Regioselectivity of the protonation of captodative enamines bearing a CF3 group

Article abstract of DOI:10.1016/j.jfluchem.2009.10.001

Capodative enamines bearing a CF₃ group are protonated at the N- or β-C-atom depending on the structure of the initial base and the nature of protonating reagent.

Full text of DOI:10.1016/j.jfluchem.2009.10.001

Journal of Fluorine Chemistry 131 (2010) 53–58
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Regioselectivity of the protonation of captodative enamines bearing a CF3 group
*
Alexander Yu. Rulev , Igor A. Ushakov
A.E. Favorsky Institute of Chemistry, Siberian Branch of Russian Academy of Sciences, 1, Favorsky Str., 664033 Irkutsk, Russian Federation
A R T I C L E I N F O
A B S T R A C T
Article history:
Capodative enamines bearing a CF3 group are protonated at the N- or
structure of the initial base and the nature of protonating reagent.
b-C-atom depending on the
Received 21 July 2009
Received in revised form 29 September 2009
Accepted 1 October 2009
Available online 7 November 2009
ß 2009 Elsevier B.V. All rights reserved.
Keywords:
Enamines
Protonation
Regioselectivity
1. Introduction
undergo a slow conversion into the C-protonated isomers. Finally,
cyclic aminoenones add the proton at the heteroatom as well as at
The regioselectivity of the protonation is an attractive and
intricate problem underpinning the fascinating chemistry of
enamines [1]. Understanding the relationships between structure
and protonation site preference of enamine is a key-issue since
their reactivity is directly related to their basicity [2,3]. In general,
the
b-carbon with subsequent enolization [11,12].
The chemistry of carbonyl bearing captodative aminoalkenes
has appealed an increasing interest in the recent decades [13]
while enamines having geminal trifluoromethyl group remained
poorly studied so far. The introduction of fluorine atom into a
molecule is known to often drastically perturb the properties of the
parent compound [14,15]. Fluorine-containing enamines are
versatile building blocks for the construction of new types of
biologically active compounds and analogues of natural products.
Attention has been recently paid to the synthesis of gem-
amino(trifluoromethyl)alkenes [16]. Previously, it has been
demonstrated that the protonation of such type of derivatives
leads to the corresponding enammonium salts only because the
presence of the CF3 group favors their formation [17]. This
observation raises an important question: whether the N-
protonation of CF3-substituted enamines is really regiospecific
and enammonium salt can be stabilized by the trifluoromethyl
group or do the structural changes in these compounds influence
the site of electrophilic attack? This information is needed to better
delineate the synthetic potential of these systems and their use in
the organic synthesis. In the present communication, the proto-
enamines are ambident conjugated systems in which the N- or C -
b
atom of the enamine moiety as well as (in some cases) the
heteroatom of the activating group serve as the nucleophilic
center. All earliest studies of the proton affinity of enamines have
shown that the nature of the product of the reaction depends on
relatively trivial changes in reaction conditions or in the structure
of the initial base [4]. Indeed, the simple enamines react with most
acids to generate usually the stable iminium salts. The existence of
the N-protonated forms as intermediates at the initial stages of the
reaction was fully supported by NMR, IR, and UV data [4]. If the
push–pull aminoenones are protonated predominantly at the
oxygen atom [5], the regioselectivity of the electrophilic attack on
the captodative ones dramatically depends on the nature of the
protonating reagent [6]. The particular case of the captodative
formyl(amino)alkenes deserves to be underlined since they react
with both mineral and strong organic acids to give regiospecifically
the enammonium salts which do not transform into the
corresponding iminium ones, probably because of the stabilizing
effect of the intramolecular hydrogen bond [7,8]. Captodative
aminoalkenes bearing gem-cyano [9] or azomethine group [10]
generally afford the corresponding enammonium salts which
nation of
and carboxylic acids is reported.
a-trifluoromethylated enamines 1a–d by both mineral
2. Results and discussion
The enamines 1a–d were obtained as described previously [16]
and exist as a mixture of geometric isomers. Their Z,E-configura-
tions were established by the application of a 1H–1H 2D NOESY
homonuclear experiments (Fig. 1). For example, the presence of a
* Corresponding author. Fax: +7 3952 419346.
E-mail address: rulev@irioch.irk.ru (A.Yu. Rulev).
0022-1139/$ – see front matter ß 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2009.10.001

54
A.Y. Rulev, I.A. Ushakov / Journal of Fluorine Chemistry 131 (2010) 53–58
142 ppm) as well as upfield shifts of the
in all enamines 1a–d suggest a higher electron density on the latter
carbon atom. The difference Dd (C ) reaches +35 ppm
b one (d 101–116 ppm)
=
d
(C ) ꢀ
a
d
b
and is comparable to that observed for the simple enamines (30–
45 ppm) [11]. These data are indicative of a high polarization of the
double bond C55C and argue in favor of the iminium salts
formation.
In fact, the treatment of enamine 1a with an excess of
trifluoromethanesulfonic acid 2a in dichloromethane or chloro-
form resulted in the formation of iminium salt 3aa only (the
notation 3aa means that this salt has been obtained from enamine
1a and acid 2a) (Scheme 1). It should be underlined that in all cases
it proved impossible to isolate pure samples because of the highly
reactive nature of the salts; hence characterisation is based solely
upon 1D and 2D NMR spectroscopy data. The signals of the olefinic
proton on the 1H NMR spectrum of the two isomers 1a disappear
and a singlet assigned to the methylene protons appears at
4.84 ppm. A downfield shift of more than 1 ppm is observed for the
Fig. 1. Configurations of Z- and E-isomers of enamine 1a.
quite intensive cross-peaks between the NCH2 protons and both
ortho- and meta-aromatic protons in the NOESY spectrum of the
major isomer of the enamine 1a confirms unambiguously its Z-
configuration. In contrast, in the spectrum of the minor isomer
there is one NOE peak between the resonance of the olefinic proton
and the NCH2 protons of the amine moiety, whereas no
correlations are seen between the proton of the amine and
aromatic moieties.
It should be noted that for each pair of isomers there is no
significant difference in chemical shifts in both 13C and 15N NMR
spectra while the chemical shift difference of olefinic protons
achieves 0.5 ppm probably due to the anisotropic influence of
substituents (Table 1).
a
-methylene protons of the amino moiety with respect to the
same signal of the initial enamine 1a. In the 13C NMR spectrum two
resonance signals appear: a singlet at 40.17 ppm (a triplet
(1JCH = 135.2 Hz) in the coupling 13C NMR spectrum) and quad-
ruplet at 170.41 ppm which were assigned to carbon of CH2 and
C55N+ groups, respectively. No significant shift of the resonance
was observed in the 19F NMR spectrum (from ꢀ64.9 (for Z-1a) and
ꢀ58.7 (for E-1a) to ꢀ64.7 ppm) while a large downfield shift of the
resonance of pyrrolidine moiety in 15N NMR spectrum was noted
(from ꢀ305.4 (for E-1a) and ꢀ312.5 (for Z-1a) to ꢀ146.9 ppm)
when the initial base 1a is transformed into the iminium salt 3aa.
The similar alterations occur when the same enamine 1a is
treated with CF3COOH in CD2Cl2 or when enamine 1b reacts with
CF3SO3H in CDCl3. The formation of salts 3ab and 3ba is
The enamines 1a–d are typical captodative olefins bearing
attractive (CF3) and donor (NR2) substituents at the same carbon
atom. The analysis of their NMR spectra showed that the enamine
function is predominating in these compounds. In fact, the
downfield chemical shifts of the
a-carbon atom (d 135–
Table 1
NMR Spectra of Enamines 1a–d
.
Enamine
1H NMR,
CH5
d
, ppm
13C NMR,
d, ppm
15N NMR,
d, ppm
Ar
NR2
C
b
C
Z-
E-
a
Z-
E-
Z-
E-
Z-
E-
1a
1b
1c
1d
2-O2NC6H4
2-BrC6H4
N(CH2)4
N(CH2)4
N(CH2)5
NEt2
6.25
6.07
6.46
6.44
5.78
5.56
6.00
5.98
100.6
104.6
116.4
116.2
101.1
135.8
134.8
139.3
137.9
135.8
135.4
142.3
138.6
ꢀ312.5
ꢀ315.5
ꢀ326.8
ꢀ323.7
ꢀ305.4
ꢀ306.4
ꢀ313.8
ꢀ310.8
106.0
116.7
114.5
2-BrC6H4
4-O2NC6H4
Scheme 1. 1: Ar = 2-NO2C6H4, NR2 = N(CH2)4 (a); Ar = 2-BrC6H4, NR2 = N(CH2)4 (b); Ar = 2-BrC6H4, NR2 = N(CH2)5 (c); Ar = 4-NO2C6H4, NR2 = NEt2 (d). 2: X = CF3SO3 (a),
CF3COO (b), and Cl (c).

A.Y. Rulev, I.A. Ushakov / Journal of Fluorine Chemistry 131 (2010) 53–58
55
accompanied by an appearance of small quantity of the hydrolysis
products 5a and 5b, respectively. The ketone 5b was obtained upon
treatment of salts 3ba and 3bb with water and isolated by column
chromatography.
Surprisingly, the trivial replacement of the pyrrolidine moiety
in enamine 1b by a piperidine triggers a significant change in the
reaction route. Thus, when enamine 1c was treated with
trifluoroacetic or triflic acids, a mixture of iminium 3 and
enammonium 4 salts was formed. The mixture obtained was
examined by both 1D and 2D (1H–13
C
and 1H–15N) NMR
spectroscopy. Thus, the structure of the salts 4ca and 4cb is easily
confirmed by the presence, in the 1H NMR spectra, of a singlet at
ꢁ4.5 ppm which characterised the C-protonated form. On the
other hand, the retention of a singlet assigned to the CH55group in
the same spectra confirms the formation of an enammonium salt.
The olefin proton resonance is strongly shifted downfield and
clearly displayed in the aromatic range, while the signal of the NH+
proton appears at ꢁ10.5 ppm. A downfield shift of the
b-olefin
-carbon atom
carbon (ꢁ20 ppm) as well as the upfield shift of the
a
(ꢁ12 ppm) observed in the 13C NMR spectra of enammonium salts
4ca and 4cb are in good agreement with the principal change in the
conjugation of enamine moiety after protonation. Therefore, the N-
protonation of the captodative trifluoromethylated enamines 1
results in the umpolung of the C55C bond since the electron density
is shifted to the C atom bearing the electron withdrawing group
a
CF3.
Analysis of the 2D NOESY spectrum of salt 4cb leads to the
conclusion that the enammonium salt obtained has E-configura-
tion. Its geometry was confirmed by the presence of an intensive
cross-peak between the olefinic proton and the proton of the NCH2
group of the piperidine moiety (Fig. 2). In contrast, no correlations
is observed between the proton of the CH55 group or the amine
moiety and any of aromatic signals. Taking into account that the
initial base 1b consists of a mixture of geometrical isomers
(E:Z = 1:3) one can conclude that the formation of the enammo-
nium salt is accompanied by a partial isomerization of the double
bond. The results obtained are in excellent agreement with the
early described a Lewis acid-mediated conversion of push–pull Z-
trifluoromethyl enamines into their E-isomers [18] Such ease E,Z-
isomerization was also observed for captodative formyl(ami-
no)alkenes and their azomethine analogues [6,7,10]. Similar
transformations were observed on the initial steps of the reaction
of enamine 1c with trifluoroacetic acid (Fig. 3) as well as when the
base 1c was treated with a mild acid such as AcOH (Supporting
Information). No N- or C-protonated forms are detected in the
latter case.
Fig. 3. E,Z-Isomerization of enamine 1c at initial steps of the reaction with CF3COOH.
Initial enamine 1c at rt (Z:E = 2:1) (a); the reaction mixture after addition of 0.05 (b),
0.10 (c) and 0.15 (d) eq of CF3COOH at rt.
enamine 1d with deuterated acid CF3COOD in CDCl3 showed fast
disappearance of the signal of olefinic proton of E-1d caused by the
H–D exchange and much more slow exchange process for its Z-
isomer. In time, the signals of amine and aromatic moieties of the
N- and C-protonated forms appeared.
The differences in the behavior of the enamines 1b and 1c is
likely to be related to the higher p-character of the nitrogen lone-
pair in the pyrrolidine appendage compared with the six-member
ring of the piperidine. The particular properties of these hetero-
cycles decrease the polarization of the double bond of the enamine
1c [19]. Interestingly, the values of the chemical shift differences
between the adjacent carbon atoms of the enamine 1c are smaller
It should be underlined that the cross-peaks originating from
chemical exchange between the protons of initial enamine 1c,
enammonium and iminium salts 3cb and 4cb, as well as the acid
proton appeared in the 2D NOESY spectrum during the reaction of
these enamines with acids. Moreover, monitoring of the reaction of
than for its analogue 1b (Table 1). Since the electron density at C
b
atom of 1c is decreased, the protonation of both N- and C-
nucleophilic centers occurs.
The regioselectivity of protonation also depends not only on the
nature of the acid but the geometry of the initial base. Thus, the
treatment of enamine 1d with an equimolar quantity of
trifluoroacetic acid in CD2Cl2 at room temperature leads to the
mixture of the initial base 1d and the enammonium salt 4db with a
small quantity of hydrolysis product 5. No signals of the
corresponding iminium salt can be detected. While the E-isomer
of the initial enamine 1d undergoes the N-protonation immedi-
ately, more than 60% of the Z-isomer remains unreacted even at the
presence of two equivalents of the acid! To our knowledge, it is a
first example of the influence of the geometry of enamine on its
protonation. The addition of an excess (ꢁ5 equiv.) of acid 2b leads
to the corresponding iminium salt 3db. In contrast, if dry HCl is
bubbled into a CD2Cl2 cooled solution of 1d, the enammonium salt
4dc is formed exclusively. This difference of behavior between the
Fig. 2. Relative stereochemistry of the salt 4cb.

56
A.Y. Rulev, I.A. Ushakov / Journal of Fluorine Chemistry 131 (2010) 53–58
Fig. 4. 1H NMR spectra of the protonation of enamine 1d with CF3SO3H in CD2Cl2. Initial enamine 1d at rt (a); the reaction mixture after protonation with CF3SO3H at ꢀ80 8C
(b), +20 8C (c), ꢀ80 8C after a short heating cycle (d), and standing at +30 8C during 10 (e), 20 (f) and 30 (g) min.
mineral and strong carboxylic acids was attributed to the
bifunctional catalysis of trifluoroacetic acid on the nitrogen-to-
carbon transfer of the proton [20]. According to 1H, 13C and 15N
NMR spectra, compound 4dc exists as a single isomer. The NOE
experiments suggest that this salt has the E-configuration, that is
opposite to the geometry of the initial enamine 1d but is similar to
that of the enammonium salt 4cb. In contrast to the iminium salts
formation, only a slight shielding of the resonance signal in 15N
NMR spectrum occurs in this case (from ꢀ310.8 and ꢀ323.7 for the
initial base 1d to ꢀ308.1 ppm for salt 4dc). These data are in
general agreement with the characteristic changes in 15N spectra
during the protonation of a lone electron pair of the nitrogen atom
[21]. Note that the enammonium chloride 4dc is quite stable: no
iminium-type compounds were observed in the proton spectra
after a day at room temperature in CD2Cl2 solution. But after a
week a mixture of the enammonium salt 4dc and initial base 1d in
a ratio 1.7:1 as well as a hydrolysis product 5 is detected by 1H
NMR spectroscopy. This fact support that the N-protonation is a
reversible process.
the sole existence of the pure triflate form 4da together with the
initial enamine 1d (only Z-isomer). No traces of any other
protonated forms in the reaction mixture were detected (Fig. 4).
Varying the temperature from ꢀ90 8C to 0 8C did not show any
change in this spectrum. Upon heating to +20 8C, the intensity of
the olefinic proton signals of triflate 4da was decreased and the
singlets of the methylene group protons of the iminium salt 3da
(d = 4.66) and the corresponding hydrolysis product 5d (d = 4.21)
appeared progressively for the same quantity. Thus, we have
received a strong evidence to support a nitrogen–carbon proton
transfer by acid or solvent assisted process. The signals of these
enammonium and iminium salts mixture were recorded while
the temperature was decreased to ꢀ90 8C then increased to
+30 8C. During this temperature cycle, the 1H NMR singlet of the
olefinic proton of one isomer of the salt 4da
disappeared and, simultaneously, the singlet of the olefinic
proton of the other isomer ( = 7.98) appeared, suggesting that
(d = 8.03)
d
the a Z,E-isomerization of the enammonium salt taking place.
The corresponding 2D NMR spectra (NOESY and HMBC)
confirmed that the geometry of the major isomer 4da finally
obtained is actually opposite to the configuration of the initial
enamine 1d.
Therefore, we have shown that the first step of these
transformations involves the formation of enammonium salt 4
exhibiting the same configuration that of the initial enamine 1
(Scheme 2). Its isomerization into the corresponding iminium salt
One of the recurrent problems of enamine chemistry is to know
whether the initial enamine 1 undergoes direct C-protonation or if
the enammonium salt 4 is converted into the iminium 3 under acid
conditions?
To answer this question, we monitored by NMR the reaction
of the enamine 1d with acid 2a in CD2Cl2 at low temperature. In
this case, the 1H NMR spectrum recorded at ꢀ90 8C substantiates

A.Y. Rulev, I.A. Ushakov / Journal of Fluorine Chemistry 131 (2010) 53–58
57
Scheme 2.
3 and the simultaneous Z,E-isomerization lead to the thermo-
dynamically more stable E-isomer 4. The same sequence of
transformations has been recorded by NMR spectroscopy during
the monitoring of the reaction of enamine 1d with trifluoroacetic
acid.
HMBC [25] were used for the distinction of the carbon and proton
resonances in all cases. The IR spectrum was measured with a
Specord IR-75 Instrument. The GC/MS analysis was performed on
a Hewlett-Packard HP 5971A Instrument (EI, 70 eV). The silica gel
used for flash chromatography was 230–400 mesh. All the
solvents for NMR research were dried according to standard
procedures and freshly distilled prior to use. The synthesis of gem-
trifluoromethylated enamines 1a–d was described in our
previous paper [16].
3. Conclusion
In conclusion, we have shown that gem-trifluoromethylated
enamines can undergo both N- and C-protonations under the
action of both strong carboxylic and hard mineral acids. The N-
protonation N- vs C-protonation depends on both the structure of
initial base and the nature of the protonating agent. We have thus
successfully showed that the mechanistic course of the reaction
4.1. The reaction of enamines 1a–d with acids
The reaction of protonation was carried out directly in tube of
RMN. The following salts were obtained by this procedure.
suggests
a
N ! C proton shift of the enammonium salt.
b
4.2. Triflate 3aa
Unfortunately, no convincing arguments for the direct C-proto-
nation of the enamines 1 could be obtained in this research. The
absence of the signals of the N-protonated forms in some cases is
probably a result of the fast N ! C-transformation. We found that
the presence of acid could promote the rearrangement of Z-gem-
trifluoro(amino)alkenes into their E-isomers at very mild condi-
tions that allows to prepare these derivatives in high stereo-
selectivity. The results presented here are significant since
showing a detail picture of the key transformations of the
captodative trifluorinated enamines under the action of acids
and will help to understand their behavior in organic synthesis.
The theoretical studies on such enamines are in progress and will
be published in due course.
dH (400 MHz, CD2Cl2): 8.27 (dd, J = 8.0, 1.2 Hz, 1H), 7.81 (dt,
J = 7.6, 1.2 Hz, 1H), 7.73–7.63 (m, 2H), 4.84 (s, 2H), 4.50–4.40 (m,
4H), 2.40–2.30 (m, 4H); dC (100.6 MHz, CD2Cl2): 23.76, 25.44 (CH2
pyrrolidine), 40.17 (CH2), 59.61, 60.28 (N(CH2)2), 117.45 (q,
J = 284 Hz, CF3), 125.08 (C-1), 125.96 (C-3), 130.89 (C-4), 134.97
(C-6), 135.76 (C-5), 147.25 (C-2), 170.41 (q, J = 42.7 Hz, C55N); dF
(376.5 MHz, CD2Cl2): ꢀ64.7;
d
N (40.55 MHz, CD2Cl2): ꢀ10.3 (NO2),
ꢀ146.9 (55N+).
4.3. Triflate 3ba
d
H (400 MHz, CDCl3): 7.47 (d, J = 7.8 Hz, 1H), 7.30–7.20 (m, 2H),
7.15–7.05 (m, 1H), 4.53 (s, 2H), 4.45–4.35 (m, 4H), 2.35–2.25 (m,
4H); dC (100.6 MHz, CDCl3): 23.58, 24.04 (CH2 pyrrolidine), 41.17
(CH2), 59.53, 59.98 (N(CH2)2), 117.21 (q, J = 282 Hz, CF3), 124.12 (C-
2), 129.02 (C-5), 129.71 (C-1), 130.91 (C-4), 131.52 (C-6), 133.49
(C-3), 170.56 (q, J = 42.7 Hz, C55N).
4. Experimental
General remarks. Dynamic 1H, 13C, 19F and 15N NMR spectra
were recorded on a Bruker DPX 400 spectrometer at 400.16,
100.61, 376.5 and 40.55 MHz, respectively, for solution in CD2Cl2
or CDCl3. Chemical shifts (d) in parts per million (ppm) are
reported using residual dichloromethane (5.32 for 1H and 54.00
for 13C) or chloroform (7.25 for 1H and 77.20 for 13C) as internal
reference. The coupling constants (J) are given in Hertz. 19F NMR
chemical shifts are reported in ppm downfield to CFCl3. 15N NMR
chemical shifts were obtained from 2D{1H–15N} spectra recorded
by the use of a gradient probe working in the hmbcgp mode
optimized to the long-range coupling constant JNH of 9 Hz and
reported in ppm downfield to CH3NO2. The concerted application
of 1H–1H 2D homonuclear experiments COSY [22] and NOESY [23]
as well as 1H–13C 2D heteronuclear experiments HSQC [24] and
4.4. Triflate 3ca
dH (400 MHz, CDCl3): 7.65–7.50 (m, 2H), 7.45–7.15 (m, 2H),
4.59 (s, 2H), 4.45–4.25 (m, 4H), 2.20–1.70 (m, 6H); dF (376.5 MHz,
CDCl3): ꢀ61.7; dN (40.55 MHz, CDCl3): ꢀ146.7 (55N+).
4.5. Triflate 3da
dH (400 MHz, CD2Cl2): 8.30–8.20 (m, 2H), 7.45–7.35 (m, 2H),
4.70 (s, 2H), 4.43 (q, J = 7.3 Hz, 2H), 4.33 (q, J = 7.3 Hz, 2H), 1.68 (t,

58
A.Y. Rulev, I.A. Ushakov / Journal of Fluorine Chemistry 131 (2010) 53–58
J = 7.3 Hz, 3H), 1.59 (t, J = 7.3 Hz, 3H); dF (376.5 MHz, CD2Cl2):
ꢀ62.1.
4.14. Chloride 4dc
dH (400 MHz, CD2Cl2): E-isomer: 10.25 (br.s., 1H), 8.61 (s, 1H),
8.28 (d, J = 8.5 Hz, 2H), 7.56 (d, J = 8.5 Hz, 2H), 3.51 (q, J = 7.3 Hz,
4H), 1.52 (t, J = 7.3 Hz, 6H); dC (100.6 MHz, CD2Cl2): 11.17 (CH3),
52.66 (N(CH2)2), 120.77 (q, J = 277 Hz, CF3), 124.29 (C-3,5), 126.18
(q, J = 34 Hz, 55C–N), 130.02 (C-2,6), 137.03 (C-1), 141.78 (br.s.,
4.6. Trifluoroacetate 3ab
dH (400 MHz, CD2Cl2): 8.29 (d, J = 8.0 Hz, 1H), 7.78 (dt, J = 7.6,
1.0 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 4.67 (s,
2H), 4.43–4.33 (m, 4H), 2.40–2.30 (m, 4H);
ꢀ64.5.
d
F (376.5 MHz, CD2Cl2):
CH55), 149.15 (C-4);
d
F (376.5 MHz, CD2Cl2): ꢀ56.5;
dN (40.55 MHz,
CD2Cl2): ꢀ12.9 (NO2), ꢀ308.1 (55N+).
4.7. Trifluoroacetate 3cb
4.15. 3-(2-Bromophenyl)-1,1,1-trifluoroacetone 5b
d
H (400 MHz, CDCl3): 7.55–7.40 (m, 2H), 7.35–7.10 (m, 2H), 4.53
[Found: C, 40.47; H, 2.28. C9H6BrF3O requires C, 40.48; H,
2.26%]; H (400 MHz, CDCl3): 7.60 (d, J = 8.0 Hz, 1H), 7.35–7.25 (m,
1H), 7.27–7.18 (m, 2H), 4.19 (s, 2H); C (100.6 MHz, CDCl3): 43.81
(s, 2H), 4.35–4.20 (m, 4H), 2.20–1.70 (m, 6H).
d
d
4.8. Trifluoroacetate 3db
(CH2), 115.89 (q, J = 292 Hz, CF3), 125.07 (C-2), 127.96 (C-5), 129.93
(C-4), 131.24 (C-1), 131.99 (C-6), 133.16 (C-3), 187.79 (q, J = 36 Hz,
dH (400 MHz, CD2Cl2): 8.24 (d, J = 8.7 Hz, 2H), 7.38 (d, J = 8.7 Hz,
C55O); n
max (film) 1769 (C55O) cmꢀ1; m/z (EI): 268 (M++1, 55), 266
2H),4.66(s, 2H), 4.41(q,J = 7.3 Hz, 2H), 4.34(q, J = 7.3 Hz, 2H), 1.65(t,
(M+ꢀ1, 55), 187 (60), 169 (100).
J = 7.3 Hz, 3H), 1.58 (t, J = 7.3 Hz, 3H);
4.9. Triflate 4ca
d
F (376.5 MHz, CD2Cl2): ꢀ63.6.
4.16. 3-(4-Nitrophenyl)-1,1,1-trifluoroacetone 5d
d
H (400 MHz, CDCl3): 8.21 (d, J = 8.8 Hz, 1H), 7.39 (d, J = 8.8 Hz,
dH (400 MHz, CDCl3): 10.40 (br.s., 1H), 7.88 (s, 1H), 7.65–7.50
(m, 2H), 7.45–7.15 (m, 2H), 3.90–3.70 (m, 2H), 3.70–3.50 (m, 2H),
2.20–1.70 (m, 6H); dC (100.6 MHz, CDCl3): 20.70, 23.01 (CH2
piperidine), 57.43 (N(CH2)2), 127.62 (55C–N), 122.11, 129.46,
1H), 4.13 (s, 2H); dC (100.6 MHz, CDCl3): 43.29 (CH2), 115.20 (q,
J = 286 Hz, CF3), 124.24 (C-3,5), 130.92 (C-2,6), 137.81 (C-1),
147.88 (C-4), 186.87 (q, J = 38 Hz, C55O).
Acknowledgment
131.62, 132.55, 133.86 (Car), 138.77 (CH55); dF (376.5 MHz, CDCl3):
ꢀ56.6; dN (40.55 MHz, CDCl3): ꢀ317.4 (55N+).
This work was supported by the Russian Foundation for Basic
Research (Grant No. 08-03-00067-a).
4.10. Trifluoroacetate 4cb
Appendix A. Supplementary data
d
H (400 MHz, CDCl3): 7.60 (s, 1H), 7.55–7.40 (m, 2H), 7.35–7.10
(m, 2H), 3.70–3.50 (m, 4H), 2.20–1.70 (m, 6H).
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jfluchem.2009.10.001.
4.11. Chloride 4cc
References
d
H (400 MHz, CDCl3): 9.44 (br.s., 1H), 8.57 (s, 1H), 7.55–7.45 (m,
2H), 7.30–7.15 (m, 2H), 3.60–3.40 (m, 4H), 2.40–2.20 (m, 4H),
1.80–1.60 (m, 2H).
[1] G. Alvarez, J. Palomar, J.L.G. de Paz, J. Mol. Struct. (Theochem.) 541 (2001) 111.
[2] J. Catalan, F.G. Blanco, in: Z. Rappoport (Ed.), The Chemistry of Enamines, Wiley,
NY, 1994, p. 695.
[3] B. Kempf, N. Hampel, A.R. Ofial, H. Mayr, Chem. Eur. J. 9 (2003) 2209.
[4] P.W. Hickmott, Tetrahedron 38 (1982) 1975.
4.12. Triflate 4da
[5] J.V. Greenhill, Chem. Soc. Rev. 6 (1977) 277.
dH (400 MHz, CD2Cl2): E-isomer: 9.37 (br.s., 1H), 8.33 (d,
J = 8.7 Hz, 2H), 8.06 (s, 1H), 7.40 (d, J = 8.7 Hz, 2H), 3.80–3.40 (m,
4H), 1.41 (t, J = 7.3 Hz, 6H); Z-isomer: 10.63 (br.s., 1H), 8.30 (d,
J = 8.8 Hz, 2H), 7.98 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 3.80–3.40 (m,
4H), 1.50 (t, J = 7.3 Hz, 6H); dC (100.6 MHz, CD2Cl2): E-isomer:
10.74 (CH3), 55.20 (N(CH2)2), 125.35 (C-3,5), 125.17 (q, J = 35 Hz,
55C–N), 129.02 (C-2,6), 132.60 (C-1), 139.17 (br.s., CH55), 149.20 (C-
4); Z-isomer: 10.81 (CH3), 54.55 (N(CH2)2), 119.77 (q, J = 277 Hz,
CF3), 124.12 (C-3,5), 125.17 (q, J = 35 Hz, 55C–N), 129.94 (C-2,6),
135.01 (C-1), 140.14 (br.s., CH55), 149.07 (C-4); dF (376.5 MHz,
CD2Cl2): E-isomer: ꢀ56.8; Z-isomer: ꢀ57.1; dN (40.55 MHz,
CD2Cl2): Z-isomer: ꢀ14.4 (NO2), ꢀ306.8 (55N+).
[6] A.Yu. Rulev, S.V. Zinchenko, Mendeleev Commun. (2001) 70.
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Chem. Sci. 37 (1988) 957.
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4.13. Trifluoroacetate 4db
d
H (400 MHz, CD2Cl2): 8.30 (d, J = 8.7 Hz, 2H), 7.97 (s, 1H), 7.58
(d, J = 8.7 Hz, 2H), 3.62 (q, J = 7.3 Hz, 4H), 1.42 (t, J = 7.3 Hz, 6H); dC
(100.6 MHz, CD2Cl2): 10.61 (CH3), 53.20 (N(CH2)2), 123.80 (C-3,5),
126.39 (q, J = 35 Hz, 55C–N), 129.60 (C-2,6), 136.10 (C-1), 139.42
(br.s., CH55), 148.7 (C-4); dF (376.5 MHz, CD2Cl2): ꢀ56.8; dN
(40.55 MHz, CD2Cl2): ꢀ14.2 (NO2), ꢀ307.5 (55N+).