Intramolecular 1,3-dipolar cycloaddition to ester carbonyl of azomethinylides prepared from aldimines and difluorocarbene

Article abstract of DOI:10.1023/B:RUJO.0000034942.42778.e0

Azomethinylides generated by reaction of difluorocarbene with N-alkyl- and N-arylimines of O-acylated salycilaldehyde undergo intramolecular 1,3-dipolar cycloaddition to the ester carbonyl group forming regioselectively 2,5-epoxy-1,4-benzoxazepine derivat

Full text of DOI:10.1023/B:RUJO.0000034942.42778.e0

Russian Journal of Organic Chemistry, Vol. 40, No. 2, 2004, pp. 199-205. Translated from Zhurnal Organicheskoi Khimii, Vol. 40, No. 2, 2004,
pp. 226-233.
Original Russian Text Copyright Ó 2004 by Voznyi, Novikov, Khlebnikov, Kopf, Kostikov.
Intramolecular 1,3-Dipolar Cycloaddition to Ester Carbonyl
of Azomethinylides Prepared from Aldimines and Difluorocarbene
I. V. Voznyi1, M. S. Novikov1, A. F. Khlebnikov1, J. Kopf2, and R. R. Kostikov1
1St. Petersburg State University, St. Petersburg, 198504 Russia
e-mail: Alexander.Khlebnikov@pobox.spbu.ru
2Institut fur Anorganische Chemie, Martin-Luther-King-Platz 6, D-20146 Hamburg, Germany
Received July 2002
Abstract—Azomethinylides generated by reaction of difluorocarbene with N-alkyl- and N-arylimines of O-acylated
salycilaldehyde undergo intramolecular 1,3-dipolar cycloaddition to the ester carbonyl group forming regioselectively
2,5-epoxy-1,4-benzoxazepine derivatives.
Reactions of 1,3-dipolar cycloaddition of azo-
methinylides are among the most promising synthetic
approaches in the chemistry of the nitrogen-containing
heterocycles [1].An intramolecular version of this reaction
became owing to recent investigations a convenient
procedure for preparation of complex polycyclic and
cage-like heterocyclic systems, including naturally
occurring compounds [2]. The high synthetic potential of
the intramolecular 1,3-dipolar addition of azomethinylides
is due both to the large choice of methods for their
generation and to the high regio- and stereoselectivity of
the cycloaddition. Furthermore the intramolecular version
of the reaction is relatively insensitive to variation of
substituents attached to C=C and CºC bond that serve
as the most typical dipolarophile traps. The
azomethinylides cycloaddition to the carbonyl bonds of
aldehydes and ketones [3] and to imine C=N bonds [4–
6] was performed only intermolecularly. The ester
carbonyl group is famous for its passivity with respect to
1,3-dipoles and therefore it is often used for activation of
C=C- and CºC dipolarophiles [2, 3]. However we showed
recently that under certain conditions the carbonyl bond
of an ester functional group could serve for efficient
capture of azomethinylides [7]. We report here the results
of the study of intramolecular 1,3-dipolar cycloaddition
to the ester carbonyl of azomethinylides generated by
reaction of difluorocarbene with O-acylated salicyl-
aldimines.
dipolarophile that grows in parallel with its electrophilic
quality in case of nucleophilic azomethiylides. We
formerly found that azomethinylides I generated from
O-alkenylated salicylaldimines II and difluorocarbene
readily added across a C=C bond connected to the ylide
fragment of the molecule by a 4-atomic linker C =C –
2
sp
2
sp
O–Csp3, affording chromenopyrrole derivatives III,
Scheme 1.
Scheme 1.
2
2
ꢀ&)
B
) &
1
ꢁ
&2 (W
1
&2 (W
3K
,
3K
,,
2
+
)
&2 (W
ꢀ+)
+
1
3K
,,,
Moreover, in the molecules with this linker the
intramolecular cycloaddition of a number of azo-
methinylides was performed even with so inert
dipolarophile as the double bond of furan ring [8].
In order to test whether the intramolecular 1,3-dipolar
cycloaddition of difluoromethylides would occur with a
carbonyl of an ester group we generated from imine IV
and difluorocarbene ylide V where the dipole and the
potential dipolarophile were linked by the chain C =C –
Among the main factors facilitating the intramolecular
1,3-dipolar cycloaddition should be named the nature of
the chain (linker) connecting the dipole with the
dipolarophile, and the activity of the multiple bond of the
2
sp
2
sp
O–Csp (Scheme 2).
3
1070-4280/04/4002-0199Ó2004 MAIK “Nauka/Interperiodica”

200
VOZNYI et al.
Scheme 2.
2
2(W
2
2
2
1
2
2
)
3K
2(W
)
2(W
ꢀ&)
9,
(W2
2 )
1
B
) &
1
1
ꢁ
)
3K
2
3K
9
,9
3K
9,,
Scheme 3.
5ꢂ
5ꢂ
2
5ꢂ
2
2 )
1
ꢀ&)
2
)
)
B
2
2
)
ꢁ
5
1
1
5
5
9,,,
R
;
R
,;
R
cycloadduct VI or VII, and also their transformation
products. The study of ylide system with a shorter,
The difluorocarbene was generated be reduction of
CF2Br2 with active lead in the presence of tetrabutyl-
ammonium bromide under ultrasonic irradiation. However
we failed to detect in the reaction mixture either
2
2
triatomic, linker Csp =Csp –O was carried o ut by an
example of ylides VIII generated from imines IX.
Successful intramolecular cycloadditions of
azomethinylides connected to dipole with a triatomic linker
are known for the bonds C=C [9–11], CºC [12], and
even for the multiple bond of the benzene ring (although
under very severe conditions [13]).
Yields of compounds Xa–Xo and time of reaction
of difluorocarbene with imines IXa–IXo
Srhp‡v‚ꢀ `vryqꢂꢀꢀ
D€vrꢀ
Sꢀ
Sꢁꢀ
‡v€rꢂꢀuꢀ
&!ꢀ
ꢃꢀ
&#ꢀ
Synthesis of arylimines IXa–IXn and N-alkylimine
IXo was performed by condensation of the O-acylated
salicylaldehyde with an appropriate amine. The synthesis
of N-alkylimines by this procedure was not always
successful due to fast hydrolysis of the ester group
affording salicylaldimine. Therefore O-benzoylsalicyl-
aldehyde N-trimethylsilylmethylimine IXo was prepared
from O-benzoylsalicylaldehyde and trimethylsilylmethyl
azide.
,;Dꢀ Quꢀ
,;Eꢀ Quꢀ
,;Fꢀ Quꢀ
,;Gꢀ Quꢀ
,;Hꢀ Quꢀ
,;Iꢀ Quꢀ
,;Jꢀ Quꢀ
,;Kꢀ Quꢀ
,;Lꢀ Quꢀ
Quꢀ
#ꢄHrP8 C ꢀ
#ꢄI88 C ꢀ
(ꢀ
#ꢀ
(!ꢀ
&ꢅꢀ
&"ꢀ
&$ꢀ
&&ꢀ
%'ꢀ
$%ꢀ
&ꢅꢀ
&$ꢀ
'$ꢀ
ꢀ
!ꢂ#ꢄ8y 8 C ꢀ
ꢄIhƒu‡u’yꢀ
8C 28Hrꢀ
'ꢅꢀ
($ꢀ
&ꢀ
ꢅꢀ
!ꢅꢀ
'ꢅꢀ
"&ꢀ
$%ꢀ
ꢀ
##ꢀ
'$ꢀ
&ꢀ
WUDQVꢄHr8C28Cꢀ
WUDQVꢂꢀꢄQu8C28Cꢀ
WUDQVꢄQu8C28Quꢀ
!ꢄAˆꢆ’yꢀ
Keeping a mixture of O-benzoylsalicylaldehyde anil
IXa, CF2Br2, active lead, and Bu4NBr in dichloromethane
at 45°C under ultrasonic irradiation of 160 W for 72 h
resulted in formation of compound Xa that was isolated
by column chromatography in 74% yield.
,;Mꢀ #ꢄ7ꢆ8 C ꢀ
,;Nꢀ #ꢄ7ꢆ8 C ꢀ
,;Oꢀ #ꢄ7ꢆ8 C ꢀ
,;Pꢀ #ꢄ7ꢆ8 C ꢀ
Quꢀ
#ꢄHrP8 C ꢀ
#ꢄI88 C ꢀ
ꢀ
Compound Xa is a product of intramolecular 1,3-dipolar
cycloaddition to the C=O bond of ester group of ylide
VIIIa formed at difluorocarbene attack on the unshared
electron pair of the nitrogen in imine IXa. Imines IXb-
IXo reacted analogously to furnish adducts Xb-Xo (see
,;Qꢀ !ꢂ#ꢄ8y 8 C ꢀ Quꢀ
,;Rꢀ ꢇ#ꢄ8y8 C ꢈ 8CꢀQuꢀ
&ꢅꢀ
''ꢀ
ꢀ
a Compounds Xl, XIm were isolated from mixtures obtained in runs
of concurrent reactions.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

201
INTRAMOLECULAR 1,3-DIPOLAR CYCLOADDITION
Scheme 4.
Scheme 3, and table). The reaction in all the cases occur-
red regioselectively affording exclusively bridged adducts
X; no ortho-fused isomers of VI type was detected in
the reaction mixtures. The regiochemistry of cycloaddi-
tion was consistent with that observed in intermolecular
cycloaddition of difluoroazomethinylides to the carbonyl
group of aldehydes and ketones [14]: the carbon atom of
the difluoromethylene group of ylide always added to the
carbon of the carbonyl group.
3K
2
3K
2
)
2
)
ꢀꢁ&)
2
6L0H
1
1
6L0H
,;
;
3K
2
2
2
The composition and structure of compounds Xa–o
+ 2
1
were established basing on elemental analysis, N and
6L0H
1
13C NMR and IR spectra, sometimes using also the data
of 19F NMR spectroscopy and mass spectra. In the 1N
NMR spectra of all compounds are present doublets from
H5 protons at 6.04–6.50 ppm (4JHF 5.8–7.3 Hz). In the
13C NMR spectra appears a singlet signal from C5 at
85.8–88.6 ppm and doublets of doublets from atoms C2
at 101.1–106.2 ppm (2JCF 25.3–27.6, 33.1–37.0 Hz) and
C3 at 120.8–123.6 ppm (1JCF 255–260, 259–268 Hz). In
the 19F NMR spectra of compounds Xa, g fluorine signals
are observed at 57.5–59.8 and 84.5–88.7 ppm with respect
to C6F6 with the coupling constant JFF 176 Hz. In the
mass spectra of compounds Xa, Xd, Xe, Xg, Xi mole-
cular ion peaks were present. In addition the structure of
compound Xg was solved by X-ray diffraction method
[7].
;,
Scheme 5.
2
2 )
1
2
2
2
)
&+&O
1
+
3K
2
;E
2+
2
ꢀ
Difluoride Xp formed from N-alkyl-substituted imine
IXp under conditions of difluorocarbene generation was
unstable and at chromatography of the reaction mixture
on silica gel suffered hydrolysis. Lactam XI was isolated
in 67% yield (Scheme 4).
on silica gel at room temperature compounds Xa-o are
hydrolyzed to the corresponding lactams, and in weakly
acidic solutions occurs decomposition of the bicyclic
skeleton. For instance, after keeping a chloroform solution
Compounds Xa–Xo and XI, mostly crystalline sub-
stances, are relatively stable and can be stored at 4°C
for indefinitely long time. However at prolonged keeping
Scheme 6.
5ꢀ
2
)
)
2
1
5
2
1
5ꢀ
2
5ꢀ
;N P
ꢁꢂ&)
2
5
2
5
2
5ꢀ
;
,
,
,
ꢃ
B
) &
1
2
1
,;N P
9,,,N P
&2 0H
&2 0H
5
)
;,,N P
;,,ꢄꢁ5ꢁ ꢁꢅꢆ%U& + ꢄꢁ5ꢀꢁ ꢁ& + ꢇNꢈꢉꢁꢁ5ꢁ ꢁꢅꢆ%U& + ꢄꢁ5ꢀꢁ ꢁ0H2& + ꢇOꢈꢉꢁꢁ5ꢁ ꢁꢅꢆ%U& + ꢄꢁ5ꢀꢁ ꢁ&& + ꢁꢇPꢈꢊ
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

202
VOZNYI et al.
The transition state A corresponds to a concerted
cycloaddition with simultaneous formation of C–C and
C–O bonds. The like cycloaddition mechanism is
presumed for intermolecular reactions of
difluoromethylides with C=C bonds [16]. The paths
involving transition states B and C imply that the ylide
addition to C=O bond is not concerted and occurs via
zwitter-ion intermediates. These intermediates arising
through transition state B are in particular the cause of
rearranged products formation in reaction of sterically
loaded C,C-diaryl-substituted difluoromethylides with
aldehydes [14]. Structure C also cannot be ignored for
here a positive charge might be delocalized to the aryl
ring of the benzoyl group. In transition states B and C
the charges on the atoms of the carbonyl group should
suffer strong changes compared to the initial molecule,
and hence if these transition states were operative a
considerable influence of substituents R on the rate of
intramolecular cycloaddition should be expected and
of compound Xb for 3.5 months were isolated p-methoxy-
phenylglyoxylic acid anilide and salicylaldehyde in 62%
yield (Scheme 5).
The reactions of difluorocarbene with aromatic
aldehydes N-alkyl- and N-arylimines in the presence of
electron-deficient alkynes are known to afford fluoro-
pyrroles [15]. The rate of intramolecular 1,3-dipolar
cycloaddition to the C=O bond of ylide VIIIl proved to
be comparable with the rate of intermolecular addition to
one of the most active dipolarophiles, dimethyl
acetylenedicarboxylate XIII.In reaction of imine IXl with
difluorocarbene in the presence of double molar excess
of compound XIII formed both difluoride Xl and
fluoropyrrole XIIl the latter was isolated in 17% yield.
1
According to H NMR data compounds Xl and
XIIlformed in the ratio 1:1.08.
Similar experiments with imines IXk, m showed that
the ratio of difluoride Xk, Xm to fluoropyrrole XIIk, XIIm
was relatively weakly affected by the character of sub-
stituents in the benzoyl moiety of the initial imine (1:1.08
for imine IXk and 1:0.99 for imine IXm). Inasmuch as
the substituents in the aromatic ring of the benzoyl group
should not considerably affect the intermolecular cycload-
dition for they are significantly removed from the reac-
tion sites, the experimental data obtained indicate that the
intramolecular cycloaddition to C=O group also is not
notably sensitive to the electronic effect of substituents
in the aromatic ring. This fact may be rationalized by analy-
sis of the probable transition states A, B, and C in the
cycloaddition reaction of ylides VIII.
therefore on the ratio of products Xk–m and XIIk–m.
On the contrary, if the reaction goes via the concerted
transition state A the substituents effect should not be
very conspicuous. The experimentally observed weak
effect of R substituents of quite different electronic
character on the rate of the intramolecular cycloaddition
leads to conclusion that the reaction occurs by the
concerted mechanism.
Although the intramolecular cycloaddition of
fluorinated azomethinylides VIII to the ester carbonyl
occurred quite readily giving the corresponding
cycloadducts in high yields our attempt to carry out the
reaction in an intermolecular fashion under similar
conditions (benzalaniline and difluorocarbene as the
source of azomethinylide, and methyl benzoate as external
dipolarophile) was unsuccessful. At the same time the
imtermolecular cycloaddition of fluorinated azo-
methinylides to aldehydes occurs without difficulty [14].
Apparently the unfavorable electronic factor that
decreases the activity of the ester carbonyl compared to
that of aldehyde (relatively higher LUMO energy in the
former) in the intramolecular version of the reaction is
overcome with the favorable entropic facctor.
5
5
B
2
)
)
)
2
2
2
)
ꢁ
1
1
5ꢀ
5ꢀ
%
5
Ylides VIIIf–I alongside the ester carbonyl contain
one more dipolarophile fragment , C=C bond activated
by a carbonyl group and connected to 1,3-dipole through
)
B
2
)
2
ꢁ
2
2
2
a 4-atomic linker Csp =Csp –O–Csp . The lack of
competition between C=O dipolarophile and activated
C=C dipolarophile is unexpected: the cycloaddition in all
cases occurs only at the ester carbonyl. However the
1
5ꢀ
&
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

203
INTRAMOLECULAR 1,3-DIPOLAR CYCLOADDITION
activated and even nonactivated C=C bond connected to
Then the flask was tightly stoppered and placed into an
ultrasonic bath (160 W), and the reaction mixture was
subjected to ultrasonic irradiation at 45°C till complete
dissolution of lead. Then 4.0 g of silica gel (LS 40/100,
Chemapol) was added to the reaction mixture, the solvent
was evaporated to dryness in a vacuum, and the powder
obtained was charged to the top of a chromatographic
column packed with silica gel (LS 5/40, Chemapol). The
products were eluted by a mixture hexane–ethyl acetate.
Crystalline products were additionally recryatallized.
2
2
3
1,3-dipole with a 4-atomic linker Csp =Csp –O–Csp is
known to readily undergo intramolecular cycloaddition
[17]. This difference in reactivity is apparently caused
by a higher rigidity of the first linker (containing one
additional sp2-center) that hampers efficient overlapping
of orbitals from the dipole and the C=C bond.
Hence the intramolecular 1,3-dipolar cycloaddition of
difluoroazomethinylides VIII to the ester carbonyl group
occurs by concerted mechanism with complete
regioselectivity yielding 2,5-epoxy-1,4-benzoxazepine
derivatives. The rate of the reaction is comparable with
the rate of intermolecular cycloaddition to the most active
acetylene dipolarophiles.
Physical and spectral characteristics of compounds
Xa, f and XI were published in [7].
2-(4-Methoxyphenyl)-4-phenyl-3,3-difluoro-
2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxazepine
(Xb). mp 139–141°C (hexane–EtOAc). 1N NMR
spectrum (CDCl3), d, ppm: 3.89 s (3H, MeO), 6.36 d
(1H, H5, 4JHF 6.6 Hz), 6.95–7.84 m (13H, H arom). 13C
NMR spectrum (CDCl3), d, ppm: 55.0 (MeO), 86.0 (C5),
104.3 d.d (C2, JCF 26.5, 33.7 Hz), 113.3, 115.0, 116.1,
120.5 (C arom), 121.2 d.d (C3, JCF 257, 261 Hz), 121.5,
122.1 d (JCF 5.0 Hz), 124.0, 127.4 d (JCF 1.7 Hz), 129.1,
130.4, 136.4 d.d (JCF 2.2, 4.0 Hz), 150.5, 160.7 (C arom).
Found, %: C 69.02; H 4.41; N 3.47. C22H17F2NO3.
Calculated, %: C 69.29; H 4.49; N 3.67.
EXPERIMENTAL
Melting points of compounds synthesized were
..
measured on Boetius heating block; the values obtained
are presented without correction. IR spectra were
recorded on a spectrophotometer Carl Zeiss UR-20, a
cell 400 mm of thickness. NMR spectra were registered
on a spectrometer Bruker DPX- 300, operating
frequencies 300 (1H) and 75 (13C) MHz. Mass spectra
were measured on MKh-1303 and HP-59970C
instruments (ionizing energy 70 eV). The elemental
analysis was “carried out on a CHN-analyzer HP-185B.
The reaction progress was monitored by TLC on Silufol-
254 plates. The reaction mixtures separation by column
chromatography was performed on silica gel LS 5/40
(Chemapol). Dichloromethane, the solvent for imines
reactions with difluorocarbene, was dried by distillation
from P2O5.
4-(4-Phenyl-3,3-difluoro-2,3,4,5-tetrahydro-2,5-
epoxy-1,4-benzoxazepin-2-yl)benzonitrile (Xc). mp
–1
149–150°C (EtOH). IR spectrum (CNCl3), n, cm : 2240.
1N NMR spectrum (CDCl3), d, ppm: 6.41 d (1H, H5,
4JHF 6.5 Hz), 6.99–8.00 m (13H, H arom). 13C NMR
spectrum (CDCl3), d, ppm: 86.5 (C5), 103.6 d.d (C2, JCF
26.5, 34.3 Hz), 113.9, 115.4, 116.1, 117.9, 121.07 (C arom),
121.1 d.d (C3, JCF 258, 262 Hz), 121.9 d (JCF 5.0 Hz),
122.0, 124.2, 126.9 d (JCF 1.7 Hz), 129.2, 130.6, 131.8,
136.0 d.d (JCF 2.2, 4.4 Hz), 136.5 d (JCF 1.7 Hz), 150.0
(C arom). Found, %: C 70.27; H 3.86; N 7.43.
C22H14F2N2O2. Calculated, %: C 70.21; H 3.75; N 7.44.
O-Acylsalicylaldehydes were obtained by acylation
of salicylaldehyde with appropriate acyl chlorides in
anhydrous DMF in the presence of anhydrous K2CO3.
Imines IXa–o were prepared by aldehydes condensation
with amines in ethanol. Imine IXp was synthesized from
O-benzoylsalicylaldehyde and trimethylsilylmethyl azide
by procedure from [18]. Active lead was prepared by
the method described in [15].
2-(2,4-Dichlorophenyl)-4-phenyl-3,3-difluoro-
2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxazepine
1
(Xd). N NMR spectrum (CDCl3), d, ppm: 6.39 d (1H,
H5, 4JHF 6.3 Hz), 6.96–7.96 m (12H, H arom). 13C NMR
spectrum (CDCl3), d, ppm: 85.9 d (C5, JCF 2.2 Hz),
104.4 d.d (C2, JCF 27.4, 36.2 Hz), 115.7 t (JCF 2.5 Hz),
116.2, 120.9 (C arom), 121.00 d.d (C3, JCF 258, 268 Hz),
121.6 d (JCF 4.4 Hz), 122.0, 124.3, 126.5, 128.8, 129.1,
129.5, 130.6, 131.1, 133.7, 136.2 d.d (JCF 1.4, 4.1 Hz),
136.5, 150.1 (C arom). Mass spectrum (70 eV), m/z (Irel,
%): 423 (2) [M]+, 421 (11) [M]+, 419 (17) [M]+, 246
(28), 196 (10), 173 (95), 163 (67), 161 (100), 77 (46), 51
(28).
General procedure for reactions between imines
and difluorocarbene. Into a flask of 50 ml capacity
containing 1.2 g (5.8 mmol) of active lead was charged
in succession under argon atmosphere 7 ml of anhydrous
dichloromethane, 2.0 g (6.0 mmol) of tetrabutylammonium
bromide, and 2.7 mmol of imine. The mixture was cooled
to 10–15°C with cold water, and into the flask was
charged 1.95 g (9.3 mmol) of dibromodifluoromethane.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

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VOZNYI et al.
2-(1-Naphthyl)-4-phenyl-3,3-difluoro-2,3,4,5-
4-(4-Bromophenyl)-3,3-difluoro-2-(2-furyl)-
2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxazepine
(Xj). mp 159–160°C (hexane–EtOAc). 1H NMR
spectrum (CDCl3), d, ppm: 6.26 d (1H, H5, 4JHF 6.2 Hz),
6.56 t (1H, H furyl, J 1.8 Hz), 6.93–7.64 m (10H, H
furyl, H arom). 13C NMR spectrum (CDCl3), d, ppm:
86.3 (C5), 101.1 d.d (C2, JCF 27.4, 34.0 Hz), 110.3, 111.3 d
(JCF 1.7 Hz), 114.7, 116.3, 117.1 t (C arom, JCF 2.8 Hz),
120.8 d.d (C3, JCF 260, 263 Hz), 121.0, 121.6 d (JCF 4.4
Hz), 124.1, 130.8, 132.1, 135.2 d.d (JCF 2.2, 3.9 Hz), 144.0,
144.3, 149.8 (C arom). Found, %: C 54.43; H 3.02;
N 3.17. C19H12BrF2NO3. Calculated, %: C 54.31; H 2.88;
N 3.33.
tetrahydro-2,5-epoxy-1,4-benzoxazepine (Xd). 1H
4
NMR spectrum (CDCl3), d, ppm: 6.50 d (1H, H5, JHF
5.9 Hz), 6.99–8.82 ì (16H, H arom). 13C NMR spectrum
(CDCl3), d, ppm: 85.7 (C5), 106.2 d.d (C2,JCF 27.6, 35.6
Hz), 115.4 t (JCF 2.3 Hz), 116.2, 120.8, 121.7, 121.8 d.d
(C3, JCF 258, 264 Hz), 122.0 d (JCF 3.4 Hz), 124.3 d (JCF
3.4 Hz), 125.3, 125.6, 125.9, 126.0, 126.2, 126.3, 128.2,
128.4, 129.1, 130.2, 130.5, 131.1, 133.9, 136.4 d.d (JCF
2.3, 4.5 Hz), 150.4 (C arom). Mass spectrum (70 eV),
m/z (Irel., %): 401 (5) [M]+, 335 (5), 246 (12), 196 (3), 181
(3), 177 (3), 155 (100), 152 (3), 127 (23), 77 (11).
(E)-2-(Prop-1-enyl)-4-phenyl-3,3-difluoro-2,3,4,5-
tetrahydro-2,5-epoxy-1,4-benzoxazepine (Xg). mp
4-(4-Bromophenyl)-2-phenyl-3,3-difluoro-
2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxazepine
(Xk). mp 134–135°C (hexane–EtOAc). 1H NMR
spectrum (CDCl3), d, ppm: 6.32 d (1H, H5, 4JHF 6.3 Hz),
6.95–7.87 m (13H, H arom). 13C NMR spectrum
(CDCl3), d, ppm: 86.2 (C5), 104.2 d.d (C2, JCF 25.3,
34.5 Hz), 114.4, 116.3, 116.8, 120.7 (C arom), 121.1 d.d
(C3, JCF 259, 262 Hz), 121.7 d (JCF 4.6 Hz), 123.9, 125.8,
128.0, 130.0, 130.6, 131.6, 132.0, 135.4 m, 150.4 (C arom).
Found, %: C 58.44; H 3.34; N 3.08. C21H14BrF2NO2.
Calculated, %: C 58.62; H 3.28; N 3.26.
1
108–110°C (hexane–Et2O). H NMR spectrum (CDCl3),
d, ppm: 1.96 d (3H, Me, J 6.6 Hz), 5.89 d.q (1H, H1
propenyl, J 1.6, 15.7 Hz), 6.21 d (1H, H5, 4JHF 6.2 Hz),
6.61 d.q (1H, H2 propenyl, J 6.6, 15.0 Hz), 6.93–7.37 m
(9H, H arom). 13C NMR spectrum (CDCl3), d, ppm:
17.7 (Me), 86.0 (C5), 102.8 d.d (C2, JCF 27.1, 33.1 Hz),
115.0, 116.0, 120.4 t (JCF 2.2 Hz) (C arom), 121.1 d.d
(C3, JCF 257, 261 Hz), 121.5, 122.4 d (JCF 3.9 Hz),
124.0, 129.0, 130.3, 134.4 d (JCF 1.7 Hz), 136.4 d.d
(JCF 2.2, 4.4 Hz), 135.4 (C arom). Found, %: C 68.53;
N 4.83; N 4.07. C18H15F2NO2. Calculated, %: C 68.57;
N 4.79; N 4.44.
4-(4-Bromophenyl)-2-(4-methoxyphenyl)-3,3-di-
fluoro-2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxaze-
pine (Xl). mp 150–151°C (hexane–EtOAc). 1H NMR
spectrum (CDCl3), d, ppm: 3.89 s (3H, MeO), 6.29 d
(1H, H5, 4JHF 5.8 Hz), 6.94–7.81 m (12H, H arom). 13C
NMR spectrum (CDCl3), d, ppm: 55.0 (MeO), 86.0 (C5),
104.3 d.d (C2, JCF 26.5, 33.7 Hz), 113.4, 114.2, 116.2,
116.7 t (JCF 2.8 Hz), 120.6 (C arom), 121.1 d.d (C3, JCF
258, 263 Hz), 121.7 d (JCF 5.0 Hz), 123.8, 123.9, 127.4,
130.6, 132.0, 135.4 d.d (JCF 2.2, 4.4 Hz), 150.4, 160.7
(C arom).
(Å)-2-Styryl-4-phenyl-3,3-difluoro-2,3,4,5-
tetrahydro-2,5-epoxy-1,4-benzoxazepine (Xh). mp
1
92–94°C (hexane–Et2O). H NMR spectrum (CDCl3),
d, ppm: 6.27 d (1H, H5, 4JHF 6.8 Hz), 6.50 d.d (1H, H1
styryl, JHH 16.2, 4JHF 2.5 Hz), 6.96–7.60 m (13H, H2 styryl,
H arom). 13C NMR spectrum (CDCl3), d, ppm: 86.2
(C5), 103.4 d.d (C2, JCF 26.5, 33.2 Hz), 115.2 t (JCF
2.5 Hz), 116.1, 117.7, 120.6 (C arom), 121.2 d.d (C3, JCF
258, 262 Hz), 121.6, 122.3 d (JCF 5.0 Hz), 124.0, 127.1,
128.4, 128.8, 129.1, 130.4, 134.8, 136.5 d (JCF 1.7 Hz),
150.3 (C arom). Found, %: C 73.16; N 4.57; N 3.30.
C23H17F2NO2. Calculated, %: C 73.20; N 4.54; N 3.71.
4-(2,4-Dichlorophenyl)-2-phenyl-3,3-difluoro-
2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxazepine
(Xn). mp 100–101°C (pentane). 1N NMR spectrum
(Z)-2-(1,2-Diphenylvinyl)-4-phenyl-3,3-difluoro-
4
(CDCl3), d, ppm: 6.04 d (1H, H5, JHF 6.6 Hz), 6.82–
2,3,4,5-tetrahydro-2,5-epoxy-1,4-benzoxazepine
7.93 m (12H, H arom). 13C NMR spectrum (CDCl3), d,
ppm: 88.6 (C5), 104.1 d.d (C2, JCF 26.8, 33.0 Hz), 116.0,
120.6 (C arom), 121.7 d.d (C3, JCF 259, 259 Hz), 122.4 d
(JCF 3.3 Hz), 123.9, 125.9 d (JCF 1.7 Hz), 127.6, 127.9,
129.8, 130.1, 130.4, 131.8 t (JCF 2.5 Hz), 132.0, 134.5,
135.6 d.d (JCF 1.1, 2.8 Hz), 150.4 (C arom). Found, %: C
60.00; H 3.19; N 3.14. C21H13Cl2F2NO2. Cal-
culated, %: C 60.02; H 3.12; N 3.33.
1
(Xi). H NMR spectrum (CDCl3), d, ppm: 6.29 d (1H,
H5, 4JHF 6.9 Hz), 6.93–7.51 m (20H, H arom). 13C NMR
spectrum (CDCl3), d, ppm: 85.8 (C5), 104.6 d.d (C2, JCF
25.3, 34.5 Hz), 115.1 t (JCF 2.5 Hz), 116.1, 120.5, 121.5
(C arom), 121.6 d.d (C3, JCF 258, 263 Hz), 122.0 d (JCF
5.0 Hz), 123.9, 127.6, 127.7, 128.1, 129.0, 129.6, 130.3,
130.4,132.4, 132.5, 134.5, 134.8, 136.3 d.d (JCF 2.5,
4.4 Hz), 150.6 (C arom). Mass spectrum (70 eV), m/z
(Irel., %): 453 (6) [M]+ , 387 (23), 246 (16), 207 (62), 196
(5), 179 (100), 178 (27), 152 (8), 77 (19), 39 (11).
4-[Bis(4-chlorophenyl)methyl]-2-phenyl-3,3-di-
fluoro-2,3,4,5-tetrahydro-2,5-epoxy-1,4- benzo-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004

205
INTRAMOLECULAR 1,3-DIPOLAR CYCLOADDITION
xazepine (Xo). mp 192–194°C (hexane–EtOAc).
1H NMR spectrum (CDCl3), d, ppm: 4.92 d (1H,
03-32735a), of the Ministry of Education of the Russian
Federation (grant E02-5.0-30), and INTAS program
(grant 00-0549).
4
6
CHAr2N, JHF 4.9 Hz), 5.73 d (1H, H arom, JHF 5.7
Hz), 6.41 d.d (1H, H5, 4JHF 7.3, 4JHH 1.1 Hz), 6.87–7.80
m (16H, H arom). 13C NMR spectrum (CDCl3), d, ppm:
61.7 d (CHAr2N, JCF 5.0 Hz), 88.0 d (C5, 3JCF 4.4 Hz),
104.7 d.d (C2, JCF 26.0, 37.0 Hz), 120.2 d (JCF 3.9 Hz),
120.3 (C arom), 123.6 d.d (C3, JCF 255, 268 Hz), 124.9,
125.6 d (JCF 1.1 Hz), 127.9, 128.3, 128.5, 129.0, 129.7,
130.6, 132.4, 133.5, 133.7, 137.8, 138.4, 150.6 (C arom).
Found, %: C 65.71; N 3.79; N 2.46. C28H18Cl2F2NO2.
Calculated, %: C 65.90; N 3.75; N 2.74.
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Dimethyl 1-(4-bromophenyl)-2-[2-(4-methoxy-
benzoyloxy)phenyl]-5-fluoropyrrole-3,4-dicarb-
oxylate (XIIl). The reaction was carried out along the
general procedure using as internal dipolarophile a double
excess of dimethyl acetylenedicarboxylate 1H NMR
spectrum (CDCl3), d, ppm: 3.72 s (3H, CO2Me), 3.85 s
(3H, CO2Me), 3.91 s (3H, MeOAr), 6.96–7.98 m (12H,
H arom). 13C NMR spectrum (CDCl3), d, ppm: 51.3;
51.4 (Me), 55.1 (Me), 94.6 d (JCF 5.0 Hz), 113.5, 120.7,
122.1, 122.5, 122.7, 123.5 d (JCF 2.8 Hz), 125.0, 128.3 d
(JCF 1.1 Hz), 130.0, 131.7, 131.97, 132.05, 132.1 (C arom),
146.9 d (CF, JCF 278 Hz), 149.5 (C arom), 161.6 d (JCF
5.0 Hz), 163.6 d (MeOC=O, JCF 2.8 Hz), 163.7 (ArC=O).
Concurrent reactions. Concurrent reactions of
intra- and intermolecular cycloaddition with dimethyl
acetylenedicarboxylate were carried out taking a double
molar excess of the latter with respect to imine and at
equal concentrations of the corresponding reagents in all
experiments. Imine conversion was 50–95%. Ratio of
compounds Xk–Xm and XIIk–XIIm was determined
by comparison of intensity in the 1N NMR spectra of the
reaction mixtures of proton signal from H
5 belonging to
compounds VIIIk–VIIIm (d, ppm: 6.32, 6.29, 6.32
respectively), and of signal from methoxycarbonyl group
of compounds XIIk–XIIm (d 3.72 ppm).
The study was carried out under financial support of
the Russian Foundation for Basic Research (grant 02-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 40 No. 2 2004