Reactions of 1,5-π-cyclization of gem-difluoro-substituted azomethine ylides involving an aromatic ring

Article abstract of DOI:10.1134/S1070428006050071

Reactions of N-(5-R-furan-2-ylmethylidene)anilines with difluorocarbene proceeds through intermediate azomethine ylides suffering 1,5-π-cyclization to yield 6,6-difluorocyclopropa[b]furo[2,3-c]pyrrole and/or 4,4,6,6- tetrafluorocyclopropa[b]furo[2,3-c]pyr

Full text of DOI:10.1134/S1070428006050071

ISSN 1070-4280 Russian Journal of Organic Chemistry, 2006, Vol. 42, No. 5, pp. 689-695. Ó Pleiades Publishing, Inc. 2006.
Original Russian Text Ó I.V. Voznyi, M.S. Novikov, A.F. Khlebnikov, R.R. Kostikov, 2006, published in Zhurnal Organicheskoi Khimii, 2006,
Vol. 42, No. 5, pp. 708-714.
Reactions of 1,5-p-Cyclization of gem-Difluoro-Substituted
Azomethine Ylides Involving an Aromatic Ring
I.V. Voznyi, M.S. Novikov,A.F. Khlebnikov, and R.R. Kostikov
St. Petersburg State University, St. Petersburg, 198504 Russia
e-mail: Mikhail.Novikov@pobox.spbu.ru
Received April 25, 2005
Abstract—Reactions of N-(5-R-furan-2-ylmethylidene)anilines with difluorocarbene proceeds through intermediate
azomethine ylides suffering 1,5-p-cyclization to yield 6,6-difluorocyclopropa[b]furo[2,3-c]pyrrole and/or 4,4,6,6-
tetrafluorocyclopropa[b]furo[2,3-c]pyrrole. The heating of these compounds without solvent resulted in high
yields of 2,5-disubstituted 7-fluoro-4,5-dihydrofuro[3,2-c]pyridin-4(5H)-ones.
DOI: 10.1134/S1070428006050071
Reactions of difluorocarbene with imines is a con-
venient procedure for generation of gem-difluoro-
substituted azomethine ylides, unstable intermediates used
in the synthesis of 2-fluoropyrroles [1], 2-fluoro-2-
pyrrolines [2], derivatives of pyrrolidine [3–5], oxazolidine
[6], imidazolidine [7], 2,5-epoxy-1,4-benzoxazepine [8, 9],
and 2,2-difluoro-1-azabicyclo[3.1.0]hex-3-ene [10, 11].
These synthetic methods are based on intermolecular and
intramolecular cycloadditions of the difluoro-substituted
ylide intermediate to the multiple bonds C=C, CºC, C=O,
and C=N. Incidentally it is known that the azomethine
ylides alongside the cycloaddition reactions are capable
to undergo 1,3-, 1,5-, and 1,7-p-cyclization affording 3-, 5-,
and 7-membered nitrogen-containing heterocycles. For
instance, the 1,3-cyclization is characteristic of many gem-
dibromo-, gem-dichloro-, gem-bromochloro-, gem-
bromofluoro-, and gem-fluorochloro-substituted azo-
methine ylide [12] generated from Schiff bases and the
corresponding dihalocarbenes, and also ylides formed in
Schiff bases reactions with metallocarbenoids from diazo
compounds [13]. Several instances are known of 1,5-
cyclizations of azomethine ylides involving C=C bond [14–
17], C=O bond [18–21], and the pyridine ring [22].
Recently 1,7-cyclization of azomethine ylides was
observed involving a benzene ring and resulting in forma-
tion of 2-benzazepine derivatives [23, 24]. No p-cyclization
reactions are known for difluoro-substituted ylides. We
report here on the first example of 1,5-electrocyclization
of gem-difluoro-substituted azomethine ylides originating
from the reaction of Schiff bases with difluorocarbene
generated by reduction of dibromodifluoromethane with
active lead in the presence of tetrabutylammonium
bromide.
In the study of intramolecular 1,3-dipolar cycloaddition
of difluoro-substituted ylides to endocyclic C=C-dipolaro-
philes imine IIa was introduced into the reaction with the
difluorocarbene as ylide Ia precursor. However instead
of the expected cycloaddition product IIIa isoindolone
IVa was isolated in a 20% yield (Scheme 1). The
formation of this compound is likely due to the low
dipolarophile activity of the multiple bond in the furan ring
favoring the competing process involving the 1,5-p-cycliz-
ation of intermediate ylide Ia, a formal proton shift and
a hydrolysis during the chromatographic workup of the
reaction mixture.
In the 1H NMR spectrum of compound IVa apart from
the signals of the methylene protons of the CH2O group
at 5.20 ppm a singlet signal is present corresponding to
the methylene protons of the dihydroisoindole system at
4.78 ppm. In the 13C NMR spectra the characteristic
signals of two methylene carbon atoms appear at 48.2
and 62.2 ppm, those of carbonyl carbons, at 158.6 and
167.0 ppm. The mass spectrum contained two peaks of
m/z 399 and 397 with the intensity ratio 1:3 corresponding
to the molecular ion. The reaction with p-bromo-
689

VOZNYI et al.
690
Scheme 1.
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P
P
I
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P
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I
I
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A 8
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A
8P Hr
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,,, ꢀꢁ,,,E
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8P Hr
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substituted analog Ib proceeded in the same fashion, and
we isolated isoindolone IVb in a 4% yield.
Scheme 2.
5
5
2
2
ꢁ&)
The 1,5-cyclization of ylides generated from substituted
N-benzylideneanilines and difluorocarbene proved to be
sensitive to the structural parameters. For instance, we
failed to obtain products of 1,5-cyclization analogous to
compound IV from ylides generated from 2-methoxy-
and 3,4,5-trimethoxybenzylideneanilines. We suggested
that the replacement of the benzene ring by a furan one
should significantly facilitate the 1,5-cyclization of the
corresponding difluoroylide and thus increase the yields
of the reaction products.Actually, the anils of substituted
furfurals Va–Vf under conditions of difluorocarbene
generation afford ylides VIa–VIf that sufficiently readily
undergo the 1,5-cyclization involving the furan ring to
furnish pyrroline ring (Scheme 2). We did not succeed in
any case to isolate the primarily cyclization products,
furopyrroles VIIa–VIIf, for the highly nucleophilic double
bond of the pyrroline ring suffered fast cyclopropanation
giving cyclopropa[b]furo[2,3-c]pyrroles VIIIa–VIIIf that
were hydrolyzed in the course of chromatography on
silica gel to furnish compounds IXa, IXb, IXe, and IXf
(Table 1). In two cases, namely, in reactions of ylides
generated from imines Vc and Vd, we succeeded to
obtain the precursoes of lactams IXc and IXd, tetra-
fluorides VIIIc and VIIId.
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Table 1. Yields of products and time of reaction between imines
Va–Vf and difluorocarbene
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The structure of compounds VIII and IX was proved
by the data of NMR and IR spectroscopy and was
confirmed by elemental analysis. In the 1H NMR spectra
of compounds VIII a triplet signal from H5a proton was
observed in the region 3.88–3.95 ppm (JHF 7.3–7.5 Hz),
9Gꢀ #ꢄ7ꢅ8 C ꢁ
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Imine conversion: a 70%, b 45%.
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 5 2006

REACTIONS OF 1,5-p-CYCLIZATION OF gem-DIFLUORO-SUBSTITUTED AZOMETHINE YLIDES
691
Table 2. Yields of thermolysis products from compounds VIII
and IX
and the multiplet in the region 4.55–4.60 ppm (J ~13, 7,
13
4, 3 Hz), corresponded to proton H3a. In the C NMR
spectra of compounds VIII difluoromethyl atoms C6 and
C4 gave rise to doublets of doublets of doublets in the
region 109.7–109.8 (JCF 320, 301–302, 9.4–10.0 Hz) and
128.6–128.8 ppm (JCF 259–260, 247–250, 5.5–7 Hz)
respectively. In the 1H NMR spectra of compounds IX
two doublets of doublets are present in the 3.91–4.06
(JHF 7.9–8.2, 1.4–1.8 Hz) and 4.20–4.40 ppm (J 2.4–
4.5, 1.3–2.6 Hz) corresponding to protons H5a and H3a
respectively. In the 13C NMR spectra of compounds IX
C6 atom of the difluoromethyl group appeared as a doublet
of doublets in the region 107.5–108.3 ppm (JCF 319–320,
301 Hz). Atom C4 of the carbonyl group appeared in the
13C NMR spectra as a signal in the region 169.5–
171.4 ppm; the frequency of the stretching vibrations of
the C=O bond in the IR spectra was observed at 1725–
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(J 307, 298 Hz), and a single doublet of doublets from
atom C6 in compound IXg at 108.3 ppm (J 319, 301 Hz).
The singlets at 170.0 and 170.8 ppm belong to the carbon
atoms of the lactam carbonyls in these compounds.
The heating of compounds IXa, IXb, and IXf without
solvent for 10 min at 160°C is accompanied with HF
liberation and formation of 7-fluoro-4,5-dihydrofuro-
[3,2-c]pyridin-4-ones XIIa, XIIb, and XIIf which were
isolated in 80–93% yields.Analogous result was obtained
in the thermolysis of the tetrafluoride VIIIc (Scheme 4,
Table 2).
–1
1730 cm .
For preparation of compounds VIII and IX the
optimum ratio of imine and the components for carbene
generation (CF2Br2–Pb*––Bu4NBr) equals 1:4:3:3. The
decrease in the carbene excess in the reaction mixture
reduces the conversion of the initial imine, and the greater
excess of carbene leads to difluorocyclopropanation of
the double bond in the furan ring of compounds VIII.
For instance, at the reagents ratio (Vg) : CF2Br2 : Pb* :
Bu4NBr = 1:8:6:6 a mixture was obtained consisting of
compounds VIIIg and X in a ratio 1:0.8 (Scheme 3)
which we failed to separate by chromatography, but
succeeded in assignment of individual peaks in the
We have consequently established that the gem-di-
fluoro-substituted azomethine ylides apart from the intra-
molecular cycloaddition and ylide-ylide isomerization are
capable to undergo one more type of intramolecular
Scheme 3.
S
P
I
S
13
1
1H and C NMR spectra. In the H NMR spectrum of
compound VIIIg the singlet belonging to the olefin atom
H3 was observed at 5.68 ppm, whereas the corresponding
H3b atom in compound X was attached to the cyclo-
propane ring and appeared in the spectrum as a doublet
at 3.05 ppm (JHF 14.5 Hz). In the 13C NMR spectrum of
compound X an additional carbon signal was observed
as a doublet of doublets at 109.7 ppm (JCF 305, 297 Hz)
that belonged to atom C4 of the cyclopropane difluoro-
methyl group. The keeping of the mixture of compounds
VIIIg and X on silica gel at room temperature for 24 h
furnished a mixture of compounds IXg and XI in the
same ratio. In the 1H NMR spectrum of the latter mixture
the doublet at 3.13 ppm (JHF 13.8 Hz) corresponded to
H3b proton of compound XI, and the doublet of doublets
at 5.85 ppm (J 2.6, 1.7 Hz) belonged to proton H3 of
compound IXg. The 13C NMR spectrum of the mixture
contained two characteristic doublets of doublets of
difluoromethylene groups of atoms C1 and C4 in
compound XI at 107.4 (J 319, 301 Hz) and 109.8 ppm
9J
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 5 2006

VOZNYI et al.
692
Scheme 4.
the reaction mixtures by column chromatography was
used silica gel LS 5/40 (Chemapol). Dichloromethane was
dried by distillation from P2O5.
)
2
Imines I, IX, X, XIII, XVII, XXI, and XXIII were
prepared by condensation of aldehydes with amines in
ethanol. The active lead was obtained by the method
described in [1].
5ꢀ
1
5
2
;,, ;,,Fꢀꢁ;,,I
General procedure for imines reactions with the
difluorocarbene. Into a flask of 50 ml capacity contain-
ing 1.2 g (5.8 mmol) of active lead was added in succes-
sion under an argon atmosphere 7 ml of dichloromethane,
2.0 g (6 mmol) of tetrabutylammonium bromide, 2.7 mmol
of imine, and 1.95 g (9.3 mmol) of dibromodifluoro-
methane. The flask was tightly stoppered and was
immersed into an ultrasonic bath (160 W) at 45°C for
a time interval sufficient for the lead to react completely.
On cooling 4 g of silica gel was added to the mixture, the
solvent was evaporated in a vacuum, and the powder
obtained was charged into a chromatographic column
packed with silica gel, and the products were eluted with
a mixture hexane–EtOAc.
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transformation, 1,5-electrocyclization with the participa-
tion of the aromatic ring. Difluoroylides generated from
N-(furylmethylidene)anilines undergo cyclization
essentially more readily than the ylides obtained from
N-benzylideneanilines obviously due to the difference in
the resonance energy of the furan and benzene systems.
Nevertheless, even with the furan derivatives the
1,5-cyclization of difluoroylides occurs with a rate
relatively low for an intramolecular process for it cannot
compete, for example, with the reaction of intermolecular
1,3-dipolar cycloaddition to dimethyl acetylenedi-
carboxylate: The reaction of N-(furylmethyidene)aniline
with difluorocarben in the presence of dimethyl acetyl-
enedicarboxylate affords the corresponding 2-fluoropyr-
role in a 69% yield, and not the products of 1,5-cyclization
of VIII or IX type [1]. The cleanly occurring thermal
isomerization of furopyrroles VIII or IX suggests a simple
procedure for the synthesis of 2,5-disubstituted 7-fluoro-
4,5-dihydrofuro[3,2-c]pyridin-4(5H)-ones from cheap and
available compounds.
The physical and spectral characteristics of com-
pounds VIIId, IXa, and XIIa were reported in [25].
From 0.96 g (2.60 mmol) of imine IIa (reaction time
23 h) using as eluent hexane–EtOAc, 3:1, at chromato-
graphic purification of the mixture we obtained 0.207 g
(20%) of methyl 5-{[1-oxo-2-(4-chlorophenyl)-2,3-
dihydro-1 H-isoindol- 4-yl]oxymethyl}-2-
furancarboxylate (IVa), mp 200–201°C (EtOH–
1
CH2Cl2). H NMR spectrum (CDCl3), d, ppm: 3.93 s
(3H, CH3), 4.78 s (2H, NCH2), 5.20 s (2H, OCH2),
6.60 d (1H, Hfuryl, J 2.3 Hz), 7.13–7.87 m (8H, Hfuryl
,
Harom). Mass spectrum, m/z (Irel, %): 399 (23) [M]+,
397 (69) [M]+, 260 (15), 258 (46), 230 (19), 167 (15),
139 (950), 137 (100), 111 (81), 79 (100), 59 (27), 51 (42),
41 (15), 38 (12).
From 1.08 g (2.61 mmol) of imine IIa (reaction time
17 h) using as eluent hexane–EtOAc, 3:1, at chromato-
graphic purification of the mixture we obtained 0.044 g
(4%) of methyl 5-{[2-(4-bromophenyl)-1-oxo-2,3-
dihydro-1H-isoindol-4-yl]oxymethyl}-2-furan-
carboxylate (IVb), mp 205–207°C (MeOH–CH2Cl2).
1H NMR spectrum (CDCl3), d, ppm: 3.93 s (3H, CH3),
EXPERIMENTAL
Melting points of the substances have been measured
on the Bo¸tius heating block and are reported without
correction. IR spectra were recorded on a spectro-
photometer Carl Zeiss UR-20 using a cell with the
absorbing layer thickness 400 mm. NMR spectra were
registered on a spectrometer Bruker DPX-300 at
operating frequancies 300 (1H) and 75 (13C) MHz. Mass
spectra were obtained on MKh-1303 instrument (ionizing
energy 70 eV). Elemental analysis was carried out on a
CHN-analyzer HP-185B. The reaction progress was
monitored by TLC on Silufol-254 plates. In separation of
4.77 s (2H, NCH2), 5.20 s (2H, OCH2), 6.60 d (1H, Hfuryl
,
J 3.5 Hz), 7.13–7.82 m (8H, Hfuryl, Harom). 13C NMR
spectrum (CDCl3), d, ppm: 48.2 (C3), 51.8 (Me), 62.2
(CH2O), 111.7, 114.2, 116.8, 118.3, 120.3, 128.4, 129.9,
131.7, 134.6, 138.3, 144.6, 152.5, 153.2 (Cfuryl, Carom), 158.6
(C=O), 167.0 (C=O).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 5 2006

REACTIONS OF 1,5-p-CYCLIZATION OF gem-DIFLUORO-SUBSTITUTED AZOMETHINE YLIDES
693
spectrum (CDCl3), d, ppm: 14.0 (Me), 49.5 d.d (C5a,
J 17.7, 15.5 Hz), 52.7 d (C3a, J 2.2 Hz), 60.9 (CH2),
68.3 d.d (C6a, J 19.6, 11.1 Hz), 96.3 (C3), 108.3 d.d (C6,
J 319, 301 Hz), 120.8, 124.9, 125.8, 128.9, 129.5, 131.1,
132.1, 137.2 (Carom), 157.0 (C2), 165.5 (CO2Et), 170.6 t
(C4, J 3.5 Hz). Found, %: C 66.60; H 4.37; N 3.42.
C22H17F2NO4. Calculated, %: C 66.50; H 4.31; N 3.52.
From 0.38 g (2.22 mmol) of imine Va (reaction time
5 h) using as eluent hexane–EtOAc, 5:1, at chromato-
graphic purification of the mixture we obtained 0.295 g
(53%) of 5-phenyl-6,6-difluoro-5a,6-dihydro-3aH-
cyclopropa[b]furo[2,3-c]-pyrrol-4(5H)-one (IXa).
From 1.32 g (5.0 mmol) of imine Vb (reaction time
5 h) using as eluent hexane–EtOAc, 5:1, at chromato-
graphic purification of the mixture we obtained 0.61 g
(36%) of 5-(4-bromophenyl)-2-methyl-6,6-difluoro-
5a,6-dihydro-3aH-cyclopropa[b]furo[2,3-c]pyrrol-
4(5H)-one (IXb), mp 121–123°C (hexane–Et2O). IR
From 0.53 g (1.54 mmol) of imine Vd (reaction time
12 h) using as eluent hexane–EtOAc, 5:1, at chromato-
graphic purification of the mixture we obtained 0.350 g
(51% with respect to applied imine, 73% with respect to
reacted imine) of 5-(4-bromophenyl)-4,4,6,6-
tetrafluoro-2-(2-fluorophenyl)-4,5,5a,6-tetra-hydro-
3aH-cyclopropa[b]furo[2,3-c]pyrrole (VIIId) and
0.085 g (30%) of 5-(2-fluorophenyl)furfural.
–1
1
spectrum (CHCl3), n, cm : 1725 (C=O). H NMR
spectrum (CDCl3), d, ppm: 1.97 s (3H, Me), 3.91 d.d
(1H, H5a, J 8.0, 1.4 Hz), 4.18 d.d (1H, H3a, J4.4, 2.2 Hz),
5.13 s (1H, H3), 7.40–7.54 m (4H, Harom). 13C NMR
spectrum (CDCl3), d, ppm: 13.3 (Me), 49.1 d.d (C5a,
J 17.6, 15.6 Hz), 52.4 d (C3a, J 2.3 Hz), 68.2 d.d (C6a,
J 19.4, 10.4 Hz), 94.9 d (C3, J 1.1 Hz), 108.3 d.d (C6,
J 319, 301 Hz), 118.5, 122.0, 131.8, 136.6 (Carom),
157.7 (C2), 171.4 d.d (C4, J 4.2, 2.6 Hz). Found, %:
C 49.07; H 3.10; N 3.98. C14H10BrF2NO2. Calculated,
%: C 49.15: H 2.95; N 4.09.
From 0.71 g (2.53 mmol) of imine Ve (reaction time
6 h) using as eluent hexane–EtOAc, 5:1, at chromato-
graphic purification of the mixture we obtained 0.455 g
(50%) of 2-bromo-5-(4-methoxyphenyl)-6,6-difluoro-
5a,6-dihydro-3aH-cyclopropa[b]furo-[2,3-c]pyrrol-
4(5H)-one (IXe), mp 111–112°C (hexane–Et2O). IR
–1
1
spectrum (CHCl3), n, cm : 1730 (C=O). H NMR
spectrum (CDCl3), d, ppm: 3.82 s (3H, Me), 4.05 d.d
(1H, H5a, J 8.1, 1.9 Hz), 4.20 t (1H, H3a, J 2.3 Hz),
From 0.70 g (2.2 mmol) of imine Vc (reaction time
14 h) using as eluent hexane–EtOAc, 5:1, at chromato-
graphic purification of the mixture we obtained 0.336 g
(36%) of ethyl 4-(5-phenyl-4,4,6,6-tetrafluoro-
4,5,5a,6-tetrahydro-3aH-cyclopropa-[b]furo[2,3-
c]pyrrol-2-yl)benzoate (VIIIc) and 0.052 g (6%) of
ethyl 4-(4-oxo-5-phenyl-6,6-difluoro-4,5,5a,6-
tetrahydro-3aH-cyclopropa[b]furo[2,3-c]-pyrrol-2-
yl)benzoate (IXc). Compound VIIIc, mp 158–161°C
(decomp.) (hexane–Et2O). IR spectrum (CHCl3), n,
5.56 d.d (1H, H3, J 2.3, 1.7 Hz), 6.95 d (2H, Harom
,
J 9.0 Hz), 7.37 d (2H, Harom, J 9 Hz). 13C NMR spectrum
(CDCl3), d, ppm: 49.8 d.d (C5a, J 17.6, 15.6 Hz), 51.9 d
(C3a, J 2.3 Hz), 55.2 (Me), 69.4 d.d (C6a, J 20.1,
10.4 Hz), 100.9 (C3), 107.5 d.d (C6, J 319, 301 Hz), 114.1,
122.9, 129.7, 132.6 (Carom), 157.7 (C2), 169.5 d.d (C4,
J 4.0, 2.9 Hz). Found, %: C 46.75; H 2.92; N 3.70.
C14H10BrF2NO3. Calculated, %: C 46.95; H 2.81; N 3.91.
From 0.73 g (2.41 mmol) of imine Vf (reaction time
4 h) using as eluent hexane–EtOAc, 5:1, at chromato-
graphic purification of the mixture we obtained 0.307 g
(34% with respect to applied imine, 76% with respect to
reacted imine) of 4-{5-(4-methoxyphenyl)-4-oxo-6,6-
difluoro-4,5,5a,6-tetra-hydro-3aH-cyclopropa[b]-
furo[2,3-c]pyrrol-2-yl}benzonitrile (IXf) and 0.175 g
(55%) of 4-(5-formyl-2-furyl)benzonitrile. Compound IXf,
mp 145–147°C (CH2Cl2–Et2O). IR spectrum (CHCl3),
–1
cm : 1725 (C=O). 1H NMR spectrum (CDCl3), d, ppm:
1.44 t (3H, CH3, J 7.1 Hz), 3.95 t (1H, H5a, J 7.4 Hz),
4.43 q (2H, CH2, J 7.1 Hz), 4.58 d.d.d.d (1H, H3a, J13.2,
6.8, 4.2, 2.6 Hz), 5.79 br.s (1H, H3), 7.07–8.11 m (9H,
Harom). 13C NMR spectrum (CDCl3), d, ppm: 13.9 (CH3),
50.8 t (C5a, J 15.6 Hz), 58.0 d.d (C3a, J 32.3, 2.2 Hz),
60.9 (CH2), 71.7 m (C6a), 94.9 (C3), 109.8 d.d.d (C6,
JCF 320, 302, 10 Hz), 116.9 t (J 2.2 Hz), 122.6,
125.1 (Carom), 128.6 d.d.d (C4, J 259, 248, 7 Hz), 128.9,
129.4, 131.3, 132.1, 138.5 d (Carom, J 4.4 Hz), 158.0 (C2),
165.5 (C=O). Found, %: C 63.21; H 4.16; N 3.15.
C22H17F4NO3. Calculated, %: C 63.01; H 4.09; N 3.34.
Compound IXc, mp 143–145, 149–151°C dimorphous
–1
n, cm : 2235 (CºN), 1725 (C=O). 1H NMR spectrum
(CDCl3), d, ppm: 3.82 s (3H, Me), 4.03 d.d (1H, H5a,
J 7.9, 1.4 Hz), 4.40 d.d (1H, H3a, J 2.8, 1.6 Hz), 6.00 d.d
(1H, H3, J 2.8, 1.4 Hz), 6.94 d (2H, 4-MeOC6H4,
J 9.0 Hz), 7.39 d (2H, 4-MeOC6H4, J 9.0 Hz), 7.70 s
(4H, 4-NCC6H4). 13C NMR spectrum (CDCl3), d, ppm:
49.8 d.d (C5a, J 17.1, 15.5 Hz), 52.4 d (C3a, J 2.2 Hz),
55.1 (Me), 68.4 d.d (C6a, J 19.4, 11.1 Hz), 97.7 (C3),
108.2 d.d (C6, J 320, 301 Hz), 112.8, 114.1 (Carom), 117.9
–1
(hexane–Et2O). IR spectrum (CHCl3), n, cm : 1730
(C=O). 1H NMR spectrum (CDCl3), d, ppm: 1.43 t (3H,
CH3, J 7.1 Hz), 4.06 d.d (1H, H5a, J 8.2, 1.7 Hz), 4.41 q
(2H, CH2, J 7.1 Hz), 4.41 m (1H, H3a), 5.97 d.d (1H, H3,
J 2.9, 1.5 Hz), 7.23–8.10 m (9H, Harom). 13C NMR
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 5 2006

VOZNYI et al.
694
(CºN), 112.9, 125.5, 129.8, 132.0, 132.3 (Carom), 156.0,
157.6 (C2, Carom), 170.3 t (C4, J 3.3 Hz). Found, %:
C 66.31; H 3.74; N 7.32. C21H14F2N2O3. Calculated, %:
C 66.31; H 3.71; N 7.37.
cyclopropa-[b]cyclopropa[4,5]furo[2,3-c]pyrrol-
3(1H)-one (XI) in a ratio 1:0.8. Compound IXg. 1H NMR
spectrum (CDCl3), d, ppm: 4.04 d.d (1H, H5a, J 8.1,
1.7 Hz), 4.38 d.d (1H, H3a, J 2.6, 2.1 Hz), 5.85 d.d (1H,
H3, J 2.6, 1.7 Hz), 7.27–7.59 m (8H, Harom). 13C NMR
spectrum (CDCl3), d, ppm: 49.5 d.d (C5a, J 17.6,
16.0 Hz), 52.7 d (C3a, J 2.5 Hz), 68.2 m (C6a), 94.7 d (C3,
J 1.1 Hz), 108.3 d.d (C6, J 319, 301 Hz), 120.5, 123.2,
125.8, 126.6, 127.2, 128.9, 131.5, 137.3 (Carom), 157.0 (C2),
170.8 (C4). Compound XI. 1H NMR spectrum (CDCl3),
d, ppm: 3.13 d (1H, H3b, JHF 13.8 Hz), 3.89 d.d (1H, H1a,
J 8.3, 1.8 Hz), 3.95 d.d (1H, H3a, J 3.0, 1.8 Hz), 7.27–
7.59 m (8H, Harom). 13C NMR spectrum (CDCl3), d, ppm:
33.9 t (C3b, J 11.9 Hz), 47.0 d.d (C1a, J 17.6, 16.0 Hz),
49.1 t (C3a, J 3.6 Hz), 68.1 m (C5a), 74.5 t (C4a, J 12 Hz),
107.4 d.d (C1, J 319, 301 Hz), 109.8 d.d (C4, J 307, 298
Hz), 120.8, 123.7, 126.2, 127.9 t (J 1.7 Hz), 128.5, 129.0,
131.7, 137.0 (Carom), 170.0 (C3).
Reaction of imine Vg with difluorocarbene. The
reaction was carried out by the general procedure using
a 6-fold excess of the difluorocarbene source. From
0.300 g (0.74 mmol) of imine Vg, 0.92 g (4.44 mmol) of
active lead, 1.43 g (4.44 mmol) of tetrabutylammonium
bromide, and 0.55 ml (6.0 mmol) of CBr2F2 (reaction
time 4 h) using as eluent hexane–EtOAc, 5:1, at
chromatographic purification of the mixture we obtained
0.124 g of a mixture of 2,5-bis(4-bromophenyl)-
4,4,6,6-tetrafluoro-4,5,5a,6-tetrahydro-3aH-
cyclopropa[b]furo-[2,3-c]pyrrole (VIIIg) and 2,4a-
bis(4-bromophenyl)-1,1,3,3,4,4-hexafluoro-
octahydrocyclopropa[b]cyclopropa[4,5]-furo[2,3-c]-
pyrrole (X) in a ratio 1:0.8 according to the data of
1H NMR spectrum, and 0.113 g of 5-(4-bromophenyl)-
furfural. Compound VIIIg. 1H NMR spectrum (CDCl3),
d, ppm: 3.93 t (1H, H5a, J 7.5 Hz), 4.55 d.d.d.d (1H, H3a,
J 13.1, 6.4, 4.2, 2.7 Hz), 5.68 br.s (1H, H3), 7.12–7.61 m
(8H, Harom). 13C NMR spectrum (CDCl3), d, ppm: 50.8 t
(C5a, J 15.2 Hz), 58.0 d.t (C3a, J 32.9, 2.2 Hz), 70.8 m
(C6a), 93.3 d.d (C3, J 1.4, 1.1 Hz), 109.7 d.d.d (C6, J 320,
302, 9.4 Hz), 116.9 t (J 2.3 Hz), 122.6, 123.7, 124.9, 126.8
(Carom), 128.8 d.d.d (C4, J 260, 250, 6 Hz), 128.9, 131.8,
138.2d(Carom,J 4.4Hz), 157.9(C2).CompoundX. 1H NMR
spectrum (CDCl3), d, ppm: 3.05 d (1H, H3b, J 14.5 Hz),
3.73 t (1H, H1a, J 7.4 Hz), 4.06 d.d.d (1H, H3a, J 11.8,
7.2, 1.2 Hz), 7.12–7.61 m (8H, Harom). 13C NMR spec-
trum (CDCl3), d, ppm: 31.4 d.t (C3b, J 12.0, 5.0 Hz),
47.8 t (C1a, J 16.0 Hz), 54.2 t.t (C3a, J 30.8, 2.9 Hz),
70.8 m (C4a), 75.3 t (C4a, J 12.2 Hz), 109.0 d.d.d (C1,
J 320, 302, 9.4 Hz), 109.7 d.d (C4, J 305, 297 Hz),
117.1 t (J 2.3 Hz), 123.1, 123.9 (Carom), 126.3 d.d.d
(C3, JCF 261, 249, 6 Hz), 127.2, 128.9 t (J 1.5 Hz),
129.0, 131.5, 138.1 d (J 5.0 Hz) (Carom).
General procedure for thermolysis of compounds
VIIIc, IXa, IXb, and IXf. Furopyrroles VIIIc, IXa, IXb,
and IXf were kept for 10 min in a test tube placed into an
oil bath heated at 160°C. Therewith the initial compounds
melted with HF liberation. On cooling the solid reaction
product was recrystallized from a mixture CHCl3–CH2Cl2
or CH2Cl2–Et2O.
From 0.130 g (0.52 mmol) of compound IXa was
obtained 0.099 g (83%) of 5-phenyl-7-fluoro-4,5-
dihydro-furo[3,2-c]pyridin-4-one (XIIa).
From 0.090 g (0.21 mmol) of compound VIIIc was
obtained 0.070 g (86%) of ethyl 4-(4-oxo-5-phenyl-7-
fluoro-4,5-dihydrofuro[3,2-c]pyridin-2-yl)benzoate
(XIIc), mp 220–221°C (CH2Cl2–Et2O). IR spectrum
–1
(CHCl3), n, cm : 1735 (C=O), 1700 (C=O), 1630 (C=C).
1H NMR spectrum (CDCl3), d, ppm: 1.44 t (3H, CH3,
J 6.8 Hz), 4.42 q (2H, CH2, J 6.8 Hz), 7.34 d (1H, H6,
J 6.0 Hz), 7.43–8.16 m (10H, H3, Harom). 13C NMR
spectrum (CDCl3), d, ppm: 14.0 (CH3), 60.9 (CH2),
104.6 d (C3, J 2.3 Hz), 119.4 d (C3a, J 3.1 Hz), 120.5 d
(C6, J 32.2 Hz), 124.0, 126.5, 128.3, 129.1, 129.9, 130.2,
132.4 (Carom), 138.0 d (C7, J 239 Hz), 140.0 (Carom),
148.7 d (C7a, J 15.0 Hz), 155.1 (C2), 156.8 (C4), 165.6
(CO2Et). Found, %: C 70.26; H 4.40; N 3.63.
C22H16FNO4. Calculated, %: C 70.02; H 4.27; N 3.71.
Into a solution of 0.08 g of a mixture of compounds
VIIIg and X in 2 ml of chloroform was added 0.5 g of
silica gel, the solvent was evaporated in a vacuum, and
the mixture obtained was maintained at room temperature
for 24 h. The reaction products were extracted with
1
chloroform and analyzed by H NMR spectroscopy.
From 0.120 g (0.35 mmol) of compound IXb was
obtained 0.091 g (80%) of 5-(4-bromophenyl)-2-
methyl-7-fluoro-4,5-dihydrofuro[3,2-c]pyridin-4-
one (XIIb), mp 251–253°C (CH2Cl2–Et2O). IR spectrum
According to the spectral data the sample obtained
consisted of a mixture of 2-(4-bromophenyl)-5-phenyl-
6,6-difluoro-5a,6-dihydro-3aH-cyclopropa[b]furo-
[2,3-c]-pyrrol-4(5H)-one (IXg) and 4a-(4-bromo-
phenyl)-2-phenyl-1,1,4,4-tetrafluorohexahydro-
–1
1
(CHCl3), n, cm : 1695 (C=O), 1630 (C=C). H NMR
spectrum (CDCl3), d, ppm: 2.50 s (3H, Me), 6.67 m (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 42 No. 5 2006

REACTIONS OF 1,5-p-CYCLIZATION OF gem-DIFLUORO-SUBSTITUTED AZOMETHINE YLIDES
695
H3), 7.17 d (1H, H6, J 5.7 Hz), 7.30 d (2H, Harom
,
5. Novikov, M.S., Khlebnikov, A.F., Sidorina, E.S., Masa-
lev, A.E., Kopf, Yu., and Kostikov, R.R., Zh. Org. Khim.,
2002, vol. 38, p. 1895.
6. Novikov, M.S., Khlebnikov, A.F., Krebs, A., and Kosti-
kov, R.R., Eur. J. Org. Chem., 1998, p. 133.
7. Novikov, M.S., Khlebnikov,A.F., Egarmin, M.A., Kopf,Yu.,
and Kostikov, R.R., Zh. Org. Khim., 2002, vol. 40, p. 1542.
8. Voznyi, I.V., Novikov, M.S., Khlebnikov,A.F., Kopf, J., and
Kostikov, R.R., J. Chem. Soc., Perkin Trans. 1, 2000, p. 231.
9. Voznyi, I.V., Novikov, M.S., Khlebnikov,A.F., Kopf,Yu., and
Kostikov, R.R., Zh. Org. Khim., 2004, vol. 40, p. 226.
10. Khlebnikov,A.F., Novikov, M.S., andAmer,A.A., Tetrahe-
dron Lett., 2002, vol. 43, p. 8523.
11. Khlebnikov,A.F., Novikov, M.S., andAmer,A.A. , Izv. Akad.
Nauk, Ser. Khim., 2004, p. 1049.
12. Khlebnikov, A.F. and Kostikov, R.R. , Izv. Akad. Nauk,
Ser. Khim., 1993, p. 646.
13. Khlebnikov,A.F., Novikov, M.S., and Kostikov, R.R., Usp.
Khim., 2005, 74, p. 183.
14. Romashin, Y.N., Liu, M.T.H., and Bonneau, R., J. Chem. Soc.
Chem. Commun., 1999, p. 447.
15. Bonneau, R., Romashin, Y.N., and Liu, M.T.H., J. Photochem.
Photobiol. A: Chemistry., 1999, vol. 126, p. 31.
16. Romashin,Y.N., Liu, M.T.H., Ma, W., and Moss, R., Tetra-
hedron, Lett., 1999, vol. 40, p. 7163.
17. Reinhoudt, D.N., Trompenaars, W.P., and Geevers, J., Tet-
rahedron Lett., 1976, vol. 17, p. 4777.
18. Taylor, E.C. andTurchi, I.J., Chem. Rev., 1979, vol. 79, p. 181.
19. Padwa, A. and Eisenhardt, W., J. Chem. Soc., Chem.
Commun., 1968, p. 380.
20. Baldwin, J.E., Pudussery, R.G., Qureshi,A.K., and Sklarz, B.,
J. Am. Chem. Soc., 1968, vol. 90, p. 5325.
J 8.7 Hz), 7.62 d (2H, Harom, J 8.7 Hz). 13C NMR
spectrum (CDCl3), d, ppm: 13.4 (Me), 104.0 d (C3, JCF
2.2 Hz), 118.2 d (C6, J 32.6 Hz), 118.9 d (C3a, J 3.3 Hz),
122.0, 128.3, 132.2 (Carom), 138.0 d (C7, J 239 Hz),
139.2 (Carom), 148.2 d (C7a, J 15 Hz), 155.8 (C2), 156.6
(C4). Found, %: C 52.02; H 2.90; N 4.15. C14H9BrFNO2.
Calculated, %: C 52.20; H 2.82; N 4.35.
From 0.049 g (0.129 mmol) of compound IXf was
obtained 0.049 g (93%) of 4-{5-(4-methoxyphenyl)-4-
oxo-7-fluoro-4,5-dihydrofuro[3,2-c]pyridin-2-yl}-
benzonitrile (XIIf) as a monohydrate, mp 285–286°C
1
(CHCl3–CH2Cl2). H NMR spectrum (DMCO-d6), d,
ppm: 3.83 s (3H, MeO), 7.07 d (2H, 4-MeOC6H4,
J 8.7 Hz), 7.39 d (2H, 4-MeOC6H4, J 8.7 Hz), 7.97 d
(2H, 4-NCC6H4, J 8.7 Hz), 7.97 d (1H, H3, J 2.8 Hz),
8.06 d (1H, H6, J 6.5 Hz), 8.10 d (2H, 4-NCC6H4,
J 8.7 Hz). 13C NMR spectrum (DMCO-d6), d, ppm:
52.9 (Me), 104.1 d (C3, J 2.2 Hz), 108.4, 111.7 (Carom),
115.8 (CºN), 115.9 d (C3a, J 3.0 Hz), 120.5 d (C6,
J 32.0 Hz), 122.4, 125.7, 130.0, 130.3, 130.5 (Carom),
133.9 d (C7, J 235 Hz), 146.4 d (C7a, J 15.5 Hz), 151.1
(Carom), 153.8 (C2), 156.4 (C4). Found, %: C 66.82;
H 3.69; N 7.36. C21H13FN2O2·H2O. Calculated, %:
C 66.66; H 4.00 N 7.40.
The study was carried out under financial support of
the Program of the Ministry of Education and Science of
the Russian Federation “Universities of Russia” (grant
no. yp.05.01.316) and of the Russian Foundation for Basic
Research (grant no. 05-03-33257).
21. Ueno, Y. and Okawara. M.V., Bull. Chem. Soc. Jpn., 1972,
vol. 45, p. 1797.
22. Pinter, A., Nyerges, M., Viranyi, A., and Toke, L., Tetrahe-
dron Lett., 2003, vol. 44, p. 2343.
23. Arany, A., Groundwater, P. W., and Nyerges, M., Tetrahe-
dron Lett., 1998, vol. 39, p. 3267.
REFERENVES
1. Novikov, M.S., Khlebnikov, A.F., Sidorina, E.S., and
Kostikov, R.R., J. Chem. Soc., Perkin Trans. 1, 2000, p. 231.
2. Novikov, M.S., Khlebnikov, A.F., and Shevchenko, M.V.,
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3. Novikov, M.S., Khlebnikov, A.F., Masalev, A.E., and
Kostikov, R.R., Tetrahedron Lett., 1997, vol. 38, p. 4187.
4. Novikov, M.S., Khlebnikov, A.F, and Kostikov, R.R., Zh.
Org. Khim., 2002, vol. 38, p. 1704.
24. Nyerges, M., Viranyi, A., Pinter, A., and Toke, L., Tetrahe-
dron Lett., 2003, vol. 44, p. 793.
25. Voznyi, I.V., Novikov, M.S., and Khlebnikov,A. F., Synlett.,
2005, p. 1006.
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