A convenient synthesis and chemical properties of 3-acylamino-6- polyfluoroalkyl-2H-pyran-2-ones

Article abstract of DOI:10.1055/s-2005-865290

A number of 3-acylamino-6-polyfluoroalkyl-2H-pyran-2-ones 3 were synthesized from β-alkoxyvinyl polyfluoroalkyl ketones 1 and N-acylglycines 2 in acetic anhydride in high yield. The reactions of trifluoromethyl- containing 2H-pyran-2-one 3b with O-and N-n

Full text of DOI:10.1055/s-2005-865290

PAPER
1269
A Convenient Synthesis and Chemical Properties of 3-Acylamino-6-poly-
fluoroalkyl-2H-pyran-2-ones
S
ynthesi
g
s
and Propert
o
ies of 3-Acy
r
lamino-6-polyf
I
luoroalk
.
yl-2
H
-pyran
G
-2-ones erus,*a Nataliya A. Tolmachova,a Sergey I. Vdovenko,a Roland Fröhlich,b Günter Haufe*b
a
Institute of Bioorganic Chemistry and Petrochemistry NASU, Murmanska 1, 02094 Kiev, Ukraine
Fax +38(44)5732552; E-mail: igerus@hotmail.com
b
Organisch-Chemisches Institut der Universität Münster, Corrensstraße 40, 48149 Münster, Germany
Fax +49(251)8339772; E-mail: haufe@uni-muenster.de
Received 10 November 2004; revised 21 January 2005
of both physico-chemical properties and bioactivity.7
However, only a few papers devoted to 6-trifluoromethyl-
substituted 2H-pyran-2-ones are available in the litera-
ture.3,4
Abstract: A number of 3-acylamino-6-polyfluoroalkyl-2H-pyran-
2-ones 3 were synthesized from b-alkoxyvinyl polyfluoroalkyl ke-
tones 1 and N-acylglycines 2 in acetic anhydride in high yield. The
reactions of trifluoromethyl-containing 2H-pyran-2-one 3b with O-
and N-nucleophiles were studied and 3-N-benzoylamino-6-hy-
droxy-6-trifluoromethyl-5,6-dihydro-2H-pyran-2-one (13), 3-N-
benzoylamino-6-hydroxy-6-trifluoromethyl-5,6-dihydro-2H-pyri-
din-2-one (14a), and N- and O-substituted 3-(N-benzoylamino)-6-
trifluoromethyl-2H-pyridin-2-ones (15c,e, and 16) were synthe-
sized.
1,3-Dicarbonyl compounds and their derivatives such as
b-(alkoxy, amino)vinyl alkyl ketones are frequently used
as starting materials to synthesize 2H-pyran-2-ones.8 We
systematically investigated the physico-chemical proper-
ties of readily available b-alkoxyvinyl polyfluoroalkyl ke-
tones 1, that may be considered as synthetic equivalents of
trifluoroacetylacetaldehyde.9,10 Several examples demon-
strated the versatile applications of enones 1 to the synthe-
sis of polyfluoroalkyl-containing heterocycles such as
pyrimidines,10,11 imidazopyridines,12 pyrazoles, and isox-
azoles.13 Despite the fact that enones 1 are useful starting
materials for the synthesis of heterocyclic systems,9,14
they have not been used for the synthesis of 6-polyfluoro-
alkyl-2H-pyran-2-ones.
Key words: enones, heterocycles, 2H-pyran-2-ones, 2H-pyridin-2-
ones, aminations, alkylations, trifluoromethyl
The 2H-pyran-2-one ring is often present in various natu-
ral substances1 that are biologically active.2–4 This ac-
counts for the high interest in the chemistry of this
heterocycle. Furthermore, 2H-pyran-2-one containing
compounds are frequently used in organic synthesis as
useful building blocks.5,6 It is well known that the intro-
duction of polyfluoroalkyl groups in heterocyclic systems
is a common and effective instrument for the modification
We report here a new and practical method for the general
synthesis of 3-acylamino-6-polyfluoroalkyl-2H-pyran-2-
ones 3 by condensation of b-alkoxyvinyl polyfluoroalkyl
Scheme 1
SYNTHESIS 2005, No. 8, pp 1269–1278
x
x
.
x
x
.2
0
0
5
Advanced online publication: 07.04.2005
DOI: 10.1055/s-2005-865290; Art ID: T13504SS
© Georg Thieme Verlag Stuttgart · New York

1270
I. I. Gerus et al.
PAPER
ketones 1 and N-acylglycines 2 in acetic anhydride. Also deviations in the 1H NMR spectra of 2H-pyran-2-one 3b
the physico-chemical properties of the synthesized 6- and oxazolone 5b are the upfield shift of the doublet of
polyfluoroalkyl-2H-pyran-2-ones 3 were studied.
corresponding to H-4 of the pyrone ring from 8.4 ppm to
5.7 ppm and the appearance of a new very broad signal at
14.9 ppm. In the 19F NMR spectrum of compound 5b the
signal of the trifluoromethyl group was shifted by only 2
ppm to higher field in comparison to the 2H-pyran-2-one
3b.
Heating of the enones 1a–c and N-acylglycines 2a–h in
acetic anhydride gave the corresponding 3-acylamino-6-
polyfluoroalkyl-2H-pyran-2-ones 3a–j in good yields
(Scheme 1, Table 1). In order to explore the scope and
limitations of the reaction we varied both acyl groups in
N-acylglycines 2 and the polyfluoroalkyl group in enones The NMR and IR spectroscopic data suggest that the enol
1. Thus, the reaction of trifluoromethylenone 1a with hip- tautomer 5b1 is favored in solution, though the structure
puric acid gave the 2H-pyran-2-one 3b in high yield after was also found in the solid state. X-Ray analysis showed
6 hours at 60 °C. The introduction of electron-donating that the C=C double bonds prefer the (Z,Z)-arrangement
substituents onto the benzene ring of hippuric acid facili- due to the stabilization of this structure by an intramolec-
tated the reaction (shorter reaction time for 2H-pyran-2- ular hydrogen bond between the hydroxyl group neigh-
ones 3c–e), while electron withdrawing substituents delay boring the trifluoromethyl group and the nitrogen atom of
the product formation (longer reaction time for 2H-pyran- the oxazolone ring (Figure 1).
2-ones 3f–h) (Table 1).
It is noteworthy that oxazolone 5b is not stable at elevated
As a key step in the synthesis of 2H-pyran-2-ones 3a–k, temperature. Compound 5b is completely converted to the
in acetic anhydride, we postulated the formation of inter- 2H-pyran-2-one 3b in good yield after heating in toluene
mediate oxazolones 4a–h from N-acylglycines 2a–h. at 70 °C for several hours. This fact explains the absence
These activated methylene compounds subsequently un- of oxazolones 5 in reaction mixtures of pyrones 3a–j.
dergo a C–C coupling reaction with the enones 1a–c. Ear-
lier a similar suggestion was made for the reaction of 1,3-
Therefore, the correlation of the reaction time with the
yield of 2H-pyran-2-ones 3a–j with respect to the nature
diketones with N-acylglycines in the presence of triethyl
of the R¢ group in N-acylglycines 2a–g may be explained
orthoformate.15 However, we did not observe oxazolones
by the influence of the R¢ group either on the formation of
5 in the reaction mixtures by 19F NMR spectroscopy.
intermediate oxazolones 4a–g or its reactivity in the nu-
cleophilic substitution of the ethoxy group of enones 1a–
c with subsequent formation of intermediates 5. Thus, in
the case of a strong electron-withdrawing substituent
(R¢ = 3-NO2C6H4) the reaction needed harsher conditions
(Table 1) and a mixture of products 3a (R¢ = CH3) and 3g
(R¢ = 3-NO2C6H4) was formed. This is a result of trans-
acylation of the hippuric acid (2g) to aceturic acid (2a) un-
der prolonged heating in acetic anhydride. The reaction of
enone 1a with aceturic acid (2a) gave the 2H-pyran-2-one
3a in low yield even under forced conditions as compared
to hippuric acid 2b (Table 1).
We monitored the reaction progress by 19F NMR because
the signals of polyfluoroalkyl groups of enones 1a–c and
Figure 1 Crystal structure of (4Z)-2-phenyl-4-[(2Z)-4,4,4-trifluoro-
3-hydroxybut-2-enylidene]-1,3-oxazol-5(4H)-one (5b).
pyrones 3a-j are quite different, e.g. the signal of the tri-
The oxazolone 5b, which can exist in two tautomeric
forms 5b1 and 5b2 can be obtained through a different
pathway, by heating the 2H-pyran-2-one 3b with potassi-
um hydroxide in DMF and subsequent acidification
fluoromethyl group of enone 1a shifted from –79.25 ppm
by 8–9 ppm to lower field as the result of the formation of
2H-pyran-2-ones 3a–h (Table 2). By this method we de-
tected the formation of the desired pyrone 3l from 4-nitro-
hippuric acid (2l) and enone 1a in only 10% yield after
heating at 80 °C for 160 hours. This product was not iso-
lated from the reaction mixture.
19
13
(Scheme 2). From the 1H, F, and C NMR spectra it is
observed that the chemical shifts of oxazolone 5b are
quite similar to those of 2H-pyran-2-one 3b. Significant
CF3
CF3
i. KOH, DMF, 60 °C
ii. H2O, 7% HCl
95%
O
NHCOPh
O
H
N
N
70 °C, toluene
CF3
O
O
Ph
O
Ph
O
O
O
3b
5b2
5b1
Scheme 2
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

PAPER
Synthesis and Properties of 3-Acylamino-6-polyfluoroalkyl-2H-pyran-2-ones
1271
We also used other fluorinated enones 1b,c (Scheme 1,
Table 1) in order to estimate the influence of different
polyfluoroalkyl groups. The substitution of one fluorine
atom with chlorine in trifluoromethyl group, (1b), or the
longer perfluoroalkyl group of 1c did not influence the
yield of corresponding pyrones 3i,j. A comparison of the
reactivity of fluorinated enone 1a and its parent non-fluo-
rinated enone 1d was also carried out under the same re-
action conditions. The pyrone 3k was obtained in only 2%
yield after work up and column chromatography. This
shows a strong activation of the carbonyl group by elec-
tron-withdrawing substituents such as polyfluoroalkyl
groups is needed to facilitate the reaction.
NMe2
Ac2O, 80 °C
15%
+
3b
2b
CF3
O
6
Scheme 3
The replacement of the ethoxycarbonyl group by a trifluo-
roacetyl group (more electron-withdrawing group) at the
a-position of enone 7 accelerated the reaction even fur-
ther. Thus, the enone 9 and the N-acylglycines 2b and 2h
gave the products 11a,b even at room temperature
(Scheme 5). In the 19F NMR spectra of the reaction mix-
ture two pairs of signals corresponding to the trifluoro-
methyl groups were observed in a variable ratio. One of
the pairs are consistent with quartets at –60.2 and –83.4
ppm, and the others are singlets at –65.6 and –74.8 ppm.
However, after work-up we obtained only the products
with quartet signals in high yield. This fact can be easily
explained by initial formation of the keto-form of pyrones
10a,b in acetic anhydride. These compounds were easily
transformed to the hydrate-forms 11a,b upon addition of
a water molecule to the carbonyl group directly connected
to the trifluoromethyl group. It can be deduced from the
19F NMR spectra that this reaction is accompanied by both
downfield shift of the 6-trifluoromethyl group signal as a
result of decreased electron-withdrawing influence of the
CF3C(OH)2 group in comparison to the CF3C(O) group
and upfield shift of the 5-trifluoroacetyl group signal,
which is typical for a-trifluoromethyl-hem-diol forma-
tion. In the 1H NMR spectra of compounds 11a,b the char-
acteristic singlet of H-4 on the 2H-pyran-2-one ring at 8.8
ppm, broad singlets of the NH proton at 9.2 ppm, and two
hem-hydroxyl protons at 7.4 ppm were observed.
The structure of the synthesized 2H-pyran-2-ones 3a–k
was confirmed by elemental analysis, IR, and NMR spec-
tra (Tables 1 and 2). The 1H NMR spectra of compounds
3a–k were characterized by doublets for H-4 and H-5 of
the 2H-pyran-2-one ring found at 8.5 and 6.8 ppm (8.35
and 6.09 ppm for the methyl substituted pyrone 3k), re-
spectively, with a cis-vicinal coupling constant of ~7 Hz
as well as a broad singlet for the NH group at 8.8 ppm.
The reaction of non-fluorinated enamino ketones with
hippuric acid was used earlier for the synthesis of 2H-py-
ran-2-ones,16 but in our case the 2H-pyran-2-one 3b was
obtained in low yield from the enamino ketone 6 and hip-
puric acid (2b) (Scheme 3).
Insertion of an electron-withdrawing substituent at the a-
position of the enone 1a enhances the reactivity. Thus,
from the enone 7, the 2H-pyran-2-ones 8 were obtained in
high yield under milder conditions compared to the reac-
tions of 1. The enone 7 was reacted with N-acylglycines
such as hippuric acid (2b) or N-thienoylglycine (2h) but
also with 4-nitrohippuric acid (2l) for several hours at
60 °C (Scheme 4). The structure of the synthesized py-
rones 8a–c was confirmed by elemental analysis, IR, and
The insertion of electron-withdrawing substituents such
as polyfluoroalkyl groups into the 2H-pyran-2-one ring
increased the sensitivity of the heterocycle towards nu-
cleophilic attac, which is usually used in synthetic meth-
ods based on non-fluorinated 2H-pyran-2-one systems.17
As an example of the reactions of 3-acylamino-6-poly-
fluoroalkyl-2H-pyran-2-ones 3 with O- and N-nucleo-
philes, alkaline hydrolysis and aminolysis of the
trifluoromethyl-2H-pyran-2-one 3b have been studied.
1
NMR spectra (Tables 1 and 2). In the H and 19F NMR
spectra of compounds 8a–c the characteristic singlet of H-
4 of the 2H-pyran-2-one at 8.6 ppm, the broad singlet of
the proton of the NH group at 8.7 ppm, the usual signals
of the protons of the ethoxy group, and the signal of the
trifluoromethyl group at about –65 ppm were observed.
Analysis of the 19F NMR spectra of the reaction mixtures
proved the high regioselectivity of the reaction, only sig-
nals of the 2H-pyran-2-ones 8a–c were observed.
Although oxazolone 5b formed under anhydrous condi-
tions (DMF, KOH, 60 °C), the effect of an aqueous medi-
Scheme 4
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

1272
I. I. Gerus et al.
PAPER
Scheme 5
Scheme 6
um was studied. The pyrone 3b was dissolved in aqueous In the case of ammonia and 2-methoxyethylamine inter-
1 N NaOH and a yellow solution of salt 12 is proposed to mediate hydroxypyridones 14a,b were obtained, whereas
form. This structure is analogous to that of a salt obtained in the other cases the formation of corresponding hy-
before from the parent 2H-pyran-2-one.18 In the 19F NMR droxypyridones was only detected in the reaction mix-
spectrum of the crude salt 12 the signal corresponding to tures by 19F NMR spectroscopy. The characteristic signal
the trifluoromethyl group at –78.0 ppm was observed. Af- of the trifluoromethyl group of intermediate dihydropyri-
ter careful acidification of the solution to pH ca. 3 with 6 dones 14 was usually observed at –82 ppm to –85 ppm,
N HCl, hydroxypyrone 13 precipitated, the formation of while for the final pyridones 15 signals at approximately
the corresponding hydroxypyridones was detected as a 20 ppm lower field were found.
white friable solid (Scheme 6). The hemiacetal structure
was confirmed by elemental analysis, IR, and NMR spec-
troscopic data (Tables 1 and 2).
In the 19F NMR spectrum of compound 13 the signal of high yield (90%) by heating 2H-pyran-2-one 3b with 2-
the trifluoromethyl group was observed at –85.17 ppm methoxyethylamine in toluene at 90 °C for 10 hours. The
and in the 1H NMR spectrum the typical ABX system of structures of hydroxypyridones 14a,b were confirmed by
vicinal protons of methylene and ethylene groups was ob- elemental analysis, IR, and NMR spectra (Tables 1
served as well as the aromatic signals of the benzoyl and 2). In the 1H NMR spectra of hydroxypyridones 14a,b
group. The enantiotopic protons of the methylene group a typical ABX system of vicinal protons corresponding to
Compound 14a was obtained in low yield (15%) by heat-
ing the pyrone 3b and ammonia in methanol at 60 °C for
four hours, whereas hydroxypyridone 14b was formed in
(neighboring the stereogenic carbon atom) give a pair of the methylene and ethylene groups was observed, similar
1
doublet of doublets at 3.24 ppm and 3.00 ppm with 2JHH
=
to that of the hydroxypyrone 13. Moreover, in the H
19 Hz and 3JHH = 2.5 Hz and 6.7 Hz. Olefinic and aromatic
protons do partially overlap and appear as complicated
multiplets. Also, two broad singlets corresponding to the
OH and NH protons were observed at 8.0 ppm and 8.8
ppm, respectively.
6-Trifluoromethyl-containing pyridones are of interest as
potential pharmaceutical and agrochemical products.19
The nucleophilic reactions of 2H-pyran-2-ones with
amines have often been used for the synthesis of pyri-
dones and intermediates similar in structure to the salt 12
formed.20 We studied the reaction of pyrone 3b with vari-
ous amines and found that the structure of products de-
pends on the nature of amines and the reaction conditions
(Scheme 7).
Scheme 7
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

PAPER
Synthesis and Properties of 3-Acylamino-6-polyfluoroalkyl-2H-pyran-2-ones
1273
NMR spectrum of hydroxypyridone 14b the ABXY-sys- 5 of pyridine and pyridone rings are observed at 8.52 ppm
tem of protons typical for an NCH2CH2 group was found. and 6.82 ppm, or 8.88 ppm and 7.33 ppm, respectively.
The singlet of the methyl group of the N-alkylation prod-
uct was observed at 3.74 ppm, whereas the singlet of the
methoxy group of pyridine 16 appeared at 4.12 ppm.
The hydroxypyridone 14b was completely converted to
the pyridone 15b by heating in acetic acid. Compounds
15a,b can be obtained in one step by prolongation of the
reaction time and elevated reaction temperature. In this In summary, we have disclosed new general approaches
manner we obtained pyridones 15a–e by the reaction of to 3-acylamino-6-polyfluoroalkyl-2H-pyran-2-ones 3 by
2H-pyran-2-one 3b with various amines (Scheme 7). The condensation reaction of N-acylglycines 2 with readily
pyridones 15a–e were obtained in good yields by heating available b-alkoxyvinyl polyfluoroalkyl ketones 1 in ace-
2H-pyran-2-one 3b with aqueous ammonia or alkyl- tic anhydride. We found that strong activation of the car-
amines, whereas the reaction with benzylamine gave a bonyl group of enones 1 by electron-withdrawing
mixture of products, which contained the pyridone 15e as substituents such as polyfluoroalkyl groups and the intro-
the main product. In 19F NMR spectra of pyridones 15a–e duction of electron-donating substituents onto the ben-
one singlet representative of the trifluoromethyl group zene ring of hippuric acid are needed to facilitate the
1
was observed at –59 ppm to –63 ppm; in the H NMR reaction. Moreover, we investigated the reactions of the
spectra characteristic doublets for H-4 and H-5 of the py- synthesized 2H-pyran-2-ones 3 with some O- and N-nu-
ridone ring were found at 8.8 ppm and 7.4 ppm, respec- cleophiles. Also the regioselectivity of alkylations of 3-
tively, with
a
cis-vicinal coupling-constant of benzoylamino-6-trifluoromethylpyridone-2 15a was stud-
approximately 7.5 Hz. Moreover, a broad singlet appeared ied. High yields and simple preparation of the new com-
at around 9.2 ppm typical of NH.
pounds and opens the possibility for their application as
building blocks to synthesize biologically active com-
pounds bearing a polyfluoroalkyl unit.
Pure compound 15e was also obtained by benzylation of
pyridone 15a in high yield (Scheme 8). In this case the re-
gioselectivity of the reaction is high and we obtained only
the isomer resulting from N-alkylation of the endocyclic
nitrogen atom. The 1H and 19F NMR spectra of substance
15e obtained from pyrone 3b (Scheme 7) or from pyri-
done 15a (Scheme 8) were identical. This result differs
significantly from the earlier observed O-alkylation of 2-
oxo-6-trifluoromethylpyridine-3-carbonitrile with benzyl
bromide.21
Melting points are uncorrected. NMR spectra were recorded at 300
MHz (1H), 75.4 MHz (13C), and 283.3 MHz (19F) on a Varian VXR-
300 or at 400 MHz (1H) and 100.6 MHz (13C) on a Bruker AMX-
400 instrument in CDCl3 solution (if not stated otherwise). TMS
(1H), CDCl3 (13C), or CCl3F (19F) were used as internal standards.
IR spectra were recorded on a Specord M-80 spectrometer. Column
chromatography was performed on silica gel 60 (Merck). Starting
materials were of the highest commercial quality and were used
without further purification. The following compounds were pre-
pared according to literature methods: 4-ethoxy-1,1,1-trifluoro-
but-3-en-2-one,21 1-chloro-4-ethoxy-1,1-difluoro-but-3-en-2-one,22
1-ethoxy-4,4,5,5,6,6,6-heptafluoro-hex-1-en-3-one,22 ethyl 3-
ethoxy-2-(2,2,2-trifluoro-acetyl)-acrylate,23 3-ethoxymethylene-
Atlhough there is a precedent for N-benzylation, with
benzyl bromide, of pyridone 15a at the endocyclic nitro-
gen atom,21 the reaction with methyl iodide gave a mix-
ture of products of both N-methylation at the endocyclic
nitrogen atom (pyridone 15c) and O-methylation at the
lactam oxygen atom (pyridine 16) in a ratio of 70:30
(Scheme 8). The products 15c and 16 were separated by
column chromatography and fully characterized by spec-
troscopic methods. Spectral data of the products 15c and
16 are quite different. Thus, in the 19F NMR spectra the
signal corresponding to the trifluoromethyl group of pyri-
1,1,1,5,5,5-hexafluoro-pentane-2,4-dione,24
4-(dimethylamino)-
1,1,1-trifluoro-3-buten-2-one.25 All compounds have satisfactory
elemental analysis data: C 0.30, H 0.20, N 0.30.
Pyrones 3a–j, 8a–c, 11a,b; General Procedure
A mixture of N-acylglycines 2a–m (10 mmol) and enones 1a–c, 7,
or 9 (10 mmol) in Ac2O (12 mL) was stirred at 20–130 °C for 2–120
h. When the reaction had reached completion (monitored by
done 15c and pyridine 16 were observed at –63.6 ppm and 19F NMR spectroscopy) Ac2O was evaporated (30–40 °C; 30–60
–68.4 ppm, respectively. In the 1H NMR spectra, the sig-
mmHg). The residue was treated with a mixture of hexane–Et2O
(3:1) and the product was purified as described in Table 1. Yield, re-
action conditions, physical constants, and NMR data are shown in
nal of the NH of pyridone 15c appeared at lower field
(9.34 ppm) compared to the corresponding signal of pyri-
Tables 1 and 2.
dine 16 (8.51 ppm); characteristic doublets for H-4 and H-
Scheme 8
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

1274
I. I. Gerus et al.
PAPER
2-Oxo-6-trifluoromethyl-2H-pyran-3-yl-N-benzamide (3b)
A mixture of hippuric acid (2b) (1.00 g, 5.58 mmol) and the enam-
ino ketone 4 (0.93 g, 5.58 mmol) in Ac2O (10 mL) was stirred at
130 °C for 120 h. When the reaction had reached completion (mon-
itored by 19F NMR spectroscopy) Ac2O was evaporated (30–40 °C;
30–60 mmHg). The residue was purified by column chromatogra-
phy (silica gel; EtOAc–hexane, 1:1; Rf 0.3) to furnish 3b in 15%
yield (0.199 g). The physical constants and NMR data agree with
those of the pyrone 3b obtained from enone 1a.
washed with water, air-dried, and crystallized from toluene. Yield,
physical constants, and NMR data are shown in Tables 1 and 2.
1,2-Dihydro-1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridinyl-
N-benzamide (15c)
In a tube with a teflon-lined screw cap a mixture of pyrone 3b (0.50
g, 1.76 mmol) and 25% aq solution of NH2Me (7 mL) was heated at
110 °C for 8 h. After cooling the solid was filtered, washed with wa-
ter (20 mL), hexane (10 mL; careful 15c is soluble in hexane) and
crystallized from toluene–hexane (3:1). Yield, physical constants,
and NMR data are shown in Tables 1 and 2.
2-Phenyl-4-(4,4,4-trifluoro-3-hydroxybut-2-enylidene)-4H-ox-
azol-5-one (5b)
A mixture of pyrone 3b (0.50 g, 1.76 mmol) and KOH (0.22 g, 4.08
mmol) was stirred in anhyd DMF (5 mL) at 60 °C for 2 h. When the
reaction had reached completion, the mixture was poured into ice-
water (5 mL) and adjusted to pH 3 with 7% HCl. The precipitated
yellow solid was filtered, washed with water, air-dried, and dis-
solved in MeOH (5 mL). The solution was kept in refrigerator for 1
d while the product 5b crystallized. Yield, physical constants, and
NMR data are shown in Tables 1 and 2.
1-Butyl-1,2-dihydro-2-oxo-6-(trifluoromethyl)-3-pyridinyl-N-
benzamide (15d)
In a tube with teflon-lined screw cap a mixture of pyrone 3b (0.50
g, 1.76 mmol) and BuNH2 (2 mL) was heated at 110 °C for 8 h. The
excess BuNH2 was removed in vacuum, and the residue was crys-
tallized from hexane. Yield, physical constants, and NMR data are
shown in Tables 1 and 2.
1-Benzyl-1,2-dihydro-2-oxo-6-(trifluoromethyl)-3-pyridinyl-N-
benzamide (15e)
A mixture of pyrone 3b (0.25 g, 0.88 mmol) and BnNH2 (0.20 g,
1.86 mmol) was heated at 140 °C for 16 h. After termination of the
reaction the crude product was purified by column chromatography
(silica gel; EtOAc–hexane, 1:2) as an eluent (Rf 0.5). Yield, physi-
cal constants, and NMR data are shown in Tables 1 and 2.
5,6-Dihydro-6-hydroxy-2-oxo-6-(trifluoromethyl)-2H-pyran-3-
yl-N-benzamide (13)
The pyrone 3b (1.00 g, 3.53 mmol) was dissolved in 1 N NaOH (25
mL) at r.t. The pH of the yellow solution which formed was careful-
ly adjusted to pH 6 with 7% HCl. The white precipitate formed was
filtered, washed with water, and crystallized from MeCN (the re-
crystallization temperature should not exceed 50 °C). Yield, physi-
cal constants, and NMR data are shown in Tables 1 and 2.
1,2-Dihydro-1-methyl-2-oxo-6-(trifluoromethyl)-3-pyridinyl-
N-benzamide (15c) and 2-Methoxy-6-(trifluoromethyl)-3-py-
ridinyl-N-benzamide (16)
1,2,5,6-Tetrahydro-6-hydroxy-1-methyl-2-oxo-6-(trifluoro-
methyl)-3-pyridinyl-N-benzamide (14a)
To a solution of pyridone 15a (0.25 g, 0.89 mmol) in anhyd acetone
(20 mL) MeI (0.57 g, 4.07 mmol), K2CO3 (0.56 g, 4.07 mmol) and
KI (0.02 g, 1.21 mmol) were added. The reaction mixture was
stirred at 15 °C for 12 h. The insoluble salts were filtered off and
washed with acetone (10 mL). The organic layers were combined,
acetone was evaporated, the residue was washed with hexane (10
mL), and purified by column chromatography (silica gel; CHCl3–
hexane, 1:2; 15c Rf 0.4; 16 Rf 0.3). Yields of 15c and 16 were 0.11
g (43%) and 0.05 g (18%), respectively. Physical constants and
NMR data are shown in Tables 1 and 2.
The pyrone 3b (1.00 g, 3.53 mmol) was dissolved in MeOH (10
mL) and NH3 (2.00 g, 0.12 mmol) was bubbled through the solu-
tion, which was then heated at 90 °C in a sealed tube for 5 h. The
solvent was evaporated and the residue was crystallized from
MeCN. Yield, physical constants, and NMR data are shown in
Tables 1 and 2.
1,2,5,6-Tetrahydro-6-hydroxy-1-(2-methoxyethyl)-2-oxo-6-(tri-
fluoromethyl)-3-pyridinyl-N-benzamide (14b)
In a tube with teflon-lined screw cap a mixture of pyrone 3b (0.50
g, 1.76 mmol) and 2-methoxyethylamine (0.13 g 1.76 mmol) in tol-
uene (5 mL) was heated at 90 °C for 2 h. After termination of the
reaction toluene was evaporated and the resulting oil was purified
by column chromatography (silica gel; CHCl3–EtOAc, 1:1). Yield,
physical constants, and NMR data are shown in Tables 1 and 2.
1-Benzyl-1,2-dihydro-2-oxo-6-(trifluoromethyl)-3-pyridinyl-N-
benzamide (15e) (from pyridone 15a)
To a solution of pyridone 15a (1.00 g, 3.54 mmol) in anhyd acetone
(20 mL), BnBr (0.74 g 4.07 mmol), K2CO3 (0.56 g 4.07 mmol) and
KI (0.02 g, 1.21 mmol) were added. The reaction mixture was
stirred at 15 °C for 20 h. The insoluble salts were filtered off and
washed with acetone (10 mL). The acetone layers were combined,
the solvent was evaporated, the residue was washed with hexane (20
mL), and crystallized from toluene. The yield of 15e was 0.60 g
(45%). Physical constants and NMR data are shown in Tables 1 and
2.
1,2-Dihydro-2-oxo-6-(trifluoromethyl)-3-pyridinyl-N-benz-
amide (15a)
In an open flask a solution of pyrone 3b (0.50 g, 1.76 mmol) in 25%
aq solution of NH3 (25 mL) was stirred at 100 °C for 6 h (water
bath), while the volume of the reaction mixture was reduced to
about 5 mL. Another portion of 25% aq solution of NH3 (25 mL)
was added, after which heating and stirring was continued until the
volume of the reaction mixture reduced to ca. 5 mL. Then water (20
mL) was added and the precipitate was filtered, washed with water,
and crystallized from MeCN–CHCl3 (3:1). Yield, physical con-
stants, and NMR data are shown in Tables 1 and 2.
X-Ray Structure
(4Z)-2-Phenyl-4-[(2Z)-4,4,4-trifluoro-3-hydroxybut-2-
enylidene]-1,3-oxazol-5(4H)-one (5b)
Formula C13H8F3NO3, M = 283.20, yellow crystal 0.45 × 0.15 ×
0.10 mm, a = 6.591(1), b = 13.365(1), c = 13.615(1) Å,
b = 101.12(1)°, V = 1176.8(2) Å3, rcalcd = 1.598 gcm–3, m = 12.76
cm–1, empirical absorption correction (0.598 £ T £ 0.883), Z = 4,
monoclinic, space group P21/n (No. 14), l = 1.54178 Å, T = 223 K,
w and f scans, 6759 reflections collected ( h, k, l), [(sinq)/
l] = 0.59Å–1, 1991 independent (Rint = 0.043) and 1522 observed
reflections [I ≥ 2s(I)], 183 refined parameters, R1 = 0.041,
wR2 = 0.115, max residual electron density 0.19 (–0.22) eÅ–3, hy-
drogens calculated and refined as riding atoms.
1,2-Dihydro-1-(2-methoxyethyl)-2-oxo-6-(trifluoromethyl)-3-
pyridinyl-N-benzamide (15b)
In a tube with teflon-lined screw cap a mixture of pyrone 3b (0.50
g, 1.76 mmol) and 2-methoxyethylamine (0.13 g, 1.76 mmol) in
HMPA (2 mL) was heated at 140 °C for 5 h. Then the solution was
poured onto cold water (50 mL) and the precipitate was filtered,
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

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Synthesis and Properties of 3-Acylamino-6-polyfluoroalkyl-2H-pyran-2-ones
1275
Table 1 Physical Properties and Reaction Conditions for Compounds 3a–k, 5, 8a–c, 11a,b, 13, 14a,b, 15a–e, 16
Compound
Time (h)/T (°C) Yield (%)
Mp (°C), (solvent)
149a
IR (CHCl3 or KBr) (cm–1)
3a
60/120
30
80
75
65
75
40
2817, 1729 1704, 1517, 1375, 1352, 1312, 1201, 1156,
1087
3b
3c
3d
3e
3f
6/60
179
(toluene)
3392, 1640, 1578, 1534, 1481, 1376, 1320, 1272, 1184,
1160, 1125, 1073
6/60
165
(toluene)
3400, 2968, 1729, 1684, 1520, 1504, 1353, 1312, 1238,
1200, 1154, 1080
5/60
180
(toluene)
3402, 3020, 1729, 1680, 1608, 1526, 1504, 1352, 1312,
1256, 1212, 1176, 1154, 1080, 1032
3/60
194
(toluene)
3404, 1733, 1680, 1601, 1506, 1464, 1352, 1312, 1272,
1240, 1199, 1178, 1156, 1100, 1082, 1024
20/60
205
(toluene)
3399, 1731, 1688, 1596, 1580, 1519, 1488, 1356, 1312,
1237, 1200, 1156, 1096, 1083
3g
3h
3i
120/80
120/80
10/60
10
20
60
169a
181a
3390, 1733, 1691, 1523, 1352, 1312, 1234, 1158, 1084
3390, 1733, 1703, 1525, 1352, 1312, 1250, 1187, 1104
3452, 3106, 1745, 1700, 1598, 1576, 1287, 1168, 1127
163
(toluene)
3j
10/80
65
138
3399, 3020, 1733, 1687, 1600, 1576, 1518, 1352, 1287,
1238, 1192, 1168, 1123, 1096, 1072
(CHCl3–hexane, 2:1)
3k
5b
140/80
2/120
2
133a
3403, 1709, 1672, 1524, 1252
93
90b
(MeOH)
3403, 3040, 1800, 1656, 1624, 1600, 1564, 1338, 1289,
1192, 1155
8a
8b
5/20
8/20
6/20
30/20
35/20
–
90
81
80
61
74
60
137
(toluene)
3400, 1732, 1689, 1520, 1492, 1383, 1346, 1299, 1248,
1168, 1112, 1032
138
(toluene)
3402, 1753, 1706, 1527, 1525 1350, 1344, 1251, 1182,
1100
8c
136
(toluene)
3400, 1735, 1693, 1525, 1384, 1344, 1298, 1248, 1169,
1111, 1032
11a
11b
13
131b
(CHCl3)
3318, 3143, 2824, 2320, 2176, 1736, 1634, 1600, 1576,
1524, 1368, 1340, 1261, 1075, 1016
135b
(CHCl3)
3402, 3143, 2818, 2320, 1753, 1600, 1527, 1565 1353,
1344, 1260, 1082, 1047
136b
3355, 3200, 3112, 1736, 1646, 1608, 1584, 1538, 1496,
(MeCN)
1448, 1416.0, 1360, 1321, 1240, 1196, 1144, 1096, 1064,
1023
14a
6/100
15
192b
(MeCN)
3388, 3216, 3103, 2516, 2344, 1700, 1632, 1580, 1528,
1493, 1458, 1419, 1346, 1307, 1239, 1176, 1156, 1082,
1064, 1048
14b
15a
15b
2/90
55
70
60
93b,c
3388, 1643, 1524, 1492, 1452, 1440, 1412, 1386, 1362,
1341, 1187, 1154, 1099
–
–
245b
3392, 2825, 2174, 1640, 1578, 1534, 1481, 1376, 1320,
1272, 1240, 1184, 1160, 1125, 1073, 1000
(MeCN–CHCl3, 3:1)
91
(toluene)
3372, 3010, 2932, 1683, 1654, 1616, 1582, 1568, 1522,
1492, 1460, 1432, 1375, 1336, 1308, 1206, 1190, 1134,
1096, 1072, 1004
15c
–
80
131
3363, 3083, 1880, 1680, 1648, 1599, 1536, 1451, 1400,
(toluene–hexane, 3:1) 1379, 1322, 1288, 1232, 1176, 1115, 1064
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

1276
I. I. Gerus et al.
PAPER
Table 1 Physical Properties and Reaction Conditions for Compounds 3a–k, 5, 8a–c, 11a,b, 13, 14a,b, 15a–e, 16 (continued)
Compound
Time (h)/T (°C) Yield (%)
Mp (°C), (solvent)
IR (CHCl3 or KBr) (cm–1)
15d
–
60
88
(hexane)
3368, 2964, 2872, 2176, 1680, 1650, 1616, 1564, 1536,
1488, 1472, 1431, 1371, 1306, 1237, 1216, 1192, 1176,
1136, 1112, 1080
15e
16
–
–
45
18
117
(toluene)
3430, 1658, 1553, 1450, 1398, 1225, 1155, 1150
84d
3490, 1700, 1550, 1498, 1421, 1400, 1277, 1120, 1101
a Chromatographed by EtOAc–hexane, 1:2 as eluent.
b With decomposition.
c Chromatography (CHCl3–EtOAc, 1:1).
d Chromatography (CHCl3–hexane, 1:2).
Table 2 NMR Spectral Data of Compounds 3a–k, 5, 8a–c, 11a,b, 13, 14a,b, 15a–e, 16
Compound
19F NMR (d, ppm)
1H NMR (d, ppm)
13C NMR (d, ppm)
3a
–70.71 (s)
8.30 (d, J = 7.3 Hz, 1 H), 8.11 (s, 1 H), 6.78 (d, 169.68, 157.10, 141.00 (q, J = 40.0 Hz), 128.12,
J = 7.3 Hz, 1 H), 2.26 (s, 3 H)
119.89, 117.96 (q, J = 271 Hz), 106.71 (q, J =
4.0 Hz), 24.67
3b
3c
3d
3e
3f
–71.05 (s)
–70.61 (s)
–70.59 (s)
–70.00 (s)
–71.00 (s)
–70.40 (s)
8.82 (s, 1 H), 8.49 (d, J = 7.5 Hz, 1 H), 7.93 (m, 166.22, 157.41, 141.15 (q, J = 40.0 Hz), 133.98,
2 H), 7.55 (m, 3 H), 6.84 (d, J = 7.5 Hz, 1 H)
133.04, 129.12, 128.39, 127.30, 119.86, 113.83
(q, J = 271.0 Hz), 106.75 (q, J = 4.0 Hz)
8.79 (s, 1 H), 8.47 (d, J = 7.5 Hz, 1 H), 7.83 (d, 166.18, 157.11, 141.08 (q, J = 40.0 Hz), 130.04,
J = 8.5 Hz, 2 H), 7.54 (d, J = 8.5 Hz, 2 H), 6.82 128.45, 127.18, 126.07, 125.51, 119.68, 118.20
(d, J = 7.5 Hz, 1 H), 1.36 (s, 9 H)
(q, J = 271.0 Hz), 106.76, 35.19, 30.06
8.73 (s, 1 H), 8.44 (d, J = 7.5 Hz, 1 H), 7.87 (d, 165.69, 163.52, 157.49, 140.89 (q, J = 40.0 Hz),
J = 8.7 Hz, 2 H), 7.00 (d, J = 8.7 Hz, 2 H), 6.82 129.31, 128.58, 125.15, 119.37, 118.25 (q, J =
(d, J = 7.5 Hz, 1 H), 3.88 (s, 3 H)
271.0 Hz), 114.34, 106.85 (q, J = 4.2 Hz), 55.60
8.76 (s, 1 H), 8.45 (d, J = 7.5 Hz, 1 H), 7.46 (m, 169.87, 157.11, 149.11, 141.87 (q, J = 40.0 Hz),
2 H), 6.95 (d, J = 7.4 Hz, 2 H), 6.83 (d, J = 7.5
Hz, 1 H), 3.97 (s, 6 H)
128.17, 119.79, 119.60, 118.25 (q, J = 271.0
Hz), 106.85 (q, J = 4.2 Hz), 55.60
8.73 (s, 1 H), 8.44 (d, J = 7.5 Hz, 1 H), 7.83 (d, 165.10, 157.18, 141.22 (q, J = 40.0 Hz), 139.47,
J = 9.2 Hz, 2 H), 7.50 (d, J = 9.2 Hz, 2 H), 6.80 129.34, 128.60, 128.46, 120.08, 117.91 (q, J =
(d, J = 7.5 Hz, 1 H)
270.1 Hz), 106.60 (q, J = 4.0 Hz)
3g
8.85 (s, 1 H), 8.76 (s, 1 H), 8.49 (d, J = 7.7 Hz, 163.89, 157.16, 148.67, 141.81 (q, J = 40.0 Hz),
2 H), 7.83 (d, J = 9.2 Hz, 2 H), 8.2 (d, J = 7.7 Hz, 134.67, 132.70, 130.39, 127.88, 127.34, 122.65,
1 H), 7.77 (t, J = 8.0 Hz, 1 H), 6.86 (d, J = 7.7
121.02, 118.09 (q, 271.0), 106.61 (q, J = 4.2 Hz)
Hz, 1 H)
3h
3i
–70.35 (s)
–56.00 (s)
8.63 (s, 1 H), 8.38 (d, 7.5, 1 H), 7.69 (d, J = 3.8 165.10, 157.18, 141.22 (q, J = 40.0 Hz), 139.47,
Hz, 1 H), 7.65 (d, J = 5.1 Hz, 1 H), 7.30 (dd, J = 137.26, 131.79, 128.46, 124.00, 117.91 (q, J =
5.1, 3.8 Hz, 1 H), 6.82 (d, J = 7.5 Hz, 1 H).
270.1 Hz), 106.60 (q, J = 4.0 Hz)
8.80 (s, 1 H), 8.47 (d, J = 7.5 Hz, 1 H), 7.89 (m, 162.27, 153.44, 141.27, 129.09, 125.37 (t, J =
2 H), 7.56 (m, 3 H), 6.78 (d, J = 7.5 Hz, 1 H)
62.8 Hz), 125.15, 123.95, 123.32, 116.24,
115.96 (t, J = 287.2 Hz), 101.02 (t, J = 5.1 Hz)
3j
–80.95 (t, J = 9.2
Hz, 3 F), –117.77
(q, J = 9.2 Hz, 2 F),
–127.14 (s, 2 F)
8.81 (s, 1 H), 8.51 (d, J = 7.5 Hz, 1 H), 7.89 (m, 166.31, 157.40, 140.94 (t, J = 29.8 Hz), 133.03,
2 H), 7.59 (m, 3 H), 6.85 (d, J = 7.5 Hz, 1 H)
129.15, 128.44, 127.34, 119.98, 109.25 (signals
of carbon atoms of polyfluoropropyl group are
overlapping multiplets)
3k
5b
–
8.61 (s, 1 H), 8.35 (d, J = 7.2 Hz, 1 H), 7.87 (m, 164.23, 158.69, 153.16, 131.72, 130.33, 126.88,
2 H), 7.53 (m, 3 H), 6.08 (d, J = 7.2 Hz, 1 ), 2.26 125.03, 122.49, 121.11, 101.97, 17.36
(s, 3 H)
–72.76 (s)
14.95 (s, 1 H), 8.02 (m, 2 H), 7.60 (m, 3 H), 6.82 166.39, 159.52, 153.00 (q, J = 33.3 Hz), 134.47,
(d, J = 8.9 Hz, 1 H), 5.72 (d, J = 8.9 Hz, 1 H)
129.33, 128.98, 128.20, 127.17, 127.13, 119.87,
(q, J = 274.4 Hz), 95.56 (q, J = 4.0 Hz)
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

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Synthesis and Properties of 3-Acylamino-6-polyfluoroalkyl-2H-pyran-2-ones
1277
Table 2 NMR Spectral Data of Compounds 3a–k, 5, 8a–c, 11a,b, 13, 14a,b, 15a–e, 16 (continued)
Compound
19F NMR (d, ppm)
1H NMR (d, ppm)
13C NMR (d, ppm)
8a
–65.00 (s)
8.75 (s, 1 H), 8.68 (s, 1 H), 7.89 (m, 2 H), 7.56
(m, 3 H), 4.40 (q, J = 7.3 Hz, 2 H), 1.39 (t, J =
7.3 Hz, 3 H)
166.20, 162.23, 156.13, 141.14 (q, J = 43.9 Hz),
133.18, 132.79, 129.11, 127.56, 127.27, 120.51,
117.89 (q, J = 277.8 Hz), 115.96, 63.15, 13.53
8b
8c
–65.06 (s)
–65.01 (s)
8.59 (s, 1 H), 8.56 (s, 1 H) 7.70 (d, J = 3.8 Hz, 1 162.80, 160.95, 156.34, 141.82 (q, J = 43.9 Hz),
H), 7.67 (d, J = 5.0 Hz, 1 H), 7.18 (dd, J = 5.0, 137.90, 133.28, 130.29, 128.67, 127.65, 120.88,
3.8 Hz, 1 H), 4.40 (q, J = 7.3 Hz, 2 H), 1.38 (t, 118.24 (q, J = 277.8 Hz), 116.22 (q, J = 2.3 Hz),
J = 7.3 Hz, 3 H) 63.19, 14.08
8.75 (s, 1 H), 8.68 (s, 1 H) 7.64 (d, J = 8.7 Hz, 2 164.70, 162.41, 156.39, 152.17, 141.14 (q, J =
H), 7.50 (d, J = 8.7 Hz, 2 H), 4.41 (q, J = 7.3 Hz, 43.9 Hz), 136.70, 134.92, 129.11, 127.56,
2 H), 1.39 (t, J = 7.3 Hz, 3 H)
125.72, 121.96, 116.89 (q, J = 277.8 Hz),
116.12, 63.15, 13.53
11aa
11ba
–60.21 (s),
–83.32 (s)
9.14 (s, 1 H), 8.89 (s, 1 H), 8.01 (m, 2 H), 7.59
(m, 3 H), 7.40 (s, 2H )
167.39, 157.29, 142.27 (q, J = 40.8 Hz), 134.76,
134.19, 133.89, 130.14, 128.94, 128.78, 125.95,
124.36, 123.79 (q, J = 288.3 Hz), 93.59 (q, J =
40.8 Hz),
–60.30 (s),
–83.41 (s)
8.90 (s, 1 H), 8.77 (s, 1 H), 7.85 (d, J = 3.9 Hz, 161.18, 146.89, 142.25, (q, J = 40.8 Hz),
2 H), 7.36 (s, 2 H), 7.60 (d, J = 3.9 Hz, 2 H)
134.76, 134.19, 133.89, 130.14, 128.94, 128.78,
128.51, 124.36, 123.79 (q, J = 288.3 Hz), 93.59
(q, J = 40.8 Hz)
13a
–85.17 (s)
–84.42 (s)
8.79 (s, 1 H), 8.01 (s, 1 H), 7.95 (m, 2 H), 7.53
(m, 4 H), 3.23 (dd, J = 18.7, 3.3 Hz, 1 H), 3.00
(dd, J = 18.7, 6.1 Hz, 1 H)
165.44, 162.00, 133.54, 132.05, 129.15, 129.69,
127.97, 126.53, 122.13 (q, J = 290.0 Hz),
116.63, 81.49 (q, J = 29.6 Hz)
14aa
8.90 (s, 1 H), 8.23 (s, 1 H), 7.89 (m, 2 H), 7.56
165.23, 162.12, 134.74, 132.27, 129.19, 129.14,
(m, 3 H), 7.42 (dd, J = 5.3, 3.5 Hz, 1 H) 6.68 (s, 127.49, 126.66, 124.03 (q, J = 286.0 Hz),
1 H), 3.17 (dd, J = 18.5 Hz, 3.5, 1 H), 3.00 (dd, 114.63, 81.41 (q, J = 29.6 Hz)
J = 18.5, 5.3 Hz, 1 H)
14ba
–82.23 (s)
8.80 (s, 1 H), 7.87 (m, 2 H), 7.54 (m, 3 H), 7.40 165.60, 161.63, 134.14, 131.92, 128.67, 126.87,
(dd, J = 6.2, 3.4 Hz, 1 H), 5.81 (s, 1 H), 4.23 (m, 126.46, 123.00 (q, J = 290.0 Hz), 113.2, 82.96
1 H), 3.65 (m, 1 H), 3.57 (m, 1 H) 3.45 (s, 3 H) (q, J = 29.6 Hz), 69.21, 59.06, 41.52, 31.59
3.14 (dd, J = 18.7, 6.2 Hz, 1 H), 2.82 (dd, J =
18.7, 3.4 Hz, 1 H)
15aa
15b
–60.00 (s)
–63.10 (s)
11.61 (s, 1 H), 9.24 (s, 1 H), 8.63 (d, J = 7.8 Hz, 166.36, 159.97, 135.00, 133.70, 132.51, 128.90,
1 H), 8.01 (m, 2 H), 7.72 (m, 3 H), 7.06 (d, J =
7.8 Hz, 1 H)
128.44 (q, J = 37.0 Hz), 127.27, 118.80 (q, J =
191.1 Hz), 118.53, 100.03 (q, J = 6.1 Hz)
9.33 (s, 1 H), 8.51 (d, J = 7.8 Hz, 1 H), 7.94 (m, 166.36, 157.92, 137.43, 135.00, 133.70, 132.51,
2 H), 7.66 (m, 3 H), 6.83 (d, J = 7.8 Hz, 1 H),
4.36 (t, J = 6.9 Hz, 2 H), 3.68 (t, J = 6.9 Hz, 2
H), 3.37 (s, 3 H)
128.88 (q, J = 38.0 Hz), 127.27, 120.80 (q, J =
191.1 Hz), 118.53, 108.64 (q, J = 6.1 Hz), 68.94,
59.20, 45.89
15c
15d
–62.04 (s)
–62.38 (s)
9.34 (s, 1 H), 8.52 (d, J = 7.8 Hz, 1 H), 7.93 (m, 166.00, 158.01, 134.00, 132.49, 132.35, 128.89
2 H), 7.53 (m, 3 H), 6.82 (d, J = 7.8 Hz, 1 H),
3.74 (s, 3 H)
(q, J = 38.0 Hz), 128.92, 127.30, 120.15 (q, J =
272.0 Hz), 118.35, 108.18 (q, J = 6.1 Hz), 32.58
9.38 (s, 1 H), 8.51 (d, J = 7.8 Hz, 1 H), 7.94 (m, 164.11, 155.69, 131.76, 130.46, 130.05, 127.00
2 H), 7.52 (m, 3 H), 6.83 (d, J = 7.8 Hz, 1 H), (q, J = 30.0 Hz), 126.79, 125.21, 118.20 (q, J =
4.11 (t, J = 8.3 Hz, 2 H), 1.74 (m, 2 H), 1.46 (m, 272.0 Hz), 116.31, 106.34 (q, J = 6.1Hz), 45.20,
2 H), 1.00 (t, J = 7.6 Hz, 3 H) 28.28, 18.12, 11.43
15e
16
–59.87 (s)
–68.18 (s)
9.18 (s, 1 H), 8.88 (d, J = 7.7 Hz, 1 H), 7.96 (d, 165.80, 152.30, 136.19, 134.02, 132.49, 132.35,
J = 8.0 Hz, 2 H), 7.58 (m, 6 H), 7.36 (m, 2 H),
7.40 (d, J = 7.7 Hz, 1 H), 5.58 (s, 2 H)
129.17, 127.76 (q, J = 38 Hz), 128.66, 127.30,
127.08, 126.22, 125.74, 121.58 (q, J = 274.0
Hz), 114.86 (q, J = 6.1 Hz), 69.01
8.89 (d, J = 7.5 Hz, 1 H), 8.52 (s, 1 H), 7.90 (m, 165.93, 152.73, 138.23 (q, J = 35.5 Hz), 134.06,
2 H), 7.59 (m, 3 H), 7.34 (d, J = 7.5 Hz, 1 H),
132.46, 128.98, 127.15, 125.87, 125.65, 121.47
4.12 (s, 3 H)
(q, J = 274.0 Hz), 114.62 (q, J = 3.2 Hz), 54.54
a NMR spectra were obtained for solution in acetone-d6.
Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York

1278
I. I. Gerus et al.
PAPER
Crystallographic data (excluding structure factors) for the reported
structure have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-254022. Cop-
ies of the data can be obtained free of charge on application to The
Director CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [Fax:
+44(1223)336033, E-mail:deposit@ccdc.cam.ac.uk].
(6) Ram, V. J.; Srivastava, P.; Agarwal, N.; Sharon, A.; Maulik,
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Acknowledgment
(9) Gerus, I. I.; Gorbunova, M. G.; Kukhar, V. P. J. Fluorine
Chem. 1994, 69, 195.
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Financial support by the International Association Foundation (IN-
TAS-UA-95-0005), the Deutsche Forschungsgemeinschaft (Gradu-
iertenkolleg ’Hochreaktive Mehrfachbindungssysteme’) and the
NRW Graduate School of Chemistry is gratefully acknowledged.
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Synthesis 2005, No. 8, 1269–1278 © Thieme Stuttgart · New York