New method of alkenylation of anilines by acetylene compounds in the superacid HSO3F

Article abstract of DOI:10.1016/j.tet.2008.04.092

Vinyl cations, generated by protonation of the triple bond of α,β-alkynylcarbonyl compounds in the superacid HSO₃F, react efficiently with arylammonium (anilinium) ions at low temperatures -75 and -30 °C in 30-75 min with the formation of Fried

Full text of DOI:10.1016/j.tet.2008.04.092

Tetrahedron 64 (2008) 6334–6340
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Tetrahedron
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New method of alkenylation of anilines by acetylene compounds
in the superacid HSO3F
*
Andrey O. Shchukin, Aleksander V. Vasilyev , Andrey P. Rudenko
Department of Organic Chemistry, Saint-Petersburg State Forest Technical Academy, Institutsky per. 5, Saint-Petersburg 194021, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
Vinyl cations, generated by protonation of the triple bond of
a,b-alkynylcarbonyl compounds in the
Received 25 January 2008
Received in revised form 7 April 2008
Accepted 24 April 2008
superacid HSO3F, react efficiently with arylammonium (anilinium) ions at low temperatures ꢀ75 and
ꢀ30 ꢁC in 30–75 min with the formation of Friedel–Crafts-type products of anilinium ring alkenylation in
14–62% yields. Regio- and stereoselectivity of such electrophilic aromatic substitution has been studied
in detail.
Available online 29 April 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Arene alkenylation
Friedel–Crafts reactions
Acetylene compounds
Anilines
Superacids
Fluorosulfonic acid
1. Introduction
finally leads to alkenylation product (E/Z)-2 after quenching of the
superacidic reaction mixture with aqueous NaHCO3.
Arylamines (anilines) are widely used for industrial production
of dyes, pharma-, and agrochemicals. In organic chemistry, anilines
are objects of special interest for the preparation of various
heterocyclic compounds.1,2
The classical syntheses of arylamines bearing alkenyl (vinyl)
substituents in the aromatic ring are based on the Heck reaction.3,4
Recently, new methods of alkenyl substituted anilines have been
developed with the use of Grignard reagents.5,6
Vinyl cations A containing electron-withdrawing groups X¼CO2R,
CORareconsideredasstrong(orsuper-)electrophilicspecies17–19,21,22
due to the additional electrophilic activation of the vinyl cationic
center by the electron-withdrawing groups X solvated in the super-
acids.8,9,13,14 The cations A are sufficiently electrophilic to attack such
deactivated
p-nucleophiles as aromatic systems of arylammonium
ions B (Scheme 1).
In this paper, we present a new synthesis of vinyl-substituted
anilines on the basis of alkenylation of aniline rings by acetylene
compounds in the superacid HSO3F. This study is based on our work
on the chemistry of alkynes in superacids,7–14 in particular on the
alkenylation of arenes,8,11,12 and on other studies on acetylene
chemistry in superacids.15–19
The superacid HSO3F is a unique medium for generating vinyl
cations A by the protonation of the triple bond of acetylene
compounds 1 (Scheme 1).7–19 Arylamines exist in superacids in the
form of arylammonium (anilinium) ions B20 (Scheme 1). Electro-
philic aromatic substitution with a participation of these cations A
and B results in the formation of arenium dication C. Deprotonation
of the latter gives vinyl-substituted arylammonium ion D, which
2. Results and discussion
Simply dissolution of arylamine in HSO3F at low temperature,
and consequent addition of acetylene compound 1 to the obtained
arylamonium ion B solution followed by the final basic quenching
of the reaction mixture affords compound 2 (Scheme 1). The
reaction conditions (amount of reagents, temperature, and time)
for the alkenylation of arylamonium ions by acetylene compounds
1a–c in HSO3F with the formation of products 2a–o are given in
Table 1. Reaction temperature (Table 1) was chosen according to the
temperature at which the acetylene substrates 1a–c undergo
protonation in superacids. In HSO3F, acetylene esters 1a,b form
reactive vinyl cations A at ꢀ75 and ꢀ30 ꢁC, respectively;11,13,14 and
ketone 1c gives vinyl cation at ꢀ30 ꢁC.12–14
As it has been shown before,11,12 the addition of a proton and an
aryl moiety to alkynes proceeds in a syn-fashion in superacids at low
temperature (ꢀ75 to ꢀ50 ꢁC). At higher temperature (ꢀ30 to 20 ꢁC)
* Corresponding author.
E-mail address: aleksvasil@mail.ru (A.V. Vasilyev).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.04.092

A.O. Shchukin et al. / Tetrahedron 64 (2008) 6334–6340
6335
NH2
X = CO2R, COR
Ar
1
C
C
C
X
R
R
H+
H+
X
H
Ar
Ar
Ar
NH3
C
CHX
C
CHX
C
C
H
NaHCO3 - H2O
Ar
CHX
+
-H+
R
R
NH3
A
R
NH3
NH2
(E)-, (Z)- (syn-, anti-) 2
D
B
C
Scheme 1.
in superacids, the syn-adducts are isomerized into their anti-ana-
logues. In this study, we have observed the same regularity for the
compounds 2a–o. Thus, individually isolated (E)-isomer 2l (entry
10) was transformed into (Z)-2l in HSO3F at ꢀ30 ꢁC (Scheme 2).
The E/Z-configuration of the alkenylation products 2a–o was
determined by 1H NMR spectroscopy. Similarly to our previous
X-ray and NMR investigations of 3,3-diarylpropenone systems,11,12
in this study, we used a signal of vinyl proton of compounds (E/Z)-
2a–o as a stereochemical reference point to make an assignment of
E/Z-configuration. The vinyl proton signal of the E-isomers of 3,3-
1). 1H NMR spectrum of the compound (E)-2a reveals the typical set
of signals corresponding to proton spin system of 1,2,4-
trisubstituted benzene (aniline ring in the structure (E)-2a). These
signals are two doublets at 6.55 and 6.99 ppm with coupling
constants J 1.7 and 7.8 Hz, respectively, and the doublet of doublets
at 6.67 ppm with the same constants J 7.8 and 1.7 Hz (see Section
4). In case of alternative substitution at position 3 (also meta-
position to group NHþ3 ) in the 2-methylphenylammonium ion, the
aniline ring in the formed alkenylation product should be 1,2,3-
trisubstituted benzene, which shows a rather complex proton
spectrum, but that does not take place indeed.
Alkenylation of the 2,4-dimethylphenylammonium ion by com-
pounds 1a,c proceeds selectively at the position 5 of arylammonium
ring (entries 3 and 4). Acetylene ester 1a forms a mixture of
stereoisomers (E/Z)-2c (entry 3), but ketone 1c gives only the iso-
merized compound (Z)-2d (entry 4).26
a
d
d
diarylpropenoates 2a–c,e–g,i–l,n,o (resonance at
are up-field shifted compared to the corresponding signal for their
Z-isomers 2b,c,l (resonance at 6.38–6.60 ppm) and to the vinyl
proton signal for the Z-isomers of 4,4-diarylbut-3-en-2-ones
2d,h,m (resonance at
6.63–6.80 ppm) (see Section 4).11,12
d 5.82–6.28 ppm)
d
d
Additional proof for stereochemical configuration of the com-
pound (E)-2g has been provided by a ROESY experiment, which
The 3,4-dimethylphenylammonium ion gives two alkenylation
products (E)-2e and (E)-2f as a result of substitution at the positions
6 and 5 of the arylammonium ring, respectively, in reaction with
ester 1a (entry 5). Identification of compounds (E)-2e and (E)-2f has
been done on the basis of their 1H NMR spectra. Thus, the proton
reveals strong correlation between the vinyl proton (
d 5.82 ppm)
and two methyl substituents ( 2.05 and 2.06 ppm) in aniline ring
d
(Fig. 1). This type of correlation is only possible for the E-isomer due
to the spatial closeness of these proton groups. Also confirmation of
the E-configuration is the absence of any correlation between the
vinyl proton and aromatic ortho-protons in the para-tolyl ring.23
The electron-withdrawing ammonium group, NHþ3 , deactivates
spectrum of isomer (E)-2f contains two doublets at
d 6.39 and
6.51 ppm with constant J 2.3 Hz that corresponds to two aromatic
meta-protons in the positions 2 and 4 of the aniline ring. On the
contrary, two singlets of aniline ring para-protons of compound
the aromatic
p-system of ion B (Scheme 1) in electrophilic sub-
stitution. Thus, N-protonated forms of aniline and N,N-dimethyla-
niline do not react with vinyl cations generated from the
compounds 1b,c in HSO3F at ꢀ30 ꢁC; no alkenylation products are
formed. In these cases, the initial acetylenes 1b,c react with HSO3F
and afford the corresponding vinyl fluorosulfonates.14
The presence of only one methyl group in the aniline ring
permits reaction of the corresponding arylammonium ions with
vinyl cations. ortho- and para-Methyl substituted anilines give
compounds (E/Z)-2a,b (entries 1 and 2) as products of the regio-
selective substitution into meta-position to electron-acceptor
group NHþ3 . The same position selectivity has been observed in the
trifluoromethylation and bromination of these mono-methyl-
substituted anilines in the superacidic system HF–SbF5.24,25
Substitution in the 2-methylphenylammonium ion goes selec-
tively at the position 5, leading solely to the product (E)-2a (entry
(E)-2e appear at d
6.43 and 6.83 ppm in 1H NMR spectrum (see
Section 4).
Vinyl cations, generated from acetylenes 1a–c, are sufficiently
active to attack sterically protected arylammonium substrates
(entries 6–11) bearing even a bulky tert-butyl group (entry 8). Ke-
tone 1c forms products of anti-addition to the triple bond (Z)-2h,m
(entries 7 and 11). Acetylene esters 1a,b lead to the formation of
syn-addition products (E)-2g,i–l (entries 6 and 8–10).26
The 2,4,5-trimethylphenylammonium ion is attacked at both
available positions of its aromatic ring giving two alkenylation
products (E)-2j and (E)-2k (entry 9). The latter is substitution pro-
duct into ortho-position to ammonium group despite its electron-
withdrawing character; it is also substitution into ortho-position to
Me
Me
Me
ortho
H
H
CO2Me
CO2Me
H
HSO3F
Me
C
C
C
C
Me
C
C
Me
2.06
-30 °C, 1h
CO2Me
H
5.82
Me
H2N
Me
Me
H2N
Me
Me
2.05
Me
Me
Me
NH2
(E)-2g
(E)-2l
(Z)-2l
Scheme 2.
Figure 1. ROESY data for compound (E)-2g (green arrows show correlations).

6336
A.O. Shchukin et al. / Tetrahedron 64 (2008) 6334–6340
Table 1
Reaction conditions and products of alkenylation of arylammonium ions by acetylene compounds in HSO3F
Entry
Acetylene compound,
number (amount, mmol)
Arylammonium ion
(amount, mmol)
Reaction conditions
HSO3F, ml
Temperature, ꢁC
Alkenylation product,
number (yield, %)
Time, min
p-Tol
CO2Me
H
NH3
Me
C C
Me
C C CO2Me
H2N
1
1
ꢀ75
60
1a (0.17)
Me
(E)-2a (17)
(0.23)
H
CO2Me
Ph
Ph
Me
C
C
Me
C C
NH3
CO2Me
H
+
C
C
CO2Me
2
3
4
5
1
1
1
1
ꢀ30
ꢀ75
ꢀ30
ꢀ75
30
60
60
45
1b (0.31)
NH2
(Z)-2b (2)
NH2
(E)-2b (12)
Me
(0.77)
p-Tol
Me
p-Tol
Me
H
CO2Me
C
C
NH3
Me
C C
+
CO2Me
H
1a (0.17)
Me
NH2
(Z)-2c (13)
Me
NH2
Me
(0.17)
(E)-2c (24)
p-Tol
Me
H
C
C
NH3
Me
COMe
Me
C
C COMe
Me
NH2
(Z)-2d (56)
1c (0.32)
Me
(0.64)
CO2Me
H
p-Tol
Me
p-Tol
CO2Me
C
C
C
C
NH3
+
H
Me
Me
NH2
1a (0.20)
Me
NH2
(E)-2f (7)
Me
(E)-2e (34)
Me
(0.40)
p-Tol
CO2Me
H
C
C
NH3
Me
Me
Me
Me
6
1a (0.09)
0.7
ꢀ75
60
Me
NH2
Me
(E)-2g (38)
(0.79)
H
p-Tol
C
C
NH3
Me
COMe
Me
Me
Me
7
1c (0.32)
1
ꢀ30
75
Me
NH2
(Z)-2h (44)
Me
(0.79)

A.O. Shchukin et al. / Tetrahedron 64 (2008) 6334–6340
6337
Table 1 (continued )
Entry Acetylene compound,
Arylammonium ion
(amount, mmol)
Reaction conditions
HSO3F, ml
Temperature, ꢁC
Alkenylation product,
number (yield, %)
number (amount, mmol)
Time, min
p-Tol
CO2Me
C
C
t-Bu
NH3
H
Me
Me
Me
Me
8
1a (0.13)
0.7
ꢀ75
ꢀ30
ꢀ75
60
Me
NH2
t-Bu
(0.13)
(E)-2i (34)
Ph
Ph
CO2Me
CO2Me
H
Me
C
C
Me
C C
NH3
+
H
Me
Me
Me
NH2
9
1b (0.31)
1
60
Me
Me
NH2
Me
(0.37)
(E)-2j (30)
(E)-2k (18)
CO2Me
H
p-Tol
Me
C
C
NH3
Me
Me
Me
Me
Me
H2N
Me
10
1a (0.23)
1
60
Me
(E)-2l (25)
(0.28)
H
p-Tol
C
C
Me
NH3
COMe
Me
Me
Me
Me
Me
Me
11
1c (0.32)
1
ꢀ30
60
H2N
Me
(0.60)
(Z)-2m (31)
CO2Me
p-Tol
p-Tol
CO2Me
H
C
C
NH3
C
C
MeO
H
+
12
1a (0.16)
1
ꢀ75
60
OMe
NH2
(E)-2o (17)
MeO
NH2
(0.20)
(E)-2n (45)
methyl group. In this case the electron-donating methyl groups in
the anilinium ion rule the electrophilic substitution.
are more reactive in aromatic electrophilic substitution, afford re-
action products in higher yields, 25–56% (entries 3–11). The highest
yield, 62% totally for two isomers, has been reached by the alke-
nylation of the activated 2-methoxy-substituted aniline (entry 12).
All amount of the starting acetylenes 1a–c has been completely
consumed under the reaction conditions for all examples shown in
Table 1. The formation of reaction products in modest yields in
HSO3F can be explained by secondary reactions of the obtained
compounds (E/Z)-2a–o, which are enones with conjugated carbon–
carbon double and carbonyl bonds. These enone structures
undergo various transformations in superacids.27 Apart from that,
in HSO3F, the fluorosulfonation of aromatic rings of the products
(E/Z)-2a–o may take place decreasing the yields.12
It is worth noting the unusual chromatographic behavior of
compounds (E)-2e and (E)-2k (entries 5 and 9). They have lower
retention parameters in column chromatography on silica gel
(higher Rf values in TLC) than their isomers (E)-2f and (E)-2j
respectively and even than initial anilines. Most likely, it is caused
by sterical shielding of the ortho-amino group in the structures (E)-
2e and (E)-2k.
2-Methoxy-substituted anilinium ion gives two alkenylation
products (E)-2n,o (entry 12) as a result of substitution into the para-
and ortho-position relatively to the methoxy group. In this reaction,
at low temperature, ꢀ75 ꢁC, only the products resulting from
overall syn-addition to the acetylene bond of compound 1a are
formed (entry 12).
3. Conclusion
Yields of alkenylation products (E/Z)-2a–o are quite moderate in
a range of 14–62%. The lowest yields in 14 and 17% have been
obtained at the transformations of mono-methyl-substituted
anilines (entries 1 and 2). Di-, tri- and tetramethyl-anilines, which
A new simple regio- and stereoselective synthesis of alkenyl-
(vinyl-)substituted anilines has been developed on the basis of
Friedel–Crafts-type alkenylation of alkyl- and methoxy-substituted

6338
A.O. Shchukin et al. / Tetrahedron 64 (2008) 6334–6340
anilines by vinyl cations, generated from acetylene compounds in
the superacid HSO3F at low temperature ꢀ75 or ꢀ30 ꢁC.
4.4.2. (E)-Methyl-3-(5-amino-2-methylphenyl)-3-phenyl-
propenoate (E)-2b and (Z)-methyl-3-(5-amino-2-methylphenyl)-
3-phenylpropenoate (Z)-2b
Compounds (E)-2b and (Z)-2b were obtained as oily inseparable
mixture of isomers from 4-methylphenylamine (83 mg, 0.77 mmol)
and acetylene 1b (50 mg, 0.31 mmol) in HSO3F (1 ml) at ꢀ30 ꢁC in
30 min in 11 mg (12%) for (E)-2b, and 1.5 mg (2%) for (Z)-2b
according to the general alkenylation procedure. IR (for mixture)
nmax (KBr) 3450, 3362, 1722, 1610 cmꢀ1. (E)-2b Rf [20% hexanes/
ethyl acetate (8.5:1 v/v)]. 1H NMR (500 MHz, CDCl3) (from the
spectrum of mixture) 1.94 (s, 3H, Me), 3.64 (s, 3H, OMe), 3.58 (br s,
2H, NH2), 5.98 (s, 1H, ]CH–), 6.54 (d, 1Harom., J¼2.5 Hz), 6.59 (dd,
1Harom., J¼8.1, 2.5 Hz), 6.92 (d, 1Harom., J¼8.1 Hz), 7.23–7.30 (m,
5Harom.). (Z)-2b Rf [20% hexanes/ethyl acetate (8.5:1 v/v)]. 1H NMR
(500 MHz, CDCl3) (from the spectrum of mixture) 1.95 (s, 3H, Me),
3.60 (s, 3H, OMe), 3.58 (br s, 2H, NH2), 6.41 (d, 1Harom., J¼2.5 Hz),
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded on Brucker AM-500 NMR
spectrometer (working frequencies 500 and 125 MHz, respectively)
in CDCl3 solutions. The residual proton–solvent peak of CDCl3
(d
7.25 ppm) for 1H NMR spectra, the signal of CDCl3 (
d
77.0 ppm) for
13C NMR spectra were used as internal references. Mass spectra
(electron impact, ionization energy 70 eV) were measured on
a machine MKh-1321. IR spectra of compounds in CHCl3 solutions
were recorded on Specord 75 IR spectrometer. IR spectra of com-
pounds in KBr pressed tablets were recorded on FSM 1201 IR
spectrometer. Analytical thin-layer chromatography (TLC) was
performed using Silufol silica gel UV-254 plates. Preparative
separation of reaction mixtures was carried out by column chro-
matography on silica gel Chemapol 60/100. Chromatography
eluent: hexanes/ethyl acetate.
6.48 (s, 1H, ]CH–), 6.63 (dd, 1Harom., J¼8.1, 2.5 Hz), 7.02 (d, 1Harom.
,
J¼8.1 Hz), 7.23–7.30 (m, 5Harom.). MS (for mixture), m/z (Irel, %): 267
(Mþ, 100), 236 (33), 207 (56), 206 (47), 197 (47), 130 (33), 115 (28).
Anal. Calcd for C17H17NO2: C, 76.38; H, 6.41; N, 5.24. Found: C,
76.47; H, 6.30; N, 5.43.
4.4.3. (E)-Methyl-3-(5-amino-2,4-dimethylphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2c and (Z)-methyl-3-(5-amino-2,4-
4.2. Starting materials
dimethylphenyl)-3-(4-methylphenyl)propenoate (Z)-2c
Synthesis and properties of methyl-3-(4-methylphenyl)propiolate
1a, methyl-3-phenylpropiolate 1b, and 4-(4-methylphenyl)but-3-yn-
2-one 1c were previously published.12,28 Arylamines are commer-
cially available substances.
Compounds (E)-2c and (Z)-2c were obtained as oily inseparable
mixture of isomers from 2,4-dimethylphenylamine (21 mg,
0.17 mmol) and acetylene 1a (30 mg, 0.17 mmol) in HSO3F (1 ml)
at ꢀ75 ꢁC in 60 min in 13 mg (24%) for (E)-2c, and 6 mg (13%) for
(Z)-2c according to the general alkenylation procedure. IR (for
mixture) nmax (KBr) 3450, 3373, 1720, 1621 cmꢀ1. (E)-2c Rf [20%
hexanes/ethyl acetate (8.5:1 v/v)]. 1H NMR (500 MHz, CDCl3) (from
the spectrum of mixture) 1.93 (s, 3H, Me), 2.14 (s, 3H, Me), 2.34 (s,
3H, Me), 3.47 (s, 2H, NH2), 3.65 (s, 3H, OMe), 5.93 (s, 1H, ]CH–),
6.51 (s, 1Harom.), 6.82 (s, 1Harom.), 7.09 (d, 2Harom., J¼8.0 Hz), 7.14 (d,
2Harom., J¼8.0 Hz). (Z)-2c Rf [20% hexanes/ethyl acetate (8.5:1 v/v)].
1H NMR (500 MHz, CDCl3) (from the spectrum of mixture) 1.94 (s,
3H, Me), 2.17 (s, 3H, Me), 2.34 (s, 3H, Me), 3.60 (s, 3H, OMe), 3.69
(s, 2H, NH2), 6.38 (s, 1Harom.), 6.45 (s, 1H, ]CH–), 6.92 (s, 1Harom.),
7.10 (d, 2Harom., J¼7.8 Hz), 7.23 (d, 2Harom., J¼7.8 Hz). MS (for
mixture), m/z (Irel, %): 295 (Mþ, 100), 280 (9), 264 (26), 235 (22),
221 (38), 147.5 (Mþþ, 5). Anal. Calcd for C19H21NO2: C, 77.26; H,
7.17; N, 4.74. Found: C, 77.41; H, 7.05; N, 4.73.
4.3. General alkenylation procedure
Arylamine (0.1–0.79 mmol) was added to cooled HSO3F (0.7–
1.0 ml) at the temperature of ꢀ75 or ꢀ30 ꢁC with vigorous mag-
netic stirring. After complete dissolving of arylamine in HSO3F at
the above-mentioned temperature, acetylene compound (0.09–
0.32 mmol, 0.4–1 equiv) was also added. Reaction mixture was
stirred at the temperature of ꢀ75 or ꢀ30 ꢁC for 30–75 min (see
Table 1). Then the mixture was quenched with a cooled (ꢀ75 ꢁC)
concentrated aqueous HCl (w10 ml). CAUTION: very vigorous
decomposition of HSO3F into H2SO4 and HF. The resulting mixture
was diluted with water (w100 ml). Products were extracted with
CHCl3 (3ꢂ50 ml). Combined extracts were subsequently washed
with H2O (w50 ml), saturated aqueous NaHCO3 (w30 ml), H2O
(w30 ml), and dried over Na2SO4. After solvent evaporation under
the reduced pressure, the reaction products were finally isolated by
column chromatography on silica gel.
4.4.4. (Z)-4-(5-Amino-2,4-dimethylphenyl)-4-(4-methylphenyl)-
but-3-en-2-one (Z)-2d
Compound (Z)-2d was obtained from 2,4-dimethylphenylamine
(77 mg, 0.64 mmol) and acetylene 1c (50 mg, 0.32 mmol) in HSO3F
(1 ml) at ꢀ30 ꢁC in 60 min in 49 mg (56%) according to the general
alkenylation procedure. Yellow oily compound. Rf [20% hexanes/
4.4. Characterization of the products
4.4.1. (E)-Methyl-3-(3-amino-4-methylphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2a
ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3470, 3363, 1655, 1594 cmꢀ1
.
1H NMR (500 MHz, CDCl3) 1.80 (s, 3H, Me), 1.93 (s, 3H, Me), 2.19 (s,
3H, Me), 2.33 (s, 3H, Me), 3.55 (br s, 2H, NH2), 6.43 (s, 1Harom.), 6.63
(s, 1H, ]CH–), 6.93 (s, 1Harom.), 7.10 (d, 2Harom., J¼8.3 Hz), 7.22 (d,
2Harom., J¼8.3 Hz). MS, m/z (Irel, %): 279 (Mþ, 53), 264 (100), 236
(30), 221 (20). Anal. Calcd for C19H21NO: C, 81.68; H, 7.58; N, 5.01.
Found: C, 81.61; H, 8.02; N, 4.93.
Compound (E)-2a was obtained from 2-methylphenylamine
(24 mg, 0.23 mmol) and acetylene 1a (30 mg, 0.17 mmol) in HSO3F
(1 ml) at ꢀ75 ꢁC in 60 min in 8 mg (17%) according to the general
alkenylation procedure. Slightly yellow oily compound. Rf [20%
hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3415, 3375, 1717,
1618 cmꢀ1. 1H NMR (500 MHz, CDCl3) 2.15 (s, 3H, Me), 2.38 (s, 3H,
Me), 3.59 (br s, 2H, NH2), 3.60 (s, 3H, OMe), 6.28 (s, 1H, ]CH–), 6.55
(d, 1Harom., J 1.7¼Hz), 6.67 (dd, 1Harom., J¼7.8, 1.7 Hz), 6.99 (d,
4.4.5. (E)-Methyl-3-(2-amino-4,5-dimethylphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2e
1Harom., J¼7.8 Hz), 7.09 (d, 2Harom., J¼8.0 Hz), 7.17 (d, 2Harom.
,
Compound (E)-2e was obtained from 3,4-dimethylphenylamine
(49 mg, 0.4 mmol) and acetylene 1a (35 mg, 0.2 mmol) in HSO3F
(1 ml) at ꢀ75 ꢁC in 45 min in 20 mg (34%) according to the general
alkenylation procedure. White solid. Mp 200 ꢁC (decomposition). Rf
[30% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3462, 3373,
1720, 1621 cmꢀ1. 1H NMR (500 MHz, CDCl3) 2.13 (s, 3H, Me), 2.17 (s,
J¼8.0 Hz). 13C NMR (125 MHz, CDCl3) 17.15, 21.36, 51.08, 114.83,
115.40, 118.81, 124.00, 128.45, 129.13, 130.33, 137.84, 140.02, 144.36,
157.65, 166.60. MS, m/z (Irel, %): 281 (Mþ, 100), 266 (3), 250 (28).
Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C,
76.60; H, 7.15; N, 4.87.

A.O. Shchukin et al. / Tetrahedron 64 (2008) 6334–6340
6339
3H, Me), 2.35 (s, 3H, Me), 3.42 (br s, 2H, NH2), 3.64 (s, 3H, OMe), 6.10
(17), 294 (14), 276 (34), 262 (43). Anal. Calcd for C23H29NO2: C, 78.59;
H, 8.32; N, 3.99. Found: C, 78.65; H, 8.27; N, 4.01.
(s, 1H, ]CH–), 6.43 (s, 1Harom.), 6.83 (s, 1Harom.), 7.14 (d, 2Harom.
,
J¼8.0 Hz), 7.21 (d, 2Harom., J¼8.0 Hz). MS, m/z (Irel, %): 295 (Mþ, 59),
264 (70), 263 (88), 248 (26), 236 (100), 222 (23). Anal. Calcd for
4.4.10. (E)-Methyl-3-(3-amino-2,5,6-trimethylphenyl)-3-phenyl-
propenoate (E)-2j
C
19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.21; H, 7.17; N, 4.82.
Compound (E)-2j was obtained from 2,4,5-trimethylphenyl-
amine (50 mg, 0.37 mmol) and acetylene 1b (50 mg, 0.31 mmol) in
HSO3F (1 ml) at ꢀ30 ꢁC in 60 min in 38 mg (30%) according to the
general alkenylation procedure. White solid. Mp 126–128 ꢁC. Rf
[20% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3490, 3393,
1719, 1618 cmꢀ1. 1H NMR (500 MHz, CDCl3) 2.02 (s, 3H, Me), 2.03 (s,
3H, Me), 2.17 (s, 3H, Me), 3.48 (br s, 2H, NH2), 3.68 (s, 3H, OMe), 5.87
(s, 1H, ]CH–), 6.53 (s, 1Harom.), 7.27 (m, 5Harom.). MS, m/z (Irel, %):
295 (Mþ, 100), 264 (10), 248 (11), 236 (29), 220 (42), 134 (23). Anal.
Calcd for C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.35; H,
7.21; N, 4.69.
4.4.6. (E)-Methyl-3-(5-amino-2,3-dimethylphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2f
Compound (E)-2f was obtained from 3,4-dimethylphenylamine
(49 mg, 0.4 mmol) and acetylene 1a (35 mg, 0.2 mmol) in HSO3F
(1 ml) at ꢀ75 ꢁC in 45 min in 4 mg (7%) according to the general
alkenylation procedure. Slightly yellow oily compound. Rf [20%
hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3453, 3368, 1723,
1618 cmꢀ1. 1H NMR (500 MHz, CDCl3) 1.89 (s, 3H, Me), 2.15 (s, 3H,
Me), 2.32 (s, 3H, Me), 3.65 (s, 5H, OMe, NH2), 5.91 (s, 1H, ]CH–),
6.39 (d, 1Harom.
,
J¼2.3 Hz), 6.51 (d, 1Harom.
,
J¼2.3 Hz), 7.09
(d, 2Harom., J¼8.0 Hz), 7.14 (d, 2Harom., J¼8.0 Hz). MS, m/z (Irel, %):
295 (Mþ, 100), 280 (14), 264 (25), 236 (35), 221 (39). Anal. Calcd for
4.4.11. (E)-Methyl-3-(2-amino-3,5,6-trimethylphenyl)-3-phenyl-
propenoate (E)-2k
C
19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found: C, 77.08; H, 7.45; N,
4.76.
Compound (E)-2k was obtained from 2,4,5-trimethylphenyl-
amine (50 mg, 0.37 mmol) and acetylene 1b (50 mg, 0.31 mmol) in
HSO3F (1 ml) at ꢀ30 ꢁC in 60 min in 22 mg (18%) according to the
general alkenylation procedure. White solid. Mp 98–100 ꢁC. Rf [30%
hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3485, 3388, 1720,
1616 cmꢀ1. 1H NMR (500 MHz, CDCl3) 2.04 (s, 3H, Me), 2.13 (s, 3H,
Me), 2.15 (s, 3H, Me), 3.57 (br s, 2H, NH2), 3.68 (s, 3H, OMe), 6.03 (s,
1H, ]CH–), 6.86 (s, 1Harom.), 7.29–7.30 (m, 3Harom.), 7.35–7.37 (m,
2Harom.). MS, m/z (Irel, %): 295 (Mþ, 70), 264 (29), 248 (8), 236 (100),
221 (29). Anal. Calcd for C19H21NO2: C, 77.26; H, 7.17; N, 4.74. Found:
C, 77.30; H, 7.28; N, 4.74.
4.4.7. (E)-Methyl-3-(3-amino-2,4,6-trimethylphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2g
Compound (E)-2g was obtained from 2,4,6-trimethylphenyl-
amine (14 mg, 0.1 mmol) and acetylene 1a (15 mg, 0.09 mmol) in
HSO3F (0.7 ml) at ꢀ75 ꢁC in 60 min in 10 mg (38%) according to the
general alkenylation procedure. Colorless oily compound. Rf [20%
hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3460, 3393, 1717,
1616 cmꢀ1. 1H NMR (500 MHz, CDCl3) 2.05 (s, 3H, Me), 2.06 (s, 3H,
Me), 2.16 (s, 3H, Me), 2.31 (s, 3H, Me), 3.51 (br s, 2H, NH2), 3.68 (s,
3H, OMe), 5.82 (s, 1H, ]CH–), 6.79 (s, 1Harom.), 7.06 (d, 2Harom.
,
J¼8.1 Hz), 7.15 (d, 2Harom., J¼8.1 Hz). 13C NMR (125 MHz, CDCl3)
14.73, 17.57, 19.53, 21.27, 51.22, 119.15, 121.32, 124.63, 127.02, 128.33,
129.12, 129.51, 134.90, 138.57, 140.24, 140.63, 155.67, 167.16. MS, m/z
(Irel, %): 309 (Mþ, 100), 278 (7), 249 (13), 234 (25), 221 (14). Anal.
Calcd for C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C, 77.48; H,
7.47; N, 4.53.
4.4.12. (E)-Methyl-3-(4-amino-2,3,5,6-tetramethylphenyl)-3-(4-
methylphenyl)propenoate (E)-2l
Compound (E)-2l was obtained from 2,3,5,6-tetramethylphe-
nylamine (41 mg, 0.28 mmol) and acetylene 1a (50 mg, 0.31 mmol)
in HSO3F (1 ml) at ꢀ75 ꢁC in 60 min in 19 mg (25%) according to the
general alkenylation procedure. White solid. Mp 197–199 ꢁC. Rf
[20% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3485, 3390,
1720, 1615 cmꢀ1. 1H NMR (500 MHz, CDCl3) 2.09 (s, 6H, 2Me), 2.13
(s, 6H, 2Me), 2.31 (s, 3H, Me), 3.62 (br s, 2H, NH2), 3.67 (s, 3H, OMe),
4.4.8. (Z)-4-(3-Amino-2,4,6-trimethylphenyl)-4-(4-methylphenyl)-
but-3-en-2-one (Z)-2h
Compound (Z)-2h was obtained from 2,4,6-trimethylphenyl-
amine (106 mg, 0.79 mmol) and acetylene 1c (50 mg, 0.32 mmol) in
HSO3F (1 ml) at ꢀ30 ꢁC in 75 min in 41 mg (44%) according to the
general alkenylation procedure. Slightly yellow oily compound. Rf
[20% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (CHCl3) 3400, 3300,
1630, 1590 cmꢀ1. 1H NMR (500 MHz, CDCl3) 1.72 (s, 3H, Me), 1.94 (s,
3H, Me),1.95 (s, 3H, Me), 2.21 (s, 3H, Me), 2.33 (s, 3H, Me), 3.56 (br s,
5.82 (s, 1H, ]CH–), 7.06 (d, 2Harom., J¼7.5 Hz), 7.15 (d, 2Harom.
,
J¼7.5 Hz). MS, m/z (Irel, %): 323 (Mþ, 100), 308 (24), 292 (12), 250
(47), 235 (52), 161.5 (Mþþ, 10). Anal. Calcd for C21H25NO2: C, 77.98;
H, 7.79; N, 4.33. Found: C, 78.01; H, 7.70; N, 4.35.
4.4.13. (Z)-Methyl-3-(4-amino-2,3,5,6-tetramethylphenyl)-3-(4-
methylphenyl)propenoate (Z)-2l
2H, NH2), 6.80 (s, 1H, ]CH–), 6.86 (s, 1Harom.), 7.10 (d, 2Harom.
,
Compound (Z)-2l was obtained under the stirring of solution of
compound (E)-2l (15 mg, 0.05 mmol) in HSO3F (0.8 ml) at ꢀ30 ꢁC in
60 min in 13 mg (87%) with a quenching of the reaction mixture
according to the general alkenylation procedure. Colorless oily
compound. Rf [20% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr)
3480, 3380, 177, 1610 cmꢀ1. 1H NMR (500 MHz, CDCl3) 1.97 (s, 6H,
2Me), 2.10 (s, 6H, 2Me), 2.33 (s, 3H, Me), 3.58 (s, 5H, OMe, NH2), 6.60
(s, 1H, ]CH–), 7.09 (d, 2Harom., J¼8.3 Hz), 7.23 (d, 2Harom., J¼8.3 Hz).
Anal. Calcd for C21H25NO2: C, 77.98; H, 7.79; N, 4.33. Found: C,
77.88; H, 7.85; N, 4.38.
J¼8.1 Hz), 7.24 (d, 2Harom., J¼8.1 Hz). MS, m/z (Irel, %): 293 (Mþ, 100),
278 (96), 263 (10), 234 (31), 220 (21). Anal. Calcd for C20H23NO: C,
81.87; H, 7.90; N, 4.77. Found: C, 81.90; H, 7.68; N, 4.71.
4.4.9. (E)-Methyl-3-(6-tert-butyl-3-amino-2,4-dimethylphenyl)-3-
(4-methylphenyl)propenoate (E)-2i
Compound (E)-2i was obtained from 4-tert-butyl-2,6-dimethyl-
phenylamine (22 mg, 0.13 mmol) and acetylene 1a (22 mg,
0.13 mmol) in HSO3F (0.75 ml) at ꢀ75 ꢁC in 60 min in 15 mg (34%)
according to the general alkenylation procedure. Slightly yellow oily
compound. Rf [20% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr)
3460, 3393, 1717, 1616 cmꢀ1. 1H NMR (500 MHz, CDCl3) 1.22 (s, 9H,
CMe3), 2.00 (s, 3H, Me), 2.22 (s, 3H, Me), 2.31 (s, 3H, Me), 3.60 (br s,
4.4.14. (Z)-4-(4-Amino-2,3,5,6-tetramethylphenyl)-4-(4-methyl-
phenyl)but-3-en-2-one (Z)-2m
Compound (Z)-2m was obtained from 2,3,5,6-tetramethylphe-
nylamine (89 mg, 0.60 mmol) and acetylene 1c (50 mg, 0.32 mmol)
in HSO3F (1 ml) at ꢀ30 ꢁC in 60 min in 30 mg (31%) according to the
general alkenylation procedure. Slightly yellow oily compound. Rf
[20% hexanes/ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3480, 3387,
1647, 1593 cmꢀ1. 1H NMR (500 MHz, CDCl3) 1.65 (s, 3H, Me), 2.00 (s,
2H, NH2), 3.72 (s, 3H, OMe), 5.86 (s, 1H, ]CH–), 7.05 (d, 2Harom.
,
J¼8.3 Hz), 7.13 (s, 1Harom.), 7.20 (d, 2Harom., J¼8.3 Hz). 13C NMR
(125 MHz, CDCl3) 15.05, 18.07, 21.24, 33.09, 36.19, 51.35, 119.97,
120.46, 121.12, 127.32, 128.37, 130.04, 135.12, 137.29, 138.55, 138.87,
140.35, 155.31, 167.71. MS, m/z (Irel, %): 351 (Mþ, 100), 336 (83), 304

6340
A.O. Shchukin et al. / Tetrahedron 64 (2008) 6334–6340
6H, 2Me), 2.12 (s, 6H, 2Me), 2.33 (s, 3H, Me), 3.70 (br s, 2H, NH2),
Acknowledgements
6.80 (s, 1H, ]CH–), 7.10 (d, 2Harom., J¼8.2 Hz), 7.24 (d, 2Harom
,
J¼8.2 Hz). 13C NMR (125 MHz, CDCl3) 13.45, 17.38, 21.19, 29.18,
118.42, 127.29, 127.89, 128.77, 129.33, 129.40, 131.03, 139.66, 142.43,
154.95, 200.54. MS, m/z (Irel, %): 307 (Mþ, 100), 292 (98), 264 (33),
248 (27), 234 (22). Anal. Calcd for C21H25NO: C, 82.04; H, 8.20; N,
4.56. Found: C, 82.28; H, 8.21; N, 4.48.
The authors thank the Government of the city of Saint-Peters-
burg for financial support of this work.
References and notes
1. Gilchrist, T. L. Heterocyclic Chemistry, 2nd ed.; Wiley: New York, NY, 1992.
2. Joule, J. A.; Mills, K. Heterocyclic Chemistry; Blackwell Science: Oxford, 2000.
3. Heck, R. F. Acc. Chem. Res. 1979, 12, 146.
4. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009.
5. Satoh, T.; Ogino, Y.; Ando, K. Tetrahedron 2005, 61, 10262.
6. Varchi, G.; Kofink, C.; Lindsay, D. M.; Ricci, A.; Knochel, P. Chem. Commun. 2003,
396.
7. Vasilyev, A. V.; Walspurger, S.; Pale, P.; Sommer, J. Tetrahedron Lett. 2004, 45,
337.
8. Vasilyev, A. V.; Walspurger, S.; Haouas, M.; Sommer, J.; Pale, P.; Rudenko, A. P.
Org. Biomol. Chem. 2004, 2, 3483.
9. Vasilyev, A. V.; Walspurger, S.; Pale, P.; Sommer, J.; Haouas, M.; Rudenko, A. P.
Russ. J. Org. Chem. (in Engl.). 2004, 40, 1769.
10. Walspurger, S.; Vasilyev, A. V.; Sommer, J.; Pale, P. Tetrahedron 2005, 61, 3559.
11. Savechenkov, P. Yu.; Rudenko, A. P.; Vasilyev, A. V.; Fukin, G. K. Russ. J. Org. Chem.
(in Engl.). 2005, 41, 1316.
12. Aristov, S. A.; Vasilyev, A. V.; Fukin, G. K.; Rudenko, A. P. Russ. J. Org. Chem.
(in Engl.). 2007, 43, 691.
13. Walspurger, S.; Vasilyev, A. V.; Sommer, J.; Pale, P.; Savechenkov, P. Yu.;
Rudenko, A. P. Russ. J. Org. Chem. (in Engl.). 2005, 41, 1485.
14. Vasilyev, A. V.; Walspurger, S.; Chassaing, S.; Pale, P.; Sommer, J. Eur. J. Org.
Chem. 2007, 5740.
4.4.15. (E)-Methyl-3-(3-amino-4-methoxyphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2n
Compound (E)-2n was obtained from 2-methoxyphenylamine
(25 mg, 0.2 mmol) and acetylene 1a (28 mg, 0.16 mmol) in HSO3F
(1 ml) at ꢀ75 ꢁC in 60 min in 22 mg (45%) according to the general
alkenylation procedure. Yellow oily compound. Rf [10% hexanes/
ethyl acetate (8.5:1 v/v)]. IR nmax (KBr) 3470, 3375, 1719, 1605 cmꢀ1
.
1H NMR (500 MHz, CDCl3) 2.34 (s, 3H, Me), 3.62 (s, 3H, OMe), 3.77
(br s, 2H, NH2), 3.87 (s, 3H, OMe), 6.22 (s, 1H, ]CH–), 6.54
(d, 1Harom., J¼2.0 Hz), 6.62 (dd, 1Harom., J¼8.2, 2.0 Hz), 6.78 (d,
1Harom., J¼8.2 Hz), 7.11 (d, 2Harom., J¼8.1 Hz), 7.20 (d, 2Harom.
,
J¼8.1 Hz). 13C NMR (125 MHz, CDCl3) 21.33, 51.20, 55.52, 109.80,
114.71, 119.55, 125.85, 128.92, 129.64, 133.83, 135.91, 136.37, 138.54,
148.60, 154.65, 167.10. MS, m/z (Irel, %): 297 (Mþ, 100), 282 (29), 266
(12), 222 (16), 194 (11). Anal. Calcd for C18H19NO3: C, 72.71; H, 6.44;
N, 4.71. Found: C, 72.70; H, 6.41; N, 4.65.
15. Stang, P. J.; Summerville, R. J. Am. Chem. Soc. 1969, 91, 4600.
16. Olah, G. A.; Spear, R. J. J. Am. Chem. Soc. 1975, 97, 1845.
17. Koltunov, K. Yu.; Walspurger, S.; Sommer, J. Eur. J. Org. Chem. 2004, 4039.
18. Rendy, R.; Zhang, Y.; McElrea, A.; Gomez, A.; Klumpp, D. A. J. Org. Chem. 2004,
69, 2340.
4.4.16. (E)-Methyl-3-(3-amino-2-methoxyphenyl)-3-(4-methyl-
phenyl)propenoate (E)-2o
Compound (E)-2o was obtained as oily inseparable mixture
with compound (E)-2n from 2-methoxyphenylamine (25 mg,
0.2 mmol) and acetylene 1a (28 mg, 0.16 mmol) in HSO3F (1 ml) at
ꢀ75 ꢁC in 60 min in 8 mg (17%) according to the general alkeny-
lation procedure. Rf [15% hexanes/ethyl acetate (8.5:1 v/v)]. 1H
NMR (500 MHz, CDCl3) (from the spectrum of mixture) 2.38 (s, 3H,
Me), 3.59 (s, 3H, OMe), 3.76 (br s, 2H, NH2), 3.85 (s, 3H, OMe), 6.24
(s, 1H, ]CH–), 6.64–6.71 (m, 3Harom.), 7.08 (d, 2Harom., J¼7.9 Hz),
7.17 (d, 2Harom., J¼7.9 Hz). MS (for mixture), m/z (Irel, %): 297 (Mþ,
100), 282 (29), 266 (12), 222 (16), 194 (11). Anal. Calcd for
19. Klumpp, D. A.; Rendy, R.; Zhang, Y.; McElrea, A.; Gomez, A.; Dang, H. J. Org.
Chem. 2004, 69, 8108.
20. Olah, G. A.; Dunne, K.; Kelly, D. P.; Mo, Y. K. J. Am. Chem. Soc. 1972, 94, 7438.
21. Olah, G. A. Angew. Chem., Int. Ed. Engl. 1993, 32, 767.
22. Olah, G. A.; Klumpp, D. A. Acc. Chem. Res. 2004, 37, 211.
23. Compare with our NOE and ROESY experiments on the elucidation of (E/Z)-
configuration of vinyl sulfonates.13,14
24. Debarge, S.; Violeau, B.; Jouannetaud, M.-P.; Jaquesy, J.-C. Tetrahedron Lett.
2003, 44, 1747.
25. Berrier, C.; Jaquesy, J.-C.; Renoux, A. Bull. Soc. Chim. Fr. 1990, 127, 93.
26. Compare with the same isomerization of vinyl sulfonates formed from
acetylene esters and ketones in superacids.14
27. Koltunov, K. Yu.; Repinskaya, I. B. Russ. J. Org. Chem. (in Engl.). 1994, 30, 97.
28. Savechenkov, P. Yu.; Vasilyev, A. V.; Rudenko, A. P. Russ. J. Org. Chem. (in Engl.).
2004, 40, 1279.
C
18H19NO3: C, 72.71; H, 6.44; N, 4.71. Found: C, 72.70; H, 6.41; N,
4.65.