homogeneous solution was concentrated in vacuo and purified by column chromatography
(hexane:ethyl acetate, 1.5:1). Colorless solid, 312 mg (49%), mp 56-58 °С. 1H NMR (CDCl3): δ
13
3.84 (s, 3H), 3.87 (s, 3H), 5.69 (s, 1H), 6.50-6.50 (m, 2H), 7.78 (d, 1H, J = 8.5 Hz). С NMR
(CDCl3): δ 55.6 (CH3), 55.7 (CH3), 58.8 (CH3), 78.7 (CH), 99.0 (CH), 105.2 (CH), 111.6 (C),
130.0 (CH), 158.7 (C), 161.8 (C), 162.4 (C), 173.8 (C). HRMS (ESI) m/z: 236.0917 calcd for
+
C12H14NO4 [M + H]+, found 236.0928.
4.5. Methyl 3-(2,4-dimethoxyphenyl)-2H-azirine-2-carboxylate 3f
Iron(II) chloride tetrahydrate (24 mg, 0.12 mmol, 10 mol%) was added to a stirred
solution of 3-(2,4-dimethoxyphenyl)-5-methoxyisoxazole (280 mg, 1.19 mmol) in 8 mL of dry
acetonitrile under inert atmosphere and the resulting mixture was stirred for 2 h at rt (monitoring
by TLC, hexane:ethyl acetate, 2:1). After completion of the reaction the solution was filtered
through celite, concentrated in vacuo and purified by flash column chromatography
1
(hexane:ethyl acetate, 1:1). Colorless solid, 280 mg (100%), mp 70-72 °С. H NMR (CDCl3): δ
2.64 (s, 1H), 3.70 (s, 3H), 3.88 (s, 3H), 3.95 (s, 3H), 6.46-6.56 (m, 1H), 6.60 (dd, J = 8.5, 2.2 Hz,
13
1H), 7.53 (d, J = 8.5 Hz, 1H). С NMR (CDCl3): δ 27.2 (CH), 52.2 (CH3), 55.9 (CH3), 56.1
(CH3), 98.7 (CH), 104.3 (C), 105.8 (CH), 134.8 (CH), 153.9 (C), 162.0 (C), 166.1 (C), 173.0 (C).
+
HRMS (ESI) m/z: 258.0737 calcd for C12H13NNaO4 [M + Na]+, found 258.0746.
15

ACCEPTED MANUSCRIPT
4.6. Typical procedure for the preparation of betaines 5a-h
Triethylamine (26 mg, 0.26 mmol, 1.05 equiv) was added to a suspension of 1-(2-
methoxy-2-oxoethyl)pyridin-1-ium chloride (50 mg, 0.25 mmol) and methyl 3-phenyl-2H-
azirine-2-carboxylate (65 mg, 0.37 mmol, 1.5 equiv) in 1 mL of dry acetonitrile and the reaction
mixture was stirred at rt for 12 h. Then the precipitate formed was filtered off, washed with 1 mL
of dry acetonitrile and dried to obtain pure product.
4.6.1. 5-(Methoxycarbonyl)-2-oxo-4-phenyl-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ide
(5a)
Compound 5a (56 mg, 77%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-ium
chloride 1a (50 mg, 0.25 mmol), methyl 3-phenyl-2H-azirine-2-carboxylate 3a (65 mg, 0.37
mmol) and triethylamine (26 mg, 0.26 mmol) according to the typical procedure. Dark brown
solid, mp 211–213 °С. 1H NMR (DMSO-d6): δ 3.46 (s, 3H), 7.18-7.35 (m, 5H), 7.67-7.81 (m,
13
2H), 7.90-8.06 (m, 1H), 8.44-8.64 (m, 2H), 9.67 (s, 1H). С NMR (DMSO-d6): δ 49.9 (CH3),
102.9 (C), 108.6 (C), 124.2 (C), 126.5 (CH), 127.0 (CH), 128.0 (CH), 129.8 (CH), 132.9 (C),
137.8 (CH), 140.2 (CH), 155.8 (C), 160.0 (C). HRMS (ESI) m/z: 295.1077 calcd for
+
C17H15N2O3 [M + H]+, found 295.1064. IR (KBr, cm−1): ν 1132, 1428, 1482, 1588, 1618, 1680.
4.6.2. 4-(4-Bromophenyl)-5-(methoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-
pyrrol-3-ide (5b)
Compound 5b (87 mg, 93%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-ium
chloride 1a (50 mg, 0.25 mmol), methyl 3-(4-bromophenyl)-2H-azirine-2-carboxylate 3b (95
mg, 0.37 mmol) and triethylamine (26 mg, 0.26 mmol) according to the general procedure. Dark
violet solid, mp 196–198 °С. 1H NMR (methanol-d4): δ 3.64 (s, 3H), 7.13-7.20 (m, 2H), 7.42-
7.47 (m, 2H), 7.82-7.89 (m, 2H), 8.18-8.28 (m, 1H), 8.53-8.60 (m, 2H). 13С NMR (methanol-d4):
δ 51.1 (CH3), 105.4 (C), 110.9 (C), 122.7 (C), 125.8 (C), 128.4 (CH), 132.5 (CH), 132.7 (C),
133.1 (CH), 142.6 (CH), 145.2 (CH), 155.3 (C), 162.7 (C). HRMS (ESI) m/z: 373.0182 calcd for
+
C17H14BrN2O3 [M + H]+, found 373.0618.
16

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4.6.3. 5-(Methoxycarbonyl)-4-(4-methoxyphenyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-
pyrrol-3-ide (5c)
Compound 5c (65 mg, 81%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-ium
chloride 1a (50 mg, 0.25 mmol), methyl 3-(4-methoxyphenyl)-2H-azirine-2-carboxylate 3c (76
mg, 0.37 mmol) and triethylamine (26 mg, 0.26 mmol) according to the general procedure.
Purple solid, mp 218–219 °С. 1H NMR (DMSO-d6): δ 3.48 (s, 3H), 3.76 (s, 3H), 6.83-6.92 (m,
2H), 7.10-7.20 (m, 2H), 7.72-7.81 (m, 2H), 7.95-8.03 (m, 1H), 8.51-8.60 (m, 2H), 9.57 (s, 1H).
13С NMR (methanol-d4): δ 51.1 (CH3), 55.7 (CH3), 105.3 (C), 111.2 (C), 114.8 (CH), 125.4 (C),
127.2 (C), 128.2 (CH), 132.3 (CH), 142.2 (CH), 145.1 (CH), 155.2 (C), 160.7 (C), 163.0 (C) .
+
HRMS (ESI) m/z: 325.1183 calcd for C18H17N2O4 [M + H]+, found 325.1180.
4.6.4. 5-(Methoxycarbonyl)-4-(4-nitrophenyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-
pyrrol-3-ide (5d)
Compound 5d (158 mg, 94%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-
ium chloride 1a (100 mg, 0.50 mmol), methyl 3-(4-nitrophenyl)-2H-azirine-2-carboxylate 3d
(165 mg, 0.74 mmol) and triethylamine (53 mg, 0.52 mmol) according to the general procedure.
Dark brown solid, mp >370 °С. 1H NMR (DMSO-d6): δ 3.50 (s, 3H), 7.46-7.56 (m, 2H), 7.76-
13
7.82 (m, 2H), 8.02-8.09 (m, 1H), 8.12-8.20 (m, 2H), 8.50-8.59 (m, 2H), 9.99 (s, 1H). С NMR
(methanol-d4): δ 51.3 (CH3), 105.9 (С), 124.3 (CH), 124.7 (C), 128.6 (CH), 132.5 (CH), 140.8
(C), 142.8 (CH), 145.3 (CH), 148.5 (C), 155.5 (C), 162.5 (C). HRMS (ESI) m/z: 340.0928 calcd
+
for C17H14N3O5 [M + H]+, found 340.0939.
4.6.5. 4-(2-Bromophenyl)-5-(tert-butoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-
pyrrol-3-ide (5e)
Compound 5e (94 mg, 76%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-ium
chloride 1a (60 mg, 0.30 mmol), tert-butyl 3-(2-bromophenyl)-2H-azirine-2-carboxylate 3e (132
mg, 0.45 mmol) and triethylamine (32 mg, 0.32 mmol) according to the general procedure. Dark
violet solid, mp 198-200 °С. 1H NMR (DMSO-d6): δ 1.13 (s, 9H), 7.23-7.30 (m, 1H), 7.36-7.40
17

ACCEPTED MANUSCRIPT
(m, 2H), 7.60-7.66 (m, 1H), 7.70-7.76 (m, 2H), 7.85-7.95 (m, 1H), 8.58-8.67 (m, 2H), 9.71 (s,
1H). 13С NMR (methanol-d4): δ 28.5 (CH3), 80.7 (C), 108.0 (C), 110.5 (C), 124.3 (C), 125.8 (C),
128.4 (CH), 128.6 (CH), 130.5 (CH), 133.6 (CH), 134.0 (CH), 136.1 (C), 141.9 (CH), 144.0
+
(CH), 154.8 (C), 162.2 (C). HRMS (ESI) m/z: 415.0652 calcd for C20H20BrN2O3 [M + H]+,
found 415.0664.
4.6.6. 4-(2,4-Dimethoxyphenyl)-5-(methoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-
1H-pyrrol-3-ide (5f)
Compound 5f (225 mg, 82%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-ium
chloride 1a (156 mg, 0.77 mmol), methyl 3-(2,4-dimethoxyphenyl)-2H-azirine-2-carboxylate 3f
(236 mg, 1.00 mmol, 1.5 equiv) and triethylamine (82 mg, 0.81 mmol, 1.05 equiv) according to
the general procedure. Dark violet solid, mp 228-230°С. 1H NMR (DMSO-d6): δ 3.30 (s, 3H),
3.45 (s, 3H), 3.78 (s, 3H), 6.41-6.49 (m, 1H), 6.52-6.58 (m, 1H), 7.15-7.29 (m, 1H), 7.71-7.79
13
(m, 2H), 7.90-8.02 (m, 1H), 8.51-8.66 (m, 2H), 9.51 (s, 1H). С NMR (methanol-d4): δ 51.0
(CH3), 55.6 (CH3), 55.8 (CH3), 99.1 (CH), 105.2 (C), 106.3 (CH), 112.0 (C), 114.1 (C), 123.9
(C), 128.1 (CH), 134.7 (CH), 142.0 (CH), 144.4 (CH), 154.7 (C), 158.8 (C), 162.7 (C), 163.0
+
(C). HRMS (ESI) m/z: 355.3695 calcd for C19H19N2O5 [M + H]+, found 355.1304.
4.6.7. 5-(Methoxycarbonyl)-2-oxo-4-phenyl-3-(4-phenylpyridin-1-ium-1-yl)-2,3-dihydro-1H-
pyrrol-3-ide (5g)
Compound 5g (86 mg, 90%) was prepared from 1-(2-methoxy-2-oxoethyl)-4-
phenylpyridin-1-ium bromide 1b (80 mg, 0.26 mmol), methyl 3-phenyl-2H-azirine-2-
carboxylate 3a (68 mg, 0.39 mmol) and triethylamine (28 mg, 0.27 mmol) according to the
general procedure. Dark blue solid, mp 215-217 °С. 1H NMR (DMSO-d6): δ 3.47 (s, 3H), 7.25-
7.37 (m, 5H), 7.89-7.97 (m, 3H), 7.89-7.97 (m, 2H), 8.09-8.15 (m, 2H), 8.50-8.60 (m, 2H), 9.74
(s, 1H). 13С NMR (methanol-d4): δ 51.1 (CH3), 105.4 (C), 110.7 (C), 124.8 (CH), 127.3 (C),
128.69 (CH), 128.74 (CH), 129.4 (CH), 130.8 (CH), 131.2 (CH), 132.8 (CH), 133.7 (C), 135.6
18

ACCEPTED MANUSCRIPT
(C), 144.6 (CH), 153.3 (C), 155.4 (C), 162.9 (C). HRMS (ESI) m/z: 371.1390 calcd for
+
C23H19N2O3 [M + H]+, found 371.1408.
4.6.8.
pyrrol-3-ide (5h)
Compound 5h (108 mg, 72%) was prepared from 1-(2-methoxy-2-oxoethyl)-2-
5-(Methoxycarbonyl)-3-(2-methylpyridin-1-ium-1-yl)-2-oxo-4-phenyl-2,3-dihydro-1H-
methylpyridin-1-ium bromide 1c (120 mg, 0.49 mmol), methyl 3-phenyl-2H-azirine-2-
carboxylate 3a (128 mg, 0.73 mmol, 1.5 equiv) and triethylamine (52 mg, 0.51 mmol, 1.05
equiv) according to the general procedure. Dark violet solid, mp 219-221 °С. 1H NMR (DMSO-
d6): δ 2.78 (s, 3H), 3.47 (s, 3H), 7.00-7.12 (m, 2H), 7.12-7.24 (m, 3H), 7.51-7.61 (m, 1H), 7.92-
8.04 (m, 1H), 8.07-8.30 (m, 2H), 9.45 (s, 1H). 13С NMR (methanol-d4): δ 21.0 (CH3), 51.0
(CH3), 104.6 (C), 109.44 (C), 125.8 (CH), 128.5 (CH), 129.1 (CH), 129.3 (C), 130.2 (CH), 130.8
(CH), 133.9 (C), 145.3 (CH), 149.6 (CH), 154.6 (C), 159.6 (C), 163.0 (C). HRMS (ESI) m/z:
309.1234 calcd for C18H17N2O3 [M + H]+, found 309.1248.
+
4.7. Dimethyl 5,5'-bis(4-chlorophenyl)-2,2'-dioxo-1,1',2,2'-tetrahydro-[3,3'-bipyrrolylidene]-
4,4'-dicarboxylate (6)
Compound 6 (22 mg, 18%) was prepared from 1-(2-methoxy-2-oxoethyl)pyridin-1-ium
chloride 1a (100 mg, 0.50 mmol), methyl 2-(4-chlorophenyl)-2H-azirine-3-carboxylate 3g (156
mg, 0.74 mmol) and triethylamine (53 mg, 0.52 mmol) according to the general procedure. Dark
blue solid, mp 335–337 °С. 1H NMR (DMSO-d6): δ 3.62 (s, 3H), 7.50-7.65 (m, 2H), 7.65-7.77
13
(m, 2H), 11.25 (s, 1H). С NMR (DMSO-d6): δ 51.4 (CH3), 108.5 (C), 127.2 (C), 128.4 (C),
128.6 (CH), 130.6 (CH), 136.1 (C), 151.1 (C), 164.3 (C), 167.9 (C). HRMS (ESI) m/z: 499.0458
+
calcd for C24H17Cl2N2O6 [M + H]+, found 499.0476.
4.8.
tetrafluoroborate (11a)
An excess of tetrafluoroboric acid was added to a suspension of 5-(methoxycarbonyl)-2-
1-(2-Hydroxy-5-(methoxycarbonyl)-4-phenyl-1H-pyrrol-3-yl)pyridin-1-ium
oxo-4-phenyl-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ide 5a (51 mg, 0.17 mmol) in 3
19

ACCEPTED MANUSCRIPT
mL of methanol till the complete change of the color from dark red to bright yellow. Then the
solvent was evaporated and the residue treated with diethyl ether, filtered off, washed with
1
additional amount of ether and dried. Bright yellow solid, 65 mg (98%), mp 129-131 °С. H
NMR (DMSO-d6): δ 3.60 (s, 3H), 7.10-7.19 (m, 2H), 7.20-7.31 (m, 3H), 7.98-8.19 (m, 2H),
8.47-8.70 (m, 1H), 8.81-8.98 (m, 2H), 11.68 (s, broad, 0.35H, OH), 12.23 (s, 1H). 13С NMR
(DMSO-d6): δ 51.0 (CH3), 107.3 (C), 109.8 (C), 125.6 (C), 127.8 (CH), 127.9 (CH), 128.0 (CH),
129.7 (CH), 130.6 (C), 143.0 (C), 146.2 (CH), 147.7 (CH), 160.3 (C). HRMS (ESI) m/z:
+
295.1077 calcd for C17H15N2O3 [M – BF4]+, found 295.1066. IR (KBr, cm−1): ν 1058, 1300,
1473, 1693, 3253, 3547.
4.9. Typical procedure for catalytic hydrogenation of pyrrolides 5
A
suspension of 5-(methoxycarbonyl)-2-oxo-4-phenyl-3-(pyridin-1-ium-1-yl)-2,3-
dihydro-1H-pyrrol-3-ide 5a (89 mg, 0.30 mmol) and PtO2 (7 mg, 10 mol %) was stirred in
hydrogen atmosphere overnight (completion of the reaction was indicated by TLC and
disappearance of red color). The resulting colorless solution was filtered from PtO2, concentrated
in vacuo and purified by silica gel column chromatography on silica
(dichloromethane/methanol).
4.9.1. Methyl 5-oxo-3-phenyl-4-(piperidin-1-yl)-4,5-dihydro-1H-pyrrole-2-carboxylate (12a)
Compound 12a (63 mg, 69%) was prepared from 5-(methoxycarbonyl)-2-oxo-4-phenyl-
3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ide 5a (89 mg, 0.30 mmol) and PtO2 (7 mg, 10
mol%) according to the general procedure. Pale yellow solid, mp 184-186 °С
(dichloromethane/diethyl ether). Rf (1% methanol in dichloromethane) 0.53.
1H NMR (DMSO-
d6): δ 1.35-1.50 (m, 6H), 2.67-2.81 (m, 2H), 3.06-3.18 (m, 2H), 3.45 (s, 3H), 4.96 (d, J = 1.2 Hz,
13
1H), 7.23-7.31 (m, 3H), 7.32-7.39 (m, 2H), 8.69 (s, 1H). С NMR (DMSO-d6): δ 23.7 (CH2),
25.7 (CH2), 49.7 (CH2), 52.0 (CH3), 59.1 (CH), 123.9 (C), 127.6 (CH), 127.7 (CH), 128.8 (CH),
+
133.6 (C), 139.3 (C), 170.3 (C), 170.4 (C). HRMS (ESI) m/z: 301.1547 calcd for C17H21N2O3
[M + H]+, found 301.1557.
20

ACCEPTED MANUSCRIPT
4.9.2. Methyl (2RS,3RS,4RS)-5-oxo-3-phenyl-4-(piperidin-1-yl)pyrrolidine-2-carboxylate (13a)
Compound 13a (46 mg, 50%) was prepared from obtained from 5-(methoxycarbonyl)-2-
oxo-4-phenyl-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ide 5a (89 mg, 0.30 mmol) and
PtO2 (14 mg, 20 mol%) according to the general procedure, except from that the reaction
mixture was stirred 48 h instead of overnight. White solid, mp 179-181 °С
(dichloromethane/diethyl ether). Rf (2% methanole in dichloromethane) 0.28. 1H NMR (DMSO-
d6): δ 1.12-1.33 (m, 6H), 2.19-2.32 (m, 2H), 2.56-2.76 (m, 2H), 3.27 (s, 1H), 3.35 (d, J = 7.0 Hz,
1H), 3.94 (t, J = 6.6 Hz, 1H), 4.53 (d, J = 6.1 Hz, 1H), 7.18-7.25 (m, 5H), 8.17 (s, 1H). 13С NMR
(DMSO-d6): δ 24.0 (CH2), 25.4 (CH2), 47.6 (CH), 51.3 (CH3), 51.5 (CH2), 56.9 (CH), 67.5 (CH),
127.1 (CH), 127.3 (CH), 129.2 (CH), 136.1 (C), 169.4 (C), 174.5 (C). HRMS (ESI) m/z:
+
303.1703 calcd for C17H23N2O3 [M + H]+, found 303.1713.
4.9.3.
Methyl
(2RS,3RS,4RS)-3-(4-bromophenyl)-5-oxo-4-(piperidin-1-yl)pyrrolidine-2-
carboxylate (13b)
Compound 13b (21 mg, 19%) was prepared from 4-(4-bromophenyl)-5-
(methoxycarbonyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ide 3b (106 mg, 0.28
mmol) and PtO2 (6 mg, 10 mol%) according to the general procedure. White solid, mp 175-177
1
°С (dichloromethane/diethyl ether). Rf (1% methanole in dichloromethane) 0.41. H NMR
(DMSO-d6): δ 1.17-1.30 (m, 6H), 2.17-2.24 (m, 2H), 2.65-2.75 (m, 2H), 3.30-3.35 (m, 4H, here
is an overlapping of the H2O residual peak, signal of methyl group and dublet belonging to one
of the pyrrolidine ring protons), 3.96 (t, J = 6.5 Hz, 1H), 4.54 (d, J = 6.1 Hz, 1H), 7.13-7.18 (m,
2H), 7.42-7.48 (m, 2H), 8.23 (s, 1H). 13С NMR (DMSO-d6): δ 24.0 (CH2), 25.3 (CH2), 46.9
(CH), 51.4 (CH3), 51.6 (CH2), 56.7 (CH), 67.0 (CH), 120.3 (C), 130.3 (CH), 131.4 (CH), 135.5
+
(C), 169.3 (C), 174.3 (C). HRMS (ESI) m/z: 381.0808 calcd for C17H22BrN2O3 [M + H]+, found
381.0819.
4.9.4.
Methyl
3-(4-methoxyphenyl)-5-oxo-4-(piperidin-1-yl)-4,5-dihydro-1H-pyrrole-2-
carboxylate (12c)
21

ACCEPTED MANUSCRIPT
Compound 12c (40 mg, 41%) was prepared from 5-(methoxycarbonyl)-4-(4-
methoxyphenyl)-2-oxo-3-(pyridin-1-ium-1-yl)-2,3-dihydro-1H-pyrrol-3-ide 5c (100 mg, 0.31
mmol) and PtO2 (7 mg, 10 mol%) according to the general procedure. Pale yellow solid, mp 129-
1
131 °С (dichloromethane/diethyl ether). Rf (1% methanole in dichloromethane) 0.19. H NMR
(DMSO-d6): δ 1.36-1.51 (m, 6H), 2.69-2.82 (m, 2H), 3.04-3.18 (m, 2H), 3.46 (s, 3H), 3.76 (s,
3H), 4.95 (d, J = 1 Hz, 1H), 6.88-6.95 (m, 2H), 7.22-7.29 (m, 2H), 8.60 (s, 1H). 13С NMR
(DMSO-d6): δ 23.7 (CH2), 25.7 (CH2), 49.7 (CH2), 52.0 (CH3), 55.0 (CH3), 59.1 (CH), 113.2
(CH), 125.2 (C), 125.5 (C), 130.0 (CH), 138.7 (C), 158.7 (C), 170.3 (C), 170.7 (C). HRMS (ESI)
+
m/z: 331.1652 calcd for C18H23N2O4 [M + H]+, found 331.1662.
Acknowledgements
We gratefully acknowledge the financial support of the Russian Science Foundation (Grant no.
16-13-10036). This research was carried out using the resources of the X-ray Diffraction Centre,
the Centre for Magnetic Resonance, the Computer Centre, the Centre for Chemical Analysis and
Materials of St. Petersburg State University.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.tet…
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