Product selectivity of thermal Buchner reaction of methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates with benzene, naphthalene and mesitylene, and ring-opening/closing reaction of products

Article abstract of DOI:10.1016/j.tet.2021.132153

Methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates were synthesized and the product selectivity of their thermal Buchner reaction with benzene, naphthalene and mesitylene was studied. The reaction of the isoxazolyl-substituted diazoacetates with benzene gave

Full text of DOI:10.1016/j.tet.2021.132153

Tetrahedron 88 (2021) 132153
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Product selectivity of thermal Buchner reaction of methyl
2-(3-arylisoxazol-5-yl)-2-diazoacetates with benzene, naphthalene
and mesitylene, and ring-opening/closing reaction of products
Anna V. Serebryannikova, Ekaterina E. Galenko, Mikhail S. Novikov,
Alexander F. Khlebnikov*
Saint Petersburg State University, Institute of Chemistry, 7/9 Universitetskaya nab, St. Petersburg, 199034, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates were synthesized and the product selectivity of their
thermal Buchner reaction with benzene, naphthalene and mesitylene was studied. The reaction of the
isoxazolyl-substituted diazoacetates with benzene gave a mixture of cycloheptatriene/norcaradiene
isomeric adducts, which are in a rapid equilibrium. Heating the same diazo compounds with naphtha-
lene led exclusively to stable norcaradiene adducts. In contrast, their thermal reaction with mesitylene
gave only the products of carbene insertion into CeH bond of mesitylene. According to DFT calculations,
such a difference in the product selectivity of the thermal Buchner reaction of the diazoacetates with
benzene, naphthalene and mesitylene is associated with the fact that the first two reactions proceed
under kinetic control, and the last one under thermodynamic control. Isoxazoles synthesized were
converted to a new family of functionalized enaminones, (Z)-methyl 5-amino-2,5-diaryl-3-oxo-2-
phenylpent-4-enoates, by reaction with Mo(CO)6/H2O hydrogenative reagent, wherein Mo(CO)6 cata-
lyzes also the retro-Buchner reactions of the norcaradiene moiety of the starting compounds. The ob-
tained enaminones are convenient precursors of 3,6-diaryl-4-hydroxy-3-phenylpyridin-2(1H)-ones,
which were prepared from them under thermal conditions in high yields.
Received 28 January 2021
Received in revised form
5 April 2021
Accepted 9 April 2021
Available online 13 April 2021
Keywords:
Buchner reaction
Diazoesters
Cycloaddion
Isoxazoles
Pyridines
© 2021 Elsevier Ltd. All rights reserved.
1. Introduction
substituted diazo carbonyl compounds with unfunctionalized are-
ꢀ
nes have hardly been studied. Thus, L’abbe et al. found that pro-
longed heating at 70 ꢀC methyl 2-diazo-2-(1-methyl/ethyl-1H-
tetrazol-5-yl)acetates in benzene gave the corresponding NCD de-
rivatives. In contrast, the reaction of methyl 2-diazo-2-(2-methyl/
ethyl-2H-tetrazol-5-yl)acetates under similar conditions gave NCD/
CHT equilibrium mixtures (Scheme 1) [9]. Recently benzo[e]- and
hetero[e]-fused indol-7-oles were synthesized by the Cu(II)-
catalyzed intramolecular aromatic substitution reaction of 3-aryl-
2-(diazoacetyl)pyrroles [10].
Although some methyl 2-diazo-2-(3-methylisoxazol-5-yl)ace-
tates have been synthesized [11], their reactivity towards arenes
has not been studied, and the synthesis of 2-diazo-2-(3-
arylisoxazol-5-yl) acetates has not been reported to date. Mean-
while, the introduction of the isoxazole fragment into the products
of the Buchner reaction allows them to be used in various hetero-
cyclic syntheses based on diverse reactivity of isoxazoles [12]. As
part of our ongoing studies on the synthetic use of functionalized
isoxazole derivatives [13], we synthesized a series of methyl 2-(3-
Buchner reaction of arenes with diazo compounds [1] is one of
the powerful synthetic methods for the synthesis of norcaradiene
(NCD)/cycloheptatriene (CHT) containing frameworks [2,3]. These
compounds are applied in homogeneous catalysis as ligands in
transition metal complexes, in synthesis, in modern materials, and
in pharmaceuticals [4]. The use of NCD/CHT-containing compounds
for the preparation of various classes of strained cage skeletons is
growing every year [4c,5]. The metal-catalyzed retro-Buchner re-
action of substituted NCD/CHT is a new important reason for
development of NCD/CHT chemistry [6]. Of special interest is the
study of equilibrium NCD/CHT, which began more than 60 years
ago and continues to this day [2b,7]. Various diazo carbonyl com-
pounds have been reacted with arenes under thermal, catalytic and
photolytic conditions [2,3,8]. However, the reactions of heteroaryl
* Corresponding author.
E-mail address: a.khlebnikov@spbu.ru (A.F. Khlebnikov).
https://doi.org/10.1016/j.tet.2021.132153
0040-4020/© 2021 Elsevier Ltd. All rights reserved.

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
Scheme 1. Reactions tetrazolyldiazoacetates with benzene.
arylisoxazol-5-yl)-2-diazoacetates 1a-f and experimentally studied
the product selectivity of their Buchner reaction with benzene,
naphthalene and mesitylene to use this reaction as a tool to pro-
duce a new family of isoxazole-containing compounds and, in
particular, containing NCD/CHT moieties. We also performed the
DFTcalculations of the reaction of carbene, generated from 2-diazo-
2-(3-phenylisoxazol-5-yl)acetate, with aforementioned arenes to
shed some light on the reasons for a quite different Buchner reac-
tion outcomes. The use of the prepared compounds in heterocyclic
synthesis was demonstrated by their transformation in a new
family of functionalized enaminones, methyl 5-amino-2,5-diaryl-3-
oxopent-4-enoates, followed by the conversion of the latter into
pyridine derivatives, 3,6-diaryl-4-hydroxy-3-phenylpyridin-2(1H)-
ones.
followed by the tetramethylguanidine-mediated reaction of bro-
mides 3 with acetone cyanohydrin [16]. Nitriles 4a-f then were
hydrolyzed to acids 5a-f, which were esterified with diazomethane,
and the diazo transfer in esters 6a-f obtained afforded desired diazo
compounds 1a-f [17].
Transition metal catalysts are commonly used in the Buchner
additions to arenes, but this usually refers to the reactions of diazo
compounds that do not contain a heterocyclic moiety [2,3,8]. The
behaviour of heterocyclyl-substituted diazo compound depends on
the specific heterocyclic fragment, since the catalyst can coordinate
with heteroatoms, and in this case it is impossible to predict the
selectivity and yield of the Buchner reaction. Initially, the reaction
of benzene with diazo compound 1a was carried out in the pres-
ence of a series of Rh(II) catalysts (Rh2(OAc)4, Rh2(OPiv)4, Rh2(tfa)4,
Rh2(esp)4) using DCE as a solvent due to the insolubility of the
catalyst in benzene. However, the experiments resulted in resin-
ification of the reaction mixtures and did not give the desired
product of the Buchner reaction. On the contrary, heating benzene
solutions of diazo compounds 1a-f in a thick-wall tube with screw
cap at 110 ꢀC for 2e3.5 h led to the formation of compounds 8/9a-f
(Scheme 3). All new compounds were characterized by 1H, 13C NMR
and HRMS methods. The chemical shifts of the H and C atoms in the
2. Results and discussion
Methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates 1a-f were pre-
pared via the reaction sequence shown in Scheme 2. Some 2-(3-
arylisoxazol-5-yl)acetonitriles were earlier prepared in low yield
as one of the products of reaction 6-aryl-4-(methylsylfanyl)-2-oxo-
2H-pyran-3-carbonitriles with hydroxylamine hydrochloride [14].
For the synthesis of nitriles 4a-f we, therefore, used another
approach which involved cycloaddition of nitrile oxide [15], derived
from N-hydroxybenzimidoyl chlorides, to propargyl bromide,
positions 1/6 of pure cycloheptatrienes are at
120e130 ppm, respectively, whereas shifts of the corresponding
norcaradiene atoms are at
¼ 2.8e3.5 and 35e45, respectively
d
¼ 5.2e5.3 and
d
Scheme 2. Synthesis of diazo compounds 1a-f.
2

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
Scheme 3. Thermal Buchner reaction of diazo compounds 1a-f with benzene.
[2b,18]. The corresponding chemical shifts in the systems existing
in rapid CHT%NCD equilibrium lie between these values and can
be used for quantitative estimation of the equilibrium position
[2b,18].
According to the aforementioned NMR chemical shift criteria,
products 8/9a-f, which have chemical shifts of the H and C atoms in
the positions 1 and 6 (numbering as in unsubstituted CHT/NCD)
According to the calculations the addition of singlet carbene 7f
across the carbon-carbon bond of benzene proceeds via the energy
barrier much lower than for the insertion reaction leading to iso-
xazole 10. The valence isomers 8f and 9f, which have almost equal
energies, interconvert through a low energy barrier of ca. 8.5 kcal/
mol. The isomerization of compounds 8/9f into the much more
stable CeH insertion product 10 is infeasible under the reaction
conditions due to the too high energy barrier (36.5 kcal/mol) for the
retro-Buchner reaction of 8f. The calculations of the equilibrium
8f%9f in CHCl3 at 25 ꢀC showed that NCD isomer 8f is only by
0.1 kcal/mol more stable than CHT isomer 9f. In addition, due to the
activation barrier of only 8.5 kcal/mol they must very rapidly
interconvert at 25 ꢀC. These data are in good agreement with NMR
chemical shifts of products 8/9a-e.
d
¼ 3.99e4.04 and 60.8e62.4 ppm, respectively, exist as rapid
equilibrium mixtures of CHT/NCD valence isomers. To shed some
light on the mechanism of the reaction and to estimate the 8/9 ratio
in the resulting solutions we performed the DFT calculations at the
B3LYP-D3/6-311þG(d,p) level of theory with SMD model for the
solvent (Scheme 4, for details of the calculations see the Supporting
information). It has recently been shown that this level of theory is
adequate for modeling the products of the Buchner reaction [19].
When diazo compounds 1a-f were heated in a naphthalene melt
Scheme 4. Relative Gibbs free energies for the energy profile of the diazo compound 1f thermolysis in benzene (in kcal/mol, 383 K, DFT B3LYP-D3/6-311þG(d,p) level with SMD
model for benzene).
3

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
second, to the quinoid-type. The same reason explains the much
higher stability of the NCD isomer 11f than the NCD isomer 13f. The
CeH insertion reactions, leading to isoxazoles 15 and 16, have the
much higher barrier than the Buchner reaction. The irreversible
character of the latter reaction, due to the too high energy barrier
(42.7 kcal/mol) for retro-Buchner reaction of 11f, is the reason for
the absence of much more thermodynamically stable isomers 15
and 16 among the reaction products. The calculations of the equi-
librium 11f/12f in CHCl3 at 25 ꢀC showed that NCD isomer 11f is by
19.0 kcal/mol more stable than CHT isomer 12f, and the barrier for
isomerization of 12f to 11f is only 0.1 kcal/mol. These data are in
good agreement with NMR chemical shifts of products 11a-f.
The reaction of diazo compounds 1a-f with mesitylene at 120 ꢀC
proceeds through the carbene CeH insertion to afford isoxazoles
17a-f as the only products (Scheme 7). Compounds 17a-f were
characterized by 1H, 13C NMR and HRMS methods. Moreover, the
structure of 17a was also confirmed by single-crystal X-ray
diffraction analysis (Fig. 1).
Scheme 5. Thermal Buchner reaction of diazo compounds 1a-f with naphthalene.
at 120 ꢀC only NCD type products 11a-f were isolated, which
resulted from the addition of carbenes 7a-f across the C(1)¼C(2)
double bond of naphthalene (Scheme 5). According to the afore-
mentioned NMR chemical shift criteria, products 11a-f, which have
chemical shifts of the H and C atoms in the positions 1 and 6
(numbering as in unsubstituted CHT/NCD)
3.70e3.72 and 34.4e34.5/34.7e36.5 ppm, respectively, exist in
NCD forms.
d
¼
3.31e3.32/
According to the calculations the addition of carbene 7f across
the C(1)¼C(2) naphthalene bond proceeds via the energy barrier
much lower than for the addition of carbene 7f across the C(2)¼
C(3) bond (by 4.8 kcal/mol), which makes it impossible for them to
compete (Scheme 6). This is intuitively understandable, since in the
first case the transition state is of benzenoid-type, while in the
Scheme 7. Thermolysis of diazo compounds 1a-f in mesitylene.
Scheme 6. Relative Gibbs free energies for the energy profile of the diazo compound 1f thermolysis in naphthalene (in kcal/mol, 393 K, DFT B3LYP-D3/6-311þG(d,p) level with SMD
model for benzene).
4

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
Fig. 1. X-ray crystal structure of compound 17a.
According to the calculations (Scheme 8) the addition of carbene
7f across the C]C mesitylene bond proceeds via the energy barrier
much lower than for the insertion reaction leading to isoxazole 17f.
The CHT/NCD valence isomers 18/19f, having practically equal en-
ergies, interconvert via a low energy barrier of ca. 9 kcal/mol.
However, unlike the retro-Buchner reactions of NCDs 8f and 11f,
the carbene extrusion from 18f proceeds through a much lower
barrier (30.8 kcal/mol), which can be easily overcome under the
experimental conditions. Therefore, the formation of CeH insertion
product, isoxazole 17f, in the reaction of diazo compounds 1 with
mesitylene is a consequence of the thermodynamic control of the
reaction. Although the most studied variant of the retro-Buchner
reaction is catalytic, thermally induced variants are also
mentioned [20].
Scheme 8. Relative Gibbs free energies for the energy profile of the diazo compound
1f thermolysis in mesitylene (in kcal/mol, 393 K, DFT B3LYP-D3/6-311þG(d,p) level
with SMD model for mesitylene).
Further, some transformations of the isoxazole moiety of the
Buchner reaction products were performed to demonstrate their
synthetic utility. It is known that isoxazole ring can be cleaved in
the presence of Mo(CO)6 and water to give b-aminoenones [13c,21].
Such reaction with compounds 8/9, 11, 17 could potentially lead to a
new family of functionalized enaminones. In fact, (Z)-methyl 5-
amino-5-aryl-3-oxo-2-phenylpent-4-enoates 20a-e were isolated
in 45e79% yield when compounds 8/9a-f were reacted with
Mo(CO)6/H2O in MeCN at 88 ꢀC for 4.5e5.5 h. Analogously, (Z)-
methyl 5-amino-5-aryl-3-oxo-2-(naphth-1-yl)pent-4-enoates 21a-
d were the only products of the reaction of compounds 11a, c-e
under the same reaction conditions (Scheme 9). In contrast, com-
pounds 17 were intact under the aforementioned reaction
conditions.
Scheme 9. Synthesis of enaminones 20 and 21.
This means that Mo(CO)6 catalyzes not only reductive cleavage
of the NeO isoxazole bond but also the retro-Buchner reactions of
the norcaradiene moiety of compounds 8/9 and 11. Compounds 20
reaction with benzene, naphthalene and mesitylene was experi-
mentally studied. The reaction of diazo compounds 1 with benzene
gave CHT/NCD valence isomers 8/9, which are in a rapid equilib-
rium. The reaction of diazo compounds 1 with naphthalene led
exclusively to stable norcaradiene product 11. In contrast, the re-
action with mesitylene gave only the products of carbene insertion
into CeH bond of mesitylene. According to DFT calculations, such a
difference in the product selectivity of the thermal Buchner reac-
tion of diazoacetates 1 with benzene, naphthalene and mesitylene
is associated with the fact that the first two reactions proceed
under kinetic control, and the last one under thermodynamic
control. Isoxazoles 8/9 and 11 were converted to a new family of
functionalized enaminones, (Z)-methyl 5-amino-2,5-diaryl-3-oxo-
2-phenylpent-4-enoates 20, 21, by the reaction with Mo(CO)6/H2O
hydrogenative reagent, wherein Mo(CO)6 catalyzes also the retro-
Buchner reactions of the norcaradiene moiety of compounds 8/9
and 11. Enaminones 20 and 21 are convenient precursors of 3,6-
diaryl-4-hydroxy-3-phenylpyridin-2(1H)-ones, which can be
and 21 contain the amino group in the d-position towards the
methoxycarbonyl group and consequently could potentially be
used for the preparation of pyridine derivatives via intramolecular
condensation. In fact, pyridines 22 and 23 were isolated in high
yield after heating of enaminones 20, 21 in mesitylene at 160 ꢀC for
1.5 h (Scheme 10).
Compounds 22 and 23 exist in 3,6-diaryl-4-hydroxy-3-
phenylpyridin-2(1H)-one form due to this form is much more
stable than 3,6-diarylpyridine-2,4-diol form (by 5.7e6.1 kcal/mol,
according to the DFT calculations (see the Supporting information).
3. Conclusion
A series of methyl 2-(3-arylisoxazol-5-yl)-2-diazoacetates 1 was
synthesized and the product selectivity of their thermal Buchner
5

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
4.2. General procedure for the synthesis of 3-aryl-5-(bromomethyl)
isoxazoles 3
Compounds 3 were prepared according to slightly modified
published procedure [15].
A mixture of propargyl bromide
(3e3.5 mmol), saturated aq. NaHCO3 (2 mL) and DCM (1e2 mL) was
added dropwise to the solution of benzohydroximinoyl chloride 2
(1 mmol) in dichloromethane (DCM) (1e2 mL) at 0 ꢀC. The reaction
mixture was stirred for 1 d (TLC control, light petroleum/ethyl ac-
etate 10:1 (v/v)). Then the organic layer was separated, the inor-
ganic layer was extracted with DCM, the combined organic phase
was dried (Na2SO4) and concentrated under reduced pressure. The
resulted solid was crystallized from hexanes or purified by column
chromatography on silica gel with light petroleum/ethyl acetate
(8:1, v/v) as an eluent.
4.2.1. 5-(Bromomethyl)-3-(p-tolyl)isoxazole (3a)
Compound 3a (5.27 g, 72%) was prepared from N-hydroxy-4-
methylbenzimidoyl chloride 2a (4.88 g, 28.8 mmol), propargyl
bromide (15 g, 79.3 mmol) in DCM (180 mL) and NaHCO3 (50 mL).
Beige solid, m.p. 84e85ꢀС (DCM). Rf ¼ 0.48 (light petroleum/ethyl
acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.40 (s, 3H), 4.50 (s,
d
2H), 6.60 (s, 1H), 7.26 (d, J ¼ 7.9 Hz, 2H), 7.68 (d, J ¼ 7.9 Hz, 2H). 1H
NMR (CDCl3) spectrum is in good agreement with published data
[23]. 13C NMR (100 MHz, CDCl3):
d
¼18.7 (CH2), 21.4 (CH3), 101.8
(CH), 125.7 (C), 126.7 (CH), 129.6 (CH), 140.4 (C), 162.7 (C), 167.7 (C).
Scheme 10. Synthesis of pyridones 22 and 23.
HRMS (ESI): m/z calcd. for C11H10BrNO þ Naþ: 273.9838 [M þ Na]þ;
found: 273.9845. IR (KBr) cmꢁ1
:
n
¼ 1287, 1429, 1610, 3138.
prepared from them under thermal conditions in high yields.
4.2.2. 5-(Bromomethyl)-3-(4-(tert-butyl)phenyl)isoxazole (3b)
Compound 3b (3.93 g, 67%) was prepared from 4-(tert-butyl)-N-
hydroxybenzimidoyl chloride 2b (4.24 g, 20.0 mmol), propargyl
bromide (12.5 g, 66 mmol) in DCM (160 mL) and aq. NaHCO3
(40 mL). Beige solid, m.p. 63e67ꢀС (hexanes) (lit. m.p. 75e76 ꢀC
[23]. Rf ¼ 0.56 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR
4. Experimental
4.1. General information and methods
Melting points were determined on a capillary melting point
apparatus Stuart® SM.P.30.1H (400 MHz) and 13C (100 MHz) NMR
spectra were recorded in CDCl3 or DMSO‑d6 with Bruker AVANCE III
(400 MHz, CDCl3):
d
¼1.35 (s, 9H), 4.51 (s, 2H), 6.61 (s, 1H), 7.48 (d,
J ¼ 8.4 Hz, 2H), 7.72 (d, J ¼ 8.4 Hz, 2H). 1H NMR (CDCl3) spectrum is
in good agreement with published data [24]. 13C NMR (100 MHz,
400 spectrometer. Chemical shifts (
million downfield from tetramethylsilane (TMS
d
) are reported in parts per
CDCl3):
d
¼18.7 (CH2), 31.2 (CH3), 34.8 (C), 101.9 (CH), 125.7 (C),
d
0.00). 1H NMR
125.9 (CH), 126.5 (CH), 153.6 (C), 162.7 (C), 167.7 (C). HRMS (ESI): m/
z calcd. for C14H16BrNO þ Naþ: 316.0307 [M þ Na]þ; found:
spectra were calibrated according to the residual peak of CHCl3
(7.26 ppm), DMSO‑d6 (2.50 ppm). 13C{1H} and 13C DEPT-135 were
calibrated according to the peak of CDCl3 (77.00 ppm), DMSO‑d6
(39.51 ppm). Mass spectra were recorded on a Bruker maXis HRMS-
ESI-QTOF, electrospray ionization. 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 single-crystal
of 17a was measured at HyPix diffractometer at a temperature of
316.0300. IR (KBr) cmꢁ1
:
n
¼ 1218, 1431, 1606, 1697, 2965.
4.2.3. 5-(Bromomethyl)-3-(4-fluorophenyl)isoxazole (3c)
Compound 3c (5.74 g, 75%) was prepared from 4-fluoro-N-
hydroxybenzimidoyl chloride 2c (5 g, 28.8 mmol), propargyl bro-
mide (18 g, 95 mmol) in DCM (180 mL) and aq. NaHCO3 (50 mL).
Light-yellow solid, m.p. 70e72ꢀС (hexanes). Rf ¼ 0.43 (light pe-
troleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼4.51 (s,
d
100 K using monochromated CuK
a
radiation. The crystallographic
2H), 6.59 (s, 1H), 7.15 (t, J ¼ 8.7 Hz, 2H), 7.78 (dd, J ¼ 8.7, 5.3 Hz, 2H).
data and some parameters of refinement are placed in Tables S1-S6
in the Supplementary data. Crystallographic data for structure 17a
have been deposited with the Cambridge Crystallographic Data
Centre (CCDC 2057352). Acetonitrile was distilled from P2O5, then
distilled from anhydrous K2CO3, and stored over 3 Å sieves. Ben-
zene and mesitylene was distilled from Na with benzophenone, and
stored over Na. Benzohydroxamic acid chlorides 2a-f were pre-
pared according to the published procedure [22].
13C NMR (100 MHz, CDCl3):
d¼18.5 (CH2), 101.8 (CH), 116.1 (d,
J ¼ 21.7 Hz, CH), 124.8 (d, J ¼ 3.2 Hz, C), 128.7 (d, J ¼ 8.5 Hz, CH),
161.8 (C), 163.9 (d, J ¼ 250.4 Hz, C), 168.2 (C). Both 1Н and 13С NMR
spectra are in good agreement with published data [25]. HRMS
(ESI): m/z calcd. for C10H7BrFNO þ Naþ: 277.9587 [M þ Na]þ; found:
277.9595. IR (KBr) cmꢁ1
:
n
¼ 1245, 1436, 1529, 1609, 1676, 3107.
4.2.4. 5-(Bromomethyl)-3-(4-chlorophenyl)isoxazole (3d)
Caution: Although diazo compounds 1 were found to be safe in
our hands, they are potentially explosive and should be handled
with care. Thermal decomposition of diazo compounds 1 in arenes
(up to 0.3 mmol) was safe with the equipment used, however,
scaling up the experiment will require special precautions, since
the decomposition of diazo compounds 1 is accompanied by the
evolution of nitrogen.
Compound 3d (2.42 g, 59%) was prepared from 4-chloro-N-
hydroxybenzimidoyl chloride 2d (2.85 g, 15.0 mmol), propargyl
bromide (11.2 g, 75.0 mmol) in DCM (90 mL) and aq. NaHCO3
(30 mL). Beige solid, m.p. 115e117ꢀС (DCM) (lit. m.p. 117e119 ꢀC
[24]). Rf ¼ 0.46 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR
(400 MHz, CDCl3):
d
¼4.51 (s, 2H), 6.61 (s, 1H), 7.44 (d, J ¼ 8.6 Hz,
2H), 7.73 (d, J ¼ 8.6 Hz, 2H). 1H NMR (CDCl3) spectrum is in good
6

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
agreement with published data [24]. 13C NMR (100 MHz, CDCl3):
(646 mg, 5.61 mmol) in MeCN (55 mL). Colorless solid, m.p.
d
¼18.5 (CH2), 101.7 (CH), 127.0 (C), 128.0 (CH), 129.2 (CH), 136.2 (C),
64e67 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.28 (light petro-
161.8 (C), 168.3 (C). HRMS (ESI): m/z calcd. for C10H7BrClNO þ Hþ:
leum/ethyl acetate ¼ 5:1). 1H NMR (400 MHz, CDCl3):
¼1.36 (s,
d
273.9451 [M þ H]þ; found, 273.9454. IR (KBr) cmꢁ1
:
n
¼ 1227, 1426,
9 H), 3.94 (s, 2H), 6.66 (s, 1H), 7.49 (d, J ¼ 8.4 Hz, 2H), 7.73 (d,
1605, 3135.
J ¼ 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼16.7 (CH2), 31.1 (CH3),
d
34.9 (C), 101.8 (CH), 114.0 (C), 125.3 (C), 126.0 (CH), 126.6 (CH), 153.9
4.2.5. 5-(Bromomethyl)-3-(4-bromophenyl)isoxazole (3e)
(C), 161.2 (C), 162.8 (C). HRMS (ESI): m/z calcd. for C15H16N2O þ Hþ:
Compound 3e (5.33 g, 58%) was prepared following general
procedure from 4-bromo-N-hydroxybenzimidoyl chloride 2e (6.5 g,
27.7 mmol), propargyl bromide (16.8 g, 88.9 mmol) in DCM
(200 mL) and aq. NaHCO3 (70 mL). Beige solid, m.p. 132e134ꢀС
(DCM). Rf ¼ 0.45 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR
241.1335 [M þ H]þ; found: 241.1336. IR (KBr) cmꢁ1
:
n
¼ 1405, 1435,
1605, 2263, 2942, 2967, 3117.
4.3.3. 2-(3-(4-Fluorophenyl)isoxazol-5-yl)acetonitrile (4c)
Compound 4c (405 mg, 34%) was prepared from 5-(bromo-
methyl)-3-(4-fluorophenyl)isoxazole 3c (1.5 g, 5.86 mmol), acetone
cyanohydrin (748 mg, 8.79 mmol), tetramethylguanidine (742 mg,
6.44 mmol) in MeCN (65 mL). Colorless solid, m.p. 115e116 ꢀC (light
(400 MHz, CDCl3):
d
¼4.51 (s, 2H), 6.61 (s, 1H), 7.60 (d, J ¼ 8.6 Hz,
2H), 7.67 (d, J ¼ 8.6 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼18.4
d
(CH2), 101.7 (CH), 124.6 (C), 127.5 (C), 128.3 (CH), 132.2 (CH), 161.9
(C), 168.3 (C). HRMS (ESI): m/z calcd. for C10H7Br2NO þ Naþ:
petroleum/ethyl acetate). Rf
¼
0.25 (light petroleum/ethyl
337.8787 [M þ Na]þ; found: 337.8783. IR (KBr) cmꢁ1
:
n
¼ 1284,
acetate ¼ 5:1). 1H NMR (400 MHz, CDCl3):
¼3.95 (s, 2H), 6.65 (s,
d
1425, 1602, 3041, 3138.
1H), 7.17 (t, J ¼ 8.8 Hz, 2H), 7.79 (dd, J ¼ 8.8, 5.3 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼16.7 (CH2), 101.7 (CH), 113.9 (C), 116.2 (d,
4.2.6. 5-(Bromomethyl)-3-phenylisoxazole (3f)
J ¼ 22.2 Hz, CH), 124.3 (d, J ¼ 3.3 Hz, C), 128.8 (d, J ¼ 8.5 Hz, CH),
161.6 (C), 162.0 (C), 164.0 (d, J ¼ 250.7 Hz, C). HRMS (ESI): m/z calcd.
for C11H7FN2O þ Hþ: 203.0615 [M þ H]þ;, found: 203.0620. IR (KBr)
Compound 3f (3.22 g, 70%) was prepared following general
procedure from 4-bromo-N-hydroxybenzimidoyl chloride 2f
(3.11 g, 20.0 mmol), propargyl bromide (9.80 g, 66 mmol) in DCM
(100 mL) and aq. NaHCO3 (35 mL). Beige solid, m.p. 83e86ꢀС (light
petroleum/ethyl acetate) (lit. m.p. 87e89 ꢀC [24]). Rf ¼ 0.58 (light
cmꢁ1
:
n
¼ 1394, 1432, 1528, 1609.
petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d
¼4.51
4.3.4. 2-(3-(4-Chlorophenyl)isoxazol-5-yl)acetonitrile (4d)
(s, 2H), 6.63 (s, 1H), 7.44e7.48 (m, 3H), 7.78e7.81 (m, 2H). 1H NMR
Compound 4d (647 mg, 54%) was prepared from 5-(bromo-
methyl)-3-(4-chlorophenyl)isoxazole 3d (1.5 g, 5.5 mmol), acetone
cyanohydrin (703 mg, 8.25 mmol), tetramethylguanidine (697 mg,
6.05 mmol) in MeCN (60 mL). Colorless solid, m.p. 107e110 ꢀC (light
(CDCl3) spectrum is in good agreement with published data [24].
13C NMR (100 MHz, CDCl3):
d
¼18.6 (CH2), 101.9 (CH), 126.8 (CH),
128.6 (C), 129.0 (CH), 130.2 (CH), 162.8 (C), 167.9 (C). HRMS (ESI): m/
z calcd. for C10H8BrNO þ Hþ: 237.9862 [M þ H]þ; found: 237.9866.
petroleum/ethyl acetate). Rf
¼
0.23 (light petroleum/ethyl
IR (KBr) cmꢁ1
:
n
¼ 1216, 1314, 1421, 1444, 1607, 3185.
acetate ¼ 5:1). 1H NMR (400 MHz, CDCl3):
¼3.96 (s, 2H), 6.66 (s,
d
1H), 7.45 (d, J ¼ 8.6 Hz, 2H), 7.73 (d, J ¼ 8.6 Hz, 2H). 13C NMR
4.3. General procedure for the synthesis of 2-((3-aryl)isoxazol-5-yl)
acetonitriles (4)
(100 MHz, CDCl3):
d
¼16.7 (CH2), 101.7 (CH), 113.8 (C), 126.6 (C),
128.1 (CH), 129.3 (C), 136.6 (C), 161.8 (C), 162.0 (C). HRMS (ESI): m/z
calcd. for C11H7ClN2O þ Naþ: 241.0139 [M þ Na]þ; found: 241.0141.
Nitriles 4 were prepared according to slightly modified pub-
IR (KBr) cmꢁ1
:
n
¼ 1396, 1426, 1607, 2259, 3130.
lished procedure [16]. 3-Aryl-5-(bromomethyl)isoxazole
3
(1 mmol) and acetone cyanohydrin (1.5 mmol) were dissolved in
dried acetonitrile (10 mL per 1 mmol). The solution of tetrame-
thylguanidine (1.1 mmol) in acetonitrile was added dropwise to the
reaction mixture at room temperature and stirred for 1 h (TLC
control, light petroleum/ethyl acetate ¼ 8:1, v/v). The 2-((3-aryl)
isoxazol-5-yl)acetonitriles 4 were purified by column chromatog-
raphy on silica gel with light petroleum/ethyl acetate (5:1, v/v) as an
eluent.
4.3.5. 2-(3-(4-Bromophenyl)isoxazol-5-yl)acetonitrile (4e)
Compound 4e (373 mg, 45%) was prepared from 5-(bromo-
methyl)-3-(4-bromophenyl)isoxazole 3e (1 g, 3.15 mmol), acetone
cyanohydrin (403 mg, 4.73 mmol), tetramethylguanidine (400 mg,
3.47 mmol) in MeCN (50 mL). Colorless solid, m.p.125e126 ꢀC (light
petroleum/ethyl acetate). Rf
¼
0.21 (light petroleum/ethyl
acetate ¼ 5:1). 1H NMR (400 MHz, CDCl3):
¼3.96 (s, 2H), 6.66 (s,
d
1H), 7.61 (d, J ¼ 8.6 Hz, 2H), 7.67 (d, J ¼ 8.6 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼16.7 (CH2), 101.7 (CH), 113.8 (C), 124.9 (C),
4.3.1. 2-(3-(p-Tolyl)isoxazol-5-yl)acetonitrile (4a)
127.0 (C),128.3 (CH),132.3 (CH),161.8 (C),162.1 (C). HRMS (ESI): m/z
Compound 4a (669 mg, 57%) was prepared from 5-(bromo-
methyl)-3-(p-tolyl)isoxazole 3a (1.5 g, 5.95 mmol), acetone
cyanohydrin (760 mg, 8.92 mmol), tetramethylguanidine (754 mg,
6.54 mmol) in MeCN (60 mL). Colorless solid, m.p. 98e103 ꢀC (light
calcd. for C11H7BrN2O þ Naþ: 284.9634 [M þ Na]þ; found:
284.9621. IR (KBr) cmꢁ1
:
n
¼ 1392, 1425, 1607, 2260, 3111.
petroleum/ethyl acetate). Rf
¼
0.26 (light petroleum/ethyl
4.3.6. 2-(3-Phenylisoxazol-5-yl)acetonitrile (4f)
acetate ¼ 5:1). 1H NMR (400 MHz, CDCl3):
d
¼2.41 (s, 3H), 3.94 (s,
Compound 4f (585 mg, 50%) was prepared from 5-(bromo-
methyl)-3-phenylisoxazole 3f (1.5 g, 6.30 mmol), acetone cyano-
hydrin (804 mg, 9.45 mmol), tetramethylguanidine (798 mg,
6.93 mmol) in MeCN (70 mL). Colorless solid, m.p. 76e80 ꢀC (light
petroleum/ethyl acetate) (lit. m.p. 67e68 ꢀC [26]). Rf ¼ 0.54 (light
2H), 6.66 (s, 1H), 7.28 (d, J ¼ 8.0 Hz, 2H), 7.68 (d, J ¼ 8.0 Hz, 2H). 13
C
NMR (100 MHz, CDCl3):
d
¼16.7 (CH2), 21.4 (CH3), 101.8 (CH), 114.0
(C), 125.3 (C), 126.7 (CH), 129.7 (CH), 140.7 (C), 161.2 (C), 162.9 (C).
HRMS (ESI): m/z calcd. for C12H10N2O þ Hþ: 199.0866 [M þ H]þ;
found: 199.0857. IR (KBr) cmꢁ1
3133.
:
n
¼ 1399, 1427, 1607, 2260, 2944,
petroleum/ethyl acetate ¼ 5:1). 1H NMR (400 MHz, CDCl3):
¼3.95
d
(d, J ¼ 0.9 Hz, 2H), 6.68 (s, 1H), 7.46e7.49 (m, 3H), 7.77e7.80 (m,
2H). 1H NMR (CDCl3) spectrum is in good agreement with published
4.3.2. 2-(3-(4-(tert-Butyl)phenyl)isoxazol-5-yl)acetonitrile (4b)
Compound 4b (557 mg, 45%) was prepared from 5-(bromo-
methyl)-3-(4-(tert-butyl)phenyl)isoxazole 3b (1.5 g, 5.1 mmol),
acetone cyanohydrin (651 mg, 7.65 mmol), tetramethylguanidine
data [26]. 13C NMR (100 MHz, CDCl3):
d
¼16.7 (CH2), 101.8 (CH),
113.9 (C), 126.8 (CH), 128.1 (C), 129.0 (CH), 130.5 (CH), 161.4 (C),
162.9 (C). HRMS (ESI): m/z calcd. for C11H8N2O þ Hþ: 185.0709 [M þ
H]þ; found: 185.0711. IR (KBr) cmꢁ1
:
n
¼ 1443, 1513, 2259, 3111.
7

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
4.4. General procedure for the synthesis of 2-(3-(aryl)isoxazol-5-yl)
acetic acids (5)
bromophenyl)isoxazol-5-yl)acetonitrile 4e (300 mg, 1.14 mmol),
hydrochloric acid (2 mL) in 1,4-dioxane (2 mL). Colorless solid, m.p.
156e161 ꢀC (water/1,4-dioxane). 1H NMR (400 MHz, DMSO‑d6):
The compounds 5 were prepared according to slightly modified
published procedure [27]. Conc. aq. HCl (4 mL) was added to a
solution of 2-(3-(aryl)isoxazol-5-yl)acetonitrile 4 (1 mmol) in 1,4-
dioxane (4 mL). The reaction mixture was refluxed at 105 ꢀC for
3 h (TLC control, light petroleum/ethyl acetate ¼ 8:1, (v/v)). Then
reaction mixture was cooled to room temperature and diluted with
water. The solid precipitated was filtered, washed with water and
dried on air. Rf ¼ 0.40 (dichloromethane/methanol ¼ 10:1) for all
acetic acids 5.
d
¼3.97 (s, 2H), 6.95 (s,1H), 7.71 (d, J ¼ 8.5 Hz, 2H), 7.82 (d, J ¼ 8.5 Hz,
2H), 12.91 (br. s, 1H). 13C NMR (100 MHz, DMSO‑d6):
d¼32.4 (CH2),
101.6 (CH), 123.6 (C), 127.8 (C), 128.6 (CH), 132.1 (CH), 161.1 (C), 167.7
(C), 169.1 (C). HRMS (ESI): m/z calcd. for
C
11H8BrNO3þNaþ:
303.9580 [M þ Na]þ; found: 303.9578. IR (KBr) cmꢁ1
:
n
¼ 1278,
1395, 1426, 1618, 1638, 1710, 3108.
4.4.6. 2-(3-Phenylisoxazol-5-yl)acetic acid (5f)
Compound 5f (325 mg, 84%) was prepared from 2-(3-
phenylisoxazol-5-yl)acetonitrile 4f (350 mg, 1.90 mmol), hydro-
chloric acid (2.5 mL) in 1,4-dioxane (2.5 mL). Colorless solid, m.p.
123e125 ꢀC (water/1,4-dioxane). 1H NMR (400 MHz, DMSO‑d6):
4.4.1. 2-(3-(p-Tolyl)isoxazol-5-yl)acetic acid (5a)
Compound 5a (606 mg, 92%) was prepared from 2-(3-(p-tolyl)
isoxazol-5-yl)acetonitrile 4a (604 mg, 3.0 mmol), hydrochloric acid
(4 mL) in 1,4-dioxane (4 mL). Colorless solid, m.p. 143e146 ꢀC
d
¼3.96 (s, 2H), 6.92 (s, 1H), 7.50e7.51 (m, 3H), 7.84e7.87 (m, 2H),
12.90 (br. s, 1H). 13C NMR (100 MHz, DMSO‑d6):
d
¼32.4 (CH2), 101.6
(water/1,4-dioxane). 1H NMR (400 MHz, DMSO‑d6):
d
¼2.35 (s, 3H),
3.94 (s, 2H), 6.87 (s, 1H), 7.31 (d, J ¼ 7.9 Hz, 2H), 7.74 (d, J ¼ 7.9 Hz,
2H). 13C NMR (100 MHz, DMSO‑d6):
(CH),126.5 (CH),128.6 (C),129.1 (CH),130.2 (CH),161.9 (C),167.3 (C),
1639.2 (C). HRMS (ESI): m/z calcd. for C11H9NO3þHþ: 204.0655
d
¼21.0 (CH3), 32.4 (CH2), 101.5
[M þ H]þ; found: 204.0659. IR (KBr) cmꢁ1
:
n
¼ 1181, 1243, 1275,
(CH), 125.8 (C), 126.5 (CH), 129.7 (CH), 139.9 (C), 161.8 (C), 167.1 (C),
1408, 1616, 1639, 1710, 2552, 3107.
169.3 (C). HRMS (ESI): m/z calcd. for C12H11NO3þNaþ: 240.0631
[M þ Na]þ; found: 240.0628. IR (KBr) cmꢁ1
:
n
¼ 1278, 1392, 1429,
4.5. General procedure for the synthesis of methyl 2-(3-(aryl)
isoxazol-5-yl)acetates (6)
1618, 1638, 1715, 3109.
4.4.2. 2-(3-(4-(tert-Butyl)phenyl)isoxazol-5-yl)acetic acid (5b)
Compound 5b (435 mg, 82%) was prepared from 2-(3-(4-(tert-
butyl)phenyl)isoxazol-5-yl)acetonitrile 4b (495 mg, 2.05 mmol),
hydrochloric acid (3.3 mL) in 1,4-dioxane (3.3 mL). Colorless solid,
m.p. 128e132 ꢀC (water/1,4-dioxane). 1H NMR (400 MHz,
Methyl 2-(3-(aryl)isoxazol-5-yl)acetates 6 were prepared ac-
cording to slightly modified published procedure [13f]. A suspen-
sion or solution of 2-(3-(aryl)isoxazol-5-yl)acetic acid 5 (1 mmol) in
THF (5 mL) was slowly added under stirring and ice-cooling to the
solution of diazomethane, prepared from N-nitroso-N-methylurea
(NMU) (2.5 mmol), 40% aq. KOH (25 mmol) and ether (10 mL). The
reaction mixture was stirred for 1 h at room temperature (TLC
control, light petroleum/ethyl acetate ¼ 8:1, (v/v)), the excess of
diazomethane was quenched with acetic acid and the solvents
were evaporated to give pure compound 6.
DMSO‑d6):
d
¼1.31 (s, 9H), 3.95 (s, 2H), 6.88 (s, 1H), 7.52 (d,
J ¼ 8.3 Hz, 2H), 7.77 (d, J ¼ 8.3 Hz, 2H), 12.87 (br. s, 1H). 13C NMR
(100 MHz, DMSO‑d6):
d¼30.9 (CH3), 32.4 (CH2), 34.6 (C), 101.5 (CH),
125.9 (CH), 125.9 (C), 126.3 (CH), 152.8 (C), 161.7 (C), 167.1 (C), 169.2
(C). HRMS (ESI): m/z calcd. for C15H17NO3þNaþ: 282.1101 [M þ
Na]þ; found: 282.1097. IR (KBr) cmꢁ1
1727, 2870, 2964.
:
n
¼ 1268, 1398, 1431, 1610,
4.5.1. Methyl 2-(3-(p-tolyl)isoxazol-5-yl)acetate (6a)
Compound 6a (709 mg, 99%) was prepared from 2-(3-(p-tolyl)
isoxazol-5-yl)acetic acid 5a (680 mg, 3.13 mmol) and NMU
(806 mg, 7.83 mmol) in tetrhydrofuran (20 mL) and ether (30 mL).
Colorless solid, m.p. 79e81 ꢀC (diethyl ether/THF). Rf ¼ 0.26 (light
4.4.3. 2-(3-(4-Fluorophenyl)isoxazol-5-yl)acetic acid (5c)
Compound 5c (347 mg, 90%) was prepared from 2-(3-(4-
fluorophenyl)isoxazol-5-yl)acetonitrile 4c (354 mg, 1.75 mmol),
hydrochloric acid (2.4 mL) in 1,4-dioxane (2.4 mL). Colorless solid,
m.p. 149e153 ꢀC (water/1,4-dioxane). 1H NMR (400 MHz,
petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.40
d
(s, 3H), 3.78 (s, 3H), 3.87 (s, 2H), 6.57 (s, 1H), 7.25 (d, J ¼ 7.9 Hz, 2H),
DMSO‑d6):
d
¼3.96 (s, 2H), 6.93 (s, 1H), 7.35 (t, J ¼ 8.8 Hz, 2H), 7.92
7.69 (d, J ¼ 7.9 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼21.4 (CH3),
d
(dd, J ¼ 8.8 Hz, 5.5 Hz, 2H), 12.90 (br. s, 1H). 13C NMR (100 MHz,
32.6 (CH2), 52.6 (CH3), 101.4 (CH), 126.1 (C), 126.7 (CH), 129.6 (CH),
DMSO‑d6):
d¼32.4 (CH2), 101.6 (CH), 116.1 (d, J ¼ 22.0 Hz, CH), 125.2
140.1 (C), 162.6 (C), 165.3 (C), 168.0 (C). HRMS (ESI): m/z calcd. for
(d, J ¼ 3.1 Hz, C), 128.9 (d, J ¼ 8.6 Hz, CH), 161.0 (C), 163.2 (d,
C
13H13NO3þNaþ: 254.0788 [M þ Na]þ; found: 254.0797. IR (KBr)
247.4 Hz, C), 167.5 (C), 169.2 (C). HRMS (ESI): m/z calcd. for
cmꢁ1
:
n
¼ 1215, 1339, 1394, 1436, 1615, 1743, 3123.
C
11H8FNO3þNaþ: 244.0380 [M þ Na]þ; found: 244.0374. IR (KBr)
cmꢁ1
:
n
¼ 1239, 1393, 1434, 1530, 1619, 1710, 3106.
4.5.2. Methyl 2-(3-(4-(tert-butyl)phenyl)isoxazol-5-yl)acetate (6b)
Compound 6b (402 mg, 92%) was prepared from 2-(3-(4-(tert-
butyl)phenyl)isoxazol-5-yl)acetic acid 5b (415 mg, 1.6 mmol), and
NMU (412 mg, 4.00 mmol) in THF (15 mL) and ether (25 mL). Light
yellow oil. Rf ¼ 0.32 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR
4.4.4. 2-(3-(4-Chlorophenyl)isoxazol-5-yl)acetic acid (5d)
Compound 5d (400 mg, 92%) was prepared from 2-(3-(4-
chlorophenyl)isoxazol-5-yl)acetonitrile 4d (400 mg, 1.8 mmol),
hydrochloric acid (2.6 mL) in 1,4-dioxane (2.6 mL). Colorless solid,
m.p. 147e151 ꢀC (water/1,4-dioxane). 1H NMR (400 MHz,
(400 MHz, CDCl3):
d
¼1.35 (s, 9H), 3.78 (s, 3H), 3.88 (s, 2H), 6.58 (s,
1H), 7.47 (d, J ¼ 8.4 Hz, 2H), 7.73 (d, J ¼ 8.4 Hz, 2H). 13C NMR
DMSO‑d6):
d
¼3.97 (s, 2H), 6.96 (s, 1H), 7.58 (d, J ¼ 8.5 Hz, 2H), 7.89
(100 MHz, CDCl3):
d
¼31.2 (CH3), 32.6 (CH2), 34.8 (C), 52.6 (CH3),
(d, J ¼ 8.5 Hz, 2H), 12.91 (br. s, 1H). 13C NMR 100 MHz, DMSO‑d6):
101.5 (CH), 125.8 (CH), 126.1 (C), 126.5 (CH), 153.3 (C), 162.5 (C),
d
¼32.4 (CH2), 101.6 (CH), 127.5 (C), 128.3 (CH), 129.2 (CH), 134.8 (C),
165.3 (C), 168.1 (C). HRMS (ESI): m/z calcd. for C16H19NO3þNaþ:
161.0 (C), 167.6 (C), 169.1 (C). HRMS (ESI): m/z calcd. for
296.1257 [M þ Na]þ; found, 296.1256. IR (KBr) cmꢁ1
:
n
¼ 1204,
C
11H8ClNO3þNaþ: 260.0085 [M þ Na]þ; found: 260.0080. IR (KBr)
1267, 1433, 1612, 1749, 2869, 2963.
cmꢁ1
:
n
¼ 1279, 1392, 1427, 1618, 1638, 1714, 3109.
4.5.3. Methyl 2-(3-(4-fluorophenyl)isoxazol-5-yl)acetate (6c)
Compound 6c (379 mg, 97%) was prepared from 2-(3-(4-
fluorophenyl)isoxazol-5-yl)acetic acid 5c (386 mg, 1.66 mmol)
4.4.5. 2-(3-(4-Bromophenyl)isoxazol-5-yl)acetic acid (5e)
Compound 5e (298 mg, 93%) was prepared from 2-(3-(4-
8

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
and NMU (428 mg, 4.16 mmol) in THF (10 mL) and ether (15 mL).
4.6.1. Methyl 2-diazo-2-(3-(p-tolyl)isoxazol-5-yl)acetate (1a)
Colorless solid, m.p. 55e58 ꢀC (diethyl ether/THF). Rf ¼ 0.21 (light
Compound 1a (231 mg, 90%) was prepared from methyl 2-(3-(p-
tolyl)isoxazol-5-yl)acetate 6a (231 mg, 1 mmol), potassium car-
bonate (414 mg, 3 mmol), sodium azide (163 mg, 2.5 mmol) and 3-
(chlorosulfonyl)benzoic acid (397 mg, 1.8 mmol) in water (15 mL)
and acetonitrile (15 mL). Yellow solid, m.p. 107e108 ꢀC (dichloro-
methane). Rf ¼ 0.47 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR
petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.78
d
(s, 3H), 3.88 (s, 2H), 6.56 (s, 1H), 7.13 (t, J ¼ 8.6 Hz, 2H), 7.78 (dd,
J ¼ 8.6 Hz, 5.3 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼32.5 (CH2),
d
52.6 (CH3), 101.4 (CH), 116.0 (d, J ¼ 21.6 Hz, CH), 125.2 (d, J ¼ 3.1 Hz,
C), 128.7 (d, J ¼ 8.5 Hz, CH), 161.7 (C), 163.8 (d, J ¼ 249.8 Hz, C), 165.7
(C), 167.9 (C). HRMS (ESI): m/z calcd. for
C
12H10FNO3þNaþ:
(400 MHz, CDCl3):
d
¼2.40 (s, 3H), 3.92 (s, 3H), 6.82 (s, 1H), 7.27 (d,
258.0537 [M þ Na]þ; found: 258.0535. IR (KBr) cmꢁ1
:
n
¼ 1212,
J ¼ 7.8 Hz, 2H), 7.71 (d, J ¼ 7.8 Hz, 2H). 13C NMR (100 MHz, CDCl3):
1237, 1347, 1437, 1528, 1613, 1737.
d
¼21.4 (CH3), 52.7 (CH3), 98.9 (CH), 125.7 (C),126.8 (CH), 129.6 (CH),
140.4 (C), 156.3 (C), 162.8 (C), 163.2 (C). HRMS (ESI): m/z calcd. for
4.5.4. Methyl 2-(3-(4-chlorophenyl)isoxazol-5-yl)acetate (6d)
Compound 6d (314 mg, 99%) was prepared from 2-(3-(4-
chlorophenyl)isoxazol-5-yl)acetic acid 5d (300 mg, 1.26 mmol)
and NMU (353 mg, 3.43 mmol) in THF (10 mL) and ether (15 mL).
Colorless solid, m.p. 82e85 ꢀC (diethyl ether/THF). Rf ¼ 0.26 (light
C
13H11N3O3þNaþ: 280.0700 [M þ Na]þ; found: 280.0693. IR (KBr)
cmꢁ1
:
n
¼ 1249, 1426, 1596, 1706, 2113.
4.6.2. Methyl 2-(3-(4-(tert-butyl)phenyl)isoxazol-5-yl)-2-
diazoacetate (1b)
petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d
¼3.79
Compound 1b (254 mg, 62%) was prepared from methyl 2-(3-(4-
(tert-butyl)phenyl)isoxazol-5-yl)acetate 6b (375 mg, 1.4 mmol),
potassium carbonate (569 mg, 4.1 mmol), sodium azide (223 mg,
3.4 mmol) and 3-(chlorosulfonyl)benzoic acid (545 mg, 2.5 mmol)
in water (15 mL) and acetonitrile (10 mL). Product was purified by
column chromatography on silica gel with light petroleum/ethyl
acetate (8:1, v/v) as an eluent. Yellow solid, m.p. 100e102 ꢀC (DCM).
Rf ¼ 0.51 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz,
(s, 3H), 3.89 (s, 2H), 6.58 (s, 1H), 7.43 (d, J ¼ 8.6 Hz, 2H), 7.74 (d,
J ¼ 8.6 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼32.6 (CH2), 52.7
d
(CH3), 101.4 (CH), 127.4 (C), 128.1 (CH), 129.2 (CH), 136.0 (C), 161.7
(C), 165.8 (C), 167.9 (C). HRMS (ESI): m/z calcd. for
C
n
12H10ClNO3þNaþ: [M þ Na]þ; found: 274.0238. IR (KBr) cmꢁ1
¼ 1220, 1346, 1431, 1616, 1734, 2939, 3126.
:
4.5.5. Methyl 2-(3-(4-bromophenyl)isoxazol-5-yl)acetate (6e)
CDCl3):
d
¼1.35 (s, 9H), 3.93 (s, 3H), 6.83 (s, 1H), 7.48 (d, J ¼ 8.4 Hz,
Compound 6e (276 mg, 97%) was prepared from 2-(3-(4-
bromophenyl)isoxazol-5-yl)acetic acid 5e (270 mg, 0.96 mmol)
and NMU (246 mg, 2.39 mmol) in THF (10 mL) and ether (10 mL).
Colorless solid, m.p. 81e83 ꢀC (diethyl ether/THF). Rf ¼ 0.27 (light
2H), 7.75 (d, J ¼ 8.4 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼31.2
d
(CH3), 34.8 (C), 52.7 (CH3), 99.0 (CH), 125.7 (C), 125.9 (CH), 126.6
(CH), 153.5 (C), 156.3 (C), 162.8 (C), 163.2 (C). HRMS (ESI): m/z calcd.
for C16H17N3O3þHþ: 300.1343 [M þ H]þ; found: 300.1345. IR (KBr)
petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d
¼3.78
cmꢁ1
:
n
¼ 1250, 1341, 1427, 1596, 1702, 2105.
(s, 3H), 3.88 (s, 2H), 6.58 (s, 1H), 7.58 (d, J ¼ 8.5 Hz, 2H), 7.67 (d,
J ¼ 8.5 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d¼32.6 (CH2), 52.7
4.6.3. Methyl 2-(3-(4-fluorophenyl)isoxazol-5-yl)-2-diazoacetate
(1c)
(CH3), 101.4 (CH), 124.3 (C), 127.9 (C), 128.3 (CH), 132.1 (CH), 161.7
(C), 165.9 (C), 167.9 (C). HRMS (ESI): m/z calcd. for
Compound 1c (365 mg, 89%) was prepared from methyl 2-(3-(4-
fluorophenyl)isoxazol-5-yl)acetate 6c (370 mg, 1.57 mmol), potas-
sium carbonate (652 mg, 4.72 mmol), sodium azide (256 mg,
3.93 mmol) and 3-(chlorosulfonyl)benzoic acid (625 mg,
2.83 mmol) in water (15 mL) and acetonitrile (10 mL). Yellow solid,
C
12H10BrNO3þNaþ: 317.9736 [M þ Na]þ; found: 317.9734. IR (KBr)
cmꢁ1
:
n
¼ 1218, 1345, 1429, 1615, 1734.
4.5.6. Methyl 2-(3-phenylisoxazol-5-yl)acetate (6f)
Compound 6f (295 mg, 99%) was prepared from 2-(3phenyl-
isoxazol-5-yl)acetic acid 5f (277 mg, 1.36 mmol) and NMU (351 mg,
3.41 mmol) in THF (10 mL) and ether (10 mL). Light yellow oil.
Rf ¼ 0.28 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz,
m.p. 78e81 ꢀC (DCM). Rf
¼
0.42 (light petroleum/ethyl
acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.93 (s, 3H), 6.81 (s,
d
1H), 7.15 (t, J ¼ 8.7 Hz, 2H), 7.81 (dd, J ¼ 8.7, 5.3 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼52.7 (CH3), 98.7 (CH),116.0 (d, J ¼ 21.8 Hz, CH),
CDCl3):
d
¼3.78 (s, 3H), 3.88 (s, 2H), 6.60 (s, 1H), 7.41e7.48 (m, 3H),
124.8 (d, J ¼ 3.5 Hz, C), 128.9 (d, J ¼ 8.5 Hz, CH), 156.9 (C), 162.4 (C),
7.77e7.82 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
¼ 32.6 (CH2), 52.6
162.7 (C), 163.9 (d, J ¼ 249.9 Hz, C). HRMS (ESI): m/z calcd. for
(CH3), 101.5 (CH), 126.8 (CH), 128.85 (CH), 128.91 (C), 130.0 (CH),
C
12H8FN3O3þNaþ: 284.0442 [M þ Na]þ; found: 284.0444 IR (KBr)
162.6 (C), 165.5 (C), 168.0 (C). HRMS (ESI): m/z calcd. for
cmꢁ1
:
n
¼ 1249, 1341, 1431, 1526, 1587, 1608, 1715, 2104.
C
12H11NO3þHþ: 218.0812 [M þ H]þ; found: 218.0815. IR (KBr)
cmꢁ1
:
n
¼ 1409, 1441, 1471, 1611, 1745, 3005.
4.6.4. Methyl 2-(3-(4-chlorophenyl)isoxazol-5-yl)-2-diazoacetate
(1d)
4.6. General procedure for the synthesis of methyl 2-diazo(3-(aryl)
isoxazol-5-yl)acetates (1)
Compound 1d (122 mg, 73%) was prepared from methyl 2-(3-(4-
chlorophenyl)isoxazol-5-yl)acetate 6d (150 mg, 0.6 mmol), potas-
sium carbonate (247 mg, 1.79 mmol), sodium azide (97 mg,
1.49 mmol) and 3-(chlorosulfonyl)benzoic acid (237 mg, 1.1 mmol)
in water (10 mL) and acetonitrile (10 mL). Yellow solid, m.p.
109e111 ꢀC (DCM). Rf ¼ 0.45 (light petroleum/ethyl acetate ¼ 8:1).
Compounds 1 were prepared according to slightly modified
published procedure [17]. 3-(Chlorosulfonyl)benzoic acid
(1.8 mmol) was added to a cool solution (0 ꢀC) of potassium car-
bonate (3 mmol) and sodium azide (2.5 mmol) in water, followed
by dropwise addition of a solution of methyl 2-(3-(aryl)isoxazol-5-
yl)acetate 6 (1 mmol) in acetonitrile. The reaction mixture was
warmed to room temperature and stirred for 2 d (TLC control, light
petroleum/ethyl acetate ¼ 8:1, v/v). The reaction mixture was
diluted with DCM and water, the organic layer was separated, the
aqueous layer was extracted with dichloromethane, the combined
organic layers were dried over Na2SO4 and evaporated on a rotary
evaporator in vacuo (<40 ꢀC, bath temperature) to give pure com-
pound 1.
1H NMR (400 MHz, CDCl3):
d¼3.93 (s, 3H), 6.82 (s, 1H), 7.43 (d,
J ¼ 8.5 Hz, 2H), 7.75 (d, J ¼ 8.5 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d
¼52.7 (CH3), 98.7 (CH), 127.1 (C), 128.2 (CH), 129.2 (CH), 136.2 (C),
157.0 (C), 162.3 (C), 162.6 (C). HRMS (ESI): m/z calcd. for
C
12H8ClN3O3þNaþ: 300.0146 [M þ Na]þ; found: 300.0145. IR (KBr)
cmꢁ1
:
n
¼ 1246, 1425, 1598, 1708, 2107.
4.6.5. Methyl 2-(3-(4-bromophenyl)isoxazol-5-yl)-2-diazoacetate
(1e)
Compound 1e (180 mg, 75%) was prepared from methyl 2-(3-(4-
9

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
bromophenyl)isoxazol-5-yl)acetate 6e (220 mg, 0.74 mmol), po-
tassium carbonate (308 mg, 2.23 mmol), sodium azide (121 mg,
1.86 mmol) and 3-(chlorosulfonyl)benzoic acid (295 mg,
1.34 mmol) in water (15 mL) and acetonitrile (15 mL). Yellow solid,
(100 MHz, CDCl3):
104.3 (CH), 124.5 (CH), 125.7 (CH), 126.3 (C), 126.4 (CH), 127.2 (CH),
d
¼31.2 (CH3), 34.8 (C), 53.3 (CH3), 61.4 (br. s, CH),
153.1 (C), 161.3 (C), 165.7 (C), 173.2(C). HRMS (ESI): m/z calcd. for
C
22H23NO3þNaþ: 372.1570 [M þ Na]þ; found: 372.1571. IR (KBr)
m.p. 129e130 ꢀC (DCM). Rf
¼
0.45 (light petroleum/ethyl
cmꢁ1
:
n
¼ 1250, 1433, 1614, 1727, 2957.
acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.93 (s, 3H), 6.81 (s,
d
1H), 7.59 (d, J ¼ 8.6 Hz, 2H), 7.69 (d, J ¼ 8.6 Hz, 2H). 13C NMR
4.7.3. Methyl 7-(3-(4-fluorophenyl)isoxazol-5-yl)bicyclo[4.1.0]
hepta-2,4-diene-7-carboxylate (8c)/methyl 1-(3-(4-fluorophenyl)
isoxazol-5-yl)cyclohepta-2,4,6-triene-1-carboxylate (9c)
Compound 8/9c (55 mg, 66%) was prepared from methyl 2-(3-
(4-fluorophenyl)isoxazol-5-yl)-2-diazoacetate
(100 MHz, CDCl3):
d
¼52.8 (CH3), 98.7 (CH),124.5 (C),127.5 (C),128.4
(CH), 132.2 (CH), 157.1 (C), 162.4 (C), 162.6 (C). HRMS (ESI) m/z:
calcd. for C12H8BrN3NaOþ3 : 343.9641 [M þ Na]þ, found: 343.9633. IR
(KBr) cmꢁ1
:
n
¼ 1246, 1340, 1429, 1600, 1716, 2108.
1c
(70
mg,
0.27 mmol) and benzene (4 mL) for 3 h. Colorless solid, m.p.
4.6.6. Methyl 2-(3-phenylisoxazol-5-yl)-2-diazoacetate (1f)
96e97 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.35 (light petro-
Compound 1f (263 mg, 88%) was prepared from methyl 2-(3-
phenylisoxazol-5-yl)acetate 6f (268 mg, 1.23 mmol), potassium
carbonate (511 mg, 3.70 mmol), sodium azide (201 mg, 3.08 mmol)
and 3-(chlorosulfonyl)benzoic acid (490 mg, 2.22 mmol) in water
(15 mL) and acetonitrile (10 mL). Yellow solid, m.p. 80e83 ꢀC
(DCM). Rf ¼ 0.48 (light petroleum/ethyl acetate ¼ 8:1). 1H NMR
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.73 (s,
d
3H), 4.01e4.02 (m, 2H), 6.10e6.14 (m, 2H), 6.24 (s, 1H), 6.26e6.31
(m, 2H), 7.11 (t, J ¼ 8.7 Hz, 2H), 7.73 (dd, J ¼ 8.7, 5.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d¼53.3 (CH3), 61.2 (br. s, CH), 104.2 (CH), 115.9 (d,
J ¼ 22.1 Hz, CH), 124.5 (CH), 125.4 (d, J ¼ 3.1 Hz, C), 127.2 (CH), 128.6
(d, J ¼ 8.4 Hz, CH), 160.5 (C), 163.7 (d, J ¼ 250.2 Hz, C), 166.2 (C),
173.1 (C). HRMS (ESI): m/z calcd. for C18H14FNO3þHþ: 312.1030
(400 MHz, CDCl3):
d
¼ 3.92 (s, 3H), 6.85 (s, 1H), 7.44e7.47 (m, 3H),
7.81e7.83 (m, 2H). 13C NMR (100 MHz, CDCl3):
d
¼52.7 (CH3), 98.8
[M þ H]þ; found: 312.1025. IR (KBr) cmꢁ1
:
n
¼ 1228, 1257, 1432,
(CH), 126.9 (CH), 128.6 (C), 128.9 (CH), 130.2 (CH), 156.6 (C), 162.7
1527, 1618, 1716, 2958, 3153.
(C), 163.3 (C). HRMS (ESI) m/z: calcd. for C12H9N3Oþ3 : 244.071841
[M þ H]þ, found: 244.0717. IR (KBr) cmꢁ1
:
n
¼ 1243, 1600, 1715,
4.7.4. Methyl 7-(3-(4-chlorophenyl)isoxazol-5-yl)bicyclo[4.1.0]
hepta-2,4-diene-7-carboxylate (8d)/methyl 1-(3-(4-chlorophenyl)
isoxazol-5-yl)cyclohepta-2,4,6-triene-1-carboxylate (9d)
2109.
4.7. General procedure for the synthesis of methyl 1-(3-arylisixazol-
5-yl)cyclohepta-2,4,6-triene-1-carboxylates/methyl 7-(3-aryl)
bicyclo[4.1.0]hepta-2,4-diene-7-carboxylates (8/9)
Compound 8/9d (34 mg, 58%) was prepared from methyl 2-(3-
(4-chlorophenyl)isoxazol-5-yl)-2-diazoacetate
1d
(43
mg,
0.18 mmol) and benzene (3 mL) for 3.5 h. Colorless solid, m.p.
93e96 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.38 (light petro-
A
benzene solution of methyl 2-(3-(aryl)isoxazol-5-yl)-2-
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.73 (s,
d
diazoacetate 1 in thick-wall screwcap tube was stirred at 110 ꢀC
(a bath temperature) until the reaction was completed (TLC control,
light petroleum/ethyl acetate ¼ 10:1, v/v). Then benzene was
evaporated in vacuo and residue was purified by column chroma-
tography on silica gel with light petroleum/ethyl acetate (20:1, v/v)
as an eluent.
3H), 3.99e4.00 (m, 2H), 6.09e6.14 (m, 2H), 6.25 (s, 1H), 6.26e6.32
(m, 2H), 7.40 (d, J ¼ 8.5 Hz, 2H), 7.68 (d, J ¼ 8.5 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼53.3 (CH3), 61.2 (br. s, CH), 104.2 (CH), 124.5
(CH),127.2 (CH),127.7 (C),128.0 (CH),129.1 (CH),135.8 (C),160.5 (C),
166.3 (C), 173.1 (C). HRMS (ESI): m/z calcd. for C18H14NO3þNaþ:
350.0554 [M þ Na]þ; found: 350.0554. IR (KBr) cmꢁ1
:
n
¼ 1223,
1255, 1424, 1608, 1715, 2925.
4.7.1. Methyl 7-(3-(p-tolyl)isoxazol-5-yl)bicyclo[4.1.0]hepta-2,4-
diene-7-carboxylate (8a)/methyl 1-(3-(p-tolyl)isoxazol-5-yl)
cyclohepta-2,4,6-triene-1-carboxylate (9a)
Compound 8/9a (39 mg, 75%) was prepared from methyl 2-
diazo-2-(3-(p-tolyl)isoxazol-5-yl)acetate 1a (40 mg, 0.16 mmol)
and benzene (6 mL) for 3 h. Colorless solid, m.p. 105e106 ꢀC (light
4.7.5. Methyl 7-(3-(4-bromophenyl)isoxazol-5-yl)bicyclo[4.1.0]
hepta-2,4-diene-7-carboxylate (8e)/methyl 1-(3-(4-bromophenyl)
isoxazol-5-yl)cyclohepta-2,4,6-triene-1-carboxylate (9e)
Compound 8/9e (63 mg, 74%) was prepared from methyl 2-(3-
(4-bromophenyl)isoxazol-5-yl)-2-diazoacetate
1e
(75
mg,
petroleum/ethyl acetate). Rf
¼
0.33 (light petroleum/ethyl
0.23 mmol) and benzene (5 mL) for 2 h. Colorless solid, m.p.
acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d
¼2.38 (s, 3H), 3.73 (s,
106e107 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.38 (light petro-
3H), 4.02e4.04 (m, 2H), 6.10e6.14 (m, 2H), 6.25 (s, 1H), 6.25e6.32
(m, 2H), 7.22 (d, J ¼ 8.0 Hz, 2H), 7.65 (d, J ¼ 8.0 Hz, 2H). 13C NMR
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.73 (s,
d
3H), 3.99e4.01 (m, 2H), 6.10e6.13 (m, 2H), 6.25 (s, 1H), 6.26e6.30
(m, 2H), 7.55 (d, J ¼ 8.5 Hz, 2H), 7.62 (d, J ¼ 8.5 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
(CH), 124.5 (CH), 126.3 (C), 126.5 (CH), 127.3 (CH), 129.5 (CH), 139.9
d
¼21.3 (CH3), 53.3 (CH3), 62.4 (br. s, CH), 104.2
(100 MHz, CDCl3):
d
¼53.3 (CH3), 60.8 (br. s, CH), 104.2 (CH), 124.1
(C), 161.4 (C), 165.8 (C), 173.2 (C). HRMS (ESI): m/z calcd. for
(C), 124.5 (CH), 127.2 (CH), 128.1 (C), 128.2 (CH), 132.0 (CH), 160.5
C
19H17NO3þNaþ: 330.1101 [M þ Na]þ; found: 330.1099. IR (KBr)
(C),166.3 (C),173.1 (C). HRMS (ESI): m/z calcd. for C18H14BrNO3þHþ:
cmꢁ1
:
n
¼ 1229, 1258, 1430, 1611, 1721, 2953, 3121.
372.0230 [M þ H]þ; found: 372.0225. IR (KBr) cmꢁ1
:
n
¼ 1225, 1257,
1423, 1607, 1715.
4.7.2. Methyl 7-(3-(4-(tert-butyl)isoxazol-5-yl)phenyl)bicyclo
[4.1.0]hepta-2,4-diene-7-carboxylate (8b)/methyl 1-(3-(4-(tert-
butyl)phenyl)isoxazol-5-yl)cyclohepta-2,4,6-triene-1-carboxylate
(9b)
4.7.6. Methyl 7-(3-phenylisoxazol-5-yl)bicyclo[4.1.0]hepta-2,4-
diene-7-carboxylate (8f)/methyl 1-(3-phenylisoxazol-5-yl)
cyclohepta-2,4,6-triene-1-carboxylate (9f)
Compound 8/9b (47 mg, 81%) was prepared from methyl 2-(3-
(4-(tert-butyl)phenyl)isoxazol-5-yl)-2-diazoacetate 1b (50 mg,
0.17 mmol) and benzene (3 mL) for 3 h. Colorless solid, m.p.
82e85 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.42 (light petro-
Compound 8/9f (46 mg, 77%) was prepared from methyl 2-(3-
phenylisoxazol-5-yl)-2-diazoacetate 1f (50 mg, 0.21 mmol) and
benzene (3 mL) for 3.5 h. Colorless solid, m.p. 68e69 ꢀC (light pe-
troleum/ethyl acetate). Rf
¼
0.37 (light petroleum/ethyl
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d¼1.33 (s,
acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d
¼ 3.73 (s, 3H),
9H), 3.73 (s, 3H), 4.00e4.02 (m, 2H), 6.08e6.12 (m, 2H), 6.26 (s, 1H),
6.26e6.31 (m, 2H), 7.43e7.45 (m, 2H), 7.67e7.69 (m, 2H). 13C NMR
3.99e4.03 (m, 2H), 6.09e6.14 (m, 2H), 6.29 (s, 1H), 6.26e6.31 (m,
2H), 7.41e7.44 (m, 3H), 7.74e7.76 (m, 2H). 13C NMR (100 MHz,
10

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
CDCl3):
d
¼53.3 (CH3), 61.4 (br. s., CH), 104.3 (CH), 124.5 (CH), 126.6
1.2 Hz, 1H), 7.45e7.49 (m, 2H), 7.57 (d, J ¼ 7.5 Hz, 1H). 13C NMR
(CH),127.2 (CH),128.8 (CH),129.1 (C),129.8 (CH),161.4 (C),165.9 (C),
(100 MHz, CDCl3):
d
¼19.9 (C), 34.5 (CH), 36.5 (CH), 53.3 (CH3), 104.6
173.2 (C). HRMS (ESI): m/z calcd. for C18H15NO3þHþ: 294.1125 [M þ
(CH), 115.8 (d, J ¼ 21.8 Hz, CH), 122.4 (CH), 125.3 (d, J ¼ 3.4 Hz, C),
127.6 (CH), 127.9 (CH), 128.1 (CH), 128.4 (d, J ¼ 8.3 Hz, CH), 128.6
(CH),129.5 (C),129.7 (CH),132.6 (C),160.3 (C),164.6 (d, J ¼ 249.2 Hz,
C), 164.8 (C), 173.3 (C). HRMS (ESI): m/z calcd. for C22H16FNO3þHþ:
H]þ; found: 294.1129. IR (KBr) cmꢁ1
3042.
:
n
¼ 1256, 1723, 2109, 2952,
4.8. General procedure for the synthesis of methyl 1-(3-
arylisoxazol-5-yl)-1a,7b-dihydro-1h-cyclopropa[a]naphthalene-1-
carboxylates (11)
362.1187 [M þ H]þ; found: 362.1185. IR (KBr) cmꢁ1
:
n
¼ 1245, 1429,
1524, 1614, 1730, 2954.
A mixture of methyl 2-(3-(aryl)isoxazol-5-yl)-2-diazoacetate 1
(1 mmol) and naphthalene (5 mmol) in thick-wall screwcap tube
was heated at 120 ꢀC for 2 h (TLC control, light petroleum/ethyl
acetate ¼ 10:1, v/v). The product was purified by column chroma-
tography on silica gel with light petroleum/ethyl acetate (20:1, v/v)
as an eluent.
4.8.4. Methyl 1-(3-(4-chlorophenyl)isoxazol-5-yl)-1a,7b-dihydro-
1H-cyclopropa[a]naphthalene-1-carboxylate (11d)
Compound 11d (44 mg, 65%) was prepared from methyl 2-(3-(4-
chlorophenyl)isoxazol-5-yl)-2-diazoacetate 1d (50 mg, 0.18 mmol)
and naphthalene (115 mg, 0.9 mmol). Colorless solid, m.p.
143e146 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.27 (light petro-
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.32 (d,
d
4.8.1. Methyl 1-(3-(p-tolyl)isoxazol-5-yl)-1a,7b-dihydro-1H-
cyclopropa[a]naphthalene-1-carboxylate (11a)
J ¼ 8.7, 5.1 Hz, 1H), 3.72 (d, J ¼ 8.7 Hz, 1H), 3.76 (s, 3H), 5.42 (s, 1H),
6.20 (dd, J ¼ 9.6, 5.1 Hz, 1H), 6.31 (d, J ¼ 9.6 Hz, 1H), 6.94 (d,
J ¼ 7.5 Hz, 1H), 7.22e7.26 (m, 1H), 7.30e7.36 (m, 3H), 7.41e7.44 (m,
Compound 11a (63 mg, 57%) was prepared from methyl 2-diazo-
2-(3-(p-tolyl)isoxazol-5-yl)acetate 1a (80 mg, 0.31 mmol) and
naphthalene (200 mg, 1.55 mmol). Light yellow solid, m.p.
158e160 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.30 (light petro-
2H), 7.57 (d, J ¼ 7.5 Hz, 2H). 13C NMR (100 MHz, CDCl3):
¼19.9 (C),
d
34.5 (CH), 36.5 (CH), 53.3 (CH3), 104.6 (CH), 122.3 (CH), 127.5 (CH),
127.5 (C), 127.7 (CH), 127.9 (CH), 128.1 (CH), 128.6 (CH), 129.0 (CH),
129.5 (C), 129.7 (CH), 132.5 (C), 135.7 (C), 160.3 (C), 164.9 (C), 173.3
(C). HRMS (ESI): m/z calcd. for C22H16ClNO3þHþ: 378.0891 [M þ
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.34 (s,
d
3H), 3.31 (dd, J ¼ 8.7 Hz, 5.1 Hz, 1H), 3.70 (d, J ¼ 8.7 Hz, 1H), 3.76 (s,
3H), 5.42 (s, 1H), 6.20 (dd, J ¼ 9.6, 5.1 Hz,1H), 6.30 (d, J ¼ 9.6 Hz,1H),
6.94 (d, J ¼ 7.5 Hz,1H), 7.14 (d, J ¼ 8.0 Hz, 2H), 7.23 (td, J ¼ 7.5, 1.1 Hz,
1H), 7.33 (td, J ¼ 7.5, 1.1 Hz, 1H), 7.38 (d, J ¼ 8.0 Hz, 2H), 7.56 (d,
H]þ; found: 378.0891. IR (KBr) cmꢁ1
1729, 2925.
:
n
¼ 1253, 1272, 1424, 1610,
J ¼ 7.5 Hz, 1H). 13C NMR (100 MHz, CDCl3):
¼19.9 (C), 21.3 (CH3),
d
34.4 (CH), 36.5 (CH), 53.3 (CH3), 104.7 (CH), 122.4 (CH), 126.2 (C),
126.4 (CH),127.6 (CH),127.8 (CH),128.0 (CH), 128.6 (CH),129.4 (CH),
129.55 (C),129.62 (CH),132.6 (C),139.7 (C),161.2 (C),164.3 (C), 173.5
(C). HRMS (ESI): m/z calcd. for C23H19NO3þHþ: 358.1438 [M þ H]þ;
4.8.5. Methyl 1-(3-(4-bromophenyl)isoxazol-5-yl)-1a,7b-dihydro-
1H-cyclopropa[a]naphthalene-1-carboxylate (11e)
Compound 11e (73 mg, 74%) was prepared from methyl 2-(3-(4-
bromophenyl)isoxazol-5-yl)-2-diazoacetate 1e (75 mg, 0.23 mmol)
and naphthalene (149 mg, 1.16 mmol). Light yellow solid, m.p.
150e152 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.29 (light petro-
found: 358.1434. IR (KBr) cmꢁ1
:
n
¼ 1250, 1271, 1424, 1612, 1727.
4.8.2. Methyl 1-(3-(4-(tert-butyl)phenyl)isoxazol-5-yl)-1a,7b-
dihydro-1H-cyclopropa[a]naphthalene-1-carboxylate carboxylate
(11b)
Compound 11b (41 mg, 61%) was prepared from methyl 2-(3-(4-
(tert-butyl)phenyl)isoxazol-5-yl)-2-diazoacetate 1b (50 mg,
0.17 mmol) and naphthalene (107 mg, 0.84 mmol). Light yellow
solid, m.p. 166e171 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.29
(light petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.32 (dd,
d
J ¼ 8.8, 5.1 Hz, 1H), 3.71 (d, J ¼ 8.8 Hz, 1H), 3.76 (s, 3H), 5.41 (s, 1H),
6.20 (dd, J ¼ 9.6, 5.1 Hz, 1H), 6.31 (d, J ¼ 9.6 Hz, 1H), 6.94 (d,
J ¼ 7.4 Hz, 1H), 7.22e7.25 (m, 1H), 7.32e7.35 (m, 1H), 7.36 (d,
J ¼ 8.5 Hz, 2H), 7.46 (d, J ¼ 8.5 Hz, 2H), 7.56 (d, J ¼ 7.4 Hz, 1H). 13
C
NMR (100 MHz, CDCl3):
d
¼19.9 (C), 34.5 (CH), 36.5 (CH), 53.3 (CH3),
104.6 (CH), 122.4 (CH), 123.9 (C), 127.5 (CH), 127.9 (CH), 128.0 (CH),
128.0 (C), 128.1 (CH), 128.6 (CH), 129.5 (C), 129.7 (CH), 131.9 (CH),
132.5 (C), 160.3 (C), 165.0 (C), 173.2 (C). HRMS (ESI): m/z calcd. for
d
¼1.30 (s, 9H), 3.31 (dd, J ¼ 8.7, 5.1 Hz, 1H), 3.70 (d, J ¼ 8.7 Hz, 1H),
3.75 (s, 3H), 5.44 (s, 1H), 6.20 (dd, J ¼ 9.6, 5.1 Hz, 1H), 6.29 (d,
J ¼ 9.6 Hz, 1H), 6.94 (d, J ¼ 7.5 Hz, 1H), 7.23 (td, J ¼ 7.5, 1.1 Hz, 1H),
7.33 (td, J ¼ 7.5, 1.1 Hz, 1H), 7.36 (d, J ¼ 8.5, 2H), 7.44 (d, J ¼ 8.5, 2H),
C
22H16BrNO3þHþ: 422.0386 [M þ H]þ; found: 422.0385. IR (KBr)
cmꢁ1
:
n
¼ 1252, 1272, 1424, 1611, 1727, 2949.
7.56 (d, J ¼ 7.5 Hz, 1H). 13C NMR (100 MHz, CDCl3):
¼19.9 (C), 31.2
d
(CH3), 34.4 (CH), 34.7 (C), 36.5 (CH), 53.3 (CH3), 104.7 (CH), 122.4
(CH), 125.6 (CH), 126.2 (CH), 126.2 (C), 127.6 (CH), 127.8 (CH), 128.0
(CH), 128.6 (CH), 129.57 (C), 129.64 (CH), 132.6 (C), 152.9 (C), 161.1
(C), 164.3 (C), 173.5 (C). HRMS (ESI): m/z calcd. for C26H25NO3þHþ:
4.8.6. Methyl 1-(3-phenylisoxazol-5-yl)-1a,7b-dihydro-1H-
cyclopropa[a]naphthalene-1-carboxylate (11f)
Compound 11f (46 mg, 66%) was prepared from methyl 2-(3-
phenylisoxazol-5-yl)-2-diazoacetate 1f (50 mg, 0.21 mmol) and
naphthalene (132 mg, 1.03 mmol). Colorless solid, m.p. 146e147 ꢀC
(light petroleum/ethyl acetate). Rf ¼ 0.36 (light petroleum/ethyl
400.1907 [M þ H]þ; found: 400.1908. IR (KBr) cmꢁ1
:
n
¼ 1255, 1272,
1433, 1613, 1733, 2948.
4.8.3. Methyl 1-(3-(4-fluorophenyl)isoxazol-5-yl)-1a,7b-dihydro-
1H-cyclopropa[a]naphthalene-1-carboxylate (11c)
acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.32 (dd, J ¼ 8.6,
d
5.2 Hz,1H), 3.71 (d, J ¼ 8.7 Hz,1H), 3.76 (s, 3H), 5.46 (s,1H), 6.20 (dd,
J ¼ 9.5, 5.1 Hz, 1H), 6.31 (d, J ¼ 9.5 Hz, 1H), 6.95 (d, J ¼ 7.5 Hz, 1H),
7.24 (t, J ¼ 7.4 Hz, 1H), 7.32e7.35 (m, 4H), 7.49e7.51 (m, 2H), 7.57 (d,
Compound 11c (67 mg, 69%) was prepared from methyl 2-(3-(4-
fluorophenyl)isoxazol-5-yl)-2-diazoacetate 1c (70 mg, 0.27 mmol)
and naphthalene (172 mg, 1.34 mmol) in). Light yellow solid, m.p.
90e95 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.24 (light petro-
J ¼ 7.4 Hz, 1H). 13C NMR (100 MHz, CDCl3):
¼19.9 (C), 34.4 (CH),
d
36.5 (CH), 53.3 (CH3), 104.7 (CH), 122.4 (CH), 126.5 (CH), 127.6 (CH),
127.8 (CH), 128.0 (CH), 128.6 (CH), 128.7 (CH), 129.0 (C), 129.5 (C),
129.6 (CH), 132.5 (C), 161.2 (C), 164.6 (C), 173.4 (C). HRMS (ESI): m/z
calcd. for C22H17NO3þHþ: 344.1281 [M þ H]þ; found: 344.1286. IR
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼3.32 (dd,
d
J ¼ 8.8, 5.1 Hz, 1H), 3.71 (d, J ¼ 8.8 Hz, 1H), 3.76 (s, 3H), 5.41 (s, 1H),
6.20 (dd, J ¼ 9.6, 5.1 Hz, 1H), 6.31 (d, J ¼ 9.6 Hz, 1H), 6.95 (d,
J ¼ 7.5 Hz,1H), 7.01e7.05 (m, 2H), 7.22e7.25 (m,1H), 7.34 (td, J ¼ 7.5,
(KBr) cmꢁ1
:
n
¼ 1611, 1730, 2956.
11

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
4.9. General procedure for the synthesis of methyl 2-mesityl-2-(3-
arylisoxazol-5-yl)acetates (17)
9H), 3.78 (s, 3H), 5.50 (s, 1H), 6.59 (s, 1H), 6.91 (s, 2H), 7.40 (d,
J ¼ 8.5 Hz, 2H), 7.72 (d, J ¼ 8.5 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d
¼20.4 (CH3), 20.9 (CH3), 44.7 (CH), 52.8 (CH3), 101.5 (CH), 127.6 (C),
A benzene mesitylene of methyl 2-(3-(aryl)isoxazol-5-yl)-2-
diazoacetate 1 in thick-wall screwcap tube was stirred at 120 ꢀC
(a bath temperature) until the reaction was completed (TLC control,
light petroleum/ethyl acetate ¼ 10:1, v/v). Then mesitylene was
evaporated in vacuo and residue was purified by column chroma-
tography on silica gel with light petroleum/ethyl acetate (20:1, v/v)
as an eluent.
128.1 (CH),129.1 (CH),129.4 (C),130.1 (CH),135.9 (C),137.0 (C),137.8
(C), 161.2 (C), 169.2 (C), 170.1 (C). HRMS (ESI): m/z calcd. for
C
21H20ClNO3þHþ: 370.1204 [M þ H]þ; found: 370.1208. IR (KBr)
cmꢁ1
:
n
¼ 1178, 1243, 1424, 1605, 1739.
4.9.5. Methyl 2-(3-(4-bromophenyl)isoxazol-5-yl)-2-mesitylacetate
(17e)
Compound 17e (61 mg, 68%) was prepared from methyl 2-(3-(4-
bromophenyl)isoxazol-5-yl)-2-diazoacetate 1e (70 mg, 0.22 mmol)
in mesitylene (5 mL) at 120 ꢀC for 4.5 h. Colorless solid, m.p.
93e98 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.46 (light petro-
4.9.1. Methyl 2-mesityl-2-(3-(p-tolyl)isoxazol-5-yl)acetate (17a)
Compound 17a (85 mg, 76% yield) was prepared from methyl 2-
diazo-2-(3-(p-tolyl)isoxazol-5-yl)acetate 1a (80 mg, 0.310 mmol)
and mesitylene (6 mL) at 120 ꢀC for 3 h. Colorless solid, m.p.
144e146 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.44 (light petro-
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.28 (s,
d
9H), 3.78 (s, 3H), 5.50 (s, 1H), 6.59 (s, 1H), 6.91 (s, 2H), 7.56 (d,
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d¼2.29 (s,
J ¼ 8.5 Hz, 2H), 7.66 (d, J ¼ 8.5 Hz, 2H). 13C NMR (100 MHz, CDCl3):
3H), 2.30 (s, 6H), 2.39 (s, 3H), 3.78 (s, 3H), 5.50 (s, 1H), 6.58 (d,
d
¼20.4 (CH3), 20.9 (CH3), 44.7 (CH), 52.8 (CH3),101.5 (CH), 124.2 (C),
J ¼ 1.0 Hz,1H), 6.91 (s, 2H), 7.23 (d, J ¼ 8.1 Hz, 2H), 7.68 (d, J ¼ 8.1 Hz,
128.0 (C), 128.3 (CH), 129.4 (C), 130.1 (CH), 132.0 (CH), 137.0 (C),
2H). 13C NMR (100 MHz, CDCl3):
d
¼20.4 (CH3), 20.9 (CH3), 21.4
137.8 (C), 161.3 (C), 169.2 (C), 170.1 (C). HRMS (ESI): m/z calcd. for
(CH3), 44.7 (CH), 52.8 (CH3), 101.6 (CH), 126.3 (C), 126.7 (CH), 129.5
(CH), 129.6 (C), 130.0 (CH), 137.0 (C), 137.7 (C), 140.0 (C), 162.1 (C),
168.6 (C), 170.2 (C). HRMS (ESI): m/z calcd. for C22H22NO3þHþ:
C
21H20BrNO3þHþ: 414.0699 [M þ H]þ; found: 414.0698. IR (KBr)
cmꢁ1
:
n
¼ 1168, 1189, 1424, 1599, 1742.
372.1576 [M þ Na]þ; found: 372.1569. IR (KBr) cmꢁ1
:
n
¼ 1175, 1242,
4.9.6. Methyl 2-(3-phenylisoxazol-5-yl)-2-mesitylacetate (17f)
Compound 17f (54 mg, 76%) was prepared from methyl 2-(3-
phenylisoxazol-5-yl)-2-diazoacetate 1fe (50 mg, 0.21 mmol) in
mesitylene (4 mL) at 120 ꢀC for 3.5 h. Colorless solid, m.p.
115e116 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.46 (light petro-
1380, 1430, 1462, 1605, 1740, 2868, 2923, 2956.
4.9.2. Methyl 2-(3-(4-(tert-butyl)phenyl)isoxazol-5-yl)-2-
mesitylacetate (17b)
Compound 17b (34 mg, 72%) was prepared from methyl 2-(3-(4-
(tert-butyl)phenyl)isoxazol-5-yl)-2-diazoacetate 1b (50 mg,
0.17 mmol) in mesitylene (3 mL) at 120 ꢀC for 3.5 h. Colorless solid,
m.p. 129e131 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.50 (light
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.29 (s,
d
3H), 2.30 (s, 6H), 3.78 (s, 3H), 5.51 (s, 1H), 6.62 (d, J ¼ 0.9 Hz, 1H),
6.91 (s, 2H), 7.41e7.46 (m, 3H), 7.77e7.80 (m, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼20.4 (CH3), 20.9 (CH3), 44.7 (CH), 52.8 (CH3),
petroleum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
d
¼1.34
101.7 (CH), 126.8 (CH), 128.8 (CH), 129.1 (C), 129.5 (C), 129.9 (CH),
130.0 (CH), 137.0 (C), 137.7 (C), 162.2 (C), 168.8 (C), 170.2 (C). HRMS
(ESI): m/z calcd. for C21H21NO3þHþ: 336.1594 [M þ H]þ; found:
(s, 9H), 2.29 (s, 9H), 3.78 (s, 3H), 5.50 (s, 1H), 6.60 (s, 1H), 6.90 (s,
2H), 7.45 (d, J ¼ 8.4 Hz, 2H), 7.72 (d, J ¼ 8.4 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼20.4 (CH3), 20.9 (CH3), 31.2 (CH3), 34.8 (C),
336.1597. IR (KBr) cmꢁ1
:
n
¼ 1734, 2920.
44.7 (CH), 52.8 (CH3), 101.6 (CH), 125.7 (CH), 126.2 (C), 126.5 (CH),
129.6 (C), 130.0 (CH), 137.0 (C), 137.7 (C), 153.2 (C), 162.0 (C), 168.6
(C), 170.2 (C). HRMS (ESI): m/z calcd. for C25H29NO3þHþ: 392.2220
4.10. General procedure for the synthesis of methyl 5-amino-3-oxo-
2-phenyl-5-(aryl)pent-4-enoates (20) and methyl 5-amino-2-
(naphthalen-1-yl)-3-oxo-5-(aryl)pent-4-enoates (21)
[M þ H]þ; found: 392.2221. IR (KBr) cmꢁ1
:
n
¼ 1242, 1428, 1607,
1741, 2964 cmꢁ1
.
A mixture of methyl 1-(3-arylisixazol-5-yl)cyclohepta-2,4,6-
4.9.3. Methyl 2-(3-(4-fluorophenyl)isoxazol-5-yl)-2-mesitylacetate
(17c)
triene-1-carboxylates/methyl
7-(3-aryl)bicyclo[4.1.0]hepta-2,4-
diene-7-carboxylate 8/9 (1 mmol) or methyl 1-(3-arylisoxazol-5-
yl)-1a,7b-dihydro-1H-cyclopropa[a]naphthalene-1-carboxylates
11 (1 mmol) and Mo(CO)6 (85 mol. %) was heated at 88 ꢀC in MeCN
with few drops of H2O in thick-wall screwcap tube until the reac-
tion was completed (TLC control, light petroleum/ethyl
acetate ¼ 4:1, v/v). The solvent was evaporated in vacuo and residue
was purified by column chromatography on silica gel with light
petroleum/ethyl acetate (2:1, v/v) as an eluent.
Compound 17c (55 mg, 77%) was prepared from methyl 2-(3-(4-
fluorophenyl)isoxazol-5-yl)-2-diazoacetate 1c (53 mg, 0.20 mmol)
in mesitylene (3 mL) at 120 ꢀC for 2 h. Colorless solid, m.p.
119e122 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.44 (light petro-
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.29 (s,
d
9H), 3.78 (s, 3H), 5.50 (s, 1H), 6.57 (s, 1H), 6.91 (s, 2H), 7.12 (t,
J ¼ 8.6 Hz, 2H), 7.77 (dd, J ¼ 8.6 Hz, 5.4 Hz, 2H). 13C NMR (100 MHz,
CDCl3):
d
¼20.4 (CH3), 20.8 (CH3), 44.7 (CH), 52.8 (CH3), 101.5 (CH),
115.9 (d, J ¼ 22.1 Hz, CH), 125.3 (d, J ¼ 3.2 Hz, C), 128.7 (d, J ¼ 8.5 Hz,
CH), 129.4 (C), 130.1 (CH), 137.0 (C), 137.8 (C), 161.3 (C), 163.7 (d,
J ¼ 249.8 Hz, C), 169.0 (C), 170.2 (C). HRMS (ESI): m/z calcd. for
4.10.1. Methyl 5-amino-3-oxo-2-phenyl-5-(p-tolyl)pent-4-enoate
(20a)
Compound 20a (30 mg, 75%) was prepared from methyl 7-(3-(p-
tolyl)isoxazol-5-yl)bicyclo[4.1.0]hepta-2,4-diene-7-carboxylate/
C
21H20FNO3þHþ: 354.1500 [M þ H]þ; found: 354.1503. IR (KBr)
cmꢁ1
:
n
¼ 1202, 1226, 1250, 1433, 1525, 1609, 1732, 3079.
methyl
1-(3-(p-tolyl)isoxazol-5-yl)cyclohepta-2,4,6-triene-1-
carboxylate 8/9a (40 mg, 0.13 mmol) and Mo(CO)6 (29.2 mg,
0.11 mmol) in MeCN (4 mL) for 4.5 h. Light yellow oil. Rf ¼ 0.46
(light petroleum/ethyl acetate ¼ 2:1). 1H NMR (400 MHz, CDCl3):
4.9.4. Methyl 2-(3-(4-chlorophenyl)isoxazol-5-yl)-2-mesitylacetate
(17d)
Compound 17d (50 mg, 50%) was prepared from methyl 2-(3-(4-
chlorophenyl)isoxazol-5-yl)-2-diazoacetate 1d (75 mg, 0.27 mmol)
in mesitylene (5 mL) at 120 ꢀC for 3.5 h. Colorless solid, m.p.
118e119 ꢀC (light petroleum/ethyl acetate). Rf ¼ 0.46 (light petro-
d
¼2.38 (s, 3H), 3.77 (s, 3H), 4.74 (s, 1H), 5.41 (br. s, 1H), 5.41 (s, 1H),
7.20 (d, J ¼ 8.0 Hz, 2H), 7.27e7.37 (m, 5H), 7.46e7.48 (m, 2H), 9.91
(br. s,1H). 13C NMR (100 MHz, CDCl3):
d
¼21.3 (CH3), 52.4 (CH3), 64.3
(CH), 93.3 (CH), 126.2 (CH), 127.6 (CH), 128.5 (CH), 129.3 (CH), 129.6
(CH), 133.8 (C), 135.0 (C), 141.4 (C), 163.1 (C), 170.4 (C), 191.6 (C).
leum/ethyl acetate ¼ 8:1). 1H NMR (400 MHz, CDCl3):
¼2.29 (s,
d
12

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
HRMS (ESI): m/z calcd. for C19H19NO3þNaþ: 332.1257 [MþNa]þ;
(CH), 125.2 (C), 127.7 (CH), 127.8 (CH), 128.5 (CH), 129.3 (CH), 132.2
(CH), 134.7 (C), 135.6 (C), 161.7 (C), 170.3 (C), 192.0 (C). HRMS (ESI):
m/z calcd. for C18H16BrNO3þNaþ: 396.0206 [M þ Na]þ; found:
found, 332.1261 IR (KBr) cmꢁ1
3401.
:
n
¼ 1321, 1500, 1537, 1610, 1739,
396.0206. IR (KBr) cmꢁ1
3398.
:
n
¼ 1309, 1480, 1529, 1595, 1612, 1739,
4.10.2. Methyl 5-amino-5-(4-(tert-butyl)phenyl)-3-oxo-2-
phenylpent-4-enoate (20b)
Compound 20b (15 mg, 45%) was prepared from methyl 7-(3-(4-
(tert-butyl)isoxazol-5-yl)phenyl)bicyclo[4.1.0]hepta-2,4-diene-7-
carboxylate/methyl 1-(3-(4-(tert-butyl)phenyl)isoxazol-5-yl)cyclo-
hepta-2,4,6-triene-1-carboxylate 8/9b (32 mg, 0.09 mmol) and
Mo(CO)6 (21 mg, 0.08 mmol) in MeCN (1 mL) for 4.5 h. Light yellow
oil. Rf ¼ 0.50 (light petroleum/ethyl acetate ¼ 2:1). 1H NMR
4.10.6. Methyl 5-amino-2-(naphthalen-1-yl)-3-oxo-5-(p-tolyl)
pent-4-enoate (21a)
Compound 21a (16 mg, 72%) was prepared from methyl 1-(3-(p-
tolyl)isoxazol-5-yl)-1a,7b-dihydro-1H-cyclopropa[a]naphthalene-
1-carboxylate 11a (22 mg, 62
mmol) and Mo(CO)6 (13.8 mg,
52
m
mol) in MeCN (2 mL) for 5.5 h. Light yellow oil. Rf ¼ 0.33 (light
(400 MHz, CDCl3):
d¼1.32 (s, 9H), 3.77 (s, 3H), 4.47 (s, 1H), 5.41 (br.
petroleum/ethyl acetate ¼ 2:1). 1H NMR (400 MHz, CDCl3):
¼2.34
d
s, 1H), 5.41 (s, 1H), 7.26e7.31 (m, 1H), 7.32e7.37 (m, 2H), 7.39e7.44
(s, 3H), 3.78 (s, 3H), 5.41 (br. s, 1H), 5.41 (s, 3H), 5.55 (s, 1H), 7.16 (d,
J ¼ 8.0 Hz, 2H), 7.31 (d, J ¼ 8.0 Hz, 2H), 7.47e7.56 (m, 3H), 7.68 (d,
J ¼ 7.1 Hz,1H), 7.81 (d, J ¼ 8.2 Hz,1H), 7.87 (d, J ¼ 7.9 Hz,1H), 8.07 (d,
(m, 4H), 7.46e7.48 (m, 2H), 9.90 (br. s, 1H). 13C NMR (100 MHz,
CDCl3):
d
¼31.1 (CH3), 34.8 (C), 52.3 (CH3), 64.3 (CH), 93.3 (CH),125.9
(CH), 126.0 (CH), 127.6 (CH), 128.5 (CH), 129.4 (CH), 133.7 (C), 135.0
(C), 154.5 (C), 163.0 (C), 170.4 (C), 191.7 (C). HRMS (ESI): m/z calcd.
for C22H25NO3þNaþ: 374.1727 [M þ Na]þ; found: 374.1730. IR (KBr)
J ¼ 8.4 Hz, 1H), 9.96 (br. s, 1H). 13C NMR (100 MHz, CDCl3):
¼21.3
d
(CH3), 52.5 (CH3), 60.5 (CH), 93.7 (CH), 123.2 (CH), 125.55 (CH),
125.62 (CH), 126.1 (CH), 126.5 (CH), 127.1 (CH), 128.3 (CH), 128.9
(CH), 129.6 (CH), 131.4 (C), 132.0 (C), 133.7 (C), 133.9 (C), 141.3 (C),
162.9 (C), 170.7 (C), 192.2 (C). HRMS (ESI): m/z calcd. for
cmꢁ1
:
n
¼ 1204, 1319, 1497, 1534, 1612, 1739, 3412.
4.10.3. Methyl 5-amino-5-(4-fluorophenyl)-3-oxo-2-phenylpent-4-
enoate (20c)
Compound 20c (32 mg, 79%) was prepared from methyl 7-(3-(4-
fluorophenyl)isoxazol-5-yl)bicyclo[4.1.0]hepta-2,4-diene-7-
C
23H21NO3þNaþ: 382.1414 [M þ Na]þ; found: 382.1414. IR (KBr)
cmꢁ1
:
n
¼ 1316, 1499, 1536, 1611, 1734, 2950, 3405.
4.10.7. Methyl 5-amino-5-(4-fluorophenyl)-2-(naphthalen-1-yl)-3-
oxopent-4-enoate (21b)
carboxylate/methyl
1-(3-(4-fluorophenyl)isoxazol-5-yl)cyclo-
hepta-2,4,6-triene-1-carboxylate 8/9c (40 mg, 0.13 mmol) and
Mo(CO)6 (28.8 mg, 0.11 mmol) in MeCN (3 mL) for 5 h. Light yellow
oil. Rf ¼ 0.38 (light petroleum/ethyl acetate ¼ 2:1). 1H NMR
Compound 21b (25 mg, 60%) was prepared from methyl 1-(3-(4-
fluorophenyl)isoxazol-5-yl)-1a,7b-dihydro-1H-cyclopropa[a]naph-
thalene-1-carboxylate 11c (41 mg, 0.11 mmol) and Mo(CO)6 (25 mg,
(400 MHz, CDCl3):
d
¼3.76 (s, 3H), 4.74 (s, 1H), 5.36 (br. s, 1H), 5.36
90
m
mol) in MeCN (3 mL) for 5 h. Yellow oil. Rf ¼ 0.35 (light pe-
(s, 1H), 7.09 (t, J ¼ 8.6 Hz, 2H), 7.28e7.37 (m, 3H), 7.45e7.48 (m, 4H),
troleum/ethyl acetate ¼ 2:1). 1H NMR (400 MHz, CDCl3)
¼3.78 (s,
d
9.87 (br. s, 1H). 13C NMR (100 MHz, CDCl3):
d
¼52.4 (CH3), 64.3 (CH),
3H), 5.36 (br. s, 1H), 5.36 (s, 1H), 5.54 (s, 1H), 7.01e7.05 (m, 2H),
7.37e7.41 (m, 2H), 7.47e7.56 (m, 3H), 7.66 (d, J ¼ 6.7 Hz,1H), 7.82 (d,
J ¼ 8.2 Hz, 1H), 7.87 (d, J ¼ 7.9 Hz, 1H), 8.06 (d, J ¼ 8.4 Hz, 1H), 9.91
93.7 (CH), 116.1 (d, J ¼ 21.8 Hz, CH), 127.7 (CH), 128.4 (d, J ¼ 8.8 Hz,
CH), 128.5 (CH), 129.3 (CH), 132.9 (d, J ¼ 3.5 Hz, C), 134.8 (C), 161.9
(C), 164.2 (d, J ¼ 251.6 Hz, C), 170.3 (C), 191.9 (C). HRMS (ESI): m/z
calcd. for C18H16FNO3þHþ: 314.1187 [M þ H]þ; found: 314.1187. IR
(br. s, 1H). 13C NMR (100 MHz, CDCl3)
d
¼52.5 (CH3), 60.5 (CH), 94.1
(CH), 116.0 (d, J ¼ 22.0 Hz, CH), 123.1 (CH), 125.5 (CH), 125.7 (CH),
126.6 (CH), 127.1 (CH), 128.4 (d, J ¼ 8.7 Hz, CH), 128.4 (CH), 128.9
(CH), 131.2 (C), 131.9 (C), 132.8 (d, J ¼ 3.1 Hz, C), 133.9 (C), 161.7 (C),
164.2 (d, J ¼ 251.5 Hz, C), 170.6 (C), 192.5 (C). HRMS (ESI): (m/z)
calcd. for C22H18FNO3þNaþ: 386.1163 [M þ Na]þ; found: 386.1163.
(KBr) cmꢁ1
:
n
¼ 1232, 1320, 1434, 1497, 1539, 1608, 1740, 3401.
4.10.4. Methyl 5-amino-5-(4-chlorophenyl)-3-oxo-2-phenylpent-4-
enoate (20d)
Compound 20d (34 mg, 84%) was prepared from methyl 7-(3-(4-
chlorophenyl)isoxazol-5-yl)bicyclo[4.1.0]hepta-2,4-diene-7-
IR (KBr) cmꢁ1
:
n
¼ 1495, 1537, 1608, 1736, 3399.
carboxylate/methyl
1-(3-(4-chlorophenyl)isoxazol-5-yl)cyclo-
4.10.8. Methyl 5-amino-5-(4-chlorophenyl)-2-(naphthalen-1-yl)-
3-oxopent-4-enoate (21c)
Compound 21c (21 mg, 77%) was prepared from methyl 1-(3-(4-
chlorophenyl)isoxazol-5-yl)-1a,7b-dihydro-1H-cyclopropa[a]
naphthalene-1-carboxylate 11d (27 mg, 0.0.07 mmol) and Mo(CO)6
hepta-2,4,6-triene-1-carboxylate 8/9d (40 mg, 0.12 mmol) and
Mo(CO)6 (27 mg, 0.10 mmol) in MeCN (1.2 mL) for 5 h. Light yellow
oil. Rf ¼ 0.44 (light petroleum/ethyl acetate ¼ 2:1). 1H NMR
(400 MHz, CDCl3):
d
¼ 3.76 (s, 3H), 4.74 (s, 1H), 5.32 (br. s, 1H), 5.37
(s, 1H), 7.26e7.46 (m, 9H), 9.84 (br. s, 1H). 13C NMR (100 MHz,
CDCl3):
(18 mg, 70
m
mol) in MeCN (1.5 mL) for 5 h. Yellow oil. Rf ¼ 0.45
d
¼ 52.4 (CH3), 64.3 (CH), 93.8 (CH), 127.6 (CH), 127.7 (CH),
(light petroleum/ethyl acetate ¼ 2:1). 1H NMR (400 MHz, CDCl3)
128.6 (CH), 129.1 (C), 129.2 (CH), 129.3 (CH), 134.8 (C), 135.2 (C),
d
¼3.78 (s, 3H), 5.33 (br.s,1H), 5.36 (s,1H), 5.54 (s,1H), 7.30e7.36 (m,
137.0 (C), 161.6 (C), 170.3 (C), 192.0 (C). HRMS (ESI): m/z calcd. for
4H), 7.47e7.56 (m, 3H), 7.65 (d, J ¼ 7.1 Hz, 1H), 7.82 (d, J ¼ 8.1 Hz,
1H), 7.87 (d, J ¼ 7.8 Hz, 1H), 8.05 (d, J ¼ 8.3 Hz, 1H), 9.88 (br.s, 1H).
C
18H16ClNO3þHþ: 330.0894 [M þ H]þ; found: 330.0892. IR (KBr)
cmꢁ1
:
n
¼ 1483, 1530, 1613, 1737, 3398.
13C NMR (100 MHz, CDCl3)
d
¼ 52.5 (CH3), 60.5 (CH), 94.2 (CH),123.1
(CH), 125.5 (CH), 125.7 (CH), 126.6 (CH), 127.1 (CH), 127.6 (CH), 128.5
(CH), 129.0 (CH), 129.2 (CH), 131.2, 131.9, 134.0, 135.1, 136.9, 161.5,
4.10.5. Methyl 5-amino-5-(4-bromophenyl)-3-oxo-2-phenylpent-
4-enoate (20e)
Compound 20e (17 mg, 78%) was prepared from methyl 7-(3-(4-
bromophenyl)isoxazol-5-yl)bicyclo[4.1.0]hepta-2,4-diene-7-
170.6, 192.6. HRMS (ESI): (m/z) calcd. for
C
22H18ClNO3þHþ:
380.1048 [M þ H]þ; found: 380.1050. IR (KBr) cmꢁ1
:
n
¼ 1482, 1563,
1609, 1734, 2924, 3401.
carboxylate/methyl
hepta-2,4,6-triene-1-carboxylate 8/9e (22 mg, 58
1-(3-(4-bromophenyl)isoxazol-5-yl)cyclo-
mol) and
m
4.10.9. Methyl 5-amino-5-(4-bromophenyl)-2-(naphthalen-1-yl)-
3-oxopent-4-enoate (21d)
Compound 21d (16 mg, 53%) was prepared from methyl 1-(3-(4-
bromophenyl)isoxazol-5-yl)-1a,7b-dihydro-1H-cyclopropa[a]
Mo(CO)6 (13 mg, 50 mmol) in MeCN (2 mL) for 5.5 h. Yellow oil.
Rf ¼ 0.42 (light petroleum/ethyl acetate ¼ 2:1). 1H NMR (400 MHz,
CDCl3):
d
¼3.76 (s, 3H), 4.73 (s, 1H), 5.37 (br. s, 1H), 5.37 (s, 1H),
7.28e7.37 9 (m, 5H), 7.44e7.46 (m, 2H), 7.53 (d, J ¼ 8.5 Hz, 2H), 9.82
naphthalene-1-carboxylate 11e (30 mg, 72
mmol) and Mo(CO)6
(br. s, 1H). 13C NMR (100 MHz, CDCl3):
d
¼52.4 (CH3), 64.3 (CH), 93.7
(15.9 mg, 60 mol) in MeCN (2 mL) for 5.5 h. Light yellow oil.
m
13

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
Rf ¼ 0.31 (light petroleum/ethyl acetate ¼ 2:1). 1H NMR (400 MHz,
4.11.4. 6-(4-Chlorophenyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
(22d)
CDCl3):
d
¼3.78 (s, 3H), 5.36 (br. s, 1H), 5.36 (s, 1H), 5.54 (s, 1H), 7.26
(d, J ¼ 8.5 Hz, 2H), 7.47e7.58 (m, 5H), 7.65 (d, J ¼ 7.0 Hz, 1H), 7.82 (d,
J ¼ 8.1 Hz, 1H), 7.87 (d, J ¼ 7.6 Hz, 1H), 8.05 (d, J ¼ 8.4 Hz, 1H), 9.87
Compound 22d (11 mg, 72%) was prepared from methyl 5-
amino-5-(4-chlorophenyl)-3-oxo-2-phenylpent-4-enoate
(17 mg, 52
mol). Colorless solid, m.p. 279e280 ꢀC (mesitylene). 1H
NMR (400 MHz, DMSO‑d6):
20d
(br. s, 1H). 13C NMR (100 MHz, CDCl3):
d
¼52.5 (CH3), 60.5 (CH), 94.2
m
(CH), 123.1 (CH), 125.2 (C), 125.5 (CH), 125.7 (CH), 126.6 (CH), 127.1
(CH), 127.8 (CH), 128.5 (CH), 129.0 (CH), 131.1 (C), 131.9 (C), 132.1
(CH), 133.9 (C), 135.6 (C), 161.5 (C), 170.6 (C), 192.6 (C). HRMS (ESI):
m/z calcd. for C22H18BrNO3þNaþ: 446.0362 [M þ Na]þ; found:
d
¼6.32 (s, 1H), 7.20e7.24 (m, 1H),
7.31e7.35 (m, 2H), 7.42e7.45 (m, 2H), 7.56 (d, J ¼ 8.6 Hz, 2H), 7.72 (d,
J ¼ 8.6 Hz, 2H), 10.49 (br. s, 1H), 11.49 (br. s, 1H). 13C NMR (100 MHz,
DMSO‑d6):
d
¼98.4 (CH), 110.1 (C), 126.1 (CH), 127.2 (CH), 128.5 (CH),
446.0365. IR (KBr) cmꢁ1
2925, 3420.
:
n
¼ 1433, 1479, 1527, 1593, 1610, 1735,
128.8 (CH), 130.8 (CH), 132.4 (C), 133.7 (C), 134.4 (C), 144.2 (C), 162.7
(C), 163.6 (C). HRMS (ESI): m/z calcd. for
C
17H12ClNO2þHþ:
298.0629 [M þ H]þ; found: 298.0633. IR (KBr) cmꢁ1
:
n
¼ 1611, 2922.
4.11. General procedure for the synthesis of 6-aryl-4-hydroxy-3-
phenylpyridin-2(1H)-ones (22) and 6-aryl-4-hydroxy-3-
(naphthalen-1-yl)pyridin-2(1H)-ones (23)
4.11.5. 6-(4-Bromophenyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
(22e)
Compound 22e (20 mg, 50%) was prepared from methyl 5-
Methyl 5-amino-3-oxo-2-phenyl-5-(aryl)pent-4-enoate 20 or
methyl 5-amino-2-(naphthalen-1-yl)-3-oxo-5-(aryl)pent-4-enoate
21 was heated in mesitylene (2 mL) in thick-wall screwcap tube
at 160 ꢀC for 1.5 h (TLC control, light petroleum/ethyl acetate, 3:1, v/
v). Mesitylene was evaporated in vacuo, the residue was washed
with small amount of diethyl ether (0.5e1 mL) and dry at the air to
obtain pure compound 22 or 23. Rf ~0.7 (dichloromethane/meth-
anol, 15:1 (v/v) þ 1% triethylamine) for all compounds.
amino-5-(4-bromophenyl)-3-oxo-2-phenylpent-4-enoate
(40 mg, 0.11 mmol). Colorless solid, m.p. 275e280 ꢀC (mesitylene).
1H NMR (400 MHz, DMSO‑d6):
20e
d
¼6.32 (s, 1H), 7.20e7.24 (m, 1H),
7.31e7.35 (m, 2H), 7.43e7.45 (m, 2H), 7.64 (d, J ¼ 8.5 Hz, 2H), 7.69
(d, J ¼ 8.5 Hz, 2H), 11.46 (br. s, 1H). 13C NMR (100 MHz, DMSO‑d6):
d
¼98.4 (CH), 110.1 (C), 123.2 (C), 126.1 (CH), 127.2 (CH), 128.7 (CH),
130.8 (CH), 131.8 (CH), 132.7 (C), 133.7 (C), 144.3 (C), 162.8 (C), 163.6
(C). HRMS (ESI): m/z calcd. for C17H12BrNO2þHþ: 342.0124 [M þ
H]þ; found: 342.0124. IR (KBr) cmꢁ1
1422, 1492, 1561, 1613, 2916.
:
n
¼ 1203, 1309, 1343, 1364,
4.11.1. 4-Hydroxy-3-phenyl-6-(p-tolyl)pyridin-2(1H)-one (22a)
Compound 22a (20 mg, 83%) was prepared from methyl 5-
amino-3-oxo-2-phenyl-5-(p-tolyl)pent-4-enoate 20a (27 mg,
4.11.6. 4-Hydroxy-3-(naphthalen-1-yl)-6-(p-tolyl)pyridin-2(1H)-
one (23a)
90
m
mol). Colorless solid, m.p. 262e264 ꢀC (mesitylene) (lit. m.p.
260e261 ꢀC [28]). 1H NMR (400 MHz, DMSO‑d6):
d
¼2.36 (s, 3H),
Compound 23a (12 mg, 90%) was prepared from methyl 5-
6.29 (s, 1H), 7.19e7.23 (m, 1H), 7.29e7.34 (m, 4H), 7.44e7.46 (m,
amino-2-(naphthalen-1-yl)-3-oxo-5-(p-tolyl)pent-4-enoate
(16 mg, 45
mol). Colorless solid, m.p. 303e305 ꢀC (mesitylene). 1H
NMR (400 MHz, DMSO‑d6):
¼2.38 (s, 3H), 6.35 (s, 1H), 7.31e7.35
21a
2H), 7.59e7.61 (m, 2H), 10.43 (br. s, 1H), 11.45 (br. s, 1H). 13C NMR
m
(100 MHz, DMSO‑d6):
126.4 (CH), 127.1 (CH), 129.4 (CH), 130.4 (C), 130.8 (CH), 133.9 (C),
d
¼20.8 (CH3), 97.4 (CH), 109.6 (C), 126.0 (CH),
d
(m, 3H), 7.40e7.54 (m, 3H), 7.61e7.66 (m, 3H), 7.87 (d, J ¼ 8.1 Hz,
139.5 (C), 145.1 (C), 162.8 (C), 163.7 (C). HRMS (ESI): m/z calcd. for
1H), 7.93 (d, J ¼ 8.0 Hz, 1H), 10.30 (br. s, 1H), 11.46 (br. s, 1H). 13
C
C
18H15NO3þNaþ: 300.0995 [M þ Na]þ; found: 300.0991. IR (KBr)
NMR (100 MHz, DMSO‑d6):
d
¼20.8 (CH3), 97.2 (CH), 108.6 (C),
cmꢁ1
:
n
¼ 1367, 1515, 1621, 2919.
125.30 (CH), 125.31 (CH), 125.5 (CH), 126.0 (CH), 126.5 (CH), 126.9
(CH), 127.9 (CH), 128.6 (CH), 129.4 (CH), 130.6 (C), 132.2 (C), 132.3
(C),133.3 (C),139.5 (C),145.8 (C),163.7 (C),163.9 (C). HRMS (ESI): m/
z cald for C22H17NO2þNaþ: 350.1151 [M þ Na]þ; found: 350.1151. IR
4.11.2. 6-(4-(tert-Butyl)phenyl)-4-hydroxy-3-phenylpyridin-2(1H)-
one (22b)
Compound 22b (14 mg, 87%) was prepared from methyl 5-
amino-5-(4-(tert-butyl)phenyl)-3-oxo-2-phenylpent-4-enoate 20b
(KBr) cmꢁ1
:
n
¼ 1241, 1343, 1514, 1562, 1606, 3039.
(17 mg, 48
m
mol). Colorless solid, m.p. 292e293 ꢀC (mesitylene). 1H
4.11.7. 6-(4-Fluorophenyl)-4-hydroxy-3-(naphthalen-1-yl)pyridin-
2(1H)-one (23b)
Compound 23b (16 mg, 88%) was prepared from methyl 5-
amino-5-(4-fluorophenyl)-2-(naphthalen-1-yl)-3-oxopent-4-
NMR (400 MHz, DMSO‑d6):
d
¼1.34 (s, 9H), 6.32 (s, 1H), 7.19e7.22
(m, 1H), 7.31e7.34 (m, 2H), 7.47 (d, J ¼ 7.3 Hz, 2H), 7.51 (d, J ¼ 8.4 Hz,
2H), 7.67 (d, J ¼ 8.4 Hz, 2H), 10.54 (br. s., 2H). 13C NMR (100 MHz,
DMSO‑d6):
d
¼30.7 (CH3), 34.2 (C), 97.3 (CH), 109.5 (C), 125.2 (CH),
enoate 21b (20 mg, 55
mmol) in, as a colorless solid: m.p.
125.5 (CH), 125.9 (CH), 126.7 (CH), 130.3 (C), 130.4 (CH), 133.7 (C),
321e323 ꢀC (mesitylene). 1H NMR (400 MHz, DMSO‑d6):
d¼6.39 (s,
144.7 (C), 152.2 (C), 162.5 (C), 163.3 (C). HRMS (ESI): m/z calcd. for
1H), 7.30e7.36 (m, 3H), 7.39e7.54 (m, 3H), 7.64 (d, J ¼ 8.3 Hz, 1H),
C
21H21NO2þNaþ: 342.1465 [M þ Na]þ; found: 342.1468. IR (KBr)
7.82e7.87 (m, 3H), 7.92 (d, J ¼ 8.0 Hz, 1H), 10.96 (br. s, 1H). 13C NMR
cmꢁ1
:
n
¼ 1307, 1352, 1398, 1424, 1563, 1612, 2867, 2927, 2959.
(100 MHz, DMSO‑d6):
d
¼97.8 (CH), 108.5 (C), 115.3 (d, J ¼ 21.9 Hz,
CH), 124.9 (CH), 124.9 (CH), 125.1 (CH), 125.6 (CH), 126.6 (CH), 127.6
(CH), 128.3 (CH), 128.6 (d, J ¼ 8.6 Hz, CH), 130.2 (d, J ¼ 1.8 Hz, C),
131.9 (C), 132.0 (C), 133.1 (C), 145.1 (C), 162.6 (d, J ¼ 247.6 Hz, C),
163.3 (C), 163.6 (C). HRMS (ESI): m/z calcd. for C21H14FNO2þNaþ:
4.11.3. 6-(4-Fluorophenyl)-4-hydroxy-3-phenylpyridin-2(1H)-one
(22c)
Compound 22c (16 mg, 89%) was prepared from methyl 5-
amino-5-(4-fluorophenyl)-3-oxo-2-phenylpent-4-enoate
(20 mg, 60
mol). Colorless solid, m.p. 266e270 ꢀC (mesitylene). 1H
NMR (400 MHz, DMSO‑d6):
¼6.28 (s, 1H), 7.19e7.23 (m, 1H),
7.30e7.34 (m, 4H), 7.44e7.47 (m, 2H), 7.73e7.76 (m, 2H), 11.46 (br. s,
1H). 1H NMR (100 MHz, DMSO‑d6):
20c
354.0901 [M þ Na]þ; found: 354.0906. IR (KBr) cmꢁ1
:
n
¼ 1366,
m
1430, 1507, 1582, 1610, 2702, 3050, 3429.
d
4.11.8. 6-(4-Chlorophenyl)-4-hydroxy-3-(naphthalen-1-yl)pyridin-
2(1H)-one (23c)
d
¼98.3 (CH), 109.7 (C), 115.7 (d,
J ¼ 21.7 Hz, CH), 125.9 (CH), 127.1 (CH), 128.9 (d, J ¼ 8.6 Hz, CH),
130.0 (d, J ¼ 2.8 Hz, C), 130.8 (CH), 133.9 (C), 144.2 (C), 162.9 (d,
J ¼ 247.2 Hz, C), 163.3 (C), 163.7 (C). HRMS (ESI): m/z calcd. for
Compound 23c (8 mg, 43%) was prepared from methyl 5-amino-
5-(4-chlorophenyl)-2-(naphthalen-1-yl)-3-oxopent-4-enoate 21c
(20 mg, 53
tylene). 1H NMR (400 MHz, DMSO‑d6):
J ¼ 6.9 Hz, 1H), 7.40e7.44 (m, 1H), 7.46e7.50 (m, 1H), 7.51e7.55 (m,
m
mol) in, as a colorless solid: m.p. 314e316 ꢀC (mesi-
C
17H12FNO2þHþ: 282.0925 [M þ H]þ; found: 282.0926. IR (KBr)
d
¼6.40 (s, 1H), 7.34 (d,
cmꢁ1
:
n
¼ 1238, 1427, 1514, 1595, 1616.
14

A.V. Serebryannikova, E.E. Galenko, M.S. Novikov et al.
Tetrahedron 88 (2021) 132153
e) M.L.H. Green, D.K.P. Ng, Chem. Rev. 95 (1995) 439e473.
[5] a) M.E. de Orbe, A.M. Echavarren, Eur. J. Org Chem. (2018) 2740e2752, 2018;
b) V.H. Lauridsen, L. Ibsen, J. Blom, K.A. Jørgensen, Chem. Eur J. 22 (2016)
3259e3263;
1H), 7.58 (d, J ¼ 8.5 Hz, 2H), 7.61 (d, J ¼ 8.5 Hz, 1H), 7.78 (d,
J ¼ 8.5 Hz, 2H), 7.88 (d, J ¼ 8.2 Hz, 1H), 7.94 (d, J ¼ 8.0 Hz, 1H), 10.38
(br. s, 1H), 11.57 (br. s, 1H). 13C NMR (100 MHz, DMSO‑d6):
d
¼98.2
c) W.D. Mackay, J.S. Johnson, Org. Lett. 18 (2016) 536e539;
d) V.A. Dyakonov, G.N. Kadikova, D.I. Kolokol’tsev, I.R. Ramazanov,
U.M. Dzhemilev, Eur. J. Org Chem. 2015 (2015) 4464e4470;
e) K. Yamaguchi, M. Eto, Y. Yoshitake, K. Harano, J. Phys. Org. Chem. 26 (2013)
64e69.
(CH), 109.0 (C), 125.36 (CH), 125.40 (CH), 125.5 (CH), 125.9 (CH),
127.0 (СH), 127.7 (C), 128.0 (CH), 128.5 (CH), 128.6 (CH), 128.9 (CH),
128.9 (C), 145.1 (C), 163.7 (C), 163.8 (C). HRMS (ESI): m/z calcd. for
C
21H14ClNO2þHþ: 348.0786 [M þ H]þ; found: 348.0790. IR (KBr)
cmꢁ1
:
n
¼ 1597, 1624, 2924, 3044.
[6] a) M. Mato, C. García-Morales, A.M. Echavarren, ChemCatChem 11 (2019)
53e72;
b) M. Mato, A.M. Echavarren, Angew. Chem. Int. Ed. 58 (2019) 2088e2092;
c) C. García-Morales, X.-L. Pei, J.M.S. Toro, A.M. Echavarren, Angew. Chem. Int.
Ed. 58 (2019) 3957e3961;
4.11.9. 6-(4-Bromophenyl)-4-hydroxy-3-(naphthalen-1-yl)pyridin-
2(1H)-one (23d)
Compound 23d (12 mg, 82%) was prepared from methyl 5-
amino-5-(4-bromophenyl)-2-(naphthalen-1-yl)-3-oxopent-4-
d) X. Yin, C. Zuccarello, C. García-Morales, A.M. Echavarren, Chem. Eur J. 25
(2019) 9485e9490;
ꢀ
e) M. Mato, B. Herle, A.M. Echavarren, Org. Lett. 20 (2018) 4341e4345;
enoate 21d (16 mg, 37
m
mmol). Colorless solid, m.p. 325e329 ꢀC
f) X. Yin, M. Mato, A.M. Echavarren, Angew. Chem. Int. Ed. 56 (2017)
14591e14595.
(mesitylene). 1H NMR (400 MHz, DMSO‑d6):
d
¼6.40 (s, 1H), 7.34 (d,
[7] a) M.H. Palmer, R.A. Aitken, M. Coreno, M. de Simone, C. Grazioli,
S.E. Hoffmann, N.C. Jones, J. Chem. Phys. 152 (2020) 144301;
b) L.M. Bateman, O.A. McNamara, N.R. Buckley, P. O’Leary, F. Harrington,
N. Kelly, S. O’Keeffe, A. Stack, S. O’Neill, D.G. McCarthy, A.R. Maguire, Org.
Biomol. Chem. 13 (2015) 11026e11038;
J ¼ 6.6 Hz, 1H), 7.40e7.44 (m, 1H), 7.47e7.55 (m, 2H), 7.61 (d,
J ¼ 8.3 Hz, 1H), 7.68e7.75 (m, 4H), 7.88 (d, J ¼ 8.2 Hz, 1H), 7.94 (d,
J ¼ 8.0 Hz, 1H), 10.37 (br. s, 1H), 11.57 (br. s, 1H). 13C NMR (100 MHz,
DMSO‑d6):
d
¼98.2 (CH), 109.1 (C), 123.2 (C), 125.36 (CH), 125.39
c) Z. Chen, H. Jiao, J.I. Wu, R. Herges, S.B. Zhang, P.v.R. Schleyer, J. Phys. Chem.
112 (2008) 10586e10594.
(CH),125.5 (CH),125.9 (CH),127.0 (CH),128.0 (CH),128.6 (CH),128.8
(CH), 128.8 (C), 131.8 (CH), 132.12 (C), 132.14 (C), 133.3 (C), 145.2 (C),
163.7 (C), 163.8 (C). HRMS (ESI): m/z calcd. for C21H14BrNO2þNaþ:
ꢀ
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:
n
¼ 1371,1383,
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Declaration of competing interest
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Requejo, M. Costas, P.J. Perez, Angew. Chem. Int. Ed. 55 (2016) 6530e6534.
The authors declare that they have no known competing
financial interests or personal relationships that could have
appeared to influence the work reported in this paper.
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Acknowledgments
A.V.S. is grateful to Saint Petersburg State University for post-
doctoral fellowship. Theoretical calculations were conducted under
the Russian Science Foundation project 19-13-00039. This research
used resources of the Magnetic Resonance Research Centre,
Chemical Analysis, Materials Research Centre, Centre for X-ray
Diffraction Studies and the Computer Centre of the Science Park of
Saint Petersburg State University.
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Appendix A. Supplementary data
Supplementary data to this article can be found online at
https://doi.org/10.1016/j.tet.2021.132153.
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