A simple route to side-chain fluorinated β-lactams from ring-fluorinated aziridines

Article abstract of DOI:10.1016/j.jfluchem.2006.10.013

β-Lactams bearing a Ph₂CF substituent at the C(4)-atom were synthesized from N-alkyl-2-fluoro-3,3-diphenylaziridines. The transformation was realized using SbF₃-mediated isomerization of the monofluoroaziridines to fluorinated aldimines, followed by Staudinger reaction with ketenes. It was shown that this reaction sequence can be performed as a one-pot procedure.

Full text of DOI:10.1016/j.jfluchem.2006.10.013

Journal of Fluorine Chemistry 128 (2007) 114–119
www.elsevier.com/locate/fluor
A simple route to side-chain fluorinated b-lactams from
ring-fluorinated aziridines
Alexander S. Konev a, Mikhail S. Novikov a, Alexander F. Khlebnikov a,
*
,
Kourosch Abbaspour Tehrani b
a Department of Chemistry, St. Petersburg State University, Universitetskii pr. 26, 198504 St. Petersburg, Petrodvorets, Russia
b Faculty of Science, Department of Applied Biological Sciences, Laboratory for Organic Chemistry,
Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium
Received 4 September 2006; received in revised form 18 October 2006; accepted 19 October 2006
Available online 26 October 2006
Abstract
b-Lactams bearing a Ph2CF substituent at the C(4)-atom were synthesized from N-alkyl-2-fluoro-3,3-diphenylaziridines. The transformation
was realized using SbF3-mediated isomerization of the monofluoroaziridines to fluorinated aldimines, followed by Staudinger reaction with
ketenes. It was shown that this reaction sequence can be performed as a one-pot procedure.
# 2006 Elsevier B.V. All rights reserved.
Keywords: Fluoroaziridines; Fluorinated aldimines; Fluorine-containing b-lactams
1. Introduction
are also of interest as synthetic building blocks for the
preparation of fluorine- and nitrogen-containing compounds,
such as for the synthesis of fluorinated amino acids, dipeptides,
and fluoro-taxoids [18].
The synthesis of b-lactams and their biological application
is an increasingly active area. The b-lactam structural fragment
is the base of the family of bioactive compounds: antibiotics
[1,2], fungicides [3,4], and antitumor agents [5].
Approaches to b-lactams with fluorine in the 3-position of
the ring [19,20] or F2C- [18,21] and F3C-groups in side chains
[18] were elaborated. At the same time, the diversity of b-
lactams with one a-fluorine atom in the side chain remains still
limited to b-lactams bearing CFH2 [12,13,15,17,22–26] or
CFXCO2R (X = H, Alk [27], CO2R [27,28]) groups. It was also
found that the Ph2F group enhances the effect of certain
medicines [29].
It is well known that the introduction of fluorine atoms to
bioactive molecules can often improve their pharmacological
properties because of, for example, increased membrane
permeability, enhanced hydrophobic binding, stability against
metabolic transformations, and so on [6–10]. One can expect,
therefore, that fluorine-containing b-lactams will serve as
important and useful bioactive compounds for medicinal
chemistry and chemical biology. For example, Ezetimibe, a b-
lactam containing fluorine in the side chain, is the first of the
selective cholesterol absorption inhibitors [11]. b-Lactams
bearing a fluorine atom in the alpha position of the side chain
have been intensively investigated as potential antibiotics [12–
17]. In certain cases the CH2F group in the fourth position of the
azetidinone ring enhances the antibiotic activity of lactams [12]
and their resistance [13] to b-lactamase. Fluorinated b-lactams
[2 + 2]-Cycloaddition of imine to ketene is one of the
simplest and well-developed direct routes to b-lactams
(Scheme 1). b-Lactams with fluorine in the a-position of the
side chain can be synthesized by this reaction from a-
fluoroimines, preparation of which, however, is often not a
trivial problem. That is the reason why the reported examples of
application of such an approach are rare and limited to the use
of N-(2-fluoroethylidene)amines for preparing 4-fluoromethy-
lazetidine-2-ones [25,26].
Recently we have demonstrated that some fluorinated imines
are accessible by isomerization of 2-fluoroaziridines, which in
turn can be prepared by cycloaddition of monofluorocarbenes to
imines [30,31]. In the present study reactions of diphenylketene
* Corresponding author. Tel.: +7 812 4284021; fax: +7 812 4286939.
E-mail address: Alexander.Khlebnikov@pobox.spbu.ru (A.F. Khlebnikov).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.10.013

A.S. Konev et al. / Journal of Fluorine Chemistry 128 (2007) 114–119
115
Table 1
Synthesis of lactams 4a–g
Aziridine Ketene Lactam R1
R2
R3 Reaction
conditions
Isolated
yield of
4 (%)
1a
1a
1a
1b
1b
1c
1c
3a
3b
3c
3a
3b
3b
3c
4a
4b
4c
4d
4e
4f
Ph
Ph
Ph
Ph
Ph CH2Cl2, 40 8C
22
62
30
Scheme 1.
PhO
AcO
H
CH2Cl2, rt
H
CH2Cl2, rt
and ketenes, bearing oxy-groups, with a-fluoroimines generated
from 2-fluoroaziridines were examined as a potential route to
side-chain fluorinated b-lactams (Scheme 2).
CO2Me Ph
Ph Toluene, 110 8C 22
CO2Me PhO
H
H
H
CH2Cl2, rt
CH2Cl2, rt
CH2Cl2, rt
42
48
46
H
H
PhO
AcO
4g
2. Results and discussion
The catalyst was filtered off, ketene or the corresponding acid
chloride and triethylamine was added and the mixture was
stirred at room temperature. The products were isolated by
crystallization or by using column chromatography on silica.
The yields of synthesized lactams 4a–g per starting aziridines
1a–c are presented in Table 1.
The structure of compounds 4a–g was proved from their IR,
1H, 19F and 13C NMR spectra. The cis-configuration of lactams
4b,c,e–g is evident from the values of JHH (4.7–5.0 Hz) for H-3-
4, since trans- and cis-vicinal 2JHH constants found for 3- and 4-
monosubstituted b-lactams are 1–2 and 4–5 Hz, respectively
[35].
2-Fluoroaziridines 1a–c were synthesized from N-benzyl-,
N-methoxycarbonylmethyl- and N-methyl-imines of benzo-
phenone and monofluorocarbene (generated by the reduction of
CHFBr2 with active lead according to the published procedure
[31]). Diphenylketene 3a was prepared according to the known
procedure [32] and oxy-substituted ketenes 3b,c were
generated in situ from the appropriate acid chloride and
triethylamine.
We recently found that 2-fluoroaziridines isomerize into a-
fluoroimines or/and 1,3-disubstituted indoles under protic
(TsOH) or Lewis acid (ZnCl2, TiCl4, SbF3) catalysis. The most
selective isomerization leading exclusively to a-fluoroimines
was observed with SbF3 [30]. It was supposed [30] that the
coordination of the Lewis acid with the aziridine nitrogen or
protonation of compounds 2 facilitates cleavage of the three-
membered ring, like with dichloro- and chlorofluoro-substitted
aziridines [33,34]. For preparation of target b-lactams
isomerization of 2-fluoroaziridines into a-fluoroimines 2a–c
was carried out using SbF3 as a catalyst. A solution of aziridine
1a–c in CH2Cl2 was refluxed in the presence of SbF3 until
transformation of the aziridine to imine 2a–c was completed.
The resulting lactams from phenoxy- and acetoxy-ketenes
are usually obtained in yields ranging from 42 to 62%. Yields
of diphenylketene-derived lactams are lower in consequence
of the formation of byproducts. Thus, in the reaction of imine
2a with diphenylketene in CH2Cl2 at 40 8C, in addition to
lactam 4a (22%), amide 5a (24%) was isolated (Scheme 3).
In the reaction of imine 2b with ketene 3d amide 5c was
also isolated with 19% yield instead of the expected
lactam.
Scheme 2.
Scheme 3.

116
A.S. Konev et al. / Journal of Fluorine Chemistry 128 (2007) 114–119
Scheme 4.
Probably in the case of ketenes 3a,d (having relatively low
(25H, m, Ph). 13C NMR (75 MHz, CDCl3): d 44.8 (CH2), 66.5
(d, J = 20.5 Hz, C-4), 71.2 (C-3), 95.7 (d, J = 189.5 Hz, CF),
123.6 (d, J = 10.0 Hz, C-Ph), 124.3 (d, J = 11.0 Hz, C-Ph),
126.5, 127.0, 127.26, 127.32, 127.6, 127.7 (d, J = 1.0 Hz, C-
Ph), 127.9, 128.19 (4C, C-Ph), 128.23, 128.5 (C-Ph), 128.7 (d,
J = 2.5 Hz, C-Ph), 130.0 (d, J = 3.0 Hz, C-Ph), 135.2, 137.0,
140.4 (C-Ph), 141.1 (d, J = 23.4 Hz, C-Ph), 142.3 (d,
J = 24.4 Hz, C-Ph), 171.0 (C O). 19F NMR (CDCl3): d
À172.4, broad singlet. Anal. calcd. for C35H28FNO: C, 84.5;
H, 5.7; N, 2.8. Found: C, 84.6; H, 5.7; N, 2.6.
reactivity in [2 + 2]-cycloadditions) Staudinger reaction com-
petes with hydrolysis of imine 2, giving rise to amine which
reacts with ketene with formation of corresponding amide.
The reaction of imine 2b with diphenylketene in boiling
toluene for 1.5 h gave rise to lactam 4d (22%) and lactam 8
(13%) (Scheme 4). The latter is a product of the Staudinger
reaction of the azadiene 7 which is formed as the result of
dehydrofluorination of imine 2b. The yield of 4d in the reaction
performed at room temperature was rather low. In this case
amide 5b was also isolated in 19% yield.
Synthesis of b-lactams from fluoroaziridines 1 can be also
realized by a one-pot procedure. Thus, refluxing of aziridine 1c
in CH2Cl2 with a catalytic amount of SbF3 for 14 h, followed by
addition of phenoxyacetyl chloride and triethylamine gave
lactam 4g for 1 d at room temperature in 47% yield.
3.3. cis-1-Benzyl-4-[fluoro(diphenyl)methyl]-3-
phenoxyazetidin-2-one (4b)
A mixture of 1-benzyl-3-fluoro-2,2-diphenylaziridine (1a)
(100 mg, 0.33 mmol), SbF3 (58 mg, 0.32 mmol) and CH2Cl2
(30 mL) was refluxed for 15 h. SbF3 was filtered off and Et3N
(36 mg, 0.36 mmol) and phenoxyacetyl chloride (61 mg,
0.36 mmol) were added to the filtrate. The resulting solution
was stirred at 14–17 8C for 18 h and then washed with 0.02 M aq.
Na2CO3 (20 mL). The organic layer was dried over Na2SO4,
filtered, concentrated and the residue was crystallized from ether
to give compound 4b [89 mg (62%), colorless crystals, mp 159–
162 8C (Et2O)]. IR (CHCl3): n 1760 (C O). 1H NMR (300 MHz,
CDCl3): d 3.38 (1H, d, J = 15.2 Hz, CH2), 4.80 (1H, d,
J = 15.2 Hz, CH2), 4.81 (1H, dd, JHF = 24.3 Hz, JHH = 5.0 Hz,
H-4), 5.29 (1H, d, J = 5.0 Hz, H-3), 6.50–7.50 M (20H, m, Ph).
13C NMR (75 MHz, CDCl3): d 44.9 (CH2), 62.5 (d, J = 21.4 Hz,
C-4), 81.6(d, J = 1.0 Hz, C-3), 95.4(d, J = 187.5 Hz, CF), 116.3,
122.2 (C-Ph), 124.75 (d, J = 8.0 Hz, C-Ph), 124.82 (d,
J = 10.0 Hz, C-Ph), 127.68 (d, J = 1.5 Hz, C-Ph), 127.71 (C-
Ph), 128.0 (d, J = 1.0 Hz, C-Ph), 128.2, 128.3, 128.6 (C-Ph),
128.7 (d, J = 2.0 Hz, C-Ph), 129.1, 134.9 (C-Ph), 141.1 (d,
J = 22.4 Hz, C-Ph), 142.0 (d, J = 24.9 Hz, C-Ph), 158.0 (C-Ph),
167.5 (C O). 19F NMR (CDCl3): d À165.1 broad singlet. Anal.
calcd. for C29H24FNO2: C, 79.6; H, 5.5; N, 3.2. Found: C, 79.7;
H, 5.5; N, 2.9.
3. Experimental
3.1. General
Melting points were determined on a Boetius melting point
apparatus; uncorrected values are given. The IR spectra were
recorded on a Carl Zeiss UR-20 instrument. 1H (300 MHz) and
13C (75 MHz) NMR spectra were measured with a Bruker DPX
300spectrometer and 19F NMR(235 MHz) with BruckerAvance
250 spectrometer. The elemental compositions were determined
on an HP-185B CHN analyzer. The progress of reactions was
monitored by thin-layer chromatography using Silufol UV-254
plates. SilicagelMerck 60was used forcolumnchromatography.
Methylene chloride was dried by distillation over P2O5.
3.2. 1-Benzyl-4-[fluoro(diphenyl)methyl]-3,3-
diphenylazetidin-2-one (4a)
A mixture of 1-benzyl-3-fluoro-2,2-diphenylaziridine (1a)
(100 mg, 0.33 mmol), SbF3 (59 mg, 0.33 mmol) and CH2Cl2
(30 mL) was refluxed for 15 h. SbF3 was filtered off, the solvent
evaporated in vacuo and the residue treated with diphenylketene
(3a) (61 mg, 0.31 mmol) solution in CH2Cl2 (4 mL). The
resulting solution was refluxed for 9 h, then concentrated and
chromatographed on silica, having compound 4a [35 mg (22%),
colorless crystals, mp 181–182 8C (Et2O)] and N-benzyl-2,2-
diphenylacetamide (5a) [24 mg (24%), colorless crystals, mp
126–128 8C (CH2Cl2–hexane), lit mp 126–128 8C [36]].
3.4. cis-1-Benzyl-2-[fluoro(diphenyl)methyl]-4-
oxoazetidin-3-yl acetate (4c)
A mixture of 1-benzyl-3-fluoro-2,2-diphenylaziridine (1a)
(100 mg, 0.33 mmol), SbF3 (59 mg, 0.33 mmol) and CH2Cl2
(30 mL) was refluxed for 15 h. SbF3 was filtered off and Et3N
(37 mg, 0.37 mmol) and acetoxyacetyl chloride (50 mg,
0.37 mmol) were added to the filtrate. The resulting solution
was stirred at room temperature for 2 d and then washed with
0.02 M aq. Na2CO3 (20 mL). The organic layer was dried over
Compound 4a: IR (CHCl3): n 1770 (C O). 1H NMR
(300 MHz, CDCl3): d 3.32 (1H, d, J = 16.0 Hz, CH2), 4.88 (1H,
d, J = 16.0 Hz, CH2), 5.45 (1H, d, J 25.8 Hz, CH), 6.4–7.6

A.S. Konev et al. / Journal of Fluorine Chemistry 128 (2007) 114–119
117
Na2SO4, filtered, concentrated and the residue was crystallized
from ether to give compound 4c [40 mg (30%), colorless
crystals, mp 177–178 8C (Et2O–CH2Cl2)]. IR (CHCl3): n 1770
(C O). 1H NMR (300 MHz, CDCl3): d 1.50 (3H, s, CH3), 3.29
(1H, d, J = 14.6 Hz, CH2), 4.71 (1H, d, JHF = 24.5 Hz,
b. A mixture of methyl 2-(3-fluoro-2,2-diphenylaziridin-1-
yl)acetate (1b) (105 mg, 0.37 mmol), SbF3 (66 mg,
0.37 mmol) and CH2Cl2 (20 mL) was refluxed for 2 h.
SbF3 was filtered off and the filtrate was treated with
diphenylketene (71 mg, 0.37 mmol). The resulting solution
was kept at 5–15 8C for 3 d. The solvent was evaporated in
vacuo, Et2O was added to the residue and the mixture was
seeded with a small crystal of compound 4d. After
crystallization compound 4d (20 mg, 11%) was obtained.
From the mother liquid was isolated methyl 2-[(2,2-
diphenylacetyl)amino]acetate (5b) (20 mg, 19%), which
J
HH = 4.7 Hz, H-4), 4.78 (1H, d, J = 14.6 Hz, CH2), 6.20
(1H, d, J = 4.7 Hz, H-3), 6.60–7.50 (15H, m, Ph). 13C NMR
(75 MHz, CDCl3): d 19.6 (CH3), 44.9 (CH2), 62.0 (d,
J = 20.0 Hz, C-4), 72.7 (C-3), 94.7 (d, J = 188.0 Hz, CF),
124.2 (d, J = 8.5 Hz, C-Ph), 124.4 (d, J = 10.0 Hz, C-Ph),
127.8 (C-Ph), 127.9 (d, J = 1.5 Hz, C-Ph), 128.00 (C-Ph),
128.04 (d, J = 1.0 Hz, C-Ph), 128.55 (C-Ph), 128.58 (d,
J = 1.0 Hz, C-Ph), 128.9 (d, J = 2.0 Hz, C-Ph), 134.4 (C-Ph),
140.6 (d, J = 22.4 Hz, C-Ph), 141.6 (d, J = 25.4 Hz, C-Ph),
166.1 (C O), 169.0 (C O). 19F NMR (CDCl3): d À169.3 (d,
J = 24.5 Hz). Anal. calcd. for C25H22FNO3: C, 74.4; H, 5.5; N,
3.5. Found: C, 74.5; H, 5.4; N, 3.4.
1
was identified by comparison of H and 13C NMR with
published data [37].
3.6. Methyl 2-[cis-2-[fluoro(diphenyl)methyl]-4-oxo-3-
phenoxyazetidin-1-yl]acetate (4e)
A mixture of methyl 2-(3-fluoro-2,2-diphenylaziridin-1-
yl)acetate (1b) (100 mg, 0.35 mmol), SbF3 (63 mg, 0.35 mmol)
and CH2Cl2 (20 mL) was refluxed for 2 h. SbF3 was filtered off
and Et3N (40 mg, 0.40 mmol) and phenoxyacetyl chloride
(66 mg, 0.39 mmol) were added to the filtrate. The resulting
solution was stirred at 17 8C for 3 d and then washed with
0.02 M aq. Na2CO3 (20 mL). The organic layer was dried over
Na2SO4, filtered, concentrated and the residue was crystallized
from ether to give compound 4e [(62 mg, 42%), colorless
crystals, mp 136–138 8C (Et2O)]. IR (CHCl3): n 1750 (C O)
and 1780 (C O). 1H NMR (300 MHz, CDCl3): d 2.95 (1H, d,
J = 18.3 Hz, CH2), 3.63 (3H, s, CH3), 4.31 (1H, d, J = 18.3 Hz,
CH2), 5.38 (1H, dd, JHH = 5.0 Hz, JHF = 25.3 Hz, H-4), 5.49
(1H, d, JHH = 5.0 Hz, H-3), 6.70–7.60 M (15H, Ph). 13C NMR
(75 MHz, CDCl3): d 41.6 (CH2), 52.2 (CH3), 63.6 (d,
J = 20.9 Hz, C-4), 81.8 (C-3), 95.4 (d, J = 187.0 Hz, CF),
116.2, 122.2 (C-Ph), 124.5 (d, J = 10.0 Hz, C-Ph), 124.8 (d,
J = 8.5 Hz, C-Ph), 127.8 (d, J = 1.0 Hz, C-Ph), 128.2 (d
J = 1.0 Hz, C-Ph), 128.3 (C-Ph), 128.7 (d, J = 2.0 Hz, C-Ph),
129.2 (C-Ph), 140.5 (d, J = 22.4 Hz, C-Ph), 141.7 (d,
J = 24.9 Hz, C-Ph), 157.9 (C-Ph), 167.5 (C O), 168.4
(C O). 19F NMR (CDCl3): d -166.0, broad singlet. Anal.
calcd. for C25H22FNO4: C, 71.6; H, 5.3; N, 3.3. Found: C, 71.7;
H, 5.3; N, 3.2.
3.5. Methyl 2-[2-[fluoro(diphenyl)methyl]-4-oxo-3,3-
diphenyl-1-azetidinyl]acetate (4d) and methyl 1-(2,2-
diphenylvinyl)-4-oxo-3,3-diphenylazetidine-2-carboxylate
(8)
a. A mixture of methyl 2-(3-fluoro-2,2-diphenylaziridin-1-
yl)acetate (1b) (103 mg, 0.33 mmol), SbF3 (59 mg,
0.33 mmol) and CH2Cl2 (20 mL) was refluxed for 2 h.
SbF3 was filtered off, the solvent was evaporated in vacuo
and the residue treated with diphenylketene (3a) (70 mg,
0.36 mmol) solution in toluene (5 mL). The resulting
solution was refluxed for 1.5 h, then concentrated and
chromatographed on silica to give compound 4d [38 mg,
22%, colorless crystals, mp 197–200 8C (Et2O–CH2Cl2)]
and compound 8 [21 mg (13%), colorless crystals, mp 209–
212 8C (Et2O–CH2Cl2)].
Compound 4d: IR (CHCl3): n 1770 (C O) and 1750
(C O). 1H NMR (300 MHz, CDCl3): d 2.89 (1H, d,
J = 18.3 Hz, CH2), 3.54 (3H, s, CH3), 4.34 (1H, d,
J = 18.3 Hz, CH2), 6.04 (1H, d, J = 27.4 Hz, CH), 6.70–
7.70 (20H, m, Ph). 13C NMR (75 MHz, CDCl3): d 41.6
(CH2), 52.0 (CH3), 67.6 (d, J = 20.0 Hz, C-4), 71.4 (C-3),
95.7 (d, J = 189.5 Hz, CF), 123.7 (d, J = 10.0 Hz, C-Ph),
124.1 (d, J = 11.0 Hz, C-Ph), 126.7, 127.1, 127.2, 127.6 (d,
J = 1.0 Hz, C-Ph), 127.8, 128.1, 128.4 (d, J = 1.5 Hz, C-Ph),
128.5 (C-Ph), 128.7 (d, J = 2.0 Hz, C-Ph), 129.9 (d,
J = 2.5 Hz, C-Ph), 136.8 (d, J = 2.0 Hz, C-Ph), 140.1,
140.7 (d, J = 23.4 Hz, C-Ph), 142.4 (d, J = 25.5 Hz, C-
Ph), 168.5 (C O), 170.6 (C O). 19F NMR (CDCl3): d
À173.3 (d, J = 27 Hz). Anal. calcd. for C31H26FNO3: C,
77.6; H, 5.5; N, 2.9. Found: C, 77.6; H, 5.6; N, 2.7.
Compound 8: IR (CHCl3): n 1760 (C O). 1H NMR
(300 MHz, CDCl3): d 3.10 (3H, s, CH3), 4.60 (1H, s, C-4),
6.70–8.00 M (21H, m, Ph, HC=). 13C NMR (75 MHz,
CDCl3): d 51.6 (CH3), 65.7 (C-4), 71.9 (C-3), 117.1 (=CH),
127.0, 127.2, 127.3, 127.8, 128.1, 128.3, 128.8, 131.0, 136.4,
137.1, 138.6, 139.9, 166.6 (C O), 167.1 (C O). Anal. calcd.
for C31H25NO3: C, 81.0; H, 5.5; N, 3.1. Found: C, 81.1; H,
5.7; N, 3.0.
3.7. cis-4-[Fluoro(diphenyl)methyl]-1-methyl-3-
phenoxyazetidin-2-one (4f)
A mixture of 3-fluoro-1-methyl-2,2-diphenylaziridine (1c)
(20 mg, 0.09 mmol), SbF3 (16 mg, 0.09 mmol) and CH2Cl2
(5 mL) was refluxed for 14 h. SbF3 was filtered off and the
solvent was evaporated in vacuo to give N-(2-fluoro-2,2-
diphenylethylidene)methanamine (2c) (20 mg) as a yellow
oil. 1H NMR (300 MHz, CDCl3):
d
HH = JHF = 1.7 Hz, CH3,), 7.3–7.5 (10H, m, Ph), 8.15 (1H,
3.49 (3H, t,
J
dq, JHH = 1.7 Hz, JHF = 9.8 Hz, CH). 13C NMR (75 MHz,
CDCl3): d 48.0 (CH3), 98.1 (d, JCF = 173.0 Hz, CF), 127.0 (d,
J
CF 3.0 Hz, C-o-Ph), 128.21 (C-p-Ph), 128.23 (d., JCF = 2.5 Hz,
C-m-Ph), 128.5 (d., JCF = 2.0 Hz, C-m-Ph), 139.8 (d.,
CF = 22.7 Hz, C-i-Ph), 164.5 (d, JCF = 32.2 Hz, HC = N).
J

118
A.S. Konev et al. / Journal of Fluorine Chemistry 128 (2007) 114–119
A mixture of 3-fluoro-1-methyl-2,2-diphenylaziridine 1c
chloride (77 mg, 0.45 mmol) were added. The mixture was
stirred at room temperature for 1 d and then washed with
0.02 M aq. Na2CO3 (20 mL). The organic layer was dried over
Na2SO4, filtered, concentrated and the residue was crystallized
from CH2Cl2–Et2O to give compound 4 (70 mg, 47%).
(110 mg, 0.48 mmol), SbF3 (88 mg, 0.49 mmol) and CH2Cl2
(30 mL) was refluxed for 14 h. SbF3 was filtered off and Et3N
(59 mg, 0.58 mmol) and phenoxyacetyl chloride (91 mg,
0.53 mmol) were added to the filtrate. The resulting solution
was stirred at room temperature for 2 d and then washed with
0.02M aq. Na2CO3 (20 mL). The organic layer was dried over
Na2SO4, filtered, concentrated and the residue was crystallized
from ether to give compound 4f [(84 mg, 48%), colorless
crystals, mp 193–196 8C (Et2O–CH2Cl2)]. IR (CHCl3): n 1770
(C = O). 1H NMR (300 MHz, CDCl3): d 2.51 (3H, s, CH3), 4.96
(1H, dd, JHF = 24.1 Hz, JHH = 4.9 Hz, H-4), 5.33 (1H, d,
J = 4.9 Hz, H-3), 6.6–7.6 (15H, m, Ph). 13C NMR (75 MHz,
CDCl3): d 28.1 (CH3), 64.8 (d, J = 21.4 Hz, C-4), 81.6 (C-3),
95.5 (d, J = 186.5 Hz, CF), 116.2, 122.1 (C-Ph), 124.7 (d,
J = 10.0 Hz, C-Ph), 124.9 (d, J = 8.5 Hz, C-Ph), 127.7 (d,
J = 1.3 Hz, C-Ph), 128.0 (d, J = 1.2 Hz, C-Ph), 128.3, 128.7 (d,
J = 1.5 Hz, C-Ph), 129.1, 140.8 (d, J = 22.9 Hz, C-Ph), 142.0
(d, J = 24.7 Hz, C-Ph), 158.0 (C-Ph), 167.3 (C O). 19F NMR
(CDCl3): d -163.9 broad singlet. Anal. calcd. for C23H20FNO2:
C, 76.4; H, 5.6; N, 3.9. Found: C, 76.3; H, 5.6; N, 3.7.
3.10. Reaction of methyl 2-[(2-fluoro-2,2-
diphenylethylidene)amino]acetate (2b) with ketene 3d
A mixture of methyl 2-(3-fluoro-2,2-diphenylaziridin-1-
yl)acetate (1b) (112 mg, 0.39 mmol), SbF3 (64 mg, 0.36 mmol)
and CH2Cl2 (20 mL) was refluxed for 2 h. SbF3 was filtered off
and Et3N (65 mg, 0.64 mmol) and phthalimidoacetyl chloride
(131 mg, 0.59 mmol) were added to the filtrate. The resulting
solution was stirred at 12–16 8C for 2 d and then washed with
0.02 M aq. Na2CO3 (20 mL). The organic layer was dried over
Na2SO4, filtered, concentrated and the residue was crystallized
from Et2O–CH2Cl2 to give methyl 2-phtalimido-2-acetami-
doacetate (5c) [21 mg (19%), colorless crystals, mp 201–
204 8C (Et2O–CH2Cl2)], lit. mp 203–204 8C (H2O) [38].
Acknowledgements
3.8. cis-2-[Fluoro(diphenyl)methyl]-1-methyl-4-
oxoazetidin-3-yl]acetate (4g)
We gratefully acknowledge the Russian Foundation for
Basic Research (project no. 05-03-33257) and the Russian
Foundation for Basic Research—the Government of Flanders
‘‘Bilateral Scientific Cooperation’’ program (project no. 05-03-
34811) for support of this research.
A mixture of 3-fluoro-1-methyl-2,2-diphenylaziridine (1c)
(100 mg, 0.44 mmol), SbF3 (79 mg, 0.44 mmol) and CH2Cl2
(25 mL) was refluxed for 14 h. SbF3 was filtered off and Et3N
(37 mg, 0.37 mmol) and acetoxyacetyl chloride (50 mg,
0.37 mmol) were added to the filtrate. The resulting solution
was stirred at room temperature for 2 d and then washed with
0.02 M aq. Na2CO3 (20 mL). The organic layer was dried over
Na2SO4. Concentration of the solution and purification by
column chromatography on silica gave compound 4g [66 mg
(46%), colorless crystals, mp 179–181 8C (Et2O–CH2Cl2)]. IR
(CHCl3): n 1770 (C = O). 1H NMR (300 MHz, CDCl3): d 1.53
(3H, s, CH3CO), 2.43 (3H, s, CH3N), 4.89 (1H, d,
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