A facile carbene route to 2-fluoro-2-pyrrolines via fluorinated azomethine ylides

Article abstract of DOI:10.1016/S0022-1139(03)00116-7

2-Fluoro-2-pyrrolines have been prepared by a domino reaction of difluorocarbene with N-substituted ketimines in the presence of fumaronitrile, malenitrile or dimethyl maleate, involving azomethine ylide formation, 1,3-dipolar cycloaddition, and dehydrofluorination. The reactions of 1H-dibenzo[b,e] azepine and 3,4-dihydroisoquinolines with difluorocarbene in the presence of fumaronitrile proceed with the formation of fluorinated 1H-dibenzo[c,f] pyrrolo[1,2-a]azepine and pyrrolo[2,1-a]isoquinoline derivatives. The yields of 2-fluoro-2-pyrrolines depend mostly on their resistance to chromatographic work-up and are higher for 5,5-disubstituted pyrrolines compared to 5-monosubstituted derivatives.

Full text of DOI:10.1016/S0022-1139(03)00116-7

Journal of Fluorine Chemistry 123 (2003) 177–181
A facile carbene route to 2-fluoro-2-pyrrolines via
fluorinated azomethine ylides
Mikhail S. Novikov*, Alexander F. Khlebnikov, Mikhail V. Shevchenko
Department of Chemistry, St. Petersburg State University, Universitetskii pr. 26, Petrodvorets, 198504 St. Petersburg, Russia
Received 5 April 2003; received in revised form 5 April 2003; accepted 11 April 2003
Abstract
2-Fluoro-2-pyrrolines have been prepared by a domino reaction of difluorocarbene with N-substituted ketimines in the presence of
fumaronitrile, malenitrile or dimethyl maleate, involving azomethine ylide formation, 1,3-dipolar cycloaddition, and dehydrofluorination.
The reactions of 1H-dibenzo[b,e]azepine and 3,4-dihydroisoquinolines with difluorocarbene in the presence of fumaronitrile proceed with
the formation of fluorinated 1H-dibenzo[c,f]pyrrolo[1,2-a]azepine and pyrrolo[2,1-a]isoquinoline derivatives. The yields of 2-fluoro-
2-pyrrolines depend mostly on their resistance to chromatographic work-up and are higher for 5,5-disubstituted pyrrolines compared to
5-monosubstituted derivatives.
# 2003 Elsevier Science B.V. All rights reserved.
Keywords: Pyrroles; Carbenes; Ylides; Cycloaddition; Domino reaction
1. Introduction
cannot be considered an acceptable synthetic route to
2-fluoro-2-pyrrolines, since this is a particular reaction char-
acteristic of perfluorinated cyclobuta[b]pyrroles [11]. The
reaction of N-methylpyrrolidone with carbonyl fluoride in
the presence of cesium fluoride provides 2-fluoro-1-methyl-
2-pyrroline-3-carbonyl fluoride in a yield as low as 4% [12].
Pyrrole and its derivatives are a class of compounds
among the most important heterocycles in synthetic and
pharmacological practice [1]. In recent years, special atten-
tion has been paid to fluorine-containing pyrroles as poten-
tially biologically active compounds. A number of synthetic
approaches to fluoropyrroles have been proposed, such as
direct fluorination of pyrrole derivatives [2,3], refunctiona-
lisation by Schiemann reaction [4], heterocyclisation of
fluorinated precursors [5], and 1,3-dipolar cycloadditions
involving either fluorinated azomethine ylides [6–8] or
fluorinated dipolarophiles [9,10]. A more challenging pro-
blem in this field is synthesis of partly hydrogenated pyrroles
with fluorine attached to the ring-carbon atom, e.g. 2-fluoro-
2-pyrrolines. These compounds may offer interest not only
in terms of biological activity, but also, having a fairly
reactive fluorine atom, as synthetic building blocks. How-
ever, no convenient synthetic procedures for these com-
pounds have been reported. Two types of transformations are
known, resulting in isolation of 2-pyrrolines with a fluorine
atom in the position 2 of the ring [11,12]. The photolytic
ring contraction of N-substituted perfluoroazepines to form
N-substituted perfluoro-3a,5a-dihydrocyclobuta[b]pyrroles
2. Results and discussion
In this communication we report a convenient synthesis of
2-fluoro-2-pyrrolines by a domino reaction of difluorocar-
bene with imines in the presence of but-2-enedioic acid
derivatives. As starting imines we used acyclic Schiff bases
1a,b [13], 1c [14] as well as compounds 6 [15], 10 [16]
containing an endocyclic C¼N bond. Difluorocarbene was
generated in situ by reduction of CF2Br2 with lead powder in
the presence of tetrabutylammonium bromide (TBAB). The
reaction of imines 1a–c with difluorocarbene in the presence
of fumaronitrile, malenitrile, or dimethyl maleate resulted in
isolation, after chromatographic purification, of 2-fluoro-
2-pyrrolines 4a–c, 5 (Scheme 1). The mechanism of the
reaction depicted in Scheme 1 involves attack of difluoro-
carbene onto the nitrogen lone pair of the imine to give
azomethine ylide 2 followed by 1,3-dipolar cycloaddition of
the latter to the olefin and spontaneous dehydrofluorination
of intermediate difluoropyrrolidine 3. All the synthesized
* Corresponding author. Tel.: þ7-812-3756710; fax: þ7-812-428639.
E-mail address: mikhail.novikov@pobox.spbu.ru (M.S. Novikov).
0022-1139/$ – see front matter # 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0022-1139(03)00116-7

178
M.S. Novikov et al. / Journal of Fluorine Chemistry 123 (2003) 177–181
Table 1
Preparation of pyrrolines 4a–c, 5
Imine R1
R2
R3
Dipolarophile
Reaction Yield
time (h) (%)
1a
1a
1b
1c
1a
Ph
Ph
Ph
Ph
Ph
H
H
CN
CN
Fumaronitrile
Malenitrile
7
14
17
18
84 (4a)
74 (4a)
64 (4b)
63 (4c)
64 (5)
CH2Ph CN
CO2Me CN
Fumaronitrile
Fumaronitrile
H
CO2Me Dimethyl maleate 3a
a Reaction with active lead.
Table 2
Preparation of pyrrolines 7a,b, 8a,b
Scheme 1.
Imine 6
R
Reaction
time (h)
Yield of
Yield of
7 (%)
8 (%)
compounds, except for pyrroline 5, are quite stable toward
chromatographic purification and storage at 5 8C. To isolate
compound 5, both the reaction mixture before chromato-
graphy and the eluants were treated with Et3N. The isolated
product was stored in a refrigerator at À18 8C. Moreover, the
yield of pyrroline 5 was improved by using active lead [7]
instead of lead powder due to much reduced reaction time
(Table 1).
a
Ph
H
25
36
31
26
28
a
b
À
a Pyrroline (8b) was not isolated as a pure sample because of its
hydrolysis to 3-oxo-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline-
1,2-dicarbonitrile 9 obtained in 9% yield.
The reaction of cyclic analogue of ketimines 1a–c,
1-phenyl-3,4-dihydroisoquinoline 6a, with difluorocarbene
in the presence of fumaronitrile proceeded in a similar way
but gave a mixture of stereoisomers 7a, 8a in a total yield of
59%. The stereochemical assignment for adducts 7a and 8a
were based on NOE experiments. The cis relative config-
uration of 1-CN and 10b-Ph in 7a and its trans relationship
in 8a were clearly demonstrated by enhancement of the
signal of aromatic proton at H-10 (14%) in 7a and the
absence of NOE in 8a when the resonance corresponding
to the protons at H-1 of both compounds was irradiated. This
assignment is also confirmed by an 11% NOE enhancement
between H-1 and ortho-protons of benzene ring in isomer 8a
and the absence of this correlation in isomer 7a (Scheme 2,
Table 2).
successfully synthesized and isolated provided one prevents
formation of a trace amount of acid during work-up. Thus, in
the reaction of compound 6b with difluorocarbene in the
presence of fumaronitrile a stereoisomeric mixture of fluoro-
pyrrolines 7b, 8b could be isolated in a total yield 39% by
use of Et3N-containing eluent for column chromatographic
separation. Stereochemical assignment of diastereomeres
7b, 8b rests on the magnitude of the J (H1, H10b) values
in the 1H NMR spectra: 9.9 Hz in isomer 8b is characteristic
of cis configuration and 4 Hz in isomer 8b for trans con-
figuration [17].
Cyclic imine 10 containing an aryl substituent at the
nitrogen atom gave, under the same conditions, fluoropyr-
rolines 11 and 12. Compound 11 that has a larger J (H1,
H13b) coupling constant (10.6 Hz) in the 1H NMR spectrum
was assigned cis configuration of the C1–C13b, and isomer
12, trans configuration [J (H1, H13b) 7.9 Hz], which is nicely
consistent with the magnitudes of the ffHC1C13bH dihedral
Fluoropyrrolines derived from aldimines and its cyclic
analogues, e.g. compounds 6b, are generally less stable than
those derived from ketimines. Nevertheless, they can also be
Scheme 2.

M.S. Novikov et al. / Journal of Fluorine Chemistry 123 (2003) 177–181
179
with ultrasound at 40–45 8C until the lead was consumed
completely (reaction time given in Table 1). The solvent was
removed under reduced pressure, and the residue was sepa-
rated by chromatography on silica gel to afford after recrys-
tallisation 0.66 g (84%) of pyrroline 4a as a colourless
solid: mp 143–145 8C (Et2O–CH2Cl2). Anal. Calcd. for
C19H14FN3: C, 75.23; H, 4.65; N 13.85. Found: C, 75.84;
H, 4.79; N, 13.75. IR (CHCl3); n 2220 (CBN), 1660 cmÀ1
1
(C¼C). H NMR (CDCl3): d 2.60 (3H, s, CH3), 4.77 (1H,
4
d, JHF ¼ 3:5 Hz, H-3), 7.27–7.37 (10H, m, Harom).
3
13C NMR (CDCl3): d 28.3 (d, JCF ¼ 2:8 Hz, CH3),
3
2
44.6 (d, JCF ¼ 4:4 Hz, C-3), 53.3 (d, JCF ¼ 13:8 Hz,
3
C-4), 75.7 (C-2), 112.9 (d, JCF ¼ 3:9 Hz, CN), 115.3
Scheme 3.
4
(d, JCF ¼ 2:2 Hz, CN), 126.8, 127.7, 128.7, 128.9, 129.3,
1
129.3, 136.3, 138.4 (Carom), 165.2 (d, JCF ¼ 286:4 Hz,
angles, calculated at the PM3 level (248 and 1098, respec-
tively) (Scheme 3).
C-5).
The analogous reaction of imine 1a (0.51 g, 2.6 mmol)
with maleonitrile (0.41 g, 5.2 mmol) gave 0.58 g (74%) of
pyrroline 4a.
In conclusion, a facile approach to 2-fluoro-2-pyrrolines
has been suggested that relies on a carbene-derived azo-
methine ylide formation/1,3-dipolar cycloaddition domino
sequence. The yields of 2-fluoro-2-pyrrolines depend mostly
on their resistance to chromatographic work-up and are
higher for those obtained from ketimines compared to
aldimine-derived products.
3.3. 5-Fluoro-1-phenethyl-2,2-diphenyl-2,3-
dihydropyrrole-3,4-dicarbonitrile (4b)
Prepared by the typical procedure from N-benzhydryli-
dene-N-phenethylamine 1b (0.7 g, 2.45 mmol) and fumar-
onitrile (0.38 g, 4.9 mmol). Yield 0.62 g (64%). Colourless
solid, mp 194–195 8C (Et2O–CH2Cl2). Anal. Calcd. for
C26H20FN3: C, 79.37; H, 5.12; N 10.58. Found: C, 79.32;
H, 5.12; N, 10.68. IR (CHCl3); n 2215 (CBN), 1660 cmÀ1
3. Experimental
3.1. General
1
(C¼C). H NMR (CDCl3): d 1.75–1.81, 2.32–2.38, 3.01–
Melting points were determined on a hot stage micro-
scope (Boetius) and are uncorrected. IR spectra were
3.16, 3.36–3.46 (4H, m, 2CH2), 4.86 (1H, d, 4JHF ¼ 2:6 Hz,
H-3), 6.83–7.60 (15H, m, Harom). 13C NMR (CDCl3): d 34.3
(d, 4JCF ¼ 0:6 Hz, CH2), 44.9 (d, 3JCF ¼ 4:4 Hz, C-3), 46.0
(NCH2), 52.6 (d, 2JCF ¼ 14:4 Hz, C-4), 75.9 (C-2), 112.9 (d,
3JCF ¼ 3:8 Hz, CN), 115.1 (CN), 126.6, 126.9, 127.8, 128.1,
128.4, 128.7, 129.1, 129.4, 129.7, 136.6, 136.8, 139.7
1
recorded on a Carl-Zeiss UR 20 spectrometer. H NMR
spectra were recorded on a Bruker DPX 300 spectrometer at
300 MHz with internal standard TMS (d ¼ 0) and 13C NMR
spectra at 75 MHz with internal standard CDCl3 (d ¼ 76:7).
Elemental analysis was performed on a Hewlett-Packard
185B CHN-analyser. Mass spectra were obtained using a
MX-1303 instrument. Methylene chloride was dried by
distillation over phosphorus pentoxide. Silica gel Merck
60 was used for column chromatography. Sodium borohy-
dride, lead acetate, dibromodifluoromethane, tetrabutylam-
monium bromide, fumaronitrile and dimethyl maleate were
obtained commercially.
1
(Carom), 165.1 (d, JCF ¼ 286:9 Hz, C-5).
3.4. Methyl (3,4-dicyano-5-fluoro-2,2-diphenyl-2,3-
dihydropyrrol-1-yl)acetate (4c)
Prepared by the typical procedure from methyl N-benz-
hydrylideneglycinate 1c (1.04 g, 4.1 mmol) and fumaroni-
trile (0.64 g, 8.2 mmol). Yield 0.93 g (63%). Colourless
solid, mp 178–180 8C (Et2O). Anal. Calcd. for
C21H16FN3O2: C, 69.80; H, 4.46; N 11.63. Found: C,
69.85; H, 4.60; N, 11.64. IR (CHCl3); n 2220 (CBN),
1755 (C¼O), 1655 cmÀ1 (C¼C). 1H NMR (CDCl3): d
3.38 (3H, s, CH3), 3.75 and 3.98 (2H, AB-q, J ¼ 18:3 Hz,
CH2), 4.86 (1H, d, 4JHF ¼ 3:5 Hz, H-3), 7.31À7.37 (10H, m,
The reagent ratios used were the same as in the typical
procedure, unless otherwise specified.
3.2. 5-Fluoro-1-methyl-2,2-diphenyl-2,3-dihydropyrrole-
3,4-dicarbonitrile (4a) (typical procedure)
A flask containing freshly prepared lead powder (1.7 g,
8.2 mmol) and methylene chloride (15 cm3) was charged
with Bu4NBr (2.7 g, 8.4 mmol), N-benzhydrylidene-N-
methylamine 1a (0.51 g, 2.6 mmol), fumaronitrile (0.41 g,
5.2 mmol) and CBr2F2 (1.72 g, 8.3 mmol). The flask was
tightly stoppered, immersed in a sonic cleaner and irradiated
H
arom). 13C NMR (CDCl3): d 44.0 (CH2), 44.4 (d,
2
3JCF ¼ 4:4 Hz, C-3), 52.1 (CH3), 54.3 (d, JCF ¼ 12:7 Hz,
3
C-4), 75.8 (C-2), 112.4 (d, JCF ¼ 3:9 Hz, CN), 115.0 (d,
4JCF ¼ 2:8 Hz, CN), 127.2, 127.7, 128.8, 129.4, 129.5,
1
136.6, 138.2 (Carom), 164.8 (d, JCF ¼ 289:1 Hz, C-5),
166.4 (C¼O).

180
M.S. Novikov et al. / Journal of Fluorine Chemistry 123 (2003) 177–181
3.5. Dimethyl 5-fluoro-1-methyl-2,2-diphenyl-2,3-
dihydropyrrole-3,4-dicarboxylate (5)
3.7. 3-Fluoro-8,9-dimethoxy-1,5,6,10b-
tetrahydropyrrolo[2,1-a]isoquinoline-1,2-dicarbonitriles
(7b) and (8b)
Prepared by the typical procedure from N-benzhydryli-
dene-N-methylamine 1a (0.64 g, 3.3 mmol) and dimethyl-
maleate (0.95 g, 6.6 mmol) using active lead [7] instead of
lead powder. Chromatographic separation was accom-
plished by use of hexane-ethyl acetate mixture as eluent
doped with 0.01% of Et3N. Yield 0.77 g (64%). Colourless
solid, mp 128–130 8C (Et2O–hexane). Anal. Calcd. for
C21H20FNO4: C, 68.28; H, 5.46; N 3.79. Found: C,
68.30; H, 5.50; N, 3.76. IR (CHCl3); n 1760, 1705
Prepared by the typical procedure from 6,7-dimethoxy-
3,4-dihydroisoquinoline 6b (0.53 g, 2.8 mmol) and fumaro-
nitrile (0.44 g, 5.6 mmol) (reaction time 47 h). (1RS,10bRS)-
isomer 7b. Yield 0.22 g (26%). Colourless solid, mp
191–193 8C (EtOAc). Anal. Calcd. for C16H14FN3O2: C,
64.21; H, 4.71; N 14.04. Found: C, 64.22; H, 4.65; N, 14.02.
IR (CHCl3); n 2220 (CBN), 1650 cmÀ1 (C¼C). H NMR
1
(CDCl3): d 2.61–2.68, 2.90–3.00, 3.22–3.31, 3.89–3.95 (4H,
m, 2CH2), 3.89 (3H, s, CH3), 3.92 (3H, s, CH3), 4.03 (1H, dd,
(C¼O), 1650 cmÀ1 (C¼C) H NMR (CDCl3): d 2.52 (3H,
1
4
s, NCH3), 3.07 (3H, s, OCH3), 3.72 (3H, s, OCH3), 4.71 (1H,
4
J ¼ 4:0 Hz, JHF ¼ 2:5 Hz, H-1), 5.25 (1H, d, J ¼ 4:0 Hz,
d, JHF ¼ 3:5 Hz, H-3), 7.22À7.40 (10H, m, Harom). 13C
H-10b), 6.59 and 6.61 (1H, s, H-7, H-10). 13C NMR
3
4
NMR (CDCl3): d 28.1 (d, JCF ¼ 3:3 Hz, NCH3), 50.4
(CDCl3): d 26.7 (C-6), 37.3 (d, JCF ¼ 5:3 Hz, C-5), 40.4
3
(OCH3), 51.1 (OCH3), 57.1 (d, JCF ¼ 3:9 Hz, C-3), 74.3
(d, 3JCF ¼ 1:1 Hz, C-1), 55.1 (d, 2JCF ¼ 14:8 Hz, C-2), 55.6
(CH3), 55.9 (CH3), 61.4 (C-10b), 106.8, 111.3 (C-7, C-10),
112.5 (d, JCF ¼ 5:0 Hz, CN), 117.9 (d, JCF ¼ 3:3 Hz, CN),
123.8, 125.1, 148.7, 148.8 (Carom), 166.0 (d,
2
(C-2), 76.9 (d, JCF ¼ 7:2 Hz, C-4), 127.4, 127.6, 127.7,
128.1, 128.5, 136.8, 140.4 (Carom), 162.8 (d, 1JCF ¼ 288 Hz,
C-5), 163.7 (d, JCF ¼ 5 Hz, C¼O), 170.8 (d, JCF ¼ 2:8 Hz,
C¼O).
1
1JCF ¼ 285:8 Hz, C-3). (1RS,10bSR)-isomer 8b. H NMR
(CDCl3): d 2.71-3.91 (4H, m, 2CH2), 3.90 (6H, s, 2CH3),
4.33 (1H, dd, J ¼ 9:9 Hz, 4JHF ¼ 3:4 Hz, H-1), 5.26 (1H, d,
J ¼ 9:9 Hz, H-10b), 6.21 and 6.31 (1H, s, H-7, H-10).
3.6. 3-Fluoro-8,9-dimethoxy-10b-phenyl-1,5,6,10b-
tetrahydropyrrolo[2,1-a]isoquinoline-1,2-dicarbonitriles
(7a) and (8a)
1
Compound 8b was detected in a mixture with 7b by H
NMR spectroscopy after chromatographic work-up of the
reaction mixture. Attempted separation from 7b resulted
in hydrolysis of 8b to (1RS,10bSR)-8,9-dimethoxy-3-
oxo-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline-1,
2-dicarbonitrile 9. Compound 9: yield 0.075 g (9%). Colour-
less solid, mp 205–208 8C (CHCl3) (decomp.). Anal. Calcd.
for C16H15N3O3: C, 64.64; H, 5.09; N 14.13. Found: C,
64.46; H, 5.18; N, 14.02. IR (CHCl3); n 2260 (CBN), 1740
Prepared by the typical procedure from 6,7-dimethoxy-1-
phenyl-3,4-dihydroisoquinoline 6a (0.8 g, 3.0 mmol) and
fumaronitrile (0.94 g, 12.0 mmol) (reaction time 25 h).
(1RS,10bSR)-isomer 7a. Yield 0.35 g (31%). Light-yellow
prisms, mp 196–198 8C (EtOAc). Anal. Calcd. for
C22H18FN3O2: C, 70.39; H, 4.83; N 11.19. Found: C,
70.41; H, 4.93; N, 11.17. IR (CHCl3); n 2217 (CBN),
1665 cmÀ1 (C¼C). 1H NMR (CDCl3): d 2.53–2.61,
2.91–3.03, 3.14–3.23, 3.70–3.78 (4H, m, 2CH2), 3.90
(3H, s, CH3), 3.97 (3H, s, CH3), 4.73 (1H, d,
4JHF ¼ 2:5 Hz, H-1), 6.65 (1H, s, H-10), 6.83 (1H, s,
H-7), 7.40 (5H, s, HPh). 13C NMR (CDCl3): d 26.4 (C-6),
1
(C¼O). H NMR (CDCl3): d 2.71–2.79, 2.89–3.00, 3.06–
3.16, 4.38–4.44 (4H, m, 2CH2), 3.30 (1H, dd, J ¼ 11:9 Hz,
J ¼ 9:3 Hz, H-1), 3.91 (3H, s, CH3), 3.93 (3H, s, CH3), 4.05
(1H, J ¼ 11:9 Hz, C-2), 5.02 (1H, d, J ¼ 9:3 Hz, H-10b),
6.67 and 7.00 (1H, s, H-7, H-10). 13C NMR (CDCl3): d 27.4
(C-6), 36.3, 38.1, 38.2 (C-1, C-2, C-5), 55.7, 55.8 (CH3),
57.0 (C-10b), 106.3, 111.7 (C-7, C-10), 113.3, 116.1 (CN),
122.6, 125.0, 148.6, 149.1 (Carom), 160.4 (C-3). EIMS 70 eV,
m/z (rel. int.): 297 [M]þ (58), 191 [M-CH(CN)CH(CN)CO]þ
(100), 176 [191-CH3]þ (25).
3
37.9 (C-5), 44.1 (d, JCF ¼ 5:5 Hz, C-1), 52.6 (d,
2JCF ¼ 13:8 Hz, C-2), 55.7 (CH3), 56.1 (CH3), 70.2 (C-
3
10b), 108.9, 111.6 (C-7, C-10), 113.0 (d, JCF ¼ 4:4 Hz,
4
CN), 115.7 (d, JCF ¼ 2:8 Hz, CN), 125.6, 127.1, 127.4,
128.4, 129.1, 137.5 (C-6a, C-10a, CPh), 147.8, 149.0 (C-9,
1
C-10), 165.3 (d, JCF ¼ 286:2 Hz, C-3). (1RS,10bRS)-iso-
3.8. 3-Fluoro-9,13b-dihydro-1H-dibenzo[c,f]pyrrolo-
[1,2-a]azepine-1,2-dicarbonitriles (11) and (12)
mer 8a was isolated in 28% yield (0.31 g) with 35%
1
impurity of isomer (7a). H NMR (CDCl3): d 2.71–2.77,
2.91–3.23, 3.70–3.81, (4H, m, 2CH2), 3.82 (3H, s, CH3),
Prepared by the typical procedure from 11H-dibenzo-
[b,e]azepine 10 (0.5 g, 2.6 mmol) and fumaronitrile
(0.4 g, 5.2 mmol) (reaction time 86 h). (1RS,10bSR)-Isomer
11. Yield 0.21 g (27%). Colourless solid, mp 154–156 8C
(EtOAc–CH2Cl2). Anal. Calcd. for C19H12FN3: C, 75.74; H,
4.01; N, 13.95. Found: C, 75.63; H, 4.04; N, 14.01. IR
(CHCl3); n 2220 (CBN), 1650 cmÀ1 (C¼C). 1H NMR
(CDCl3): d 3.65 (1H, d, JHH ¼ 14:6 Hz, H-9), 4.18 (1H,
3.93 (3H, s, CH3), 4.77 (1H, d, 4JHF ¼ 4:4 Hz, H-1), ), 6.54
(1H, s, H-10), 6.70 (1H, s, H-7), 7.28–7.41 (5H, m, HPh). 13
C
NMR (CDCl3): d 28.0 (C-6), 37.6 (C-5), 44.4 (C-1), 53.2 (d,
2JCF ¼ 14:4 Hz, C-2), ), 55.5 (CH3), 55.9 (CH3), 68.6 (C-
3
10b), 111.1, 111.4 (C-7, C-10), 113.2 (d, JCF ¼ 4:4 Hz,
4
CN), 115.8 (d, JCF ¼ 2:8 Hz, CN), 124.2, 125.6, 125.9,
128.8, 129.1, 142.0 (Carom), 147.6, 149.1 (C-9, C-10), 163.1
1
4
(d, JCF ¼ 285:3 Hz, C-3).
dd, JCF ¼ 3:5 Hz, JHH ¼ 10:6 Hz, H-1), 4.56 (1H, d,

M.S. Novikov et al. / Journal of Fluorine Chemistry 123 (2003) 177–181
181
JHH ¼ 14:6 Hz, H-9), 5.48 (1H, d, JHH ¼ 10:6 Hz, H-13b),
References
7.28–7.38 (8H, m, Harom). 13C NMR (CDCl3): d 37.7 (d,
2
3JCF ¼ 4:6 Hz, C-1), 38.4 (C-9), 55.1 (d, JCF ¼ 12:6 Hz,
[1] R.A. Jones (Ed.), Pyrroles, Part I, Wiley/Interscience, New York,
1990.
C-2), 66.8 (C-13b), 112.3 (d, 3JCF ¼ 3:4 Hz, CN), 117.2 (d,
3JCF ¼ 2:3 Hz, CN), 125.4, 127.0, 127.9, 128.0, 128.7,
128.8, 129.0, 130.4, 133.2, 133.3, 135.3, 138.7 (Carom),
[2] J. Wang, A.I. Scott, Tetrahedron Lett. 35 (1994) 3679.
[3] J. Wang, A.I. Scott, Tetrahedron 50 (1994) 6181.
[4] H. Onda, H. Toi, Y. Aoyama, H. Ogoshi, Tetrahedron Lett. 26 (1985)
4221.
1
163.5 (d, JCF ¼ 287:4 Hz, C-3). (1RS,10bRS)-isomer 12.
Yield 0.07 g (9%). Colourless solid, mp 258–260 8C (Et2O–
CH2Cl2). Anal. Calcd. for C19H12FN3: C, 75.74; H, 4.01; N,
13.95; Found: C, 75.98; H, 4.08; N, 14.01. IR (CHCl3);
[5] G. Shi, W. Cai, J. Org. Chem. 60 (1995) 6289.
[6] M.S. Novikov, A.F. Khlebnikov, E.S. Sidorina, R.R. Kostikov, J.
Fluor. Chem. 90 (1998) 117.
[7] M.S. Novikov, A.F. Khlebnikov, E.S. Sidorina, R.R. Kostikov, J.
Chem. Soc., Perkin Trans. 1 (2000) 231.
n 2220 (CBN), 1650 cmÀ1 (C¼C). H NMR: d 3.61 (1H,
1
4
d, JHH ¼ 13:7 Hz, H-9), 4.30 (1H, dd, JCF ¼ 2:9 Hz,
[8] M.S. Novikov, A.F. Khlebnikov, O.V. Besedina, R.R. Kostikov,
Tetrahedron Lett. 42 (2001) 533.
JHH ¼ 7:9 Hz, H-1), 4.82 (1H, d, JHH ¼ 13:7 Hz, 9-H),
[9] J. Leroy, M. Wakselman, Tetrahedron Lett. 35 (1994) 8605.
[10] J. Leroy, M. Rubinstein, C. Wakselman, J. Fluor. Chem. 25 (1984)
255.
5.40 (1H, d, JHH ¼ 7:9 Hz, H-13b), 7.02–7.40 (8H, m,
3
H
arom). 13C NMR (DMSO-d6): d 37.3 (d, JCF ¼ 3:5 Hz,
2
C-1), 37.9 (C-9), 55.3 (d, JCF ¼ 12:6 Hz, C-2), 68.7 (C-
[11] M.G. Barlow, S. Culshaw, R.N. Haszeldine, W.D. Morton, J. Chem.
Soc., Perkin Trans. 1 (1982) 2105.
3
13b), 114.9 (d, JCF ¼ 3:4 Hz, CN), 117.9 (CN), 126.7,
128.3, 128.8, 129.4, 129.6, 129.7, 131.1, 132.3, 134.1,
1
[12] F.S. Fawcett, C.W. Tullock, D.D. Coffman, J. Am. Chem. Soc. 84
(1962) 4275.
137.7, 140.1 (Carom), 163.5 (d, JCF ¼ 287:4 Hz, C-3).
[13] A. Padwa, W. Bergmark, D. Pashayan, J. Am. Chem. Soc. 91 (1969)
2659.
Acknowledgements
[14] M.J. O’Donnell, R.L. Polt, J. Org. Chem. 47 (1982) 2663.
[15] W.M. Whaley, M. Meadow, J. Chem. Soc. (1953) 1067.
[16] L.H. Werner, S. Ricca, E. Mohacsi, A. Rossi, V.P. Arya, J. Med.
Chem. 8 (1965) 74.
We gratefully acknowledge the Russian Foundation for
Basic Research (project 02-03-32735a) and the Ministry of
Education of Russian Federation (project E02-5.0-30) for
support of this research.
[17] R. Huisgen, K. Niklas, Heterocycles 22 (1984) 21.