Novel synthesis, reactivity, and stereochemistry of substituted 3-trifluoromethyl- and 3-perfluoroalkyl-3-phenoxyprop-2-enal

Article abstract of DOI:10.1021/jo060764i

Substituted 3-phenoxy-3-perfluoroalkylprop-2-enals 3a-s are synthesized in high yields starting from a gem-iodoacetoxy derivative 1 and phenoxides 2. Then efficient syntheses of push-pull derivatives 4, 5, 8a,b, and nonconjugated analogues 6 and 7 illustrate the synthetic potentialities of 3. Stereochemical studies of these perfluoroalkyl-containing trisubstituted olefinic derivatives 3-8b revealed that the ⁴J_CF coupling constant observed in the ¹³C NMR spectra was crucial in the determination of their configurations and conformations in solution. The solvent polarity effect on the stereochemistry of push-pull compounds 3-5 and 8a,b was studied. Unusual significant medium polarity effect on the stereochemistry of imino enol ether derivative 4 was observed.

Full text of DOI:10.1021/jo060764i

Novel Synthesis, Reactivity, and Stereochemistry of Substituted
3-Trifluoromethyl- and 3-Perfluoroalkyl-3-phenoxyprop-2-enal
Salem El Kharrat, Philippe Laurent,* and Hubert Blancou
Organisation Mole´culaire EVolution et Mate´riaux Fluore´s, UniVersite´ Montpellier II,
Pl. E. Bataillon, 34095 Montpellier Cedex 05, France
philippe.laurent@uniV-montp2.fr
ReceiVed April 11, 2006
Substituted 3-phenoxy-3-perfluoroalkylprop-2-enals 3a-s are synthesized in high yields starting from a
gem-iodoacetoxy derivative 1 and phenoxides 2. Then efficient syntheses of push-pull derivatives 4, 5,
8a,b, and nonconjugated analogues 6 and 7 illustrate the synthetic potentialities of 3. Stereochemical
4
studies of these perfluoroalkyl-containing trisubstituted olefinic derivatives 3-8b revealed that the JCF
coupling constant observed in the 13C NMR spectra was crucial in the determination of their configurations
and conformations in solution. The solvent polarity effect on the stereochemistry of push-pull compounds
3-5 and 8a,b was studied. Unusual significant medium polarity effect on the stereochemistry of imino
enol ether derivative 4 was observed.
Introduction
years, considerable attention has been given to the development
of new procedures for the synthesis of fluorine-containing syn-
thons, for example, trifluoromethylated â-chloroenones (ClCHd
C(Ar)COCF3 and ClC(CF3)dCHCOAr)3,4 or the â-alkoxyvinyl
R,â-Unsaturated carbonyl derivatives substituted in the
â-position with good leaving groups (chloro or alkoxy) serve
as convenient building blocks for synthesis of different classes
of acyclic, carbocyclic, and heterocyclic compounds.1,2 In recent
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Weissenfels, M. Tetrahedron Lett. 1991, 32, 643. (b) Kirsch, G.; Prim, D.;
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10.1021/jo060764i CCC: $33.50 © 2006 American Chemical Society
Published on Web 08/10/2006
6742
J. Org. Chem. 2006, 71, 6742-6752

Substituted Trifluoromethyl and Perfluoroalkyl Enals
trifluoromethyl ketones (ROCHdCHCOCF3).5,6 Generally,
nucleophiles attack the â-carbon atom with elimination of the
alkoxy group7,8 or chloride anion;3,4 therefore, those enones are
fluorinated keto aldehyde chemical analogues and are exten-
sively used for the synthesis of various trifluoromethylated
compounds which are often used in both medicine and agri-
cultural chemistry.9,10
In connection with our interest in the synthesis of perfluoro-
alkylated reactive intermediates,11-13 we report a convenient
synthesis of substituted 3-perfluoroalkyl-3-phenoxyprop-2-enal
3a-s starting from 1-iodo-2-perfluoroalkylethyl acetate 1.12,14
It must be remarked that compounds 1 are activated chemical
equivalents of aldehydes. Then we prepared compounds 4-8,
which were isolated in the course of our exploration of the
chemistry of 3. Because of the difficulties establishing the
stereochemistry of derivatives, such as 3-8, we were interested
in developing a general easy method for the determination of
the configuration of these new compounds by measurement of
coupling constants observed by NMR spectroscopy.
Fluorine-fluorine and fluorine-proton NMR spin-spin
coupling constants (JFF and JHF) have become powerful probes
for structural and stereochemical analysis of molecules in the
fields of chemistry and biology.18a The through-space transmis-
sion of a spin-spin coupling between spatially proximate nuclei
has been studied both experimentally18b and theoretically.18c
Unusually large long-range couplings between carbon and
fluorine atoms (nJCF) connected by more than three chemical
bonds have been reported in some aromatic molecules,19 for
example, 5-fluorophenanthrene and tetrafluoronaphthoxepin
derivatives.18b,19,20
Introduction of a trifluoromethyl or perfluoroalkyl group may
be accompanied by changes in spatial and electronic structure
and may consequently affect the spectral parameters.9,21,22 Often
during the synthesis of trifluoromethyl- or perfluoroalkyl-
containing vinyl compounds, both configurational isomers Z and
E are produced simultaneously. In the case of olefinic com-
pounds bearing a vinylic trifluoromethyl group, determination
of the Z or E configuration is based on the comparison between
the coupling constant of fluorine atoms and a vicinal vinylic
proton (4JHF (Z) > 4JHF (E)) or the coupling observed between
fluorine atoms and the olefinic carbon (3JCF (Z) > 3JCF (E)).23-26
However, the comparison between these coupling constants
(4JHF and 3JCF) is not sufficient to attribute the right configura-
tions because they are often hardly observable, especially in
the case of substituted trifluoromethylated olefins.27 Therefore,
Until now, most spectroscopic investigations of the relation-
ship between spatial structure and spectral parameters of
unsaturated conjugated compounds have been carried out by
comparison of chemical shifts15 or by absorption spectros-
copy.16,17
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El Kharrat et al.
SCHEME 2. Mechanisms of Formation of 3a-s
SCHEME 1. Synthesis of 3-(R1-R2-R3-Phenoxy)-3-perfluoro-
alkylprop-2-enal 3a-s
it is desirable to develop a new method based on NMR coupling
constants which has a more general applicability to the wide
range of perfluoroalkyl-containing vinyl compounds.
Synthesis of Substituted 3-Phenoxy-3-perfluoroalkylprop-
2-enal 3
The reaction of 1 with phenoxides 2 was studied, and the
optimum conditions to obtain 3a-s were 1:3 molar mixtures
of 1 and 2 in alkane solvents, such as hexane or petroleum ether
(Scheme 1).
Under such conditions, enals 3 were the major fluorinated
product in the crude mixture (the reaction was monitored by
19F NMR spectroscopy). At the end of the reaction, a simple
work up procedure (washing with 1% sodium hydroxide aqueous
solution) eliminated the excess of phenols. Final products 3 were
easily purified by silica gel column chromatography and were
obtained as a mixture of EE and ZE stereoisomers, which turned
out to be not separable except in the case of 3o and 3p (see
Supporting Information). In the case of 3f, the E isomer
precipitates in hexane at -10 °C to yield pure E-propenal. All
propenals 3a-k and 3s were obtained in high yields at room
temperature. Longer reaction times or higher temperature (40-
80 °C) were sometimes required in the presence of a strong
electron-withdrawing substituent on the aromatic rings of 3n-
p. In the case of compounds 3q and 3r, no reaction occurred
under our conditions; this could be explained by the steric bulk
of the corresponding aryl or heteroaryloxides.
The mechanism of formation of 3 could be explained by a
transesterification which occurs between the phenoxide anion
and the acetate group, leading to the elimination of the iodine
atom and formation of an aryl-OAc, which was isolated and
identified. Then elimination of HF yields a fluorinated propenal
intermediate, which by an oxa-Michael addition-elimination
mechanism 3′ (nucleophilic vinylic substitution)33-35 or by a
six-membered cyclic plane mechanism occurring between the
phenolate group, a sodium atom, and propenal intermediate 3′′
gives 3 (Scheme 2). Participation of the ortho- or para-
substituent by conjugation could favor this mechanism. Previous
reports on the nucleophilic additions to activated olefins describe
a concerted mechanism with a six-center transition state
stabilized by hydrogen bonds.34,35 A similar situation was found
during the addition of phenolate to double bonds with a great
influence on the substituents on the para-position.35
These reactions (Table 1) were found to be stereoselective;
a higher degree of EE stereoselectivity was obtained in most
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6744 J. Org. Chem., Vol. 71, No. 18, 2006

Substituted Trifluoromethyl and Perfluoroalkyl Enals
4
TABLE 1. Synthesis and JC1F Coupling Constants Observed for Substituted 3-Phenoxy-3-perfluoroalkylprop-2-enals 3a-s
a Stereoisomeric ratio determined by 19F NMR directly at the end of the reactions. b Determined by 19F NMR analysis; NMR yield based on consumed
c 4
1 and formed 3.
J
(ZE) ) 0 Hz. d Reaction conditions: 4 h at 20 °C. e Reaction conditions: 24 h at 40 °C. f Reaction conditions: 48 h at 80 °C.
C1F
SCHEME 3. Possible Stereoisomers of Phenoxypropenals
SCHEME 4. Stereochemical Assignment of 3d EE and ZE
3a-s
Using Coupling Constants
substituents on one end of a CdC double bond and with one or
two electron-accepting substituents at the other end. Allowance
for electron delocalization leads to the central CdC bond
becoming more polarized and with a lower barrier to rota-
tion.28,29 The push-pull effect is of decisive influence on both
the dynamic behavior and the chemical reactivity of this class
of compounds.30 These olefins are often involved in isomeric
equilibrium, which can be driven by heat,29a light,29 medium
polarity,28,31 or concentration.28,29 It is expected that each isomer
3a-s can be described in term of Z/E isomerism for the C2dC3
double bond and around the C1-C2 geometry (Scheme 3 and
4).
of the reactions reported, although steric hindrance favors
exclusively the EE isomer (2-naphthoxy, 3s). The role of the
electronic effect of substituents on the phenyl group appears
also to be important (compare 3o and 3p with 3d and 3f and
3g, 3h, and 3i). Finally, the prevalence of the ZE stereoisomer
could be explained by the occurrence of 3′′ transition state
(Scheme 2).
According to the literature, compounds 3a-s can be char-
acterized as push-pull ethylene derivatives.28-30 Push-pull
alkenes are substituted alkenes with one or two electron-donating
The change of solvent did not affect the EE/ZE ratio; how-
ever, we observed a thermal isomerization of the stereoisomeric
mixture in solution, and the percentage of the thermodynamically
favored EE isomer increased.28b
J. Org. Chem, Vol. 71, No. 18, 2006 6745

El Kharrat et al.
FIGURE 2. 1H NMR spectra of a mixture of EE and ZE isomers of
3d showing the aldehydic protons.
SCHEME 5. Synthesized Derivatives 4-8b
FIGURE 1. 1H-Decoupled 13C NMR spectra of a mixture of EE and
ZE isomers of 3d showing the aldehydic carbons.
To establish the Z/E configurations of the double bond of
5
3a-s, we compared the JHF coupling constant (0.5-1.5 Hz
for the E isomer and 0 Hz for the Z isomer) between the
aldehydic proton and the vinylic CF2 or CF3 group and the 3JCF
coupling constant between the carbon 2 and the fluorine atom
of the perfluoroalkyl group.26,27 These couplings were not
observed in all cases and are therefore not general.
of the ZE isomer, the difference being due to the interaction of
the adjacent CF3 group (quartet, 5JHF ) 1.5 Hz for the E isomer)5
(Figure 2).
Then we focused our attention on the measurement of the
4JCF coupling constant between the aldehydic carbon atom and
the fluorine atom of the CF3 or the CF2 groups. We observed
that in all cases (3a-s), for the EE isomer, the 4JCF was about
8.3-9 Hz, and no coupling was obtained for the ZE isomer
(Table 1). Concerning the conformation around C1-C2, the
In the course of our studies on the reactivity of compounds 3
and the applications of the 4JCF coupling constant for total stereo-
chemical assignments, we prepared compounds 4-8b, which
are obtained in high yields and are isolated after simple work
up procedures without further purification (Schemes 5-8).
For example, we found that enal 3c reacts easily with aniline
and forms imine derivative 4 with good yields (94%) (Scheme
6). Previously, the reaction of aniline with alkoxy vinyl ketones
was studied, precluding a mechanism that involves a Michael
addition of aniline with subsequent elimination of the alkoxy
group and led to the corresponding enamino enone.28b,32 In such
enol ethers, the nucleophilic replacement of the alkoxy group
is the predominant reaction.7,8 In our case, only 1,2-addition
product was observed probably because of steric hindrance of
the perfluoroalkyl group and the high conjugation of compound
4. To our knowledge, imino enol ether compounds have not
been described yet in the literature.
3
measured JH1H2 (around 8 Hz)15 proved the E geometry for
every compound 3a-s.
Some reports describe the determination of configuration of
R,â-unsaturated carbonyl compounds bearing a vinylic per-
fluoroalkyl group by comparison of the 19F NMR chemical
shifts. Authors found that chemical shifts of E isomers are higher
than those of Z isomers.7 We reached the same conclusions for
3a-s (Table 1).
Enals 3 are stable compounds compared to their alkoxy or
chloro trifluoromethylated analogues, which decompose easily.32
To our knowledge, no examples of such fluorinated â-phenoxy-
enals have been mentioned in the literature.
Concerning the push-pull olefinic derivative 4, the 1H NMR
spectra showed clearly the presence of a single isomer in
nonpolar solvent, such as benzene. In more polar solvent, such
as chloroform or acetonitrile, the NMR data are consistent with
the compound existing as an equilibrium mixture of two stereo-
isomers (Table 2).
The stereochemistry of the trisubstituted double bond of 4
was established by 13C and 19F NMR spectroscopy using 4JC1F
coupling constant observed between carbon 1 and fluorine
atoms. In nonpolar media (benzene), the coupling constant
observed between carbon 1 and fluorine atoms of the perfluoro-
alkyl chain (4JC1F ) 5.9 Hz) suggests a cis relationship between
The NMR spectra of 3d (R3 ) OMe and RF ) CF3) are
typical and will be commented upon in detail. The 13C NMR
signals at 187.9 and 188.1 ppm correspond, respectively, to the
aldehydic carbons of E and Z isomers. The difference is due to
the coupling with fluorine atoms of the adjacent trifluoromethyl
4
group in the case of isomer EE (quartet, JC1F ) 8.3 Hz)
1
(Scheme 4 and Figure 1). Moreover, the H NMR signals at
5.4 and 10 ppm represent, respectively, the vinylic and the
aldehydic protons of isomer EE, and the signals at 6 and 9.6 ppm
are due to the other isomer (Scheme 4). The assignments of
signals at 9.6 and 10 ppm are evident: the EE isomer, which
has the signals for its aldehyde proton at lower field than those
6746 J. Org. Chem., Vol. 71, No. 18, 2006

Substituted Trifluoromethyl and Perfluoroalkyl Enals
SCHEME 6. Synthesis and Determination of Stereochemistry of Compounds 4 and 5a
a 4: R1 ) R2 ) R3 ) H, RF ) C5F11; 5: R1 ) R2 ) H, R3 ) OMe, RF ) C5F11.
SCHEME 7. Synthesis and Stereochemical Assignments of Nonconjugated Derivatives 6 and 7
SCHEME 8. Synthesis and Assignments of Stereochemical Isomers of 2-Trifluoromethyl- and
2-Perfluoropentyl-N,N′-diphenyl-1,5-diazapentadienes 8a and 8ba
a 8a: starting from 3d, R1 ) R2 ) H, R3 ) OMe, RF ) CF3; 8b: starting from 3c, R1 ) R2 ) R3 ) H, RF ) C5F11.
these two groups and indicates an E configuration (Table 2).
probably the interaction between the two phenyl groups could
Moreover, the coupling constant obtained between proton 1 and
favor the very fast and highly pronounced ratio change of the
solvent-dependent EE/ZE equilibrium of 4. Finally, the absence
of the s-cis or Z conformation in the stereoisomeric forms of
compounds 3 and 4 suggests that the presence of s-cis
conformers is mainly governed by the tendency of formation
of an intramolecular hydrogen bond apparent in nonpolar
solvents15,29,30 (e.g., compounds 8a,b).
Moreover, enals 3 react with phosphonate carbanions. For
example, condensation of triethylphosphonoacetate with a
mixture EE and ZE of 3f was conducted in methanol, and the
phosphonate carbanion was generated by sodium hydride in situ.
The Wadsworth-Emmons product is obtained, and the conju-
gated ester derivative 5 is isolated as a single stereoisomer in
very high yields (>98%) (Scheme 6). There has been interest
in conjugated unsaturated systems, such as polyenes, as a
consequence of the physiological behavior exhibited by repre-
sentatives of these systems.2c,36 They have also been shown in
3
proton 2, JH1H2 ) 9 Hz, indicates a trans disposition of these
two protons and therefore an E conformation around the Nd
C-CdC single bond.15
In polar media (acetonitrile), a mixture of EE and ZE forms
is obtained with strong prevalence of the ZE stereoisomer. The
absence of coupling between carbon 1 and fluorine atoms of
4
the perfluoroalkyl chain, JC1F ) 0 Hz, on one hand and the
3
coupling observed between proton 1 and proton 2, JH1H2
)
9.1 Hz, permitted us to establish the configuration of the C2d
C3 double bond as Z and to completely assign without ambiguity
the stereochemistry of the preponderant isomer of 4 (Table 2).
The medium effect on the stereochemistry of compound 4 is
very significant and could be explained by the influence of the
solvent polarity on the CdC barrier to rotation. Very few works
deal with the solvent polarity effect on the stereochemistry of
such derivatives.31 However, according to literature, the more
polar the solvent, the lower the corresponding barrier to rotation,
which favors isomerizations of push-pull ethylene com-
pounds.28,31 In comparison with that of 3, the electronic conju-
gation on the phenyl group relative to the imine function and
(36) (a) Ogawa, Y.; Maruno, M.; Wakamatsu, T. Heterocycles 1995, 4,
2587. (b) Baeckstrom, P.; Jacobsson, U.; Norin, T.; Unelius, C. R.
Tetrahedron 1988, 44, 2541.
J. Org. Chem, Vol. 71, No. 18, 2006 6747

El Kharrat et al.
TABLE 2. Determination of the Content of Isomeric Forms and Stereochemistry in Solutions of 4-7 by NMR Coupling Constant
3
(4JC1F and JH1H2
)
C6D6
4JCIF (Hz)
CDCl3
4JCIF (Hz)
CD3CN
4JCIF (Hz)
compound
isomers
%
3JH1H2 (Hz)
%
3JH1H2(Hz)
%
3JH1H2 (Hz)
4
EE
ZE
99
1
5.7
0
9
8.8
85
15
5.9
0
9
8.9
8
92
5.7
0
9.2
8.8
C6D6 or CD3CN
%
4JC3F (Hz)
3JH2H3 (Hz)
15.1
3JH3H4 (Hz)
12
5
6
EEE
100
6.4
C6D6 or CDCl3
%
4JC1F (Hz)
3JH1H2 (Hz)
Z
E
5
95
0
6.6
6.1
6.8
C6D6 or CDCl3
%
4JC3F (Hz)
3JH1H2 (Hz)
7
E
100
8
7.5
many cases to serve as effective synthons in the construction
of a wide variety of interesting molecules, such as retinoid
analogues.37
alcohol 6 as a mixture of stereoisomers (Scheme 7). This
reaction was run with complete conversion. The two stereo-
isomers of 6 were differentiated using the four-bond carbon-
4
The stereochemistry of the Wadsworth-Emmons product 5
is shown to be EEE based on the coupling constants observed
fluorine coupling JC1F; the difference observed between the
coupling constants of the sp3 carbon 1 and the fluorine atoms
(4JC1F ) 6.6 Hz for the E isomer and 0 for the Z isomer) allowed
us to clearly assign the configuration of the double bond of 6
(Table 2).
3
4
(3JH2H3, JH3H4, and JC3F) (Table 2). The configuration of the
1
C2dC3 double bond of 5 was established as E by H NMR
coupling constants (3JH2H3 ) 15.1 Hz). On the other hand, the
coupling observed between C3 and fluorine atoms of the per-
fluoroalkyl group in the 13C NMR spectrum (4JC3F ) 6.4 Hz)
suggest a cis relationship between these two groups and allowed
us to assign without ambiguity the configuration of the tri-
substituted olefin C4dC5 as E (Table 2). Finally the E or s-trans
conformation of the CdCH-CHdC moiety is proved by the
coupling constant of the H3-H4 atoms (3JH3H4 ) 12 Hz).
The stereochemistry of 5 was unaffected when the solvent
was changed from benzene to chloroform or acetonitrile. Our
results are in accord with reported works for similar systems.26,38
Compounds 3, 4, and 5 are all trisubstituted conjugated
Interestingly, the allylic alcohol obtained 6 is very stable in
acidic media even in concentrated acids. This proves that the
fluorinated groups provide greater stability to such molecules
since enol ethers of nonfluorinated 1,3-dicarbonyl analogues
undergo, after reduction, an allylic rearrangement when treated
with aqueous acids and give mainly unsaturated ketones.41
On heating in ethanol in the presence of p-toluenesulfonic
acid, triethyl orthoformate reacts with enal 3f to give (E)-acetal
7 in 86% yield (Scheme 7). The coupling constants observed
between the sp3 carbon 1 and fluorine atoms permitted us to
establish the stereochemistry of the double bond of this com-
pound (4JC1F ) 8 Hz for the E isomer) (Table 2). This coupling
constant relationship can be used to determine the configura-
tional assignments not only in the mixture of two stereoisomers
but also in the case where only one isomer is obtained. In con-
trast, the use of other coupling constant (nJCF, n < 4) needs the
presence of a mixture of stereoisomers identified by comparison
of the obtained values.
This compound 7, which is less sensitive to moisture than
its nonfluorinated analogues,42 was isolated and could be used
further in synthesis. In contrast, the other â-dicarbonyl deriva-
tives give under similar conditions regioisomers which are
difficult to separate.43
Because derivatives 6 and 7 are unconjugated, there must be
a contribution of the through-space transmission of the coupling.
This behavior can be attributed to structural features, such as
changes in the bond angles, hybridization due to steric hindrance,
and through-space orbital interactions.18
4
4
olefinic derivatives. The coupling constants JC1F and JC3F
observed for 3, 4, and 5 are mainly transmitted through chemical
bonds. Previous results have shown that coupling between
carbon or proton and fluorine atoms occurs with significant
contribution of the through-bond components when strong
π-conjugation intervenes between coupled centers.39 Likewise,
other molecular systems might exhibit exclusive through-space
coupling via the contribution of fluorine lone pairs and fluorine
core orbitals.40
4
To investigate whether the JCF correlation established for
conjugated derivatives 3, 4, and 5 is still reliable for noncon-
jugated perfluoroalkyl chain-containing vinylic systems, we
synthesized compounds 6 and 7 starting from propenals 3.
Reduction of perfluoroalkyl enal 3f by sodium borohydride
in methanol afforded, after usual treatment, the corresponding
(37) (a) Anastasia, L.; Xu, C.; Negishi, E. Tetrahedron Lett. 2002, 43,
5673. (b) Bellina, F.; Biagetti, M.; Carpita, A.; Rossi, R. Tetrahedron 2001,
57, 2857.
(38) Segre, A.; Zetta, L.; Di Corato, A. J. Mol. Spectrosc. 1969, 32,
296.
Besides the configurational assignments of perfluoroalkyl-
containing vinyl compounds and to verify if the through-space
(39) Peralta, J. E.; Barone, V.; Ruiz de Azua, M. C.; Contreras, R. H.
Mol. Phys. 2001, 99, 655.
(40) (a) Peralta, J. E.; Contreras, R. H.; Snyder, J. P. Chem Commun.
2000, 2025. (b) Bryce, D. L.; Wasylishen, R. E. J. Am. Chem. Soc. 2000,
122, 11236.
(41) (a) Gannon, W. F.; House, H. O. Org. Synth. 1960, 40, 14. (b) Stiles,
M.; Longroy, A. Tetrahedron Lett. 1961, 10, 337.
(42) Pohland, A. E.; Benson, W. R. Chem. ReV. 1964, 64, 161.
(43) Pashkevich, K. I.; Saloutin, V. I.; Postovskii, I. Ya. Russ. Chem.
ReV. 1981, 50, 180.
6748 J. Org. Chem., Vol. 71, No. 18, 2006

Substituted Trifluoromethyl and Perfluoroalkyl Enals
TABLE 3. Conformational and Configurational Assignments of Compounds 8a and 8b Using Coupling Constants JC3F, JH2H3, and JH3NH
4
3
3
C6D6
DMSO-d6
δCF2,CF3
(ppm)
4JC3F
(Hz)
3JH2H3
(Hz)
3JH3NH
(Hz)
δCF2,CF3
(ppm)
4JC3F
(Hz)
3JH2H3
(Hz)
3JH3NH
(Hz)
compound
isomer
%
%
8a
ZZE
EEE
ZZE
EEE
64
36
28.5
71.5
-62.3
-66.6
-107.8
-109.5
0
3.5
0
7.9
14
8.2
10*
14
0
100
0
-65.8
3
13.7
13.7
12.3
12.4
8b
10a
14
5.2
13.9
100
-109.6
5.5
a Broad doublet.
SCHEME 9. Mechanism of Formation of 2-Perfluoropentyl-N,N′-diphenyl-1,5-diazapentadiene 8b
4JCF coupling constant could be used for the determination of
conformational preferences, we synthesized the dissymmetric
imino enamine derivatives 8a,b.
The reaction of 3c or 3d with 2 equiv of aniline in refluxing
dichloromethane gives the corresponding N,N′-diphenyl-1,5-
diazapentadienes 8a and 8b with elimination of their phenoxy
groups in 94 and 96% yields, respectively (Scheme 8).
To reveal the mechanism of formation of 8a,b, we monitored
the reaction of 3c with 2 equiv of aniline by 19F NMR spec-
troscopy and TLC. We observed that NMR signals which were
assigned to 4 (Scheme 9) appear quite quickly during the
reaction and after 1 h disappear to give new peaks corresponding
to 8b (Scheme 9). This observation leads us to the conclusion
that compound 4 is the intermediate of the synthesis of
diazapentadiene 8b.
exchange between them at room temperature.44 The stereo-
chemistry of these compounds was determined by comparison
3
1
of the vicinal JHH couplings constants observed in their H
NMR spectra: in nonpolar media, open chain diazapentadienes
have a NH group existing predominantly in the ZZ form,
wherein they are stabilized by intramolecular hydrogen bond-
ing.39,44 In contrast, their salts take up the EE configuration in
polar solvents.44 The NMR spectra have been investigated by
several workers, with results agreeing with those obtained from
IR studies and excluding the presence of tautomeric forms.45,46
However, the application of this method to the stereochemical
assignments of such derivatives is limited by the substitution
pattern of the propene moiety: in the case of substituent occur-
ring on the propene bridge, structure of the corresponding diaza-
pentadienes could not be established completely.47
To verify the assumption that the synthesis of 8a and 8b
proceeds through intermediates of type 4 and to reveal the reac-
tion route as a whole, we decided to test after its isolation the
reactivity of 4 toward 1 molar equiv of aniline in dichloro-
methane at 40 °C, and in these conditions, diazapentadiene 8b
was formed with elimination of the phenoxy group in high yield
(conversion of 4 to 8b ) 90%) (Scheme 9).
In our case, the NMR spectra of diaryl-1,5-diazapentadienes
8a,b in polar solvent (DMSO) show that the compounds exist
solely in the EEE form as deduced from the 3JH2H3, 3JH3NH, and
4JC3F couplings, whereas in nonpolar solvent (benzene), an
equilibrium is established between this form and the intra-
molecularly bonded ZZE form (Table 3).
Such processes are analogous to nucleophilic addition at the
â-carbon of the R,â-unsaturated carbonyl compounds and could
be explained by an aza-Michael addition-elimination mecha-
nism28,29 such as in the case of intermediate 3′ (Schemes 2
and 9).
It has been shown that the salts of N,N′-diaryl-1,5-diaza-
pentadienes (Ar-NHdCH-CHdCHNH-Ar) exist as conju-
gated amino imines, generally as a mixture of the all-trans (or
EE), all-cis (or ZZ), and cis-trans (ZE or EZ) isomers with slow
(44) (a) Richards, C. P.; Webb, G. A. Org. Magn. Reson. 1975, 7, 401.
(b) Lloyd, D.; McNab, H. Angew. Chem., Int. Ed. Engl. 1976, 15, 459. (c)
Barry, W. J.; Finar, I. L.; Mooney, E. F. Spectrochim. Acta 1965, 21, 1095.
(d) Limbach, H. H.; Seiffert, W. Tetrahedron Lett. 1972, 371.
(45) (a) Nair, V.; Vietti, D. E.; Cooper, C. S. J. Am. Chem. Soc. 1981,
103, 3030. (b) Kikugawa, K.; Maruyama, T.; Machida, Y.; Kurechi, T.
Chem. Pharm. Bull. 1981, 29, 1423.
(46) (a) McNab, H. J. Chem. Soc., Perkin Trans. 2 1981, 1283. (b)
Radeglia, R. J. Prakt. Chem. 1973, 315, 1121.
(47) (a) Honeybourne, C. L.; Webb, G. A. Spectrochim. Acta 1969, 25A,
1075. (b) Bayer, E. Angew. Chem., Int. Ed. Engl. 1964, 3, 325.
J. Org. Chem, Vol. 71, No. 18, 2006 6749

El Kharrat et al.
In the case of the EEE isomer, the configuration of the C2d
C3 double bond was determined as E by the coupling constant
of proton 2 and proton 3 (3JH2H3 ) 13.7-14 Hz), then the
coupling observed between proton 3 and the proton of the NH
group (3JH3NH ) 12.3-14 Hz) is consistent with the E geometry
around the dC3-NH single bond.5,15 Finally, the coupling
observed between carbon 3 and fluorine atoms (4JC3F ) 3-5.5
Hz) suggests that this carbon is spatially proximate (or in a cis-
position) to the perfluoroalkyl group and permitted us to attribute
an E conformation around the NdC1-C2dC3 single bond
(Scheme 8 and Table 3).
lish a valuable methodology for the determination of configura-
tions of unsaturated derivatives, such as 3-7, and even the
determination of conformational preferences of compounds, such
as 8a and 8b, in favorable solvents.
Experimental Section
General Procedure for the Preparation of Perfluoroalkylated
Propenals 3a-k and 3s. In a typical procedure, to a stirred solution
of gem-iodoacetoxy compound 1 (1 equiv) in n-heptane or petro-
leum ether (5 mL/1 g of 1) was added portion wise 3 equiv of the
corresponding sodium phenoxides 2 at 0 °C. After 30 min, the
resulting brown mixture was stirred at 20 °C until 19F NMR signals
disappeared, corresponding to the starting product 1 (1-2 h). At
the end of the reaction, the brown precipitate which had formed
was eliminated by vacuum filtration and was washed five times
with heptane or petroleum ether. The filtrate was concentrated in
vacuo to give brown oil. Then it was diluted in dichloromethane,
washed five times with 1% aqueous sodium hydroxide solution to
eliminate excess of phenols, and concentrated under reduced pres-
sure. The resulting yellow oil was purified by column chromatog-
raphy on silica gel (EtOAc/petroleum ether, 6/94) to afford 3. All
of these enol ethers are described for the first time. In each case,
the corresponding substituted phenylacetate was isolated (1 equiv
compared to 1) and identified. Here we describe only the pheny-
lacetates obtained in reactions of 3a, 3l, and 3o.
In benzene solution, the coupling constants of proton 2 and
proton 3 (3JH2H3 ) 7.9-8.2 Hz) and proton 3 and a NH proton
(3JH3NH ) 10 Hz) permitted us to establish the ZE stereochem-
istry of the CHdCH-NH moiety. Moreover, the absence of
coupling between carbon 3 and fluorine atoms (4JC3F ) 0 Hz)
allowed us to attribute a Z conformation around the NdC-
CdC single bond and to assign unequivocally the ZZE isomer
of 8a and 8b.
In the case of 8a, the resonance-assisted hydrogen bonding
(RAHB) occurring in nonpolar solvent (benzene) governs the
stereoisomeric equilibrium,28,30 and the ZZE isomer prevails
(64%). However, the results observed for 8b suggest that the
length of the perfluoroalkyl group plays a crucial role; the EEE
isomer is considerably more stable and comprises more than
71% of the equilibrium of 8b in benzene solution (Table 3).
The more polar solvent (DMSO) totally shifts the equilibrium
of 8a and 8b to the EEE isomer, stabilized by intermolecular
hydrogen bonds, strong electrostatic interactions, and minimal
steric hindrance.30,44
In a previous publication,11 we reported that 2-trifluoromethyl-
1,5-diazapentadiene 8a exists as a single stereochemically pure
tautomer. Other works describe that the two nitrogen atoms in
this imino enamine compound are not entirely equivalent.44 The
signals in the 13C NMR spectrum obtained for 8a and 8b
confirmed these results (for both isomers, the imine carbon
showed coupling with fluorine atoms (1JC1F), and in both cases,
a coupling between proton 3 and a NH proton is obtained
(3JH3NH)).
3-Phenoxy-3-trifluoromethylprop-2-enal (3a). Sodium phen-
oxide (15.7 g, 0.135 mol) was added to a solution of 15 g (4.5 ×
10-2 mol) of 1 (RF ) CF3) in 75 mL of dry heptane at 0 °C. The
mixture was stirred for 30 min at 0 °C then for 2 h at 20 °C. In
this case, no chromatographic purifications were needed (only
washing five times with 1% aqueous sodium hydroxide solution
to eliminate excess of phenols); 9.3 g of the title product was
obtained, with a total yield of 90% (EE/ZE: 64:36): 1H NMR
(300.13 MHz, CDCl3) δ (EE) 5.6 (d, J ) 7.3 Hz, 1H), 7-7.5 (m,
5H), 9.9 (d, J ) 7.3 Hz, 1H); (ZE) 6.2 (d, J ) 7.2 Hz, 1H), 7-7.5
(m, 5H), 9.6 (d, J ) 7.1 Hz, 1H); 13C NMR (75.4 MHz, CDCl3)
δ 113.5, 115, 117.5, 121, 144.3, 156.5, 157.5, 159 (q, C-CF3,
4
2JCF ) 28.6 Hz), 186.8 (s, CHO (Z)), 187.5 (q, CHO (E), JCF
)
9 Hz); 19F NMR (282.4 MHz, CDCl3) δ -64.8 (s, 3F, (EE), 64%),
-71 (s, 3F, (ZE), 36%). MS (m/z): 217 (M+, 100). HRMS calcd
for C10H8F3O2 217.0476, found 217.0477. Anal. Calcd for
C10H7F3O2: C, 55.56; H, 3.26; O, 14.80. Found: C, 55.55; H, 3.26;
O, 14.81. Chromatographic purification of the reaction mixture
allowed us to isolate 6.1 g (4.49 × 10-2 mol) of phenylacetate:
The case of substituted imino enamine derivatives 8a,8
indicates that the use of the 4JCF coupling constant to determine
the relative conformations of its C1-C2 bond is reliable and
permits one to attribute unambiguously conformational prefer-
ences of such compounds having an F-alkyl substituent on the
propene moiety. The nJCF basically decreases with the increase
in the spatial distance of the two nuclei;18,19 therefore, the con-
figuration or the conformation of a compound considerably
1H NMR (300.13 MHz, CDCl3) δ 2.1 (s, 3H), 7-7.4 (m, 5H); 13
C
NMR (75.4 MHz, CDCl3) δ 20.4, 121.5, 126.6, 125.5, 130.1, 155.2,
170.1. MS (m/z): 137 (M+, 100). HRMS calcd for C8H9O2
137.0603, found 137.0610. Anal. Calcd for C8H8O2: C, 70.57; H,
5.92; O, 23.50. Found: C, 70.58; H, 5.92; O, 23.49.
General Procedure for the Preparation of Perfluoroalkylated
Propenals (3l-n). To a stirred solution of perfluoroalkylated gem-
iodoacetoxy compound 1 (1 equiv) in dry n-heptane or petroleum
ether (5 mL/ 1 g of 1) was added 3 equiv of the corresponding
substituted phenoxides 2. The mixture was stirred at 40 °C (Table
1) for the desired time until complete consumption of the starting
material was judged by TLC and 19F NMR spectroscopy. At the
end of the reaction, the mixture was filtered and evaporated; the
residue was worked up and chromatographed as described previ-
ously to afford the desired products 3.
n
influences the value of JCF through the change in the inter-
4
nuclear distance. The observed JCF (for compounds 3-8)
confirmed that the more spatially proximate carbon-fluorine
4
assumes coupling. Therefore, JCF could be used as a criterion
for the determination of configurational and conformational
isomerism of F-alkyl-containing olefins. To our knowledge, such
a description of the use of nJCF coupling constants for the deter-
mination of conformations has not been reported in the literature
until now.
3-(4-Chlorophenoxy)-3-perfluoropentylprop-2-enal (3l). So-
dium 4-chlorophenoxide (12.7 g, 0.084 mol) was added to a stirred
solution of 15 g (2.8 × 10-2 mol) of 1 (RF ) C5F11) in 75 mL of
dry heptane or petroleum ether. The mixture was stirred at 40 °C
for 12 h, and 10.2 g of the title product was obtained: total yield
In conclusion, we provided new trifluoromethyl- and per-
fluoroalkyl-containing synthons 3a-s in a two-step reaction
starting from commercially available RFI. Then we explored
the reactivity of 3 and prepared push-pull derivatives 4, 5, 8a,b,
1
80% (EE/ZE: 92/8); H NMR (300.13 MHz, CDCl3) δ (EE) 5.6
4
and nonconjugated compounds 6 and 7. The JCF coupling
(d, J ) 7.3 Hz, 1H), 7 (s, 4H), 9.9 (d, J ) 7.3 Hz, 1H); (ZE) 6 (d,
constants observed in the 13C NMR spectra allowed us to estab-
J ) 7.3 Hz, 1H), 7 (s, 4H), 9.4 (d, J ) 7.3 Hz, 1H); 13C NMR
6750 J. Org. Chem., Vol. 71, No. 18, 2006

Substituted Trifluoromethyl and Perfluoroalkyl Enals
(75.4 MHz, CDCl3) δ 114.2, 115.5, 118.6, 121.6, 145.2, 158, 159.5
vacuo. The resulting oil was purified by column chromatography
over silica gel to afford 4 (4.72 g, 9.610-3 mol, 94%): 1H NMR
(300.13 MHz, C6D6, EE 99%) δ (EE) 6.4 (d, 3JH1H2 ) 9.1 Hz, H2),
2
(t, C-CF3, JCF ) 27.8 Hz), 187.5 (s, CHO (ZE)), 188.2 (t, CHO
4
(EE), JCF ) 8.3 Hz); 19F NMR (282.4 MHz, CDCl3) δ -81 (s,
3
3F), -111.2 (s, 2F, (EE), 92%), -116.5 (s, 2F, (ZE), 8%), -123.3
(s, 4F), -127 (s, 2F). MS (m/z): 451.5 (M+, 100). HRMS calcd
for C14H7ClF11O2 450.9959, found 450.9961. Anal. Calcd for C14H6-
ClF11O2: C, 37.31; H, 1.34; O, 7.10. Found: C, 37.31; H, 1.33; O,
7.11. Chromatographic purification of the reaction mixture allowed
us to isolate 4.75 g (2.79 × 10-2 mol) of 4-chlorophenylacetate:
1H NMR (300.13 MHz, CDCl3) δ 2.2 (s, 3H), 7 (d, J ) 7.5 Hz,
2H), 7.3 (d, J ) 7.5 Hz, 2H); 13C NMR (75.4 MHz, CDCl3) δ
20.6, 123.1, 123.2, 129.4, 132.1, 150.5, 170.3. MS (m/z): 171 (M+,
100). HRMS calcd for C8H8ClO2 171.0213, found 171.0216. Anal.
Calcd for C8H7ClO2: C, 56.32; H, 4.14; O, 18.76. Found: C, 56.34;
H, 4.14; O, 18.77.
6.8-7.3 (m, 10H), 8.7 (d, JH1H2 ) 9 Hz, H1); 13C NMR (75.4
MHz) δ (EE) 116.8, 117.4, 121.5, 121.7, 127.1, 127.7, 130.3, 131.4,
2
152.2 (t, C3-CF3, JCF ) 27.3 Hz), 153, 153.9, 154.4 (t, HCdN
4
(EE), JC1F ) 5.7 Hz); 19F NMR (282.4 MHz) δ -80.8 (s, 3F),
-111.4 (m, 2F, (EE), 99%), -115 (s, 2F, (ZE), 1%), -122.3 (s,
1
4F), -125.9 (s, 2F); H NMR (300.13 MHz, CDCl3, ZE/EE 15/
3
85) δ (EE) 6.2 (d, JH1H2 ) 9 Hz, 1H), 7-7.5 (m, 10H), 8.5 (d,
3JH1H2 ) 9 Hz, 1H); (ZE) 6.9 (d, 3JH1H2 ) 8.9 Hz, 1H), 7-7.5 (m,
10H), 8.2 (d, 3JH1H2 ) 8.9 Hz, 1H); 13C NMR (75.4 MHz) δ 115.1,
115.8, 120.8, 121, 123 (t, 3JC2F ) 4.9 Hz, C2, (ZE)), 126.4, 126.7,
2
127.4, 129.2, 129.3, 130.1, 130.5, 146.8 (t, C3-CF3, JCF ) 25.8
Hz), 150.7, 151.4, 152.2 (t, C3-CF3, 2JCF ) 27.3 Hz), 152.7, 153.2
4
(s, HCdN (ZE)), 154.6 (t, HCdN (EE), JC1F ) 5.9 Hz), 157.7;
General Procedure for the Preparation of 3-Perfluoroalkyl-
3-(4-nitrophenoxy)prop-2-enals (3o,p). To a stirred solution of
perfluoroalkylated gem-iodoacetoxy compound 1 (1 equiv) in dry
n-heptane (5 mL/ 1 g of 1) was added 3 equiv of 4-nitrophenoxide
2. The mixture was stirred at 80 °C for the desired time (Table 1)
until complete consumption of the starting material was judged by
TLC and 19F NMR spectroscopy. At the end of the reaction, the
mixture was filtered and evaporated; the residue was worked up
and chromatographed as described previously to afford the desired
products 3o,p.
3-(4-Nitrophenoxy)-3-perfluoropentylprop-2-enal (3o). So-
dium 4-nitrophenoxide (9 g, 0.056 mol) was added to a stirred
solution of 10 g (1.8 × 10-2 mol) of 1 (RF ) C5F11) in 50 mL of
dry n-heptane. The mixture was stirred at 80 °C for 48 h, and 5.63
g of the title product was obtained: total yield 65% (EE/ZE: 60/
40). The mixture of both stereoisomers was precipitated in heptane
at -20 °C. A white solid of pure E isomer was obtained: 1H NMR
(300.13 MHz, CDCl3) δ (EE) 5.7 (d, J ) 7 Hz, 1H), 7.3 (d, J )
7.2 Hz, 2H), 8.5 (d, J ) 7.1 Hz, 1H), 10 (d, J ) 7 Hz, 1H); (ZE)
6.6 (d, J ) 6.8 Hz, 1H), 7.3 (d, J ) 7.2 Hz, 2H), 8.5 (d, J ) 7.1
Hz, 1H), 9.8 (d, J ) 6.9 Hz, 1H); 13C NMR (75.4 MHz, CDCl3) δ
114, 115.5, 119.1, 121.4, 145.3, 151.3, 158.4, 160.2 (t, C-CF3,
19F NMR (282.4 MHz) δ -80.8 (s, 3F), -111.7 (m, 2F, (EE), 85%),
1
-114.9 (m, 2F, (ZE), 15%), -122.5 (m, 4F), -126.1 (s, 2F); H
NMR (300.13 MHz, CD3CN, ZE 92%) δ (ZE) 6.7 (d, 3JH1H2 ) 9.2
Hz, 1H), 6.8-7.3 (m, 10H), 8.1 (d, 3JH1H2 ) 9 Hz, 1H); 13C NMR
(75.4 MHz) δ (ZE) 115.6, 120.6, 122.7 (t, 3JC2F ) 4.8 Hz, C2, (ZE)),
2
123.8, 127, 128.9, 130, 145.9 (t, C3-CF3, JCF ) 25.8 Hz), 150,
152.9, 157.3 (s, HCdN (ZE)); 19F NMR (282.4 MHz) δ -81.5 (s,
3F), -111.8 (m, 2F, (EE), 8%), -115.5 (s, 2F, (ZE), 92%), -122.5
(s, 2F), -123 (s, 2F), -126.6 (s, 2F). MS (m/z): 492 (M+, 100).
HRMS calcd for C20H13F11NO 492.0821, found 492.0822. Anal.
Calcd for C20H12F11NO: C, 48,89; H, 2.46; O, 3.26. Found: C,
48.90; H, 2.46; O, 3.28.
Synthesis of Methyl (EEE)-5-(4-Methoxyphenoxy)-5-per-
fluoropentyl-2,4-pentadienoate 5. To a solution of 2.25 (1.23 ×
10-2 mol) of trimethylphosphonoacetate in methanol (8 mL) was
added portion wise 0.35 g (1.47 × 10-2 mol) of sodium hydride.
The resulting suspension was stirred at room temperature, and 5.5
g (1.23 × 10-2 mol) of 3f was added. The mixture was stirred for
2 h, filtered, and concentrated in vacuo. The resulting oil was diluted
in ether and washed with water. The organic layer was dried over
sodium sulfate and concentrated in vacuo. The resulting oil was
precipitated in petroleum ether at 0 °C to give 5 with very high
yield as a white solid (6.2 g, 0.0123 mol, 100%): 1H NMR (300.13
2JCF ) 29.1 Hz), 187.1 (s, CHO (ZE)), 188.2 (t, CHO (EE), 4JCF
)
8 Hz); 19F NMR (282.4 MHz, CDCl3) δ -81 (s, 3F), -111 (s, 2F,
(EE), 60%), -116 (s, 2F, (ZE), 40%), -122 (s, 4F), -126 (s, 2F).
Spectral data of EE isomer: 1H NMR (300.13 MHz, CDCl3) δ 5.6
(d, J ) 6.9 Hz, 1H), 7.3 (d, J ) 7.2 Hz, 2H), 8.5 (d, J ) 7.2 Hz,
2H), 10 (d, J ) 6.9 Hz, 1H); 13C NMR (75.4 MHz, CDCl3) δ 115.2,
121.6, 126.3, 146.2, 156.3, 157.2 (t, C-CF3, 2JCF ) 29.4 Hz), 187.2
3
MHz, C6D6) δ 3.3 (s, 3H), 3.4 (s, 3H), 5.5 (d, JH2H3 ) 15.1 Hz,
3
H2), 5.8 (d, JH3H4 ) 12 Hz, H4), 6.7 (d, J ) 7.8 Hz, 2H), 6.8 (d,
J ) 7.8 Hz, 1H), 8 (dd, J ) 12.6 and 14.6 Hz, H3); 13C NMR
(75.46 MHz, C6D6) δ 51.2, 55, 113.1, 115.5, 121.8, 125.1, 134.8
4
2
(t, C3dC, JC3F ) 6.4 Hz), 146.7, 149.1 (t, C-CF3, JC5F ) 25.8
Hz), 157.8, 165.8; 19F NMR (235.36 MHz, C6D6) δ -81 (s, 3F),
-113 (s, 2F), -123 (s, 4F), -126 (s, 2F). MS (m/z): 503 (M+,
100). HRMS calcd for C18H14F11O4 503.0716, found 503.0718.
Anal. Calcd for C18H13F11O4: C, 43.04; H, 2.61; O, 12.74. Found:
C, 43.06; H, 2.60; O, 12.73.
4
(t, CHO (EE), JCF ) 9 Hz); 19F NMR (282.4 MHz, CDCl3) δ
-80.6 (s, 3F), -111.2 (s, 2F), -122.5 (s, 4F), -126 (s, 2F). Spectral
data of ZE isomer: 1H NMR (300.13 MHz, CDCl3) δ 6.6 (d, J )
6.8 Hz, 1H), 7.3 (d, J ) 7.3 Hz, 2H), 8.5 (d, J ) 7.3 Hz, 1H), 9.8
(d, J ) 6.9 Hz, 1H); 13C NMR (75.4 MHz, CDCl3) δ 116.1, 122.9,
2
126.5, 144.3, 152.9 (t, C-CF3, JCF ) 27 Hz), 161.4, 186.4 (s,
Synthesis of 3-(4-Methoxyphenoxy)-3-perfluoropentylprop-
2-enol 6. To a solution of 10 g (2.24 × 10-2 mol) of 3f in 30 mL
of dry methanol was added 0.42 g (1.12 × 10-2 mol) of sodium
borohydride. The resulting solution was stirred for 6 h at room
temperature. At the end of the reaction, the mixture was concen-
trated in vacuo, diluted with ether, and washed with water. The
organic layer was dried over sodium sulfate then concentrated in
vacuo. Final alcohol 6 was obtained with total conversion (10 g,
0.0223 mol, 100%): 1H NMR (250.13 MHz, C6D6, mixture of
E and Z isomers, 95/5) δ (E) 1.6 (br s, 1H), 3.3 (s, 3H), 4.1 (m,
2H), 5.3 (t, J ) 6.8 Hz, H2), 6.6 (d, J ) 7.6 Hz, 2H), 6.8 (d, J )
7.7 Hz, 2H); (Z) 1.4 (br s, 1H), 3.3 (s, 3H), 3.9 (m, 2H), 6 (t, J )
CHO (ZE)); 19F NMR (282.4 MHz, CDCl3) δ -80.7 (s, 3F), -115.6
(s, 2F), -122.1 (s, 2F), -122.5 (s, 2F), -126.1 (s, 2F). MS (m/z):
462 (M+, 100). HRMS calcd for C14H7F11NO4 462.0199, found
462.0196. Anal. Calcd for C14H6F11NO4: C, 36.46; H, 1.31; O,
13.88. Found: C, 36.48; H, 1.33; O, 13.86. Chromatographic
purification of the reaction mixture allowed us to isolate 3.23 g
(1.78 × 10-2 mol) of 4-nitrophenylacetate: 1H NMR (300.13 MHz,
CDCl3) δ 2 (s, 3H), 7.3 (d, J ) 7.4 Hz, 2H), 7.9 (d, J ) 7.5 Hz,
2H); 13C NMR (75.4 MHz, CDCl3) δ 20.4, 122.2, 123.5, 146.1,
158.1, 169.9. MS (m/z): 182 (M+, 100). HRMS calcd for C8H8-
NO4 182.0453, found 182.0455. Anal. Calcd for C8H7NO4: C,
53.04; H, 3.89; O, 35.33. Found: C, 53.00; H, 3.91; O, 35.34.
Reaction of 3c with Aniline: Synthesis of 1-Phenylimino-3-
phenoxy-3-perfluoropentylprop-2-ene 4. To a solution of 4.27 g
(1.02 × 10-2 mol) of 3c in dichloromethane (20 mL) was added
0.95 g (1.02 × 10-2 mol) of aniline. The mixture was stirred at
room temperature for 2 h. At the end of the reaction, the solution
was diluted with dichloromethane and washed with water. The
organic layer was dried over sodium sulfate and concentrated in
6.1 Hz, H2), 6.6 (d, J ) 7.6 Hz, 2H), 6.8 (d, J ) 7.7 Hz, 2H); 13
C
NMR (100.61 MHz, C6D6) δ 36 (s, CH2OH, (Z)), 37.2 (t, CH2OH,
(E), 4JC1F ) 6.6 Hz), 55.1, 55.2, 112.4, 115.4, 115.6, 116.7, 121.9,
2
2
122.3, 141.7 (t, C-CF3, JC3F ) 25.5 Hz), 146.7 (t, C-CF3, JC3F
) 25.7 Hz), 147.1, 150.7, 156.4, 157.8; 19F NMR (235.3 MHz,
C6D6) δ -81.5 (s, 3F), -113 (s, 2F, (E), 95%), -115 (s, 2F, (Z),
5%), -123 (s, 4F), -127 (s, 2F). MS (m/z): 449 (M+, 100). HRMS
calcd for C15H12F11O3 449.0611, found 449.0614. Anal. Calcd for
J. Org. Chem, Vol. 71, No. 18, 2006 6751

El Kharrat et al.
C15H11F11O3: C, 40,19; H, 2.47; O, 10.71. Found: C, 40.21; H,
2.45; O, 10.73.
) 279.2 Hz), 122.14, 123.6, 129.3, 129.6, 140.64, 140.8 (q, C3H,
4JC3F ) 3 Hz), 149.5, 153.3 (q, C-CF3, 2JC1F ) 30.5 Hz); 19F NMR
δ -65.8 (s, 3F); 1H NMR (300.13 MHz, C6D6, EEE/ZZE 36/64) δ
Reaction of 3-(4-Methoxyphenoxy)-3-perfluoropentylprop-2-
enal 3f with Triethylorthoformate: Synthesis of Acetals 7. To
a solution of 3.6 g (8 × 10-3 mol) of 3f and 3.6 g (2.4 × 10-2
mol) of triethylorthoformate in 7 mL of dry ethanol was added
1.39 g (8 × 10-3 mol) of para-toluenesulfonic acid. The resulting
mixture was put under reflux for 6 h. At the end of the reaction,
the mixture was concentrated in vacuo, diluted with ether, and
washed with a solution of 2% sodium hydrogenocarbonate (until
the aqueous layer had pH > 7). The organic layer was then dried
over sodium sulfate and concentrated in vacuo to give final product
7 (4 g, 7.7 × 10-3 mol, 96%): 1H NMR (300.13 MHz, CDCl3,
(E)-7) δ 1.1 (t, J ) 7 Hz, 6H), 3.4 (m, 2H), 3.6 (m, 2H), 3.8 (s,
3
(EEE) 5.1 (br s, 1H, NH), 5.2 (d, JH2H3 ) 14 Hz, H2), 6.4-7.4
3
(m, 10H), 7.5 (t, J ) 14 Hz, H3); (ZZE) 5.4 (d, JH2H3 ) 7.8 Hz,
H2), 6.4-7.4 (m, 10H), 7 (m, H3), 12 (br d, 3JH3NH ) 10 Hz, NH);
13C NMR δ 90.4, 93.2, 115.5, 116.6, 119.8, 120.3, 122.8, 123.7,
124, 124.2, 128.9, 129.5, 129.7, 129.8, 139.7 (q, C3H, 4JC3F ) 3 Hz,
(EEE)), 140.4, 141.2, 142.3 (s, C3H, (ZZE)), 148.5, 150.6, 152.8
(q, C1-CF3, 2JC1F ) 27 Hz), 153.8 (q, C1-CF3, 2JC1F ) 31.9 Hz);
19F NMR δ -62.2 (s, 3F, (ZZE), 64%), -66.6 (s, 3F, (EEE), 36%).
MS (m/z): 291 (M+, 100). HRMS calcd for C16H14F3N2 291.1109,
found 291.1087 Anal. Calcd for C16H13F3N2: C, 66.20; H, 4.51; N,
9.65. Found: C, 66.15; H, 4.31; N, 9.45.
3
3
3H), 5.1 (d, JH1H2 ) 7.5 Hz, 1H), 6.1 (d, JH1H2 ) 7.5 Hz, 1H),
6.8 (d, J ) 9 Hz, 2H), 7(d, J ) 9 Hz, 2H); 13C NMR (75.4 MHz,
CDCl3) δ 15, 55.6, 62, 63.2, 95.8, 114.6, 116.5, 123.6 (t, C1-
(OEt)2, 4JC1F ) 8 Hz); 19F NMR (282.4 MHz, CDCl3) δ -80.7 (s,
3F), -114.7 (s, 2F), -122.2 (s, 2F), -122.6 (s, 2F), -126.1 (s,
2F). MS (m/z): 521 (M+, 100). HRMS calcd for C19H20F11O4
521.1186, found 521.1189. Anal. Calcd for C19H19F11O4: C, 43,-
86; H, 3.68; O, 12.30. Found: C, 43.88; H, 3.68; O, 12.31.
Reaction of 3d with Aniline: Synthesis of 2-Trifluoromethyl-
1-phenylamino-3-phenyliminopropene 8a. To a solution of 1 g
(4 × 10-3 mol) of 3d in dichloromethane (5 mL) was added 0.75
g (8.1 × 10-3 mol) of aniline. The mixture was put under reflux
for 3 h. At the end of the reaction, the solution was diluted with
dichloromethane and washed with water. The organic layer was
dried over sodium sulfate and concentrated in vacuo. The resulting
powder was recrystallized from petroleum ether at 0 °C to yield
diazapentadiene 8a (1.1 g, 3.8 × 10-3 mol, 94%): 1H NMR
(DMSO-d6, EEE) δ 5.5 (d, 3JH2H3 ) 13.7 Hz, H2), 6.8 (d, J ) 7.5
Hz, 2H), 7 (m, 3H), 7.15 (t, J ) 7.4 Hz, 1H), 7.3 (t, J ) 7.8 Hz,
2H), 7.4 (t, J ) 7.7 Hz, 2H), 7.6 (t, J ) 13 Hz, H3), 9.9 (d, 3JH3NH
) 12.3 Hz, NH); 13C NMR δ 90.8, 115, 119.2, 120.6 (q, CF3, 1JCF
Reaction of 4 with Aniline: Synthesis of 2-Perfluoropentyl-
1-phenylamino-3-phenyliminopropene 8b. To a solution of 1 g
(2 × 10-3 mole) of 4 in dichloromethane (5 mL) was added 0.19
g (2 × 10-3 mol) of aniline. The mixture was put under reflux for
2 h. At the end of the reaction, the solution was diluted with
dichloromethane and washed five times with water. The organic
layer was dried over sodium sulfate and concentrated in vacuo.
The resulting liquid was recrystallized from petroleum ether at 0 °C
to yield diazapentadiene 8b (0.9 g, 1.81 × 10-3 mol, 90%).
Acknowledgment. We would like to thank Dr. Maryse
Bejaud for NMR analyses and interesting discussions.
Supporting Information Available: Experimental procedures
and analytical data for compounds 3b-k,m,n,p,s and 8b; copies
1
1
of H, 13C, cosy H-1H, 13C-1H, or 19F NMR spectra of 3a-s,
4-7, and 8a,b. This material is available free of charge via the
Internet at http://pubs.acs.org.
JO060764I
6752 J. Org. Chem., Vol. 71, No. 18, 2006