Catalytic alkylation of aromatic amines with styrene in the presence of cationic rhodium complexes and acid

Article abstract of DOI:10.1055/s-1999-2579

The first transition metal-catalyzed Friedel-Crafts alkylation of aromatic amines with styrene is reported. ortho-Alkylation of anilines occurs using catalytic amounts of [Rh(cod)₂]BF₄/4 PPh₃ and HBF₄.

Full text of DOI:10.1055/s-1999-2579

LETTER
243
Catalytic Alkylation of Aromatic Amines with Styrene in the Presence of
Cationic Rhodium Complexes and Acid
Matthias Beller*a, Oliver R. Thielb, Harald Trauthweinc
aInstitut für Organische Katalyseforschung an der Universität Rostock e.V., Buchbinderstraße 5-6, D-18055 Rostock, Germany
Tel. +49-381466930; Fax +49-3814669324; E-mail: matthias.beller@ifok.uni-rostock.de
bAnorganisch-chemisches Institut, Technische Universtät München, Lichtenbergstr. 4, D-85747 Garching, Germany
cAventis, Industriepark Höchst, G 830, D-65926 Frankfurt, Germany
Received 2 December 1998
version of norbornene with aniline.7,8 Using
[(PEt3)2RhCl]2 / PhNHLi as catalyst the ortho-C-alkyla-
tion product (30 %) and the N-alkylation product (15 %)
was obtained after 12 days at 70 °C. When applying the
same catalyst to the reaction of styrene with aniline no C-
alkylation product was detected.9
Abstract: The first transition metal-catalyzed Friedel-Crafts alkyl-
ation of aromatic amines with styrene is reported. ortho-Alkylation
of anilines occurs using catalytic amounts of [Rh(cod)2]BF4 / 4 PPh3
and HBF4.
Key words: catalysis, alkylation, amination, rhodium, Friedel-
Crafts alkylation
Based on our recent investigations on the regioselective
amination of aromatic olefins with aliphatic amines,10 we
became interested in the reaction of styrene with various
substituted anilines in the presence of cationic rhodium
complexes. Herein, we demonstrate for the first time that
anilines afford alkylated anilines in the presence of cata-
lytic amounts of HBF4◊OEt2 and a cationic rhodium spe-
cies. Often high regioselectivities for the ortho-alkylated
aniline 1a – 5a are obtained.
There has been much effort in recent years towards the de-
velopment of catalytic electrophilic aromatic substitution
reactions.1 Of special importance are methods, e.g.
Friedel-Crafts reactions, which enable the introduction of
carbon substituents onto aromatic rings. Although these
reactions work best for electron-rich aromatic com-
pounds, frequently the observed selectivities (ortho vs.
para) are low and the reactions proceed only in the pres-
ence of stoichiometric amounts of Lewis acids.
Recently, we described the first catalytic anti-Markovnik-
ov hydroamination of styrene with aliphatic amines11 us-
ing a catalyst system consisting of HBF4◊OEt2 and a
cationic rhodium complex. Now, we used this catalyst
system for the reaction of substituted anilines with sty-
rene. In general, the experiments were performed in Ace-
pressure tubes at 140 °C in the presence of 2.5 mol%
[Rh(cod)2]BF4 / 4 mol% PPh3 and 20 mol% HBF4◊OEt2
using toluene as solvent (Table 1).
Scheme 1
Unlike typical Friedel-Crafts processes of substituted
benzenes, electrophilic carbon-carbon bond forming reac-
tions of aromatic amines are more problematic.2 This is
due to the coordination of the Lewis acid to the aromatic
nitrogen atom which leads to a deactivation of the aromat-
ic ring and side reactions. Hence, few examples of alkyla-
tions of anilines with olefins under Friedel-Crafts
conditions have been described.3 On the other hand, the
alkylation of aniline with ethylene has been reported using
basic aluminium anilide as catalyst under drastic condi-
tions (40-60 bar; 330°C).4,5 In addition, the reaction of
aniline with styrene, leading to the formation of ortho-C-
and N-alkylation products is possible when using alumin-
ium phenoxide or zeolites as catalysts.6 However, these
catalysts always produce a mixture of regioisomers (o-, p-
alkylated aniline). To the best of our knowledge the only
known transition metal-catalyzed alkylation of anilines
was previously observed by J. J. Brunet et al. for the con-
Synlett 1999, No. 2, 243–245 ISSN 0936-5214 © Thieme Stuttgart · New York

244
M. Beller et al.
LETTER
After some initial screening studies of reaction conditions It is notable that the cationic rhodium catalyst system is
(vide supra) it turned out that aniline can be successfully approximately two orders of magnitude more active under
ortho-alkylated with styrene in the presence of both acid acidic conditions (turnover frequency 1.8 h-1, reaction of
and a cationic rhodium phosphine complex at tempera- styrene with aniline vs 0.02 h-1, reaction norbornene with
tures of 140 – 160 °C. In addition to 2-(1-phenyleth- aniline) compared to Brunet´s system under basic condi-
yl)aniline (1a), N-(1-phenylethyl)aniline (1b) is obtained tions.
in 24% yield. Without either HBF4◊OEt2 or [Rh(cod)2]BF4
As stated above the reaction of aniline with styrene does
/ PPh3 no reaction is observed. To verify the generality of
not proceed in the absence of a cationic rhodium complex.
the acid effect on this reaction other acids were used as co-
catalysts (HCl; CF3CO2H; CF3SO3H; p-CH3C6H4SO3H).
So far only triflic acid shows a similar effect compared to
HBF4◊OEt2. A critical reaction parameter is the ratio of
However, it was questionable whether this is also true for
more electron-rich anilines. Indeed, when using 20 mol%
of HBF4◊OEt2 as catalyst p-anisidine and N-methylaniline
are ortho-alkylated. Again, in the presence of a large ex-
styrene to aniline. Best results are afforded applying an
cess of styrene (styrene : amine ratio of 5:1) the reaction,
excess of styrene. Although the reaction takes place with
e.g. of p-anisidine leads mainly to di- and trialkylation of
a ratio of styrene to aniline of 1:1, the yields of 1a (13%)
aniline. While in the reaction of N-methylaniline the
and 1b (6%) are significantly decreased (Table 1, entry 5).
ortho-C-alkylation product is formed regioselectively,
Also, using a large excess of styrene (> 10:1) decreased
N,N-dimethylaniline gives considerably lower yields and
selectivities. Apart from aniline p-fluoroaniline also does
not react under these reaction conditions (Table 2).
the yield in 1a and 1b due to the fact that mainly di-, tri-
and tetra-alkylated products are afforded.
Apart from aniline we studied the reaction of p-anisidine
and p-fluoroaniline.12 In the latter case the yield of the cor-
responding products is slightly lower. Interestingly, the
ratio of C- and N-alkylated products changes significantly
with the electronic nature of the aryl amine. Next, we in-
vestigated the influence of substituents on the N-atom. N-
Methylaniline gave the corresponding ortho-C-alkylated
product in good yield (82%) with excellent selectivity
(Table 1, entry 9). N,N-Dimethylaniline is much less reac-
tive and leads to considerable amounts of the para-C-
alkylation product 5c. In addition a-methylstyrene reacts
with aniline to afford 2-(1-methyl-1-phenylethyl)aniline
(6a) in 20 % yield and N-(1-methyl-1-phenylethyl)aniline
(6b) in 33 % yield.
Although it is too early to give a detailed mechanistic ex-
planation for the new rhodium/acid-catalyzed alkylation
of aniline we propose that the reaction involves the key
intermediates shown in Scheme 2.5,6 The six-membered
cyclic intermediate is more favourable, this accounts for
the formation of 1a - 5a as the main reaction products. The
beneficial effect of the rhodium catalyst is explained via a
coordination to the arene ring of styrene which results in
an activation of styrene towards nucleophiles. This as-
sumption is supported by the observation that simple ali-
phatic olefins such as cyclohexene and vinylcyclohexene
show no reactivity in preliminary catalytic tests.
Alternatively, the ortho-alkylation could be explained by
an initial ortho-metallation of aniline.13 Indeed, the reac-
tion of [d7]-aniline with with [Rh(cod)2]BF4 / 4 PPh3
shows a C-D activation in the ortho and para position of
aniline. Nevertheless, this reaction pathway seems less vi-
able since the observed Markovnikov selectivity is not ex-
plained.
Scheme 2
In summary, we have reported the first transition metal-
catalyzed alkylation of anilines with aromatic olefins.
This reaction allows a simple and straightforward access
Synlett 1999, No. 2, 243–245 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Catalytic Alkylation of Aromatic Amines
245
(9) Brunet, J.-J.; Neibecker, D.; Philippot, K. Tetrahedron Lett.
1993, 34, 3877.
(10) Beller, M.; Eichberger, M.; Trauthwein, H. Angew. Chem. Int.
Ed. Engl. 1997, 36, 2225.
to 2-(1-arylethyl)anilines which can be further exploited
for the synthesis of a wide range of heterocycles. Remark-
ably, the combination of both [Rh(cod)2]BF4 / 4 PPh3 (2.5
mol%) and HBF4◊OEt2 (20 mol%) is necessary to achieve
reactions of aniline and p-fluoroaniline. On the other hand
electron-rich anilines react already in the presence of
HBF4◊OEt2 (20 mol%) whereby the addition of
[Rh(cod)2]BF4 / 4 PPh3 (2.5 mol%) increases the yield of
alkylated anilines (exception p-anisidine at low styrene to
anisidine ratio). Extensions of rhodium-catalyzed reaction
of anilines with styrenes for the synthesis of quinoline het-
erocycles will be reported in due course.14
(11) Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Mül-
ler, T. E.; Thiel, O. R.; Herwig, Chem. Europ. J., in press.
(12) Typical experimental procedure: 45 mg (0.11 mmol)
[Rh(cod)2]BF4 and 116 mg (0.44 mmol) PPh3 were suspended
under argon in 5 ml toluene using a pressure tube as reaction
vessel. 0.4 ml (4.4 mmol) aniline and 2.52 ml (22 mmol) sty-
rene were added. After adding 120 µl (0.88 mmol) HBF4·OEt2
and hexadecane (GC-standard) the reaction mixture was heat-
ed for 20 h at 140 °C. Standard organic workup including
chromatography yielded the alkylation products.
All the new compounds were characterized by EA, MS, 1H-
NMR and 13C-NMR. Compound 2a: 1H-NMR (400 MHz,
CDCl3): δ = 7.20 - 7.07 (m, 5H), 6.82 (d, 4J(H,H) = 2.5 Hz,
1H), 6.58 (dd, 3J(H,H) = 8.5 Hz, 3J(H,H) = 2.5 Hz, 1H), 6.49
(d, 3J(H,H) = 8.5 Hz, 1H), 4.00 (q, 3J(H,H) = 7.0 Hz, 1H, CH),
3.69 (s, 3H), 3.03 (s, 2H, NH), 1.51 (d, 3J(H,H) = 7.0 Hz, 3H,
CH3); 13C-NMR (101 MHz, CDCl3): δ = 153.4, 145.8, 138.3,
132.3, 129.2, 127.9, 126.8, 117.6, 114.5, 112.1 , 56.1, 40.7,
22.2; MS (70 eV): 227 [M+], 212 [M+ - CH3], 197 [M+ - 2
CH3], 180. Compound 3a: 1H-NMR (400 MHz, CDCl3): δ =
7.19 - 7.07 (m, 5H,), 6.92 (dd, 3J(H,F) = 10.0 Hz, 4J(H,H) =
3.0 Hz, 1H), 6.68 (ddd, 3J(H,F) = 10.0 Hz, 3J(H,H) = 8.5 Hz,
4J(H,H) = 3.0 Hz, 1H), 6.44 (dd, 3J(H,H) = 8.5 Hz, 4J(H,F) =
5.0 Hz, 1H), 3.95 (q, 3J(H,H) = 7.0 Hz, 1H, CH), 3.21 (s, 2H,
NH), 1.48 (d, 3J(H,H) = 7.0 Hz, 3H, CH3); 13C-NMR (101
MHz, CDCl3): δ = 155.7 (d, 1J(C,F) = 236.2 Hz), 143.8, 139.1
(d, 4J(C,F) = 1.9 Hz), 130.7 (d, 4J(C,F) = 6.8 Hz), 127.8,
126.3, 125.6, 115.9 (d, 3J(C,F) = 7.7 Hz), 113.0 (d, 3J(C,F) =
22.3 Hz), 112.3 (d, 2J(C,F) = 22.4 Hz), 39.2, 20.7; MS (70
eV): 215 [M+], 200 [M+ - CH3], 185, 124, 109, 99, 77. Com-
pound 3b: 1H-NMR (400 MHz, CDCl3): δ = 7.26 - 7.20 (m,
4H), 7.12 (t, 3J(H,H) = 7.5 Hz, 1H), 6.69 (dd, 3J(H,F) = 9.0 Hz,
3J(H,H) = 8.5 Hz, 2H), 6.34 (dd, 3J(H,H) = 8.5 Hz, 4J(H,F) =
2.4 Hz, 2H), 4.31 (q, 3J(H,H) = 7.0 Hz, 1H, CH), 3.90 (s, 1H,
NH), 1.41 (d, 3J(H,H) = 7.0 Hz, 3H, CH3); 13C-NMR (101
MHz, CDCl3): δ = 155.0 (d, 1J(C,F) = 235.2 Hz), 142.7, 144.2,
125.1, 127.9, 126.3, 114.7 (d, 2J(C,F) = 22.4 Hz), 113.5 (d,
3J(C,F) = 7.8 Hz), 53.4, 24.2; MS (70 eV): 215 [M+], 200 [M+
- CH3], 120 [M+ - C6H5], 105, 93, 77.
Acknowledgement
This work was supported by the Deutsche Forschungsgemeinschaft
(Be 1931/3-1). Generous gifts of precious metals from Hereaus AG
and Degussa AG are gratefully acknowledged.
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Synlett 1999, No. 2, 243–245 ISSN 0936-5214 © Thieme Stuttgart · New York