A cascade approach to captodative trifluoromethylated enamines or vinylogous guanidinium salts: aromatic substituents as switches of reaction direction

Article abstract of DOI:10.1002/ejoc.200900926

β-Halo-β-(trifluoromethyl)styrenes readily react with a variety of nitrogen nucleophiles bearing primary amino groups to afford either the captodative trifluoromethylated enamines or vinylogous guanidinium salts in a selective fashion depending on the electronic natures of the aromatic substituents.

Full text of DOI:10.1002/ejoc.200900926

FULL PAPER
DOI: 10.1002/ejoc.200900926
A Cascade Approach to Captodative Trifluoromethylated Enamines or
Vinylogous Guanidinium Salts: Aromatic Substituents as Switches of Reaction
Direction
Alexander Yu. Rulev,*[a] Vasiliy M. Muzalevskiy,[b] Evgeniy V. Kondrashov,[a]
Igor A. Ushakov,[a] Aleksey V. Shastin,[c] Elizabeth S. Balenkova,[b] Günter Haufe,[d] and
Valentine G. Nenajdenko*[b]
Keywords: Amines / Nucleophilic substitution / Domino reactions
β-Halo-β-(trifluoromethyl)styrenes readily react with a vari-
ety of nitrogen nucleophiles bearing primary amino groups
to afford either the captodative trifluoromethylated enamines
or vinylogous guanidinium salts in a selective fashion de-
pending on the electronic natures of the aromatic substitu-
ents.
It is no surprise that different efforts to prepare α-poly-
fluoroalkyl-containing enamines have been undertaken, in-
cluding Wittig reactions with trifluoroacetamides,[3,4] treat-
ment of amines with perfluoroalkyl ketones,[5] additions of
amines to trifluoromethylacetylenes[6] and direct trifluoro-
methylation of pyrrolidinones.[7] A simple method for the
preparation of fluoroalkyl β-enaminophosphonates from
alkylphosphonates and perfluoroalkyl nitriles has also been
reported.[8] The most straightforward route to captodative
(trifluoromethyl)-aminoalkenes is through the substitution
of an appropriate leaving group in the corresponding alkene
by an amino function. In general, nucleophilic vinylic sub-
stitution is an important synthetic tool for the preparation
of compounds containing heteroatom-substituted carbon–
carbon double bonds.[9] Previously this methodology has
been successfully applied to the synthesis of various capto-
dative aminoalkenes containing carbonyl, formyl or alkoxy-
carbonyl functions.[10] Similar approaches using α-halo (tri-
fluoromethyl) olefins have been reported only infrequently.
Some gem-perfluoroalkylated enamines have been prepared
by treatment of β-halo- or β-alkoxy-substituted β-(trifluoro-
methyl)styrenes with lithium alkylamides.[11] Very recently,
we have developed an efficient method of synthesis of α-
trifluoromethylated aminoalkenes by treatment of β-halo-
β-(trifluoromethyl)styrenes with secondary amines.[12] The
starting alkenes can be prepared very easily by a novel gene-
ral method for catalytic olefination of carbonyl com-
pounds.[13] As a part of our research program relating to
the synthesis of novel captodative aminoalkenes and under-
standing of the particularities of their chemical behaviour,
we have now examined reactions between the same styrenes
and primary amines. Here we describe our synthetic efforts
to achieve captodative amino(trifluoromethyl)alkenes bear-
ing secondary amino groups.
Introduction
The significant progress in synthetic fluorine chemistry
over recent decades is well documented.[1] The presence of
fluorine atoms in a molecule is known often to induce un-
usual chemical, physical and biological properties. As a
consequence, much attention has been devoted to the devel-
opment of synthetic routes to various classes of fluorinated
compounds. Among these, trifluoromethylated enamines
have attracted increasing attention from organic chemists.
They have found numerous applications in the construction
of new fluorine-containing biologically active compounds
and analogues of natural products.[2] gem-Amino(trifluoro-
methyl)olefins are of great theoretical, synthetic and phar-
macological interest as distinctive captodative systems each
bearing a strongly electron-donating amino function and
a highly electronegative trifluoromethyl group at the same
carbon atom of the double bond.
[a] A. E. Favorsky Institute of Chemistry, Siberian Branch of the
Russian Academy of Sciences,
1, Favorsky Str., Irkutsk 664033, Russia
Fax: +7-3952-419346
E-mail: rulev@irioch.irk.ru
[b] Moscow State University, Department of Chemistry,
Leninskie Gory, Moscow 119992, Russia
Fax: +7-495-9328846
E-mail: nen@acylium.chem.msu.ru
[c] Institute of Problems of Chemical Physics,
Chernogolovka, Moscow Region 142432, Russia
[d] Organisch-Chemisches Institut, Westfälische Wilhelms-Uni-
versität Münster,
48149 Münster, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200900926.
300
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 300–310

Aromatic Substituents as Switches of Reaction Direction
(Table 1, Entries 13, 14). Thus, when the styrene 1d was
treated with an excess of aniline, only the signals of the
unchanged starting materials were detectable by NMR
spectroscopy even after prolonged heating of the reaction
mixture in dioxane at reflux and starting material was reco-
vered almost quantitatively after usual workup.
Results and Discussion
The β-halogen-β-(trifluoromethyl)styrenes 1a–l (see
Tables 1 and 2, below), including the parent compound 1l
and derivatives bearing either electron-withdrawing or elec-
tron-donating groups on their benzene rings, were used in
reactions with primary amines. It was found that the struc-
tural peculiarities of substrates 1 have a dramatic influence
on the pathways of the transformations, summarized in
Tables 1 and 2, below.
Initially we focused on styrenes bearing electron-with-
drawing groups, because they had previously displayed
higher activities in reactions with secondary amines.[12] The
target enamines 2 were successfully obtained from the sty-
renes 1a–e containing strong acceptors such as NO2 in their
aromatic rings. The reactions between these olefins and a
wide range of nitrogen nucleophiles bearing primary amino
groups could be performed under diverse experimental con-
ditions (from some minutes to two days, from room tem-
perature to reflux, without solvent or in THF, dioxane or
alcohol), exclusively providing mixtures of the correspond-
ing enamines 2 and azomethines 3, which could easily be
separated by column chromatography (Scheme 1, Table 1).
In all reactions studied, the enamines 2 were formed as
mixtures of Z and E isomers. The stereoselectivities of the
overall transformations were high; by 1H NMR spec-
troscopy the Z double bond geometry was seen to be
strongly favoured in most cases, by up to 9:1. The Z config-
urations were assigned to the major isomers of 2 by applica-
1
tion of H–1H 2D homonuclear NOESY (Figure 1). In the
spectrum of the major isomer of the enamine 2a, for exam-
ple, there are NOE peaks between the signal of the olefinic
proton and the ortho-protons of the aromatic ring only. In
contrast, the NOESY spectrum of the minor isomer has
cross-peaks of the olefinic proton both with the H-2 aro-
matic protons and with the protons of a CH2 group of the
cyclohexyl moiety. As in cases both of normal enamines
and of captodative carbonyl-bearing enamines,[10] the signal
for the olefinic proton of an E isomer is always observed at
lower frequency.
Scheme 1. Reactions between primary amines and styrenes 1a–e.
Generally, the position of the nitro substituent in the aryl
group or the nature of the vinylic halogen atom (Br or Cl)
in the initial substrate 1, as well as the steric and electronic
effects of the substituent on the nitrogen atom of the ali-
phatic amine, have just a small influence on the yields and
Figure 1. Main NOESY correlations for enamine 2a.
It should be noted that enamines 2 are slowly trans-
stereoselectivities. The best results were achieved when basic formed into their tautomers 3 (Scheme 1). Thus, low-inten-
primary amines were used as nucleophiles (Table 1, En- sity signals for compound 3a were observed in the proton
tries 1–12). It should be noted that decreased nucleophilic- spectra of enamine 2a after a week in CDCl3 solution at
ity resulted in reaction failure with aromatic amines ambient temperature.
Table 1. Reactions between primary amines and styrenes 1a–e.
Entry Styrene
Amine
R
Conditions
Product
Z/E ratio in 2 Yield (%)[a]
Y
X
1
2
1a
1a
4-NO2
Br
cHex
THF, reflux, 8 h
EtOH, reflux, 8 h
2a
3a
2b
3b
88:12
90:10
75
11
29
45
85
88
90
63
80
71
20[b]
97
96
96
0
4-NO2
Br
sBu
3
4
5
6
7
8
9
10
11
12
13
14
1b
1b
1b
1b
1b
1c
1c
1d
1d
1 e
1b
1d
4-NO2
4-NO2
4-NO2
4-NO2
4-NO2
3-NO2
3-NO2
2-NO2
2-NO2
2-NO2
4-NO2
2-NO2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Cl
Cl
Br
Me
iPr
Ph(CH2)2
(S)-PhCHMe
(MeO)2CHCHMe
cHex
sBu
cHex
sBu
iPr
MeOH, room temp., 1 d
neat, room temp., 2 d
neat, room temp., 1.5 d
neat, 120 °C, 18 h
neat, 120 °C, 6 h
THF, reflux, 7 h
2c + 3c (1:3)
2d + 3d (1:0.9)
2e + 3e (1:4)
2f + 3f (1:1)
2g + 3g (1:0.5)
2h + 3h (1:1.4)
3i
2j + 3j (1:1.1)
2k + 3k (1:1.5)
2l + 3l (1:0.9)
–
52:48
88:12
80:20
76:24
91:9
90:10
91:9
88:12
90:10
88:12
–
EtOH, reflux, 8 h
neat, room temp., 6 h
dioxane, reflux, 3 h
neat, room temp., 6 h
THF, reflux, 2 h
4-MeOC6H4
Ph
dioxane, reflux, 6 h
–
–
0
[a] Isolated yield. [b] 30% yield of starting material was recovered; if the reaction was carried out in THF at reflux for 15 h more than
80% of the initial styrene 1c was recovered.
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301

A. Yu. Rulev, V. G. Nenajdenko et al.
FULL PAPER
The enamine or azomethine moieties in compounds 2 or in good yields. Aminoenones of this type can be versatile
3 are easily hydrolyzed to give the corresponding carbonyl intermediates for the synthesis of various heterocycles
derivatives. The accompanying hydrolysis reaction begins (Scheme 4).[14] Additionally, these transformations provided
during silica gel column chromatography. For this reason direct chemical evidence for the structures of the unusual
the yields of the purified target compounds decreased salts 5. It should be noted that the alternative structure rep-
slightly, and sometimes the corresponding ketones 4 resented by the isomeric amides 7 was excluded by ad-
(Scheme 2) were formed simultaneously. Thus, during puri- ditional NMR spectroscopic experiments. That is, there are
fication of enamines 2a and 2b and azomethines 3a and 3b significant differences in the chemical shifts of the NH pro-
1
small quantities (up to 3–5%) of ketone 4 were isolated.
tons in the H NMR spectrum of the hydrolysis product of
compound 5a (4.12 and 11.39 ppm), due to intramolecular
hydrogen bond formation. Moreover, the low-frequency
chemical shift of the α-carbon atom (δ = 80.33 ppm), to-
gether with the high-frequency shift of the β-carbon atom
(δ = 159.21 ppm) of the obtained product, suggest the pres-
ence of an extremely polar carbon–carbon double bond: the
difference [∆δ = δ(Cβ) – δ(Cα)] amounts to +79 ppm and is
comparable to those observed for simple push-pull amino-
enones (65–70 ppm).[15] Finally, the chemical shift of the
carbonyl group (183.50 ppm) provides an additional argu-
ment for the structure of ketone 6a. The structure of this
compound was also confirmed by careful analysis of 2D
NMR spectra (NOESY, HSQC, HMBC).
Scheme 2. Hydrolysis of derivatives 2a, 2b, 3a and 3b.
Surprisingly, in reactions between primary amines and
styrenes lacking acceptor-substituted aromatic rings, nei-
ther the expected captodative enamines 2 nor their isomers
3 were obtained. In contrast to styrenes 1a–e, the analogues
1f–k, bearing functional groups such as Me, OMe, and Cl,
underwent unusual transformations on treatment with pri-
mary aliphatic amines, leading to the triamino derivatives
5a–m in moderate to high yields, independently of the sub-
stituent position in the aromatic ring (Scheme 3, Table 2).
The parent unsubstituted styrene 1l is also a suitable sub-
strate, affording the products 5n–p in good yields.
Scheme 3. Reactions between primary amines and styrenes 1f–l.
The derivatives 5 thus obtained are useful precursors of
push-pull aminoenones 6. In fact, the compounds 5 were
easily hydrolyzed with dilute HCl to give the ketones 6a–g Scheme 4. Hydrolysis of derivatives 5 to afford compounds 6.
Table 2. Reactions between primary amines and styrenes 1f–l.
Entry
Styrene
Amine
R
Conditions
Product
Yield (%)[a]
Y
X
1
2
3
4
5
6
7
8
1f
1f
1f
1g
1g
1h
1h
1i
4-Cl
4-Cl
4-Cl
4-Cl
Br
Br
Br
Cl
Cl
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
cHex
iPr
(MeO)2CHCHMe
iPr
neat, reflux, 1 h
neat, 80 °C, 5 h
neat, 120 °C, 4 h
neat, 120 °C, 18 h
diglyme, reflux, 8 h
neat, reflux, 3 h
neat, 120 °C, 4 h
neat, reflux, 8 h
neat, 120 °C, 4 h
dioxane, reflux, 7 h
dioxane, reflux, 7 h
neat, reflux, 7 h
neat, reflux, 3 h
neat, 120 °C, 6 h
THF, reflux, 7 h
EtOH, reflux, 6 h
5a
5b
5c
5d
5e
5f
5g
5h
5i
5j
5k
5l
5m
5n
5o
5p
64
63
39
34
20[b]
85
92
61
81
65
59
72
69
85
88
61
4-Cl
cHex
cHex
iPr
sBu
iPr
cHex
cHex
cHex
sBu
iPr
cHex
Bn
4-Me
4-Me
4-MeO
4-MeO
4-MeO
3-MeO
2-MeO
2-MeO
H
9
1i
10
11
12
13
14
15
16
1i
1j
1k
1k
1l
1l
1l
H
H
[a] Isolated yields. [b] 50% yield of the starting material was recovered. No reaction occurred when THF or dioxane were used as solvents.
302 Eur. J. Org. Chem. 2010, 300–310
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Aromatic Substituents as Switches of Reaction Direction
Although the data currently available do not yet allow
the assignment of detailed mechanisms for the formation of
compounds 2, 3 and 5 in the reactions between styrenes 1
and primary amines, the results obtained can be explained
in terms of the general domino transformations shown in
Scheme 5 as the most probable hypothesis.
Scheme 6. Formation of compounds (Z)-2.
withdrawing (NO2) or electron-donating (Me) substituents,
as well as the unsubstituted parent compound, as models,
together with methylamine. Full optimization of the geome-
tries of the molecules was performed, as well as calculation
of the total energies corresponding to these optimized geo-
metries. Calculations were carried out for the isolated mole-
cules of the model compounds (in vacuo) with replacement
of the complex amino fragment with the methylamine moi-
ety as a simplification. The calculations were performed for
all possible conformers of the final products of methyl-
amine addition at the α (group 1) or β (group 2) positions
of the styrenes. For each group the most stable conformers
and their energies were chosen and compared with each
other. In all cases, the formation of β adducts was preferred
over that of the α adducts by 5–6 kcalmol–1. The corre-
sponding calculated structures and their energies are listed
in the Table in the Supporting Information.
In contrast, the styrenes 1f–l, lacking electron-with-
drawing substituted aromatic rings, react with primary
amines by an alternative pathway through an elimination/
addition sequence to give the enamines C. The intermediate
acetylene derivatives B were detected by NMR and GC-
MS. When the product mixture resulting from the reaction
between the styrene 1i and sec-butylamine was applied to
column chromatography, two fractions were obtained: the
major one was the product 5h, whereas the minor one con-
tained a mixture of the initial substrate 1i and an unknown
compound. Careful analysis of the 1D (1H, 13C) and 2D
(HMBC, COSY) NMR spectra of the latter fraction con-
firmed the presence of alkyne B (Y = 4-MeO) in the mix-
ture. The 13C NMR spectrum contains two quadruplets at
δ = 74.9 ppm (J = 52.1 Hz) and δ = 87.3 ppm (J = 6.4 Hz)
attributable to the acetylenic carbon atoms, together with a
quadruplet for the CF3 group (δ = 120.9 ppm, J = 231 Hz).
The signals for the aromatic moiety were observed at δ =
114.5, 126.3, 130.2 and 161.8 ppm. The presence of a mo-
lecular ion of m/z 200 in the mass spectrum also confirmed
the structure of alkyne B (Y = MeO). Amines add to alkyne
B, leading directly to enamines C, which undergo suc-
ceeding transformations as we have described previously,[12]
so this hypothetical scheme provides a convenient explana-
tion for the selectivity of the formation either of the en-
amines 2 or of the salts 5.
Scheme 5. Possible mechanisms for the formation of compounds 2,
3 and 5.
A principal reason for the different reaction directions in
the nucleophilic substitutions of 1a–e and 1f–l would ap-
pear to be the stabilities of the intermediate zwitterions A
(stabilized by the acceptor substituents) in the cases of the
alkenes 1a–e (addition/elimination)[16] and the impossibility
of such a direction in the cases of the olefins 1f–l, for which
initial HX elimination with intermediate formation of
acetylenes B and subsequent nucleophilic addition (elimi-
nation/addition) would seem to be the most favourable re-
action pathway. From the mechanistic point of view, the key
steps of the substitution of the halogen atoms in styrenes
1a–e would seem to be β-addition of the primary amines to
the carbon–carbon double bond and subsequent elimi-
nation of the hydrogen halide: Ad – E. It should be under-
lined that the presence of an aromatic ring bearing an elec-
tron-withdrawing group should stabilize the β adduct A.
The dehydrohalogenation of this intermediate by the amine
leads directly to the enamine 2 and its tautomer 3.
Evidence in support of this hypothesis (i.e., β-addition
instead of α-addition) was obtained by stereochemical
analysis of the reaction. The geometries of the styrenes 1a
and 2a were elucidated by comparison of the vicinal cou-
pling constants between the carbon atom of the CF3 group
and the olefinic proton (3JH,CF = 5.5 Hz for both com-
pounds 1a and 2a).[17,18] Taking into account that the major
isomer of the enamine 2a has the Z configuration, we con-
cluded that the initial styrene 1a would have the same ge-
ometry. The preservation of the configuration can be easily
explained in terms of a preferable anti-elimination of HX
(Scheme 6). Moreover, no alternative intermediate, such as
a diamino derivative, has been detected (cf. ref.[19]).
The preference for the pathway involving an initial direct
β-addition of the primary amine to the double bond of the
starting styrene 1a and subsequent dehydrohalogenation re-
sulting in the formation of enamine 2a was confirmed by
Conclusions
In summary, we have demonstrated that vinylic substitu-
RHF-MP2 quantum chemical calculations at the MP2/6– tion of gem-trifluoromethylated haloalkenes with primary
311+dp level with use of styrenes bearing either electron- amines is a valuable synthetic tool for the preparation of
Eur. J. Org. Chem. 2010, 300–310
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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303

A. Yu. Rulev, V. G. Nenajdenko et al.
FULL PAPER
54.0 (CH), 104.1 (q, J = 5.0 Hz, CH=), 122.1 (q, J = 275.7 Hz,
CF3), 123.9 (C-3,5), 129.1 (C-2,6), 135.6 (q, J = 33 Hz, =C–N),
142.7 (C-1), 146.0 (C-4) ppm. 19F NMR (282 MHz, CDCl3): Z iso-
mer: δ = –69.3 ppm. E isomer: δ = –63.2 ppm. 15N NMR
(40.6 MHz, CDCl3): Z isomer: δ = –302.5 (NH), –10.8 (NO2) ppm.
captodative amino(trifluoromethyl)alkenes. However, the
synthesis of the target enamines is strongly limited by the
natures of the substituents on the aromatic rings, which can
be regarded as switches of the reaction direction: whereas
styrenes bearing electron-withdrawing groups led exclu-
sively to the target enamines 2 (or their tautomers 3), their
analogues containing electron-donating substituents in their
aromatic rings (or without substituents) underwent pre-
viously unprecedented[12] transformations into the amidin-
ium salts 5.
IR (KBr): ν = 1633, 3372 cm–1. MS (EI): m/z (%) = 314 (5) [M]+,
˜
178 (28), 83 (83), 55 (100). C15H17F3N2O2 (314.303): calcd. C
57.32, H 5.45, N 8.91; found C 57.51, H 5.60, N 9.22.
N-[2,2,2-Trifluoro-1-(4-nitrobenzyl)ethylidene]cyclohexylamine (3a):
Oil; yield 11%. 1H NMR (400 MHz, CDCl3): δ = 1.10–1.80 (m, 10
H, CH2 cyclohexyl), 3.48 (m, 1 H, CH cyclohexyl), 3.87 (s, 2 H,
CH2), 7.31 (d, J = 8.6 Hz, 2 H, CHAr), 8.17 (d, J = 8.6 Hz, 2 H,
CHAr) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 24.2, 25.4, 32.9
(CH2), 32.7 (ArCH2), 60.9 (CH), 119.9 (q, J = 279.5 Hz, CF3),
124.3 (C-3,5), 129.3 (C-2,6), 142.4 (C-1), 147.2 (C-4), 153.0 (q, J =
33 Hz, C=N) ppm. 19F NMR (376.5 MHz, CDCl3): δ = –71.9 ppm.
Experimental Section
General Remarks: 1H, 13C, 15N and 19F NMR spectra were re-
corded with Bruker ARX 300, Bruker AMX 400 and Bruker
AVANCE 400 MHz spectrometers with solutions in CDCl3, [D6]-
DMSO or (CD3)2CO. Chemical shifts (δ) in ppm are reported with
use of the residual chloroform (7.25 for 1H and 77.20 for 13C),
IR (KBr): ν = 1600 cm–1. MS (EI): m/z (%) = 314 (12) [M]+, 232
˜
(26), 83 (46), 55 (100). C15H17F3N2O2 (314.303): calcd. C 57.32, H
5.45, N 8.91; found C 57.61, H 5.24, N 8.68.
1,1,1-Trifluoro-3-(4-nitrobenzyl)acetone (4): Oil. 1H NMR
(400 MHz, CDCl3): δ = 4.13 (s, 2 H, CH2), 7.39 (d, J = 8.8 Hz, 2
H, CHAr), 8.21 (d, J = 8.8 Hz, 2 H, CHAr) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 43.3 (Ar-CH2), 115.2 (q, J = 286 Hz,
CF3), 124.2 (C-3,5), 130.9 (C-2,6), 137.8 (C-1), 147.9 (C-4), 186.9
(q, J = 38 Hz, C=N) ppm. 19F NMR (376.5 MHz, CDCl3): δ =
–78.5 ppm. MS (EI): m/z (%) = 233 (17) [M]+, 164 (24), 136 (77),
78 (100).
1
DMSO (2.50 for H and 29.90, 39.50 for 13C) or acetone (2.09 for
1H and 29.90, 206.70 for 13C) as internal references. The coupling
constants (J) are given in Hertz (Hz). The concerted application of
1H–1H 2D COSY[20] and NOESY[21] homonuclear experiments as
1
well as H–13C 2D HSQC[22] and HMBC[23] heteronuclear experi-
ments was used for the distinction of the carbon and proton reso-
nances in all cases. The IR spectra were recorded with a Bruker
Vertex 70 FT-IR spectrometer and with a portable Varian 3100 dia-
mond ATR/FT-IR spectrometer. The GC/MS analyses were per-
formed with a Shimadzu GCMS-QP5050A instrument (EI, 70 eV).
ESI-MS spectra were measured with a MicroTof Bruker Daltonics
instrument. The silica gel used for flash chromatography was 230–
400 mesh. All reagents were of reagent grade and were either used
as such or distilled prior to use. All the solvents were dried by
standard procedures and freshly distilled prior to use. The β-chloro-
and β-bromo-β-(trifluoromethyl)styrenes 1a–l were prepared as re-
ported previously.[13b,13h] The quantum chemical calculations were
carried out at the MP2/6–311+dp level with use of the PC
GAMESS/Firefly QC package.[24]
N-[2-(4-Nitrophenyl)-1-(trifluoromethyl)ethenyl]-2-butylamine (2b):
Yellow solid; m.p. 71 °C; yield 125 mg (29%). 1H NMR (400 MHz,
CDCl3): Z isomer: δ = 0.84 (t, J = 7.3 Hz, 3 H, CH3), 1.01 (d, J =
6.2 Hz, 3 H, CH3), 1.30–1.50 (m, 2 H, CH2), 3.15 (m, 1 H, NH),
3.38 (m, 1 H, CH), 5.92 (s, 1 H, CH=), 7.48 (d, J = 8.6 Hz, 2 H,
CHAr), 8.17 (d,
J = 8.6 Hz, 2
H, CHAr) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 10.2 (CH3CH2), 20.6 (CH3CH), 30.3
(CH2CH3), 52.0 (CH), 103.6 (q, J = 5.0 Hz, CH=), 122.1 (q, J =
276.0 Hz, CF3), 123.9 (C-3,5), 129.1 (C-2,6), 135.7 (q, J = 33 Hz,
=C–N), 142.7 (C-1), 146.0 (C-4) ppm. 15N NMR (40.6 MHz,
CDCl3): Z isomer: δ = –302.7 (NH), –11.8 (NO2) ppm. IR (KBr):
ν = 1627, 3379 cm–1. MS (EI): m/z (%) = 288 [M]+ (14), 259 (48),
˜
General Procedure for Reactions between the β-Chloro- and β- 198 (31), 57 (74). 41 (100%). C13H15F3N2O2 (288.266): calcd. C
Bromo-β-Trifluoromethylstyrenes 1a–e and Primary Amines: The
appropriate styrene (1a–e, 1–1.5 mmol) and the amine [10–
15 mmol; in this case methylamine in methanol (8 ) was used],
either in the solvent given or without solvent, were maintained at
room temperature or reflux or were heated in a sealed glass tube
with a Young tap. Excess amine and solvent were evaporated off at
reduced pressure and the residue was purified by column
chromatography [silica gel, CH2Cl2/pentane (2:1) or Et2O/hexane
(1:2)]. The enamines 2a and 2b and the azomethines 3a and 3b were
separated on silica gel, with Et2O/hexane (1:7) as eluent. In the
NMR spectra of some mixtures of the (Z,E)-enamines 2 and the
azomethines 3 only the most characteristic signals are given for
minor components.
54.17, H 5.24; found C 53.94, H 5.30.
N-[2,2,2-Trifluoro-1-(4-nitrobenzyl)ethylidene]-2-butylamine
(3b):
1
Oil; yield 194 mg (45%). H NMR (400 MHz, CDCl3): δ = 0.70–
1.20 (m, 6 H, CH3), 1.45–1.60 (m, 2 H, CH2), 3.56 (m, 1 H, CH),
3.84 (A-part of the AB system, J = 16 Hz, 1 H, Ar-CH2), 3.90 (B-
part of the AB system, J = 16 Hz, 1 H, Ar-CH2), 7.31 (d, J =
8.6 Hz, 2 H, CHAr), 8.16 (d, J = 8.6 Hz, 2 H, CHAr) ppm. 13C
NMR (100.6 MHz, CDCl3): δ = 10.7 (CH3CH2), 20.6 (CH3CH),
30.3 (CH2CH3), 32.8 (ArCH2), 58.4 (CH), 119.9 (q, J = 279.5 Hz,
CF3), 124.2 (C-3,5), 129.4 (C-2,6), 142.3 (C-1), 147.2 (C-4), 153.6
(q, J = 33 Hz, C=N) ppm. 15N NMR (40.6 MHz, CDCl3): δ =
–19.4 (C=N), –12.1 (NO ) ppm. IR (KBr): ν = 1599 cm–1. MS (EI):
˜
2
m/z (%)
=
288 [M]+ (7), 259 (15), 57 (93), 41 (100%).
N-[1,1,1-Trifluoro-3-(4-nitrophenyl)prop-2-en-2-yl]cyclohexanamine
(2a): Yellow solid; m.p. 77 °C; yield 235 mg (75%). 1H NMR
(400 MHz, CDCl3): Z isomer: δ = 0.95–1.90 (m, 10 H, CH2 cyclo-
hexyl), 2.95 (s, 1 H, NH), 3.45 (m, 1 H, CH cyclohexyl), 5.92 (s, 1
H, CH=), 7.49 (d, J = 8.6 Hz, 2 H, CHAr), 8.17 (d, J = 8.6 Hz, 2
C13H15F3N2O2 (288.266): calcd. C 54.17, H 5.24; found C 53.77,
H 5.44.
Mixture of (Z,E)-Enamine 2c and Azomethine 3c: Yellow-orange
solid; yield 209 mg (85%).
H, CHAr) ppm. E isomer: δ = 0.95–1.90 (m, 10 H, CH2 cyclohexyl), 3,3,3-Trifluoro-N-methyl-1-(4-nitrophenyl)prop-1-en-2-amine (2c):
3.18–3.30 (m, 1 H, CH cyclohexyl), 5.55 (s, 1 H, CH=), 7.32 (d, J
1H NMR (300 MHz, CDCl3): Z isomer: δ = 2.72 (d, J = 5.2 Hz, 3
H, Me), 5.91 (s, 1 H, CH=), 7.46 (d, J = 8.8 Hz, 2 H, Ar) ppm. E
= 8.6 Hz, 2 H, CHAr), 8.10 (d, J = 8.6 Hz, 2 H, CHAr) ppm. 13C
NMR (100.6 MHz, CDCl3): Z isomer: δ = 25.0, 25.6, 34.0 (CH2), isomer: δ = 2.35 (d, J = 5.0 Hz, 3 H, Me), 5.47 (s, 1 H, CH=), 8.12
304
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 300–310

Aromatic Substituents as Switches of Reaction Direction
(d, J = 8.3 Hz, 2 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): Z
isomer: δ = 30.3 (Me), 101.3 (q, J = 6.1 Hz, CH=), 123.6 (C-3,5),
119.7 (q, J = 279.5 Hz, CF3), 124.1 (C-3,5, 4-NO2C6H4), 126.7
(CH, Ph), 128.6 (CH, Ph), 129.0 (CH, Ph), 129.1 (C-2,6, 4-
129.0 (C-2,6), 142.4 (C-1) ppm. E isomer: δ = 33.7 (Me), 98.9 (q, J NO2C6H4), 139.0 (C-1, Ph), 141.4 (C-1, 4-NO2C6H4), 147.0 (C-4,
= 2.2 Hz, CH=), 123.3 (C-3,5), 128.9 (q, J = 2.6 Hz, C-2,6), 143.1
4-NO2C6H4), 156.0 (q, J = 32.7 Hz, C-CF3) ppm. 19F NMR
(282 MHz, CDCl3): δ = –72.0 ppm. ESI-MS (m/z): calcd. for
C17H15F3N2O2Na [M]+ 359.0983; found 359.0984.
(C-1) ppm. 19F NMR (282 MHz, CDCl3):
Z isomer: δ =
–68.7 ppm. E isomer: δ = –63.2 ppm.
N-[1,1,1-Trifluoro-3-(4-nitrophenyl)propan-2-ylidene]methanamine
(3c): H NMR (300 MHz, CDCl3): δ = 3.42 (s, 3 H, Me), 3.96 (s,
Mixture of (Z,E)-Enamine 2f and Azomethine 3f: Yellow oil; yield
212 mg (63%).
1
2 H, CH2), 7.35 (d, J = 8.7 Hz, 2 H, Ar), 8.21 (d, J = 8.7 Hz, 2 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 32.3 (CH2), 39.6 (Me),
119.6 (q, J = 278.7 Hz, CF3), 124.2 (C-3,5), 129.1 (C-2,6), 141.2
(C-1), 147.1 (C-4), 157.2 (q, J = 32.9 Hz, C-CF3) ppm. 19F NMR
(282 MHz, CDCl3): δ = –72.6 ppm. ESI-MS (m/z): calcd. for
C10H9F3N2O2Na [M]+ 269.0514; found 269.0508. C10H9F3N2O2
(246.186): calcd. C 48.79, H 3.68, N 10.38; found C 48.74, H 3.45,
N 10.33.
3,3,3-Trifluoro-1-(4-nitrophenyl)-N-(1-phenylethyl)prop-1-en-2-
amine (2f): H NMR (300 MHz, CDCl3): Z isomer: δ = 1.42 (d, J
1
= 6.7 Hz, 3 H, Me), 4.30 (quint, J = 6.7 Hz, 1 H, CH), 5.92 (s, 1 H,
CH=), 7.17–7.36 (m, 7 H, Ar), 8.12 (d, J = 8.9 Hz, 2 H, Ar) ppm. E
isomer: δ = 1.55 (d, J = 6.5 Hz, 3 H, Me), 5.32 (s, 1 H, CH=), 8.02
(d, J = 8.9 Hz, 2 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): Z
isomer: δ = 23.5 (Me), 54.4 (CH), 104.4 (q, J = 4.8 Hz, CH=), 121.9
(q, J = 275.9 Hz, CF3), 123.4 (C-3,5, 4-NO2C6H4), 125.8 (CH, Ph),
127.5 (CH, Ph), 128.6 (CH, Ph), 129.3 (C-2,6, 4-NO2C6H4), 134.5
(q, J = 30.3 Hz, C-CF3), 142.3 (C-1, 4-NO2C6H4), 142.7 (C-1, Ph),
146.0 (C-4, 4-NO2C6H4) ppm. E isomer: δ = 24.6 (Me), 53.5 (CH),
101.8 (q, J = 2.2 Hz, CH=), 123.2 (C-3,5, 4-NO2C6H4), 125.6 (CH,
Ph), 129.0 (C-2,6, 4-NO2C6H4), 134.2 (q, J = 30.9 Hz, C-CF3),
142.6 (C-1, Ph), 142.9 (C-1, 4-NO2C6H4), 145.6 (C-4, 4-
NO2C6H4) ppm. 19F NMR (282 MHz, CDCl3): Z isomer: δ =
–69.2 ppm. E isomer: δ = –62.9 ppm.
Mixture of (Z,E)-Enamine 2d and Azomethine 3d: Yellow solid;
yield 241 mg (88%).
3,3,3-Trifluoro-N-isopropyl-1-(4-nitrophenyl)prop-1-en-2-amine (2d):
1H NMR (300 MHz, CDCl3): Z isomer: δ = 1.10 (d, J = 6.0 Hz, 6
H, Me), 3.31–3.43 (m, 2 H, CH, NH), 5.99 (s, 1 H, CH=), 7.54 (d,
J = 8.7 Hz, 2 H, Ar), 8.20 (d, J = 8.7 Hz, 2 H, Ar) ppm. E isomer:
δ = 1.28 (d, J = 6.2 Hz, 6 H, Me), 3.52–3.63 (m, 1 H), 5.53 (s, 1
H, s, CH=), 8.10 (d, J = 8.9 Hz, 2 H, Ar) ppm. 13C NMR (75 MHz,
CDCl3): Z isomer: δ = 22.8 (Me), 46.6 (CH), 104.3 (q, J = 5.0 Hz,
CH=), 119.8 (q, J = 279.4 Hz, CF3), 123.6 (C-3,5), 128.9 (C-2,6),
135.5 (q, J = 30.1 Hz, C-CF3), 142.1 (C-1), 145.8 (C-4) ppm. E
isomer: δ = 21.7 (Me), 44.2 (CH), 98.9 (q, J = 2.2 Hz, CH=), 123.3
(C-3,5), 128.8 (C-2,6), 143.2 (C-1) ppm. 19F NMR (282 MHz,
CDCl3): Z isomer: δ = –69.7 ppm. E isomer: δ = –63.2 ppm.
N-[1,1,1-Trifluoro-3-(4-nitrophenyl)propan-2-ylidene]-1-phenylethan-
1
amine (3f): H NMR (300 MHz, CDCl3): δ = 1.49 (d, J = 6.5 Hz,
3 H, Me), 3.90 (A-part of the AB system, J = 16.1 Hz, 1 H), 4.00
(B-part of the AB system, J = 16.1 Hz, 1 H), 4.78 (q, J = 6.5 Hz,
1 H, CH), 6.92–6.98 (m, 1 H, Ph), 7.18–7.37 (m, 6 H, Ar), 8.10 (d,
J = 8.9 Hz, 2 H, Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 24.8
(Me), 32.9 (CH2), 60.9 (CH), 119.8 (q, J = 279.4 Hz, CF3), 124.1
(C-3,5, 4-NO2C6H4), 126.4 (CH, Ph), 127.6 (CH, Ph), 128.8 (CH,
Ph), 129.2 (C-2,6, 4-NO2C6H4), 141.6 (C-1, 4-NO2C6H4), 143.1 (C-
1, Ph), 147.0 (C-4, 4-NO2C6H4), 153.9 (q, J = 32.9 Hz, C-
CF3) ppm. 19F NMR (282 MHz, CDCl3): δ = –71.9 ppm. ESI-MS
(m/z): calcd. for C17H15F3N2O2Na [M]+ 359.0983; found 359.0978.
N-[1,1,1-Trifluoro-3-(4-nitrophenyl)propan-2-ylidene]propan-2-
1
amine (3d): H NMR (300 MHz, CDCl3): δ = 1.18 (d, J = 6.2 Hz,
6 H, Me), 3.88 (sept, J = 6.2 Hz, 1 H, CH), 3.94 (s, 2 H, CH2),
7.37 (d, J = 8.9 Hz, 2 H, Ar), 8.20 (d, J = 8.9 Hz, 2 H, Ar) ppm.
13C NMR (75 MHz, CDCl3): δ = 23.0 (Me), 32.4 (CH2), 52.4 (CH),
121.9 (q, J = 275.9 Hz, CF3), 124.1 (C-3,5), 129.1 (C-2,6), 142.5
(C-1), 147.0 (C-4), 152.8 (q, J = 32.8 Hz, C-CF3) ppm. 19F NMR
(282 MHz, CDCl3): δ = –72.1 ppm. ESI-MS (m/z): calcd. for
C12H13F3N2O2Na [M]+ 297.0827; found 297.0821. C12H13F3N2O2
(274.239): calcd. C 52.56, H 4.78, N 10.21; found C 52.63, H 4.82,
N 10.07.
Mixture of (Z,E)-Enamine 2g and Azomethine 3g: Yellow oil; yield
267 mg (80%).
3,3,3-Trifluoro-N-(1,1-dimethoxypropan-2-yl)-1-(4-nitrophenyl)prop-
1-en-2-amine (2g): 1H NMR (300 MHz, CDCl3): Z isomer: δ = 1.07
(d, J = 6.6 Hz, 3 H, Me), 3.41 (s, 3 H, OMe), 3.45 (s, 3 H, OMe),
4.06 (m, 1 H, CH), 4.16 (d, J = 2.9 Hz, 1 H, CH), 5.96 (s, 1 H,
CH=), 7.58 (d, J = 8.8 Hz, 2 H, Ar), 8.19 (d, J = 8.8 Hz, 2 H,
Ar) ppm. E isomer: δ = 1.16 (d, J = 6.5 Hz, 3 H, Me), 3.49 (s, 3
H, MeO), 3.50 (s, 3 H, MeO), 4.32 (d, J = 4.1 Hz, 1 H, CH), 5.61 (s,
1 H, CH=), 7.36 (d, J = 8.9 Hz, 2 H, Ar) ppm. 13C NMR (75 MHz,
CDCl3): Z isomer: δ = 14.9 (Me), 51.9 (CHMe), 56.3, 56.4 (OMe),
103.8 (q, J = 5.3 Hz, CH=), 106.8 [CH(OMe)2], 121.8 (q, J =
275.8 Hz, CF3), 123.8 (C-3,5), 128.8 (C-2,6), 135.6 (q, J = 30.1 Hz,
C-CF3), 142.3 (C-1), 145.9 (C-4) ppm. E isomer: δ = 13.9 (Me),
50.5 (CH), 55.6 (MeO), 56.2 (MeO), 106.1 [CH(MeO)2], 123.3 (C-
3,5), 128.9 (C-2,6, Ar) ppm. 19F NMR (282 MHz, CDCl3): Z iso-
mer: δ = –68.3 ppm. E isomer: δ = –63.1 ppm.
Mixture of (Z,E)-Enamine 2e and Azomethine 3e: Yellow oil; yield
302 mg (90%).
3,3,3-Trifluoro-1-(4-nitrophenyl)-N-phenethylprop-1-en-2-amine
(2e): 1H NMR (300 MHz, CDCl3): Z isomer: δ = 2.79 (t, J =
6.8 Hz, 2 H, CH2), 3.24 (q, J = 6.5 Hz, 2 H, CH2), 5.91 (s, 1 H,
CH=), 8.07 (d, J = 8.9 Hz, 2 H, Ar) ppm. E isomer: δ = 2.97 (t, J
= 7.1 Hz, 2 H, CH2), 3.34 (q, J = 6.5 Hz, 2 H, CH2), 5.54 (s, 1 H,
CH=) ppm. 13C NMR (75 MHz, CDCl3): Z isomer: δ = 34.5, 47.2,
103.0 (q, J = 5.5 Hz, CH=), 123.8 (C-3,5, 4-NO2C6H4), 126.9 (CH,
Ph), 128.8 (CH, Ph), 128.9 (C-2,6, 4-NO2C6H4), 136.2 (q, J =
30.1 Hz, C-CF3), 138.0 (C-1, Ph), 142.2 (C-1, 4-NO2C6H4), 145.7
(C-4, 4-NO2C6H4) ppm. E isomer: δ = 44.9 (CH), 123.7 (C-3,5,
4-NO2C6H4) ppm. 19F NMR (282 MHz, CDCl3): Z isomer: δ =
–68.2 ppm. E isomer: δ = –63.1 ppm.
N-[1,1,1-Trifluoro-3-(4-nitrophenyl)propan-2-ylidene]-1,1-dimethoxy-
1
propan-2-amine (3g): H NMR (300 MHz, CDCl3): δ = 1.16 (d, J
N-[1,1,1-Trifluoro-3-(4-nitrophenyl)propan-2-ylidene]-2-phenylethan- = 6.4 Hz, 3 H, Me), 3.43 (s, 3 H, MeO), 3.44 (s, 3 H, MeO), 3.82
1
amine (3e): H NMR (300 MHz, CDCl3): δ = 3.04 (t, J = 6.9 Hz,
(sept, J = 6.5 Hz, 1 H, CH), 3.93 (s, 2 H, CH2), 4.36 (d, J = 6.9 Hz,
2 H, CH2), 3.65 (s, 2 H, CH2), 3.78 (td, J = 6.9, 1.6 Hz, 2 H, CH2), 1 H, CH), 7.41 (d, J = 8.8 Hz, 2 H, Ar), 8.19 (d, J = 8.8 Hz, 2 H,
7.07 (d, J = 8.8 Hz, 2 H, Ar), 7.10–7.17 (m, 2 H), 7.21–7.33 (m, 3 Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 16.6 (Me), 32.8 (CH2),
H), 8.06 (d, J = 8.8 Hz, 2 H, Ar) ppm. 13C NMR (75 MHz,
54.9, 56.9 (OMe), 60.2 (CHMe), 107.7 [CH(OMe)2], 119.7 (q, J =
CDCl3): δ = 32.6 (4-NO2C6H4CH2), 36.2 (CH2Ph), 54.0 (NCH2), 279.7 Hz, CF3), 124.0 (C-3,5), 129.4 (C-2,6), 141.7 (C-1), 147.1 (C-
Eur. J. Org. Chem. 2010, 300–310
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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305

A. Yu. Rulev, V. G. Nenajdenko et al.
FULL PAPER
4), 155.5 (q, J = 32.5 Hz, C-CF3) ppm. 19F NMR (282 MHz,
(CH2), 51.5 (CHNH), 96.8 (q, J = 2 Hz, CH=), 124.4 (C-3), 148.2
(C-2) ppm. 15N NMR (40.6 MHz, CDCl3): Z isomer: δ = –306.4
CDCl3):
δ
=
–71.8 ppm. ESI-MS (m/z): calcd. for
C14H17F3N2O4Na [M]+ 357.1038; found 357.1039. C14H17F3N2O4 (NH), –12.1 (NO2) ppm. E isomer: δ = –299.1 (NH), –10.1
(334.291): calcd. C 50.30, H 5.13, N 8.38; found C 50.32, H 5.20,
N 8.30.
(NO2) ppm.
N-[2,2,2-Trifluoro-1-(2-nitrobenzyl)ethylidene]cyclohexanamine (3j):
1H NMR (400 MHz, CDCl3): δ = 0.8–1.8 (m, 10 H, CH2), 3.41 (m,
1 H, CHN=C), 4.12 (s, 2 H, ArCH2), 7.45 (m, 1 H, 4-H), 7.20 (m,
1 H, 6-H), 7.58 (m, 1 H, 5-H), 8.05 (m, 1 H, 3-H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 24.1, 25.3 (CH2), 30.2 (ArCH2), 32.7
(CH2), 60.5 (CH–C=N), 119.8 (q, J = 279.5 Hz, CF3), 125.5 (C-3),
128.5 (C-4), 129.7 (C-6), 131.2 (C-1), 133.7 (C-5), 148.7 (C-2), 152.7
(q, J = 32.2 Hz, C-CF3) ppm. 15N NMR (40.6 MHz, CDCl3): δ =
–19.4 (C=N), –11.4 (NO2) ppm. MS (EI): m/z (%) = 314 (0.6)
[M]+, 232 (3), 215 (12), 163 (6), 120 (16), 92 (22), 83 (41), 55 (100).
C15H17F3N2O2 (314.303): calcd. C 57.32, H 5.45; found C 57.22,
H 5.57.
Mixture of (Z,E)-Enamine 2h and Azomethine 3h: Yellow-orange
oil; yield 223 mg (71%).
N-[2-(3-Nitrophenyl)-1-(trifluoromethyl)ethenyl]cyclohexanamine
(2h): 1H NMR (400 MHz, CDCl3): Z isomer: δ = 0.95–1.89 (m, 10
H, CH2), 2.90 (m, 1 H, CHNH), 3.30 (d, J = 9.7 Hz, 1 H, NH),
5.96 (s, 1 H, CH=), 7.49 (m, 1 H, 5-H), 7.65 (m, 1 H, 6-H), 8.04
(m, 1 H, 4-H), 8.31 (s, 1 H, 2-H) ppm. E isomer: δ = 1.06–2.07 (m,
10 H, CH2), 3.15 (m, 1 H, CHNH), 3.71 (br. s, 1 H, NH), 5.51 (s,
1 H, CH=), 7.40 (m, 1 H, 5-H), 7.48 (m, 1 H, 6-H), 7.97 (m, 1 H,
4-H), 8.03 (s, 1 H, 2-H) ppm. 13C NMR (100.6 MHz, CDCl3): Z
isomer: δ = 24.9, 25.5, 33.9 (CH2), 53.9 (CH–NH), 104.6 (q, J =
5 Hz, CH=), 121.6 (C-2), 122.0 (q, J = 275 Hz, CF3), 123.1 (C-4),
129.3 (C-6), 134.6 (C-5), 134.9 (q, J = 30 Hz, C-CF3), 137.1 (C-1),
148.4 (C-3) ppm. E isomer: δ = 24.2, 25.9, 31.7 (CH2), 51.5 (CH–
NH), 98.4 (CH=), 120.7 (C-2), 123.2 (C-4), 128.3 (C-6), 134.7 (C-
5), 137.7 (C-1), 148.1 (C-3) ppm. 15N NMR (40.6 MHz, CDCl3):
Z isomer: δ = –303.6 (NH), –9.5 (NO2) ppm. E isomer: δ = –297.1
(NH), –9.7 (NO2) ppm. MS (EI): m/z (%)= 314 (17) [M]+, 271 (11),
232 (17), 184 (22), 83 (68), 55 (100).
Mixture of (Z,E)-Enamine 2k and Azomethine 3k: Light brown oil;
yield 277 mg (96%).
N-[2-(2-Nitrophenyl)-1-(trifluoromethyl)ethenyl]butan-2-amine (2k):
1H NMR (400 MHz, CDCl3): Z isomer: δ = 0.73 (t, J = 7.4 Hz, 3
H, CH2Me), 0.93 (d, J = 6.2 Hz, 3 H, CHMe), 1.24 (m, 2 H,
CHCH2), 2.88 (m, 1 H, CHNH), 3.13 (d, J = 9.3 Hz, 1 H, NH),
6.17 (s, 1 H, CH=), 7.22 (m, 1 H, 6-H), 7.37 (m, 1 H, 4-H), 7.57
(m, 1 H, 5-H), 7.99 (m, 1 H, 3-H) ppm. E isomer: δ = 0.64 (t, J =
7.5 Hz, 3 H, CH2Me), 0.97 (d, J = 7.4 Hz, 3 H, CHMe), 1.34 (m,
2 H, CHCH2), 3.29 (m, 1 H, CHNH), 3.71 (br. s, 1 H, NH), 5.80
(s, 1 H, CH=), 7.94 (m, 1 H, 3-H) ppm. 13C NMR (100.6 MHz,
CDCl3): Z isomer: δ = 10.0 (CH2Me), 20.1 (CHMe), 29.8
(CH2Me), 51.9 (CHNH), 100.8 (q, J = 5.4 Hz, CH=), 122.1 (q, J
= 275.5 Hz, CF3), 124.8 (C-3), 127.8 (C-4), 130.8 (C-1), 131.3 (C-
6), 132.8 (C-5), 134.6 (q, J = 29.9 Hz, C-CF3), 147.9 (C-2) ppm.
E isomer: δ = 10.1 (CH2Me), 19.1 (CHMe), 28.7 (CH2Me), 49.8
(CHNH), 96.8 (CH=), 148.3 (C-2) ppm.
N-[2,2,2-Trifluoro-1-(3-nitrobenzyl)ethylidene]cyclohexanamine (3h):
1H NMR (400 MHz, CDCl3): δ = 1.23–1.77 (m, 10 H, CH2), 3.54
(m, 1 H, CHN=C), 3.89 (s, 2 H, ArCH2), 7.49–7.56 (m, 2 H, 4,5-
H), 8.04 (s, 1 H, 2-H), 8.12 (m, 1 H, 6-H) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 24.2, 25.3, 32.3 (CH2), 32.7 (ArCH2),
60.8 (CHN=C), 119.9 (q, J = 279.5 Hz, CF3), 122.1, 123.2, 129.7,
134.1 (CHAr), 136.8 (C-1), 148.7 (C-3), 153.1 (q, J = 32.3 Hz, C-
CF3) ppm. 15N NMR (40.6 MHz, CDCl3): δ = –19.4 (C=N), –12.1
(NO ) ppm. IR (film): ν = 1617, 1676 cm–1. MS (EI): m/z (%) =
˜
2
314 (15) [M]+, 271 (8), 232 (12), 185 (15), 178 (42), 163 (10), 136
(17), 83 (73), 55 (100). C15H17F3N2O2 (314.303): calcd. C 57.32, H
5.45; found C 57.84, H 5.24.
N-[2,2,2-Trifluoro-1-(2-nitrobenzyl)ethylidene]butan-2-amine (3k):
1H NMR (400 MHz, CDCl3): δ = 0.81 (t, J = 7.4 Hz, 3 H,
CH2Me), 1.13 (d, J = 6.2 Hz, 3 H, CHMe), 1.58 (m, 2 H, CHCH2),
3.50 (m, 1 H, CHN=C), 4.08 (A-part of the AB system, J =
17.2 Hz, 1 H), 4.18 (B-part of the AB system, J = 17.2 Hz, 1 H),
7.22 (m, 1 H, 6-H), 7.45 (m, 1 H, 4-H), 7.58 (m, 1 H, 5-H), 8.04
(m, 1 H, 3-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 10.7
(CH2Me), 20.4 (CHMe), 30.3 (CH2Me), 30.3 (ArCH2), 58.2 (CH–
N=C), 119.7 (q, J = 279.5 Hz, CF3), 125.5 (C-3), 128.5 (C-4), 129.6
(C-1), 130.6 (C-6), 133.6 (C-5), 148.7 (C-2), 153.4 (q, J = 32.2 Hz,
N-[2,2,2-Trifluoro-1-(3-nitrobenzyl)ethylidene]butan-2-amine (3i):
1
Yellow oil; yield 60 mg (20%). H NMR (400 MHz, CDCl3): δ =
0.79 (t, J = 7.4 Hz, 3 H, CH2Me), 1.13 (d, J = 6.2 Hz, 3 H, CHMe),
1.51–1.62 (m, 2 H, CHCH2), 3.62 (m, 1 H, CHN=C), 3.86 (A-part
of the AB system, J = 15.6 Hz, 1 H), 3.91 (B-part of the AB system,
J = 15.6 Hz, 1 H), 7.48–7.53 (m, 2 H, 5,6-H), 8.05 (s, 1 H, 2-H),
8.12 (m, 1 H, 4-H) ppm. 13C NMR (100.6 MHz, CDCl3): δ = 10.7
(CH2Me), 20.7 (CHMe), 30.3 (CH2Me), 32.4 (ArCH2), 58.3 (CH–
C=N), 119.8 (q, J = 279.5 Hz, CF3), 122.3, 123.3, 130.0, 134.4
(CHAr), 136.7 (C-1), 148.6 (C-3), 153.6 (q, J = 32.5 Hz, C-
CF3) ppm. MS (EI): m/z (%) = 288 (17) [M]+, 259 (85), 163 (74),
136 (28), 90 (38), 57 (100).
C-CF ) ppm. IR (film): ν = 1661, 3402 cm–1. MS (EI): m/z (%) =
˜
3
288 (6) [M]+, 259 (20), 232 (11), 215 (74), 163 (19), 120 (49), 92
(78), 57 (100). C13H15F3N2O2 (288.261): calcd. C 54.16, H 5.24;
found C 54.15, H 5.25.
Mixture of (Z,E)-Enamine 2l and Azomethine 3l: Yellow oil; yield
263 mg (96%).
Mixture of (Z,E)-Enamine 2j and Azomethine 3j: Yellow oil; yield
305 mg (97%).
3,3,3-Trifluoro-N-isopropyl-1-(2-nitrophenyl)prop-1-en-2-amine (2l):
1H NMR (300 MHz, CDCl3): Z isomer: δ = 0.99 (d, J = 6.0 Hz, 6
N-[2-(2-Nitrophenyl)-1-(trifluoromethyl)ethenyl]cyclohexanamine H, Me), 3.03–3.20 (m, 2 H, CH, NH), 6.22 (s, 1 H, CH=), 7.48 (td,
1
(2j): H NMR (400 MHz, CDCl3): Z isomer: δ = 0.80–1.80 (m, 10
J = 7.6, 1.4 Hz, 1 H, Ar), 7.65 (td, J = 7.6, 1.4 Hz, 1 H, Ar), 8.02
H, CH2), 2.69 (m, 1 H, CHNH), 3.20 (d, J = 9.0 Hz, 1 H, NH), (dd, J = 7.6, 1.0 Hz, 1 H, Ar) ppm. E isomer: δ = 1.28 (d, J =
6.18 (s, 1 H, CH=), 7.37 (m, 1 H, 4-H), 7.56 (m, 1 H, 5-H), 7.61
(m, 1 H, 6-H), 7.99 (m, 1 H, 3-H) ppm. E isomer: δ = 0.80–1.80
6.1 Hz, 6 H, Me), 5.83 (s, 1 H, CH=), 7.97 (dd, J = 8.2, 1.4 Hz, 1
H, Ar) ppm. 13C NMR (75 MHz, CDCl3): Z isomer: δ = 22.8 (Me),
(m, 10 H, CH2), 3.18 (m, 1 H, CHNH), 3.63 (br. s, 1 H, NH), 5.83 46.5 (CH), 101.7 (q, J = 5.4 Hz, CH=), 119.7 (q, J = 279.4 Hz,
(s, 1 H, CH=), 7.95 (m, 1 H, 3-H) ppm. 13C NMR (100.6 MHz, CF3), 124.8 (C-3), 127.8 (C-4), 130.4 (C-1), 130.8 (C-6), 132.8 (C-
CDCl3): Z isomer: δ = 24.8, 25.5, 33.4 (CH2), 53.6 (CHNH), 101.0
5), 134.4 (q, J = 30.1 Hz, C-CF3), 147.8 (C-2) ppm. E isomer: δ =
(q, J = 5.4 Hz, CH=), 122.1 (q, J = 275.6 Hz, CF3), 124.8 (C-3), 22.0 (Me), 44.1 (CH), 124.3 (C-3), 127.3 (C-4), 132.4 (C-5) ppm.
127.8 (C-4), 130.6 (C-1), 130.9 (C-6), 132.8 (C-5), 134.2 (q, J =
30.3 Hz, C-CF3), 147.9 (C-2) ppm. E isomer: δ = 23.8, 25.9, 32.3
19F NMR (282 MHz, CDCl3): Z isomer: δ = –69.8 ppm. E isomer:
δ = –62.8 ppm.
306
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 300–310

Aromatic Substituents as Switches of Reaction Direction
N-[1,1,1-Trifluoro-3-(2-nitrophenyl)propan-2-ylidene]propan-2-
amine (3l): H NMR (300 MHz, CDCl3): δ = 1.20 (d, J = 6.1 Hz,
6 H, Me), 3.78 (sept, J = 6.1 Hz, 1 H, CH), 4.15 (s, 2 H, CH2),
N-[1,3-Bis(cyclohexylamino)-3-(4-chlorophenyl)prop-2-enylidene]cy-
clohexanaminium Chloride (5e): Light yellow solid; m.p. 221–
224 °C; yield 96 mg (20%). 1H NMR (400 MHz, CDCl3): δ = 0.90–
1
7.21 (d, J = 7.6 Hz, 1 H, Ar), 7.40 (td, J = 7.6, 1.2 Hz, 1 H, Ar), 2.10 (m, 30 H, CH2), 3.30 (br. m, 3 H, CHNH), 4.31–5.03 (4ϫbr.
7.59 (td, J = 7.6, 1.2 Hz, 1 H, Ar), 8.09 (dd, J = 7.6, 1.3 Hz, 1 H,
Ar) ppm. 13C NMR (75 MHz, CDCl3): δ = 22.8 (Me), 30.2 (CH2),
52.3 (CH), 121.9 (q, J = 275.4 Hz, CF3), 125.6 (C-3), 128.5 (C-4),
129.6 (C-1), 131.1 (C-6), 133.7 (C-5), 148.5 (C-2), 152.7 (q, J =
s, 2 H, NH, CH=C), 7.31 (d, J = 8.2 Hz, 2 H, 3,5-H), 7.40 (d, J =
8.2 Hz, 2 H, 2,6-H), 8.34 (br. s, 1 H, NH) ppm. 13C NMR
(100.6 MHz, CDCl3): δ = 24.7, 24.9, 25.0, 31.9, 32.5, 33.1 (CH2),
52.8 (CH–N), 53.8 (CH–N), 54.4 (CH–N), 78.4 (Ar–C=CH), 129.6
32.2 Hz, C-CF3) ppm. 19F NMR (282 MHz, CDCl3): δ = (C-2,3,5,6), 134.2 (C-1), 137.0 (C-4), 156.5 (br. s, Ar–C=CH), 159.6
–72.0 ppm. ESI-MS (m/z): calcd. for C12H13F3N2O2Na [M]+
297.0827; found 297.0821. C12H13F3N2O2 (274.239): calcd. C
52.56, H 4.78, N 10.21; found C 52.52, H 4.77, N 10.04.
(br. s, N–C–N) ppm. IR (KBr): ν = 1531, 1573, 1605, 3332,
˜
3382 cm–1. MS (EI): m/z (%) (direct input, relative intensity) = 438
(3) [M – HCl]+, 358 (10), 261 (5), 222 (10), 179 (10), 139 (17), 98
(33), 83 (40), 59 (72), 55 (92), 44 (100). C27H41Cl2N3·H2O
(496.555): calcd. C 65.31, H 8.73, Cl 14.28; found C 65.11, H 8.98,
Cl 13.93.
General Procedure for the Synthesis of Vinylogous Guanidinium
Salts 5a–p: The appropriate styrene (1f–l, 1–1.5 mmol) and the
amine (10–15 mmol) were heated either at reflux or in a sealed glass
tube with a Young tap. The product obtained (5a–p) was purified
by column chromatography [silica gel, CH2Cl2/CH3OH (9:1) or
CHCl3/MeOH (9:1)].
N-[1,3-Bis(cyclohexylamino)-3-(4-methylphenyl)prop-2-enylidene]cy-
clohexanaminium Bromide (5f): Light yellow solid; m.p. 245–
247 °C; yield 430 mg (85 %). 1H NMR (400 MHz, CDCl3): δ =
0.80–2.00 (br. m, 30 H), 2.33 (s, 3 H), 3.22 (br. s, 3 H), 3.32 (br. s,
1 H), 3.42 (br. s, 2 H), 4.65 (br. s, 1 H), 6.82 (br. s, 1 H), 7.10–7.40
(m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 21.0 (CH3), 24.3,
24.7, 25.2, 31.8, 32.7, 32.8 (CH2), 52.2, 54.1 (NCH), 80.6 (Ar–
C=CH), 127.7 (C-3,5), 129.6 (C-2,6), 132.6 (C-1), 140.9 (C-4),
N-[1,3-Bis(cyclohexylamino)-3-(4-chlorophenyl)prop-2-enylidene]cy-
clohexanaminium Bromide (5a): Light yellow solid; m.p. 137 °C;
yield 502 mg (64%). 1H NMR (400 MHz, CDCl3): δ = 0.80–2.00
(br. m, 30 H), 3.00–3.50 (br. s, 3 H), 4.41 (br. s, 1 H), 5.13 (br. s, 1
H), 7.10–7.40 (m, 4 H), 8.31 (br. s, 1 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 24.6, 24.8, 25.3, 31.8, 32.4, 32.9 (CH2), 52.7, 54.4
(NCH), 80.6 (Ar–C=CH), 129.2 (C-3,5), 129.6 (C-2,6), 134.1 (C-
1), 136.7 (C-4), 156.5 (Ar–C=CH), 162.5 (N–C–N) ppm. IR (KBr):
158.9 (Ar–C=CH), 162.5 (N–C–N) ppm. IR (KBr): ν = 1567, 1596,
˜
3202, 3409 cm–1. C28H44BrN3 (502.59): calcd. C 66.92, H 8.82, N
8.36; found C 66.88, H 8.62, N 8.36.
N-[1,3-Bis(isopropylamino)-3-(4-methylphenyl)prop-2-enylidene]-
propan-2-aminium Bromide (5g): Brownish sticky oil; yield 350 mg
ν = 1567, 1602, 3205, 3422 cm–1. C27H41BrClN3·H2O: calcd. C
˜
59.94, H 8.01; found C 59.67; H 7.71.
1
(92%). H NMR (300 MHz, CDCl3): δ = 0.70–1.24 (br. s, 12 H),
N-[1,3-Bis(isopropylamino)-3-(4-chlorophenyl)prop-2-enylidene]-
propan-2-aminium Bromide (5b): Pale brown crystals; m.p. 116–
118 °C; yield 253 mg (63 %). 1H NMR (300 MHz, CDCl3): δ =
0.84–1.28 (br. s, 12 H), 1.28–1.39 (br. s, 6 H), 1.65–1.75 (br. s, 1
H), 3.50–3.86 (br. s, 3 H), 4.38–4.61 (br. s, 1 H), 7.31 (d, J = 8.3 Hz,
2 H, Ar), 7.44 (d, J = 8.3 Hz, 2 H, Ar), 7.89–9.13 (br. s, 1 H) ppm.
13C NMR (75 MHz, CDCl3): δ = 21.8, 22.3 (CH3), 45.6, 46.7 (CH),
81.7 (Ar–C=CH), 129.2 (C-3,5), 129.8 (C-2,6), 133.9 (C-1), 136.5
(C-4), 157.2 (Ar–C=CH), 162.1 (N–C–N) ppm. ESI-MS (m/z)
1.24–1.39 (br. s, 6 H), 2.39 (s, 3 H, Me), 3.55–4.06 (br. s, 3 H),
4.45–4.63 (br. s, 1 H), 4.73–5.04 (br. s, 1 H), 7.24 (br. s, 4H Ar),
7.70–8.67 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.1
(4-MeC6H4-), 21.8, 22.1 (CH3), 45.2, 46.4 (CH), 75.4 (Ar–C=CH),
127.9 (C-3,5), 129.6 (C-2,6), 132.3 (C-1), 140.7 (C-4), 158.7 (Ar–
+
C=CH), 162.2 (N–C–N) ppm. ESI-MS (m/z) calcd. for C19H32N3
[M]+: 302.2596; found 302.2591. C19H32BrN3·1/3 H2O: calcd. C
58.76, H 8.48, N 10.82; found C 58.79, H 8.25, N 10.49.
N-[1,3-Bis(sec-butylamino)-3-(4-methoxyphenyl)prop-2-enylidene]-
butan-2-aminium Bromide (5h): Colourless solid; yield 405 mg
+
calcd. for C18H29ClN3 [M]+: 322.2050; found 322.2045.
1
(61%). H NMR (400 MHz, CDCl3): δ = 0.50–1.60 (br. m, 24 H),
N-{3-(4-Chlorophenyl)-1-[(1,1-dimethoxyethyl)amino]-3-[(2,2-dimeth-
oxy-1-methylethyl)amino]prop-2-enylidene}-1,1-dimethoxypropan-2-
aminium Bromide (5c): Brown sticky oil; yield 223 mg (39%). 1H
NMR (300 MHz, CDCl3): δ = 0.53–0.79 (br. s, 3 H, Me), 1.16–
1.46 (m, 6 H, Me), 2.46–2.68 (br. s, 1 H), 3.21–3.61 (m, 18 H,
MeO), 4.34–4.51 (br. s, 1 H), 4.51–4.68 (br. s, 1 H), 4.82–5.38 (br.
s, 1 H), 7.41 (d, J = 8.6 Hz, 2 H, Ar), 7.48 (d, J = 8.6 Hz, 2 H,
Ar), 7.60–7.92 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
14.4, 15.4, 16.3, 16.8, 51.8, 53.0, 55.5, 56.6, 56.8, 57.1, 57.3, 80.6
(Ar–C=CH), 129.2 (CH), 130.2 (CH), 134.9, 136.5, 160.1 (Ar–
C=CH), 162.5 (N–C–N) ppm. ESI-MS (m/z) calcd. for
3.15 (br. s, 1 H), 3.54 (s, 3 H), 4.11 (br. s, 1 H), 4.86 (br. s, 1 H),
6.65 (d, J = 8.2 Hz, 2 H), 7.04 (d, J = 8.2 Hz, 2 H) ppm. 13C NMR
(100 MHz, CDCl3): δ = 10.1 (CH3CH2), 19.1, 19.5 (CH3CH), 28.4,
29.1 (CH3CH2), 50.7 (NCH), 55.1 (OCH3), 77.4 (Ar–C=CH), 114.1
(C-3,5), 127.2 (C-1), 129.2 (C-2,6), 158.1 (Ar–C=CH), 161.2 (N–
C–N), 163.01 (C-4) ppm. IR (KBr): ν = 1570, 1609, 3222,
˜
3413 cm–1. This compound was passed through a short column (sil-
ica gel) and was used without additional purification.
N-[1,3-Bis(isopropylamino)-3-(4-methoxyphenyl)prop-2-enylidene]-
propan-2-aminium Bromide (5i): Pale brown crystals; m.p. 96–98 °C;
yield 321 mg (81%). 1H NMR (300 MHz, CDCl3): δ = 0.67–1.24
(br. s, 12 H), 1.24–1.45 (br. s, 6 H), 2.09–2.37 (br. s, 1 H), 3.51–
4.03 (br. s, 2 H), 3.84 (s, 3 H, MeO), 4.41–4.59 (br. s, 1 H), 4.65–
5.01 (br. s, 1 H), 6.96 (d, J = 8.6 Hz, 2 H), 7.30 (d, J = 8.6 Hz, 2
H), 7.81–8.73 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ =
21.8, 22.2 (CH3), 45.3, 46.5 (CH), 55.4 (MeO), 74.9 (Ar–C=CH),
114.4 (C-3,5), 127.3 (C-1), 129.6 (C-2,6), 158.5 (Ar–C=CH), 159.3
(N–C–N), 161.3 (C-4) ppm. ESI-MS (m/z) calcd. for C19H32N3O+
[M]+: 318.2545; found 318.2540. C19H32BrN3O (398.39): calcd. C
57.28, H 8.10, N 10.55; found C 57.08, H 8.01, N 10.17.
+
C24H41ClN3O6 [M]+: 502.2684; found 502.2686.
N-[1,3-Bis(isopropylamino)-3-(4-chlorophenyl)prop-2-enylidene]-
propan-2-aminium Chloride (5d): Pale brown crystals; m.p. 103–
105 °C; yield 120 mg (34 %). 1H NMR (300 MHz, CDCl3): δ =
0.71–1.26 (br. s, 12 H), 1.26–1.40 (br. s, 6 H), 2.01–2.21 (br. s, 1
H), 3.43–3.95 (br. s, 3 H), 4.44–4.57 (br. s, 1 H), 4.64–5.04 (br. s, 1
H), 7.32 (d, J = 8.0 Hz, 2 H, Ar), 7.42 (d, J = 8.0 Hz, 2 H, Ar),
8.41–9.28 (br. s, 1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 21.8,
22.4 (CH3), 45.4, 46.7 (CH), 81.8 (Ar–C=CH), 129.3 (C-3,5), 129.6
(C-2,6), 134.1 (C-1), 136.7 (C-4), 156.7 (Ar–C=CH), 162.4 (N–C–
+
N) ppm. ESI-MS (m/z) calcd. for C18H29ClN3 [M]+: 322.2050;
N-[1,3-Bis(cyclohexylamino)-3-(4-methoxyphenyl)prop-2-enylidene]-
cyclohexanaminium Bromide (5j): Colourless solid; m.p. 230–
found 322.2045.
Eur. J. Org. Chem. 2010, 300–310
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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307

A. Yu. Rulev, V. G. Nenajdenko et al.
FULL PAPER
233 °C; yield 337 mg (65 %). 1H NMR (400 MHz, CDCl3): δ = H, CH2), 3.15–3.63 (3ϫbr. s, 3 H, CHN), 4.33–5.15 (2ϫbr. s, 2
0.95–2.10 (m, 30 H, CH2), 3.05–3.40 (3ϫbr. m, 3 H, CHNH), 3.80 H, CH=C, NH), 7.39 (br. d, 5 H, Ph), 8.29 (br. s, 1 H, NH) ppm.
(s, 3 H, CH3), 4.38 (br. s, 1 H), 6.89 (d, J = 8.4 Hz, 2 H, 3,5-H),
7.22 (d, J = 8.4 Hz, 2 H, 2,6-H), 8.45 (br. s, 1 H, NH) ppm. 13C 34.1 (CH2), 52.6, 53.5, 54.2 (CHN), 77.9 (CH=C), 128.0 (C-2,6),
NMR (100.6 MHz, CDCl3): δ = 24.7, 24.8, 24.9, 25.0, 25.6, 32.1, 129.2 (C-3,5), 130.6 (C-4), 135.7 (C-1), 158.0 (br. s, C=CH), 162.5
13C NMR (100 MHz, CDCl3): δ = 24.5, 24.8, 25.3, 31.9, 32.3, 32.9,
32.7, 33.1, 34.3 (CH2), 52.6 (CHN), 54.0 (br. s, CHN), 55.7 (OMe), (N–C–N) ppm. IR (KBr): ν = 1450, 1529, 1568, 1609, 3221,
˜
77.6 (Ar–C=CH), 114.8 (C-3,5), 129.6 (C-2,6), 158.0 (Ar–C=CH), 3420 cm–1. MS (EI): m/z (%) (direct input, relative intensity) = 407
161.6 (C-4), 163.3 (N–C–N) ppm. IR (KBr): ν = 1509, 1570, 1609,
(10) [M – HBr]+, 324 (34), 309 (8), 227 (10), 186 (8), 145 (24), 104
˜
3221, 3416 cm–1. MS (EI): m/z (direct input, relative intensity) = (47), 55 (100), 44 (51). C27H42BrN3 (488.547): calcd. C 66.38, H
438 (2.4) [M – HBr]+, 354 (8), 339 (2), 257 (2), 216 (3), 175 (5), 134 8.67; found C 66.11, H 8.50.
(15), 82 (7), 55 (19), 40 (100). C28H44BrN3O (518.573): calcd. C
64.85, H 8.55; found C 64.89, H 8.45.
N-[1,3-Bis(benzylamino)-3-phenylprop-2-enylidene]phenylmethan-
aminium Bromide (5p): Light brown solid; m.p. 158–161 °C; yield
N-[1,3-Bis(cyclohexylamino)-3-(3-methoxyphenyl)prop-2-enylidene]-
cyclohexanaminium Bromide (5k): Light yellow solid; m.p. 243–
312 mg (61%). 1H NMR (400 MHz, CDCl3): δ = 4.11–4.89 (br. m,
7 H, CH2, CH=C), 6.70 (br. s, 1 H, NH), 7.09–7.27 (m, 20 H, Ph),
245 °C; yield 306 mg (59 %). 1H NMR (400 MHz, CDCl3): δ = 9.06 (br. s, 1 H, NH) ppm. 13C NMR (100.6 MHz, CDCl3): δ =
0.90–2.10 (m, 30 H, CH2), 3.13–3.46 (3ϫbr. s, 3 H, CHN), 3.82 (s,
3 H, OMe), 4.25–4.90 (2ϫbr. s, 2 H, NH, CH=C), 6.84–7.00 (m,
47.9 (br. s, CH2), 77.4 (C=CH), 127.3, 127.7, 127.8, 128.3, 128.7,
128.9, 129.4 (CHAr), 130.9, 134.6, 136.6 (C-1), 160.7 (C=CH),
3 H, 2,4,6-H), 7.33 (m, 1 H, 5-H), 8.50 (br. s, 1 H, NH) ppm. 13C 161.7 (N–C–N) ppm. IR (KBr): ν = 1524, 1565, 1615, 3234,
˜
NMR (100.6 MHz, CDCl3): δ = 24.4, 24.6, 24.8, 25.3, 31.9, 32.4,
3415 cm–1. MS (EI): m/z (%) (direct input, relative intensity) = 431
32.9 (CH2), 52.3 (CHN), 55.5 (CHN), 113.6 (C-2), 116.0 (C-4), (0.3) [M – HBr]+, 354 (Ͻ1), 340 (1), 235 (1), 193 (1), 159 (1), 130
119.8 (C-6), 130.4 (C-5), 136.8 (C-1), 157.4 (Ar–C=CH), 159.9 (C- (2), 106 (9), 91 (89), 65 (18), 40 (100). C30H30BrN3 (512.483): calcd.
3), 162.3 (N–C–N) ppm. IR (KBr): ν = 1451, 1531, 1570, 1599,
C 70.21, H 5.90; found C 69.94, H 6.07.
˜
1649, 3220, 3412 cm–1. MS (EI): m/z (direct input, relative inten-
sity) = 438 (1.3) [M – HBr]+, 354 (4), 238 (5), 175 (7), 134 (9), 83
(39), 56 (51), 44 (100). C28H44BrN3O·H2O (536.60): calcd. C 62.67,
H 8.64; found C 62.58, H 8.59.
General Procedure for the Synthesis of Aminoenones 6: A concen-
trated aqueous solution of HCl (10 mL) was added to the appropri-
ate salt 5 (1 mmol) and the mixture was stirred with heating for 3–
6 h. Volatiles were then removed in vacuo, and the residue was
treated with saturated NaHCO3 solution (5 mL) and extracted with
CH2Cl2 (3ϫ20 mL). The combined extract was dried with CaCl2,
solvent was evaporated, and the residue was purified by column
chromatography [silica gel, CHCl3/MeOH (9:1)].
N-[1,3-Bis(cyclohexylamino)-3-(2-methoxyphenyl)prop-2-enylidene]-
cyclohexanaminium Bromide (5l): Colourless solid; m.p. 134 °C;
yield 374 mg (72%). 1H NMR (400 MHz, CDCl3): δ = 0.90–1.90
(br. m, 31 H), 3.14 (br. s, 1 H), 3.54 (br. s, 1 H), 3.72 (s, 3 H), 4.58
(br. s, 1 H), 6.70–7.40 (br. m, 4 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 24.5, 24.7, 24.8, 25.0, 32.1, 32.5 (CH2), 52.5 (NCH),
55.9 (OCH3), 81.2 (Ar–C=CH), 111.9 (C-3), 121.5 (C-5), 124.5 (C-
1), 129.8 (C-6), 131.9 (C-4), 154.8 (Ar–C=CH), 156.2 (C-2), 156.3
3,3-Bis(cyclohexylamino)-1-(2-methoxyphenyl)prop-2-en-1-one (6a):
Colourless solid; m.p. 219 °C; yield 225 mg (63%). 1H NMR
(400 MHz, CDCl3): δ = 1.20–2.15 (br. m, 20 H), 3.15–3.45 (br. m,
2 H), 3.83 (s, 3 H), 4.12 (br. s, 1 H), 5.18 (br. s, 1 H), 6.87 (d, J =
8.2 Hz, 1 H), 6.93 (m, 1 H), 7.25 (m, 1 H), 7.61 (d, J = 8.2 Hz, 1
H), 11.39 (s, 1 H) ppm. 13C NMR (100 MHz, CDCl3): δ = 24.5,
24.9, 25.6, 29.8, 32.9, 33.6 (CH2), 49.1, 51.0 (NCH), 55.8 (OCH3),
80.3 (CH=), 111.3 (C-3), 120.4 (C-5), 129.6 (C-4), 129.8 (C-6),
132.9 (C-1), 156.8 (C-2), 159.2 (N–C–N), 183.5 (C=O) ppm. 15N
NMR (40.6 MHz, CDCl3): δ = –285.9, –276.6 (NH) ppm. IR
(N–C–N) ppm. IR (KBr): ν = 1568, 1606, 3211, 3412 cm–1
.
˜
C28H44BrN3O·H2O (536.60): calcd. C 62.67, H 8.64; found C 62.25,
H 8.27.
N-[1,3-Bis(sec-butylamino)-3-(2-methoxyphenyl)prop-2-enylidene]-
butan-2-aminium Bromide (5m): Colourless hygroscopic solid; yield
394 mg (69%). 1H NMR (400 MHz, CDCl3): δ = 0.50–1.70 (br. m,
24 H), 3.22 (br. s, 1 H), 3.58 (br. s, 1 H), 3.72 (s, 3 H), 4.64 (br. s,
(KBr): ν = 1582, 1601, 3261 cm–1. MS (EI): m/z (%)= 356 (11)
˜
1 H), 6.70–7.40 (br. m, 4 H) ppm. 13C NMR (100 MHz, CDCl3): [M]+, 135 (78), 55 (85), 40 (100). C22H32N2O2·H2O (374.53): calcd.
δ = 9.9, 10.2 (CH3CH2), 19.2, 19.8 (CH3CH), 28.4, 28.8 (CH3CH2),
50.6 (NCH), 55.3 (OCH3), 79.9 (Ar–C=CH), 111.3 (C-3), 121.1 (C-
5), 123.8 (C-1), 129.3 (C-6), 131.5 (C-4), 154.4 (Ar–C=CH), 155.5
C 70.55, H 9.15; found C 70.93, H 8.88.
1-(4-Chlorophenyl)-3,3-bis(cyclohexylamino)prop-2-en-1-one
(6b):
Colourless solid; m.p. 167 °C; yield 220 mg (61%). 1H NMR
[400 MHz, (CD3)2CO]: δ = 1.60–2.70 (br. m, 20 H), 4.05–4.25 (br.
m, 2 H), 5.92 (br. s, 1 H), 6.22 (br. s, 1 H), 7.92 (d, J = 6.2 Hz, 2
H), 8.42 (d, J = 6.2 Hz, 2 H), 12.29 (s, 1 H) ppm. 13C NMR
(C-2), 159.3 (N–C–N) ppm. IR (KBr): ν = 1564, 1600, 3202,
˜
3407 cm–1. C22H38BrN3O·H2O (458.49): calcd. C 57.63, H 8.79;
found C 57.60, H 8.72.
N-[1,3-Bis(isopropylamino)-3-phenylprop-2-enylidene]propan-2-amin- [100 MHz, (CD3)2CO]: δ = 25.2, 26.1, 26.6, 33.9, 34.3 (CH2), 49.2,
ium Bromide (5n): Pale brown crystals; m.p. 86–88 °C; yield 312 mg 52.4 (NCH), 76.0 (CH=), 128.9 (C-3,5), 129.2 (C-2,6), 135.5 (C-1),
(85%). H NMR (300 MHz, CDCl3): δ = 0.80–1.27 (br. s, 12 H), 142.5 (C-4), 160.9 (N–C–N), 181.9 (C=O) ppm. IR (KBr): ν =
1
˜
1.27–1.38 (br. s, 6 H), 1.99–2.35 (br. s, 1 H), 3.77–4.10 (br. s, 3 H),
1580, 1605, 3284 cm–1. MS (EI): m/z (%) = 360 (12) [M]+, 197 (20),
4.44–4.68 (br. s, 1 H), 4.72–5.13 (br. s, 1 H), 7.31–7.39 (m, 2 H), 139 (56), 55 (100). C21H29ClN2O·H2O (378.95): calcd. C 66.56, H
7.40–7.55 (m, 2 H), 7.71–8.98 (br. s, 1 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 21.8, 22.1 (CH3), 45.3, 46.5 (CH), 75.8 (Ar–C=CH),
128.0, 129.1, 130.4 (CHAr), 135.3 (C-1), 158.6 (Ar–C=CH), 159.3
8.25; found C 66.88, H 8.07.
3,3-Bis(cyclohexylamino)-1-phenylprop-2-en-1-one (6c): Colourless
solid; m.p. 210 °C; yield 294 mg (90%). 1H NMR (400 MHz,
CDCl3): δ = 1.22–2.10 (m, 20 H, CH2), 3.28 (m, 1 H, CHNH), 3.42
(m, 1 H, CHNH), 4.22 (d, J = 6.1 Hz, 1 H, NH), 5.23 (s, 1 H,
CH=), 7.36 (m, 3 H, 3,4,5-H), 7.82 (m, 2 H, 2,6-H), 11.54 (d, J =
6.1 Hz, 1 H, NH) ppm. 13C NMR (100 MHz, CDCl3): δ = 24.4,
24.8, 25.6, 32.9, 33.7 (CH2), 49.0 (NCH), 51.0 (NCH), 75.6
(N–C–N) ppm. ESI-MS: m/z calcd. for C18H30N3 [M]+: 288.2440;
+
found 288.2434. C18H30BrN3 (368.36): calcd. C 58.69, H 8.21, N
11.41; found C 58.56, H 8.43, N 11.11.
N-[1,3-Bis(cyclohexylamino)-3-phenylprop-2-enylidene]cyclohexan-
aminium Bromide (5o): Colourless solid; m.p. 231–234 °C; yield
1
430 mg (88%). H NMR (400 MHz, CDCl3): δ = 0.80–2.10 (m, 30 (C=CH), 126.6 (C-3,5), 128.0 (C-2,6), 129.4 (C-4), 142.4 (C-1),
308
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Eur. J. Org. Chem. 2010, 300–310

Aromatic Substituents as Switches of Reaction Direction
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1989, 30, 4821–4824; b) I. I. Gerus, M. G. Gorbunova, V. P.
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D. Bonnet-Delpon, D. Bouvet, M. H. Rock, J. Chem. Soc. Per-
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3043–3046.
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89–93.
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Org. Chem. 2004, 69, 8767–8774.
159.5 (C=CH), 183.9 (C=O) ppm. IR (KBr): ν = 1573, 1582,
˜
3262 cm–1. MS (EI): m/z (direct input, relative intensity) = 326 (5)
[M]+, 243 (4), 227 (5), 163 (19), 146 (12), 105 (66), 77 (43), 55 (96),
41 (100). C21H30N2O (326.476): calcd. C 77.26, H 9.26; found C
77.54, H 9.08.
3,3-Bis(cyclohexylamino)-1-(4-methylphenyl)prop-2-en-1-one (6d):
Solid; m.p. 149 °C; yield 317 mg (93%). 1H NMR (400 MHz,
CDCl3): δ = 1.15–2.10 (m, 20 H, CH2 cyclohexyl), 2.34 (s, 3 H,
CH3), 3.26 (m, 1 H, CHNH), 3.40 (m, 1 H, CHNH), 4.27 (d, J =
6.9 Hz, 1 H, NH), 5.19 (s, 1 H, CH=), 7.14 (d, J = 8.0 Hz, 2 H),
[2]
7.70 (d, J = 8.0 Hz, 2 H), 11.49 (d, J = 7.0 Hz, 1 H, NH) ppm. 13
C
NMR (100.6 MHz, CDCl3): δ = 21.3 (CH3), 24.3, 24.8, 25.5, 32.8,
33.5 (CH2), 48.8, 50.9 (CH), 75.2 (CH=), 126.4 (C-3,5), 128.6 (C-
2,6), 139.3 (C-4), 139.5 (C-1), 159.3 (N–C–N), 183.6 (C=O) ppm.
IR (KBr): ν = 1582, 1606, 2929, 3197, 3269 cm–1. C H N O
˜
22 32
2
(340.504): calcd. C 77.60, H 9.47; found C 77.48, H 9.42.
3,3-Bis(cyclohexylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (6e):
Solid; m.p. 165 °C; yield 278 mg (78%). 1H NMR (400 MHz,
CDCl3): δ = 1.20–2.10 (m, 20 H, CH2 cyclohexyl), 3.25 (m, 1 H,
CHNH), 3.38 (m, 1 H, CHNH), 4.27 (d, J = 6.7 Hz, 1 H, NH),
5.16 (s, 1 H, CH=), 6.85 (d, J = 8.8 Hz, 2 H), 7.76 (d, J = 8.8 Hz,
2 H), 11.44 (d, J = 6.8 Hz, 1 H, NH) ppm. 13C NMR (100.6 MHz,
CDCl3): δ = 24.3, 24.8, 25.5, 29.7, 32.8, 33.5 (CH2), 48.8, 50.9
(CH), 55.21 (CH3), 74.7 (CH=), 113.1 (C-3,5), 128.0 (C-2,6), 134.8
[3]
[4]
[5]
[6]
[7]
(C-1), 159.3 (N–C–N), 160.6 (C-4), 183.0 (C=O) ppm. IR (KBr): ν
˜
= 1584, 1603, 2928, 3190, 3268 cm–1. C22H32N2O2 (356.502): calcd.
C 74.12, H 9.05; found C 73.93, H 8.96.
[8]
[9]
C. F. Bernasconi, Z. Rappoport, Acc. Chem. Res. 2009, 42, in
3,3-Bis(isopropylamino)-1-(4-methylphenyl)prop-2-en-1-one
(6f):
press. DOI: 10.1021/ar900048q.
Pale brown powder; m.p. 184–185 °C; yield 211 mg (81%). 1H
NMR (400 MHz, CDCl3): δ = 1.26 (br. s, 12 H, CH3), 2.35 (s, 3
H, CH3), 3.61 (m, 1 H, CHNH), 3.78 (m, 1 H, CHNH), 4.36 (br.
s, 1 H, NH), 5.21 (s, 1 H, CH=), 7.17 (s, 2 H, Ar), 7.71 (s, 2 H,
Ar), 11.37 (br. s, 1 H, NH) ppm. 13C NMR (100.6 MHz, CDCl3):
δ = 21.3 (4-CH3C6H4), 23.0, 23.2 [CH(CH3)2], 43.9, 41.8 (CH), 75.3
(CH=), 126.4 (C-3,5), 128.6 (C-2,6), 139.4 (C-4, C-1), 159.6 (N–C–
N), 183.6 (C=O) ppm. C16H24N2O (260.375): calcd. C 73.81, H
9.29; found C 74.08, H 9.38.
[10]
[11]
[12]
A. Yu. Rulev, Usp. Khim. 2002, 71, 225–254; A. Yu. Rulev,
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a) B. Jiang, F. Zhang, W. Xiong, Tetrahedron 2002, 58, 261–
264; b) W. Dmowski, J. Fluorine Chem. 1984, 26, 379–394.
V. M. Muzalevskiy, V. G. Nenajdenko, A. Yu. Rulev, I. A.
Ushakov, G. V. Romanenko, A. V. Shastin, E. S. Balenkova, G.
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[13]
For key publications, see: a) A. V. Shastin, V. N. Korotchenko,
V. G. Nenajdenko, E. S. Balenkova, Tetrahedron 2000, 56,
6557–6563; b) V. N. Korotchenko, A. V. Shastin, V. G.
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Nenajdenko, A. V. Shastin, E. S. Balenkova, G. Haufe, Synthe-
sis 2009, 2249–2259.
3,3-Bis(isopropylamino)-1-(4-methoxyphenyl)prop-2-en-1-one (6g):
Pale brown powder; m.p. 171–172 °C; yield 199 mg (72%). 1H
NMR (400 MHz, [D6]DMSO): δ = 1.17 (br. s, 12 H, CH3), 3.70–
3.96 (m, 5 H, CH3O, 2 ϫCHNH), 5.15 (s, 1 H, CH=), 6.07 (br. s,
1 H, NH), 6.89 (d, J = 7.2 Hz, 2 H), 7.71 (d, J = 7.2 Hz, 2 H),
11.29 (d, J = 6.8 Hz, 1 H, NH) ppm. 13C NMR (100.6 MHz, [D6]
DMSO): δ = 23.1, 23.4 [CH(CH3)2], 41.3, 43.7 (CH), 55.5 (CH3O),
74.0 (CH=), 113.5 (C-3,5), 128.1 (C-2,6), 135.2 (C-1), 159.8 (N–C–
N), 160.6 (C-4), 181.1 (C=O) ppm. C16H24N2O2 (276.374): calcd.
C 69.53, H 8.75; found C 69.75, H 8.87.
Supporting Information (see footnote on the first page of this arti-
cle):
[14]
[15]
U. Kuckländer, Enaminones as Synthons, in: The Chemistry of
Enamines (Ed.: Z. Rappoport.), Wiley, New York, 1994,
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J. L. Chiara, A. Gomez-Sanchez, NMR Spectra, in: The Chem-
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Z. Rappoport, Acc. Chem. Res. 1992, 25, 474–479.
A. A. Bothner-By, S. Castellano, H. Günther, J. Am. Chem.
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Acknowledgments
This project was supported by the Deutsche Forschungsgemein-
schaft (DFG) through grant Gz: 436 RUS 113/858/0-1 and by the
Russian Foundation for Basic Research (grant nos. 08-03-00736-a,
RFBR-DFG 07-03-91562-NNIO_a and 08-03-00067-a).
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Published Online: November 17, 2009
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Eur. J. Org. Chem. 2010, 300–310