Rh2(OAc)4-catalyzed reaction of 2-(2-carbonylvinyl)-3-phenyl-2H-azirines with diazo esters

Article abstract of DOI:10.1134/S1070428017080097

Rh₂(OAc)₄-catalyzed reaction of 2-(2-carbonylvinyl)-3-phenyl-2H-azirines with diazo esters proceeds through an intermediate generation of azirinium ylide suffering a nonstereoselective ring opening to form (3Z)- and (3E)-2-azahexa-1,3,5-trienes. The former depending on configuration of the C⁵=C⁶ bond may undergo cyclization either in derivative of 2,3-dihydropyridine, or in pyrrolium ylide that isomerizes into a derivative of 1H-pyrrole. According to DFT calculation, the preferred formation of pyrroles at increasing volume of Z-substituent at the atom C⁶ and of substituents at the atom C¹ of 2-azahexatriene occurs due to the destabilization of more sterically loaded transition states of 1,6-cyclization.

Full text of DOI:10.1134/S1070428017080097

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2017, Vol. 53, No. 8, pp. 1214–1221. © Pleiades Publishing, Ltd., 2017.
Original Russian Text © K.V. Zavyalov, M.S. Novikov, А.F. Khlebnikov, N.V. Rostovskii, G.L. Starova, 2017, published in Zhurnal Organicheskoi Khimii,
2017, Vol. 53, No. 8, pp. 1199–1206.
Rh2(OAc)4-Сatalyzed Reaction of 2-(2-Carbonylvinyl)-
3-phenyl-2Н-azirines with Diazo Esters
K. V. Zavyalov, M. S. Novikov,* А. F. Khlebnikov, N. V. Rostovskii, and G. L. Starova
St. Petersburg State University, Universitetskaya nab. 7/9, St. Petersburg, 199034 Russia
*e-mail: m.novikov@spbu.ru
Received April 12, 2017
Abstract—Rh2(OAc)4-catalyzed reaction of 2-(2-carbonylvinyl)-3-phenyl-2Н-azirines with diazo esters
proceeds through an intermediate generation of azirinium ylide suffering a nonstereoselective ring opening to
form (3Z)- and (3E)-2-azahexa-1,3,5-trienes. The former depending on configuration of the С5=С6 bond may
undergo cyclization either in derivative of 2,3-dihydropyridine, or in pyrrolium ylide that isomerizes into a
derivative of 1Н-pyrrole. According to DFT calculation, the preferred formation of pyrroles at increasing
volume of Z-substituent at the atom С6 and of substituents at the atom С1 of 2-azahexatriene occurs due to the
destabilization of more sterically loaded transition states of 1,6-cyclization.
DOI: 10.1134/S1070428017080097
Reactions of rhodium carbenoids generated from
diazo carbonyl compounds found a wide application in
syntheses of heterocycles [1, 2]. In recent years one of
the actively developing strategies for building up 4–6-
membered N-heterocycles is the carbenoid-mediated
transformation of cycles with a weak heteroatom-
heteroatom bond [3] or strained heterocycles [4, 5]. As
an example of such reactions may serve the synthesis
of 2Н-1,3-oxazines from isoxazoles and diazo
with the participation of NCC fragment of the substrate
and СCC fragment of the carbenoid. Recently we
demonstrated alternative approach to pyridine system
by combining fragment NCCCC of substrate, for
example, 2-alkenyl-2Н-azirine, and fragment C of
carbenoid [12]. This study consists in a detailed
experimental and theoretical investigation of the ways
of azirine ring expansion in Rh2(OAc)4-catalyzed
reaction of 2-(2-carbonylvinyl)-3-phenyl-2Н-azirines 1
with diazo esters 2.
carbonyl
compounds, allowing performing
a
recyclization of isoxazole system in one synthetic
stage to obtaining final products in high yields [6].
Later it has been demonstrated that in the framework
of this approach to 2Н-1,3-oxazines 2Н-azirine-2-
carbaldehydes may be applied instead of isoxazoles
[7–9]. The possibility of application in the synthesis of
two synthetically equivalent substrates belonging to
different classes of compounds significantly extends
the synthetic potential of the preparative method.
Examples are also known of successful application of
reactions of carbenoids both with isoxazoles and with
azirines in the synthesis of pyridines. So, for instance,
pyridine-2-carboxylates were synthesized with yields
from moderate to good by reactions of isoxazoles with
rhodium carbenoids generated from alkenyl diazo-
acetates [10]. These diazo esters were also applied in
the preparation of pyridines with carbenoid-mediated
three-atom expansion of the azirine ring [11]. In both
methods the construction of pyridine ring was realized
2-Alkenyl-substituted azirines 1a–1c were syn-
thesized from 3-phenyl-2Н-azirine-2-carbaldehyde and
the corresponding alkylidenephosphoranes by the
method [13]. At a slow addition of diazo compound 2a
solution in 1,2-dichloroethane (DCE) to a mixture of
azirine E-1a, 1b and Rh2(OAc)4 (5 mol %) in boiling
1,2-dichloroethane two products were formed: 2-
azahexatrienes E,E-3a, 3b and dihydropyridines 4a,
4b. Compounds 3 and 4 were separated by column
chromatography, their yields were compiled in the
table. In a chloroform solution at room temperature
under light a slow oxidation occurs of pyridine 4а to
pyridone 6 (Scheme 1), structure of which was con-
firmed by X-ray diffraction (XRD) analysis (Fig. 1).
In a similar reaction of azirine E-1с containing a
benzoyl substituent at the С=С bond, besides expected
products E,E-3с and 4с one more compound was
1
detected by Н NMR method in insignificant amount
1214

Rh2(OAc)4-СATALYZED REACTION OF 2-(2-CARBONYLVINYL)-3-PHENYL-2Н-AZIRINES
1215
Scheme 1.
N2
R2
CO2R3
2a_2c
E/Z
COR1
R2
CO2R3
4a_4e
hv,
CO2R3
R2
Ph
COR1
Ph
E
+
+
N
R1OC
COR1
H
N
Rh2(OAc)4,
DCE, 84°C
Ph
N
Ph
N
H
CO2R3
5a_5e
R2
1a_1c
3a_3e
e
4
r
o
f
O
i
S
for 4a
CHCl3, 48 h
CO2Me
CO2Me
O
CO2Me
CF3
Ph
N
Ph
N
CO2Et
7 (5% on 1a)
6 (66% on 4a)
failed to isolate it by chromatography due to the
instability on silica gel. However pyrrole 5d
that occurred to be more stable was isolated along
with compounds E,E-3d and 4d in reaction of
azirine E-1с with dimethyl diazomalonate 2b. The
reaction of azirine E-1а with diazo compound 2с,
F3
O2
C6
F2
C9
C7
F1
C8
C13
C14
C1
C3
O4
O3
N1
C5
containing
a
dimethoxyphosphoryl substituent,
C15
C2
C10
proceeds similarly. In this case all three compounds
E,E-3e, 4e and 5e are formed, however it was possible
to isolate in the pure state only the first of them
(yield 22%). The formation of pyrrole 5e was
confirmed by 1Н NMR data of the reaction
mixture that contained typical signals of protons of
pyrrole ring and N-substituent: 5.49 d (1H, J 17.1 Hz),
6.54–6.56 m (1Н), 6.96–6.97 m (1Н). In dihydro-
pyridine 4e already in the course of the reaction
the elimination of dimethylphosphonate occurred with
the formation of pyridine 7 that was isolated in a
5% yield. Ratio of compounds E,E-3e–7–5e in
reaction mixture according to 1Н NMR data was
1.5 : 1 : 1.
C12
C16
C17
O1
O5
C4
C11
Fig. 1. Structure of 2-ethyl 3-methyl 5-oxo-6-phenyl-2-
(trifluoromethyl)-2,5-dihydropyridine-2,3-dicarbo-xylate 6
by XRD data.
that by typical chemical shifts and signal multiplicity
of protons of the pyrrole ring and N-substituent [5.13 s
(1H), 6.77 d (1H, J 4.9 Hz), 7.17 d (1Н, J 4.9 Hz)] was
described as pyrrole structure 5с. Unfortunately, we
Reactions of azirines 1a–1c with diazo esters 2a–2c
Azirine 1
R1
Diazo ester 2
R2
R3
Et
Yield 3, %
Yield 4, %
27 (4a)
Yield 5, %
0 (5a)
E-1a
OMe
2a
CF3
45 (E,E-3a)
E-1b
E-1c
E-1c
E-1а
Z-1a
H
Ph
Ph
OMe
OMe
2a
2a
2b
2c
2a
CF3
CF3
CO2Me
P(O)(OMe)2
CF3
Et
Et
Me
Me
Et
19 (E,E-3b)
28 (E,E-3c)
32 (E,E-3d)
22 (E,E-3e)
28 (E,Z-3a)
20 (4b)
32 (4c)
11 (4d)
– (4e)b
0 (4a)
0 (5b)
– (5c)a
13 (5d)
– (5e)c
17 (5a)
Decomposed on silica gel. The ratio 4с–5с in the reaction mixture was 5 : 1 (1Н NMR data).
а
Under the reaction conditions it converted in pyridine 7 (5%), the ratio E,E-3e–7–5e in the reaction mixture was 1.5 : 1 : 1 (1Н NMR
b
data).
c
Decomposed on silica gel.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

ZAVYALOV et al.
1216
Scheme 2.
E
MeO2C
E
MeO2C
CF3
CO2Me
E
Z
CO2Me
CF3
E
E
E-1a
N
Ph
N
N2
Ph
Rh2(OAc)4
Z,E,E-3f
E,E,E-3f
CO2Me
F3C
CO2Me
2d
CO2Me
E
Ph
CO2Me
E
N
CF3
CO2Me
Z
Z
Z
E
F3C
E-8
Rh2(OAc)4
N
N
CF3
Ph
CO2Me
TS6
Ph
CO2Me
TS9
Z,Z,E-3f
E,Z,E-3f
TS2
TS5
TS1
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
Ph
Ph
Ph
CF3
CF3
N
H
N
N
H
H
Ph
N
Ph
N
CO2Me
CO2Me
F3C
CO2Me
MeO2C
CF3
CO2Me
F3C
trans-9
cis-9
5f
E-10
Z-10
TS4
TS3
TS7
Ph
TS8
TS10
4f
4f
Z
Z
CO2Me
CF3
CO2Me
CO2Me
Z
Z
Z
E
N
CO2Me
Rh2(OAc)4
CO2Me
N
N
F3C
CF3
Ph
CO2Me
Ph
Z-8
E,Z,Z-3f
Z,Z,Z-3f
N2
Z
Rh2(OAc)4
Z
CO2Me
CF3
CF3
E
E
F3C
CO2Me
Z
E
MeO2C
2d
N
MeO2C
N
Ph
Ph
Z-1a
CO2Me
E,E,Z-3f
Z,E,Z-3f
Unexpectedly in reaction of isomeric azirine Z-1a
with diazo ester 2а any trace of dihydropyridine 4а
was not discovered. In the reaction mixture with Н
NMR method the presence was observed of only two
compounds: azahexatriene E,Z-3а and pyrrol 5а which
were isolated in yields 28 and 17%.
dihydropyridine 4f, and pyrrole 5f. This simplified
reaction system (methyl ester 2d instead of ethyl ester
2a) was chosen for convenient realization of DFT
calculations of key stages of the formation of
compounds 3–5. Rhodium carbenoid generated from
diazo ester reacts with azirines E- and Z-1a, giving
rhodium-bound ylides E- and Z-8 that undergo opening
in 2-azahexatrienes: E-8 in E,E,E-, Z,E,E-, E,Z,E- and
Z,Z,E-3f, Z-8 in E,E,Z-, Z,E,Z-, E,Z,Z- and Z,Z,Z-3f.
Azahexatrienes E,E,E-, Z,E,E-3f, generated from
azirine E-1a, and azahexatrienes E,E,Z-, Z,E,Z-3f,
generated from azirine Z-1a, possess E-configuration
of the С3=С4 bond and are stable compounds to say
nothing of the quick inversion with respect to C=N
bond. Azahexatrienes with Z-configuration of С3=С4
1
By an example of Rh2(OAc)4-catalyzed reaction of
isomeric azirines E- and Z-1a with methyl 2-diаzo-
3,3,3-trifluoropropanoate 2d we demonstrate a general
scheme of the mechanism of the investigated process
furnishing three main compounds: azahexatriene E,E-
or E,Z-3f (they are shown on Scheme 2 as pairs of
invertomeres quickly transforming in each other E,E,E
-3f ⇄ Z,E,E-3f and E,E,Z-3f ⇄ Z,E,Z-3f respectively),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

Rh2(OAc)4-СATALYZED REACTION OF 2-(2-CARBONYLVINYL)-3-PHENYL-2Н-AZIRINES
1217
TS3
49.9
50
40
30
20
10
0
TS4
36.9
TS8
TS7
TS5
26.5
22.8
25.2
21.6
TS2
TS6
23.2
19.3
TS1
TS10
TS9
20.6
+
Ph
CO2Me
+
Ph
CO2Me
N
N
_
_
F3C
CO2Me
MeO2C
CF3
11.9
Z-10
E-10
9.1
7.9
CO2Me
CF3
CO2Me
2.1
2.4
0.1
CO2Me
CO2Me
N
CO2Me
0
Ph
Z,Z,Z-3f
CO2Me
CF3
CO2Me
CF3
CO2Me
–5.4
–5.8
N
CO2Me
Ph
CO2Me
CF3
N
E,Z,E-3f
CF3
Ph
N
–10
Ph
CF3
CO2Me
E,Z,Z-3f
cis-9
Ph
N
N
CO2Me
trans-9
Ph
Z,Z,E-3f
Fig. 2. Energy profile [DFT B3LYP/6-31+G(d,p), kcal mol–1, 375 K] of transformation in 1,2-dichloroethane of azahexatrienes 3f
into dihydropyridines 9 and pyrrolium ylides 10.
bond in conditions of reaction are unstable and, as the
experiment has demonstrated, depending on the con-
figuration of С5=С6 bond may undergo 1,6-cyclization into
2,3-dihydropyridines cis- and trans-9, isomerizing into
final 1,2-dihydropyridine 4f, or suffer cyclization into
pyrrolium ylides Z- and E-10, isomerizing into final
pyrrole 5f. The described mechanism of the formation of
2-azahexatrienes may include an additional stage of the
formation of free azirinium ylide (not shown on
Scheme 2), however in general it fully corresponds to
experimental and calculated results that we have
obtained for reactions of carbenoids with 2-aryl- [14],
2,2-diaryl- [15], 2,2-dialkyl- [16], 2-formyl- [7–9], and
2-bromo-2-methoxycarbonyl-substituted [17, 18], and
also with 2-nonsubstituted azirines [15]. However an
important stereochemical difference of ring opening
should be mentioned in 2-formyl-substituted azirinium
ylides and in 2-(2-carbonylvinyl)-substituted ylides of type
8. In the first case the opening of azirine cycle goes with
full 3Z-stereoselectivity [7–9], while 2-alkenyl analogs
8 give both geometric isomers of azahexatriene.
azirine on the ratio of final cyclic products 4 and 5
quantum-chemical calculations of transformation paths
of isomeric azahexatrienes E,Z,E-, Z,Z,E-, E,Z,Z-, and
Z,Z,Z-3f in dihydropyridines cis- and trans-9 and in
pyrrolium ylides Z- and E-10 were performed.
By the method of DFT B3LYP/6-31+G(d,p)
accounting for solvation (PCM) with 1,2-dichloro-
ethane free energies were calculated of the most stable
conformations of geometric isomers of azahexatriene
3f, dihydropyridines cis- and trans-9, pyrrolium ylides
Z- and E-10, and also of transition states of 1,6-
cyclization of azatrienes into dihydropyridines (TS1–
TS4), their 1,5-cyclization into pyrrolium ylides (TS5–
TS8), and Z,E-isomerization with respect to C=N bond
(TS9, TS10). The correspondence of transition states to
saddle point, connecting the initial compounds with
the reaction products, was checked by the method of
internal reaction coordinate (IRC). Transformations of
(5E)-azahexatrienes, obtained from azirine E-1a, are
drawn by solid line, and of (5Z)-azahexatrienes
obtained from azirine Z-1a, with dotted line (Fig. 2).
The inversion of nitrogen atom is also drawn on the
diagram with solid line.
To find out the reasons of strong influence of
geometry of С=С bond of alkenyl substituent at С2 in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

ZAVYALOV et al.
1218
From calculation results follows that dihydropyridi-
them from reactions with 2-formylazirines [7–9],
consists in the fact that ylide intermediates generated
in first stage open nonselectively, giving mixtures of
isomeric azahexatrienes 3: isolated from reaction
mixture stable (3E)-isomer and thermally unstable (3Z)
-isomer. The latter in conditions of reaction may
undergo either 1,6-cyclization into 2,3-dihydropyridine
isomerizing into more stable 1,2-dihydropyridine form
4, or suffer 1,5-cyclization into pyrrolium ylide which
isomerizes into final pyrrole 5. The lack of selectivity
of ylide intermediate opening in this reaction limits its
application as a method of synthesis of pyridine
derivatives. One more synthetic limitation is the
presence of competitive 1,5-cyclization of (3Z)-2-
azahexatriene intermediate, giving finally an isomer of
pyrrole series. According to DFT calculations, the
formation of pyrroles is preferable at increasing the
volume of Z-substituent at the atom С6 and substituents
at the atom С1 of 2-azahexatriene due to the
destabilization of sterically more loaded transition
states of 1,6-cyclization.
ne 9 should be formed preferably as trans-isomer by 1,6-
cyclization of azahexatriene E,Z,E-3f, whose C5=C6 bond
possesses E-configuration (TS1, ∆G≠ 18.2 kcal mol–1).
Into the same dihydropyridine the second 5E-isomer
(Z,Z,E-3f) can transfrom after preliminary overcoming
a low barrier inversion of nitrogen atom (TS9, ∆G≠
11.9 kcal mol–1) into azahexatriene E,Z,E-3f (solid lines).
On the contrary, azahexatrienes with Z-configuration
of the C5=C6 bond (E,Z,Z- and Z,Z,Z-3f) possess very
high activation barriers of 1,6-cyclization (TS3, ∆G≠
49.8 kcal mol–1; TS4, ∆G≠ 34.8 kcal mol–1) (dotted
lines) and should undergo 1,5-cyclization into ylides
E- and Z-10 respectively with significantly lower
barriers (TS7, ∆G≠ 25.1 kcal mol–1; TS8, 24.4 kcal mol–1).
Analysis of geometries of transition states of 1,6-
cyclizations of azatrienes with E-bond C5=C6 (TS1 and
TS2), on the one hand, and azatrienes with Z-bond
C5=C6 (TS3 and TS4), on the other, demonstrates
significantly higher deviations from planarity of
dihedral angle НС5С6Н (43–44 against 16–21 deg),
and also noticeable increase in the length of the formed
С1–С6 bond (2.47–2.52 against 2.34–2.37 Å) in the
transition state for 5Z-isomers that indicates high steric
hindrances created by CO2Me group and the subs-
tituent at the atom C1 in the transition states TS3 and
TS4. Hence, the calculated data for model azatriene system
3f correlate with experimental results of competition of
1,6- and 1,5-cyclization of thermally unstable (3Z)-
azahexatrienes, generated from isomeric azirines Z-
and E-1. Note that the changes in geometry of С5=С6
bond of azahexatriene have much more effect on 1,6-,
than on 1,5-cyclization. We attributed this fact to a higher
steric load of the transition state on the path to the 6-
membered cycle: the binding of two trigonal carbon
reaction centers at 1,6-cyclization comparing to binding
a trigonal carbon center to digonal nitrogen center at
1,5-cyclization. It follows that increasing volume of
substituents at the atom С1 of azahexatriene which has
acquired them from diazo ester also should change the
ratio of products of 1,6-/1,5-cyclization in favor of the
latter. Indeed, this assumption is confirmed by results
of Rh2(OAc)4-catalyzed reaction of azirine E-1a with
diazo ester 2c containing a bulky dimethoxyphos-
phoryl group that, unlike the similar reaction of trifluoro-
methyl-substituted diazo ester 2a, gave products of 1,6-
and 1,5-cyclization in equal amounts (see the table).
EXPERIMENTAL
Melting points of all substances were determined
on Boеtius heating block equipped with a microscope;
uncorrected values were reported. NMR spectra were
recorded on spectrometers Bruker DPX-300 [working
frequencies 300 (1Н), 75 (13С) МHz] or Bruker DPX-
400 [working frequencies 400 (1Н), 100 (13С) МHz].
Mass spectra were obtained on mass spectrometer
Bruker micrOTOF. Data of single crystal XRD
analysis were obtained on diffractometer Agilent
Technologies Xcalibur Eos (МоKα-radiation, 100 K).
Reactions progress was monitored by TLC on
ALUGRAM SIL G/UV254 plates. To separate reaction
mixtures silica gel Merck 60 was used. Azirines 1a–1c
were synthesized by method [13]. Quantum-chemical
calculations were realized using software package
GAUSSIAN 09 Rev. C.01 [19].
Analysis of synthesized compounds was carried out
on equipment of resource centers of Saint-Petersburg State
University “Magnetic Resonance Research Centre”,
“Centre for X-ray Diffraction Studies” and “Cgemical
Analysis and Materials Research Centre”. Quantum-
chemical calculations were performed in the resource
center of St. Petersburg State University “Computing
Centre.”
Hence, an important feature of reactions of rhodium
carbenoids generated from diazo esters with 2-(2-
carbonylvinyl)-3-phenyl-2Н-azirines 1, distinguishing
Catalytic reactions of azirines (1) with diazo
esters (2). General methods. а. A mixture of azirine
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Rh2(OAc)4-СATALYZED REACTION OF 2-(2-CARBONYLVINYL)-3-PHENYL-2Н-AZIRINES
1219
and diazo compound in 5 mL of anhydrous 1,2-
dichloroethane at stirring in an argon atmosphere was
heated till boiling (84°С), 5 mol % Rh2(OAc)4 was
added (with respect to diazo ester), the mixture was
refluxed till nitrogen evolution ended (10–15 min). The
solvent was removed in a vacuum, reaction products
were isolated by column chromatography on silica gel
eluting with a mixture of petroleum ether–EtOAc.
H
arom), 9.52 d [1Н, СН(О), J 7.9 Hz]. 13С NMR
spectrum (CDCl3, 100 МHz), δ, ppm: 13.9 (CH3), 63.1
(CH2), 111.5 (C2), 117.9 q (CF3, J 278.8 Hz), 125.2
(C4), 128.9, 129.0, 130.3, 132.6 (Carom), 146.9 q (CCF3,
J 36.0 Hz), 147.3 (C3), 155.6, 158.0 (С1, CO2Et), 193.1
[СН(О)]. Found [M + Na]+ 348.0823. С16Н14F3NNaO3.
Calculated [M + Na]+ 348.0818.
1
Compound 4b. Yellow oily substance. Н NMR
spectrum (CDCl3, 400 МHz), δ, ppm: 1.32 t (3Н, СН3,
J 7.0 Hz), 4.28–4.40 m (2Н, СН2), 5.55 br.s (1Н, NH),
5.59 d.d (1Н, C5H, J 7.0, 1.8 Hz), 7.29 d (1Н, C4H, J
7.0 Hz), 7.44–7.57 m (5Н, Harom), 9.36 s [1Н, СН(О)].
13С NMR spectrum (CDCl3, 100 МHz), δ, ppm: 13.7
(CH3), 63.2 (CH2), 65.4 q (C2, J 30.1 Hz), 94.9 (C5),
116.2 (C3), 124.2 q (CF3, J 290.5 Hz), 126.7, 129.2,
131.2, 133.9 (Carom), 147.3 (C4), 151.3 (C6), 166.7
(CO2Et), 187.6 [СН(О)]. Found [M + Na]+ 348.0821.
С16Н14F3NNaO3. Calculated [M + Na]+ 348.0818.
b. To a refluxing 0.5 M solution of azirine and
Rh2(OAс)4 (5 mol % with respect to diazo ester) in
anhydrous 1,2-dichloroethane at stirring in an argon
atmosphere was added dropwise at a rate 3.0 mL/h
0.2 M solution of diazo compound in anhydrous 1,2-
dichloroethane. The reaction progress was monitored
by TLC (eluent petroleum ether–EtOAc). The solvent
was removed in a vacuum, reaction products were
isolated by column chromatography on silica gel,
eluting with a mixture of petroleum ether–EtOAc.
Ethyl 3,3,3-trifluoro-2-[(1Е,3Е)-5-oxo-1,5-diphe-
nylpenta-1,3-dien-1-ylimino]propаnoate (E,E-3c)
and ethyl 3-benzoyl-6-phenyl-2-(trifluoromethyl)-1,2-
dihydropyridine-2-carboxylate (4c) were obtained by
method a from 200 mg (0.81 mmol) of azirine E-1c
and 295 mg (1.62 mmol) of diazo ester 2a in yields of
91 mg (28%) and 104 mg (32%) respectively.
Methyl (2E,4E)-5-(3-ethoxy-1,1,1-trifluoro-3-oxo-
propan-2-ylidenamino)-5-phenylpenta-2,4-dienоate
(E,E-3a) and 2-ethyl 3-methyl 6-phenyl-2-(trifluoro-
methyl)-1,2-dihydropyridine-2,3-dicarboxylate (4a)
were obtained by method b from 100 mg (0.50 mmol)
of azirine E-1a and 136 mg (0.75 mmol) of diazo ester
2a in yields of 79 mg (45%) and 48 mg (27%)
respectively. Spectral data of compounds E,E-3a and
4a are described in [12].
Compound E,E-3c. Orange crystals, mp 61–63°C
(hexane–Et2O). 1Н NMR spectrum (CDCl3, 400 МHz),
δ, ppm: 1.29 t (3Н, СH3, J 7.0 Hz), 4.30 q (2Н, CH2, J
7.0 Hz), 5.97 d (1Н, C2H, J 11.9 Hz), 7.13 d (1Н, C4H,
J 15.0 Hz), 7.45–7.64 m (9Н, Harom, C3H), 7.92–7.96 m
(2H, Harom). 13С NMR spectrum (CDCl3, 100 МHz) δ,
ppm: 13.9 (CH3), 63.1 (CH2), 113.2 (C2), 118.0 q (CF3,
J 278.8 Hz), 127.2 (C4), 128.3, 128.6, 128.7, 129.0,
130.0, 132.79, 132.81, 137.9 (Carom), 140.1 (C3), 146.8
q (CCF3, J 36.0 Hz), 155.1, 158.5 (С1, CO2Et), 189.7
(СОPh). Found [M + H]+ 402.1311. С22Н19F3NO3.
Calculated [M + H]+ 402.1312.
Methyl (2Z,4E)-5-(3-ethoxy-1,1,1-trifluoro-3-oxo-
propan-2-ylidenamino)-5-phenylpenta-2,4-dienoate
(E,Z-3a) and methyl 1-(3-ethoxy-1,1,1-trifluoro-3-oxo-
propan-2-yl)-5-phenyl-1Н-pyrrole-2-carboxylate (5a)
were obtained by method b from 30 mg (0.15 mmol)
of azirine Z-1a and 40 mg (0.22 mmol) of diazo ester
2a in yields of 15 mg (28%) and 9 mg (17%)
respectively. Spectral data of compounds E,Z-3a and
5a are described in [12].
Ethyl 3,3,3-trifluoro-2-[(1Е,3Е)-5-oxo-1-phenyl-
penta-1,3-dien-1-ylimino]propаnoate (E,E-3b) and
ethyl 3-formyl-6-phenyl-2-(trifluoromethyl)-1,2-di-
hydropyridine-2-carboxylate (4b) were obtained by
method b from 150 mg (0.88 mmol) of azirine E-1b
and 160 mg (0.88 mmol) of diazo ester 2a in yields of
55 mg (19%) and 58 mg (20%) respectively.
Compound E,E-3b. Yellow oily substance. 1Н NMR
spectrum (CDCl3, 400 МHz), δ, ppm: 1.32 t (3Н, СН3,
J 7.0 Hz), 4.34 q (2Н, СН2, J 7.0 Hz), 5.91 d (1Н,
C2H, J 11.3 Hz), 6.26 d.d (1Н, C4H, J 15.3, 7.9 Hz),
7.23 d.d (1Н, C3H, J 15.3, 11.3 Hz), 7.45–7.55 m (5Н,
1
Compound 4c. Yellow oily substance. Н NMR
spectrum (CDCl3, 400 МHz), δ, ppm: 1.37 t (3Н, СH3,
J 7.0 Hz), 4.35–4.55 m (2Н, CH2), 5.11 br.s (1Н, NH),
5.54 d.d (1Н, C5H, J 7.0, 1.5 Hz), 7.15 d (1Н, C4H, J
7.0 Hz), 7.43–7.59 m (8Н, Harom), 7.67–7.71 m (2Н,
H
arom). 13С NMR spectrum (CDCl3, 100 МHz), δ, ppm:
13.7 (CH3), 63.2 (CH2), 66.4 q (C2, J 30.1 Hz), 94.9
(C5), 114.8 (C3), 124.9 q (CF3, J 289.0 Hz), 126.8,
128.2, 128.8, 129.0, 130.9, 131.3, 134.1, 138.9 (Carom),
142.7 (C4), 149.1 (C6), 168.0 (CO2Et), 193.9 (СОPh).
Found [M + H]+ 402.1313. С22Н19F3NO3. Calculated
[M + H]+ 402.1312.
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ZAVYALOV et al.
1220
Dimethyl 2-[(1Е,3Е)-5-oxo-1,5-diphenylpenta-
m (2Н, CH3CH2), 7.36 s (1Н, C4H), 7.46–7.51 m (2H,
Harom), 7.53–7.59 m (1Н, Harom), 7.98–8.02 m (2Н,
H
13.8 (CH3CH2), 53.4 (ОCH3), 63.4 (CH3CH2), 71.2 q
(C2, J 27.3 Hz), 121.5 q (CF3, J 286.1 Hz), 128.3,
129.8, 131.9, 132.7, 135.7 (C4, Carom), 143.9 (C3),
162.1, 163.4, 165.5 (C6, CO2Me, CO2Et), 175.7 (C5).
Found [M + H]+ 370.0913. С17Н15F3NO5. Calculated
[M + H]+ 370.0897.
1,3-dien-1-ylimino]malonate (E,E-3d), dimethyl 3-
benzoyl-6-phenyl-1,2-dihydropyridine-2,2-dicar-
boxylate (4d), and dimethyl 2-(2-benzoyl-5-phenyl-
1Н-pyrrol-1-yl)malonate (5d) were obtained by method
a from 50 mg (0.20 mmol) of azirine E-1c and 64 mg
(0.40 mmol) of diazo ester 2b in yields of 24 mg
(32%), 8 mg (11%) and 10 mg (13%) respectively.
Compound E,E-3d. Yellow oily substance. 1Н
NMR spectrum (CDCl3, 300 МHz), δ, ppm: 3.76 br.s
(3Н, OCH3), 3.96 br.s (3Н, OCH3), 6.09 d (1Н, C2H, J
11.5 Hz), 7.13 d (1Н, C4H, J 14.8 Hz), 7.35–7.60 m
(9Н, Harom, C3H), 7.92–7.96 m (2Н, Harom). 13С NMR
spectrum (CDCl3, 75 МHz), δ, ppm: 52.8 (OCH3),
53.6 (OCH3), 114.8 (C2), 127.2 (C4), 128.3, 128.5,
128.6, 129.2, 129.8, 132.7, 133.0, 137.9 (Carom), 140.3
(C3), 149.7, 156.4 (С1, C=N), 161.2 (CO2Me), 161.8
(CO2Me), 189.7 (СОPh). Found [M + H]+ 378.1341.
С22Н20NO5. Calculated [M + H]+ 378.1336.
arom). 13С NMR spectrum (CDCl3, 100 МHz), δ, ppm:
XRD analysis (CCDC 1542058). C17H14F3NO5, m
369.29, T 100 K, monoclinic crystal system, space group
P21/c, a 10.3152(7), b 9.6779(4), c 16.5819(6) Å; β
90.288(4)°, V 1655.34(14) Å3, Z 4, d 1.482 mg/mm3, μ
(MoKα) 0.131, R 0.0863, wR2 0.1080, 6698 reflections,
of them 3255 independent (Rint 0.0382).
Methyl (2E,4E)-5-[1-(dimethoxyphosphoryl)-2-
methoxy-2-oxoethylidenamino]-5-phenylpenta-2,4-
dienoate (E,E-3e) and dimethyl 6-phenylpyridine-
2,3-dicarboxylate (7) were obtained by method b from
100 mg (0.50 mmol) of azirine E-1a and 207 mg
(1.00 mmol) of diazo ester 2c in yields 41 mg (22%)
and 7 mg (5%) respectively.
Compound E,E-3e. Yellow oily substance. 1Н NMR
spectrum (CDCl3, 400 МHz), δ, ppm: 3.72 s [3Н, С(O)
OCH3], 3.78 br.s [3Н, С(O)OCH3], 3.91 br.d [6Н, P(O)
OCH3, J 10.7 Hz], 5.82 d (1Н, C4H, J 11.9 Hz), 6.00 d
(1Н, C2H, J 15.3 Hz), 7.34–7.48 m (6Н, Harom, C3H).
13С NMR spectrum (CDCl3, 100 МHz), δ, ppm: 51.5
[С(O)OCH3], 52.9 [С(O)OCH3], 54.5 [P(O)OCH3],
112.5 (C4), 122.7 (C2), 128.6, 129.0, 129.7, 133.2
(Carom), 140.4 (C3), 167.2 (CO2Me). Signals of carbon
atoms of fragment С–N=C overlapped. Found [M +
Na]+ 404.0872. С17Н20NNaO7P. Calculated [M + Na]+
404.0870.
1
Compound 4d. Yellow oily substance. Н NMR
spectrum (CDCl3, 300 МHz), δ, ppm: 3.89 s (6Н,
OCH3), 5.56 d.d (1Н, C5H, J 6.7, 1.8 Hz), 5.76 br.s
(1Н, NH), 7.03 d (1Н, C4H, J 6.7 Hz), 7.43–7.56 m
(6Н, Harom), 7.62–7.67 m (2Н, Harom), 7.74–7.78 m
(2Н, Harom). 13С NMR spectrum (CDCl3, 75 МHz), δ,
ppm: 53.6 (OCH3), 67.5 (C2), 95.8 (C5), 118.4 (C3),
127.2, 128.1, 128.97, 129.04, 130.7, 131.1, 134.3,
139.18, 139.21 (C4, Carom), 148.5 (C6), 171.1 (CO2Me),
193.8 (СОPh). Found [M + H]+ 378.1341. С22Н20NO5.
Calculated [M + H]+ 378.1336.
Compound 5d. Yellow oily substance. 1Н NMR spec-
trum (CDCl3, 300 МHz), δ, ppm: 3.79 s (6Н, OCH3),
5.87 s [1Н, CHC(O)], 6.35 d (1Н, C4H, J 4.0 Hz), 6.92 d
(1Н, C3H, J 4.0 Hz), 7.40–7.60 m (8Н, Harom), 7.83–
7.87 m (2Н, Harom). 13С NMR spectrum (CDCl3, 75 МHz),
δ, ppm: 53.2 (OCH3), 61.8 [CHC(O)], 110.6 (C4),
123.2 (C3), 128.1, 128.9, 129.1, 129.3, 129.6, 130.9,
131.4, 131.5, 139.3 (C2, Carom), 143.6 (C5), 165.6
(CO2Me), 186.5 (СОPh). Found [M + H]+ 378.1339.
С22Н20NO5. Calculated [M + H]+ 378.1336.
Compound 7. Colorless crystals, mp 93–94°C (mp
95–96°С [20]). 1Н NMR spectrum (CDCl3, 400 МHz),
δ, ppm: 3.97 s (3Н, OCH3), 4.05 s (3Н, OCH3), 7.47–
7.54 m (3Н, Harom), 7.90 d (1Н, C5H, J 8.2 Hz), 8.07–
8.12 m (2Н, Harom), 8.32 d (1Н, C4H, J 8.2 Hz). Found
[M + H]+ 272.0911. С15Н14NO4. Calculated [M + H]+
272.0917.
2-Ethyl 3-methyl 5-oxo-6-phenyl-2-(trifluoro-
methyl)-2,5-dihydropyridine-2,3-dicarboxylate (6)
was obtained at holding of 48 mg of pyridine 4a under
light in solution of chloroform (2 mL) for 2 days. After
purification by column chromatography on silica gel
with eluent petroleum ether–EtOAc yield was 33 mg
(66%). Yellow crystals, mp 63–65°C (hexane–Et2O).
1Н NMR spectrum (CDCl3, 400 МHz), δ, ppm: 1.31 t
(3Н, CH3CH2, J 7.0 Hz), 3.94 s (3Н, ОCH3), 4.28–4.41
ACKNOWLEDGMENTS
This research was carried out with a financial
support of the Russian Foundation for Basic
Research (projects nos. 16-03-00596, 16-33-60130)
and of St. Petersburg State University (grant
no. 12.38.217.2015).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 53 No. 8 2017

Rh2(OAc)4-СATALYZED REACTION OF 2-(2-CARBONYLVINYL)-3-PHENYL-2Н-AZIRINES
1221
15. Rostovskii, N.V., Novikov, M.S., Khlebnikov, A.F.,
Starova, G.L., and Avdontseva, M.S., Beilst. J. Org.
Chem., 2015, vol. 11, p. 302.
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