Intermolecular hydroamination of vinyl arenes using tungstophosphoric acid as a simple and efficient catalyst

Article abstract of DOI:10.1016/j.tetlet.2007.08.120

The intermolecular hydroamination of vinyl arene derivatives has been efficiently carried out using a tungstophosphoric acid (TPA) catalyst under solvent free and mild reaction conditions. The present protocol provides an environmentally benign, easy to handle and highly active solid acid catalyst for hydroamination of vinyl arenes. The catalyst yields both hydroamination and hydroarylation products and the selectivity mostly depends on the reaction conditions.

Full text of DOI:10.1016/j.tetlet.2007.08.120

Tetrahedron Letters 48 (2007) 7642–7645
Intermolecular hydroamination of vinyl arenes using
tungstophosphoric acid as a simple and efficient catalyst
N. Seshu Babu, K. Mohan Reddy, P. S. Sai Prasad, I. Suryanarayana and N. Lingaiah*
Catalysis Laboratory, I&PC Division, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 24 May 2007; revised 22 August 2007; accepted 30 August 2007
Available online 4 September 2007
Abstract—The intermolecular hydroamination of vinyl arene derivatives has been efficiently carried out using a tungstophosphoric
acid (TPA) catalyst under solvent free and mild reaction conditions. The present protocol provides an environmentally benign, easy
to handle and highly active solid acid catalyst for hydroamination of vinyl arenes. The catalyst yields both hydroamination and
hydroarylation products and the selectivity mostly depends on the reaction conditions.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
contributions have been made on the use of late-transi-
tion metal complexes for the hydroamination of olefins
using iridium,8 rhodium,9 nickel,10 palladium,11 plati-
num12 and ruthenium.13 The high cost of these com-
plexes and their stabilizing ligands or the additives
constitute limitations of these protocols. Indeed, the
hydroamination mainly proceeds over long reaction
times and at high reaction temperatures. Recently, sev-
eral Bro¨nsted acids such as triflic acid and H-montmoril-
lonite have been reported for the hydroamination of
activated and unactivated alkenes with numerous reac-
tive amide derivatives.14 However, the hydroamination
of styrene and aniline derivatives is limited due to rapid
oligomerization of the styrene. Thus, it remains an
intriguing challenge for researchers to develop improved
catalytic systems for the hydroamination of vinyl arenes
with substituted aniline derivatives.
The reaction between an alkene and an amine for the
synthesis of substituted amines involves multiple steps.1
The addition of amines to unsaturated carbon–carbon
multiple bonds, a process termed hydroamination, has
proved to be the best method for preparing highly
substituted amines. This methodology has attained
considerable interest from both industry and academia.
It is well known that acid catalyzed addition of amines
to alkenes is generally unsuccessful due to the buffering
effect of the amine substrate.2 Also Friedel–Crafts alkyl-
ations of aryl amines are hindered by coordination of
the amine to the Lewis acid catalyst.3a Therefore the
development of these reactions remains an intriguing
challenge for chemists. In previous studies, hydroamina-
tion of alkenes with amine derivatives has been carried
using various ligand mediated acid catalysts.3b–d
Hartwig and Schlummer4 reported that several common
Bro¨nsted acids catalyze the intermolecular hydroamina-
tion of tosyl-protected amino olefins. Beller et al.5
reported alkylation of electron rich anilines with styrene
promoted by HBF4ÆEt2O. Furthermore, Anderson et al.
described the proton catalyzed hydroamination and
hydroarylation of an alkene with an amine,6 whereas
Kaspar et al. reported TiCl4 catalyzed hydroamination
and hydroarylation reactions.7 A number of significant
In the present Letter, we disclose an environmentally
benign, efficient, reusable tungstophosphoric acid
(TPA) catalyst for intermolecular hydroamination
of alkenes under mild and solvent-free conditions
(Scheme 1). The present catalyst promotes the complete
reaction within reasonable reaction times and affords
high product yields.
2. Results and discussion
Experimental results showed that 1 mmol of the styrene
derivative reacts with 2 mmol of the aromatic amine in
the presence of TPA under solvent-free conditions.
Keywords: Hydroamination; Vinyl arene; Solvent free; TPA.
*
Corresponding author. Tel.: +91 40 27193163; fax: +91 40
27160921; e-mail: nakkalingaiah@iict.res.in
0040-4039/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetlet.2007.08.120

N. Seshu Babu et al. / Tetrahedron Letters 48 (2007) 7642–7645
7643
NH
CH
2
CH
3
3
Ar
NH
2
N
H
TPA
Solvent free
+
+
1
1
2
R
2
R
1
R
R
R
Scheme 1. Catalytic intermolecular hydroamination of vinyl arenes.
Table 1. Acid catalyzed hydoamination of 4-methyl styrenea
CH
3
CH
2
NH
2
NH
Br
3
HN
CH
3
+
TPA
Solvent free
Temperature
+
CH
3
CH
3
Br
Br
1
2
3
4
Entry
Catalyst
Time (h)
(%) Yield 3c
(%) Yield 4c
1
2
3
4
5
6
7
TPA
TPA
TPA
H2SO4
TFA
3b
1.5
6
18
12
18
18
82
75
25
—
—
—
—
Trace
Trace
70
—
—
CH3COOH
Cp2TiCl4
—
—
a Reaction conditions: 4-methylstyrene (1.0 mmol); 4-bromoaniline, (2 mmol); catalyst wt: 30 mg; reaction temperature, 80 °C.
b Reaction temperature, 60 °C.
c Yields were determined by 1H NMR spectroscopy.
CH
Initially, the hydroamination of 4-methylstyrene with 4-
3
bromoaniline (Table 1) was carried out using TPA and
NH
CH
its activity was compared with other acid reagents such
as H2SO4, triflic acid (TFA) and CH3COOH. TPA cat-
alyzed the reaction within a reasonable time, whereas
simple Bro¨nsted acids did not catalyze this reaction
(Table 1, entries 4–6). These results are in agreement
with observations made by Hartwig and Schlummer.4
HN
2
3
TPA
Solvent free
o
,
80 C 12 h
R
R
66%
Scheme 2. TPA catalyzed rearrangement of the hydroamination
product.
Under the present reaction conditions, a mixture of
hydroamination and ortho-hydroarylation products
was obtained. In order to study the ratio of these prod-
ucts, the reaction conditions were varied with respect to
reaction time and temperature. Experiments showed
that the yield of the ortho-alkylated hydroarylation
product increased with an increase in reaction time
and temperature. Prolonged reaction times resulted in
rearrangement of the hydroamination product to give
the ortho-alkylated hydroarylation product.
the product selectivity varied with reaction time (Table
1, entries 2, 3 and Table 2, entry 11) and our results
are in good agreement with those reported.17
Catalytic intermolecular hydroaminations of styrene
derivatives were carried out using TPA to study the
scope of this catalyst (Table 2). A number of vinyl
arenes 1 and aniline derivatives 2 were converted to
hydroaminated 3 and hydroarylated 4 products in high
yields. It is interesting to note that anilines with electron
withdrawing groups present on the aromatic ring
reacted smoothly. In marked contrast, vinyl arenes with
an electron donating substituent (4-methyl) present on
the aromatic ring reacted at a faster rate compared to
those with electron withdrawing groups such as 4-chloro
or 4-bromo. Additionally, a-methylstyrene (Table 2,
entry 14) was converted into 3 and 4 (70:30). TPA also
catalyzed the reaction of a sterically demanding aniline
In order to confirm the rearrangement of the hydroam-
ination product over time, we prepared the secondary
amine independently15 and subjected it to the present
reaction conditions (Scheme 2). Indeed, the secondary
amine was converted quantitatively into the hydroaryla-
tion product by a Hofmann–Martius rearrangement.16
Marcsekova and Doye17 reported that the hydroamina-
tion reaction is favourable for aliphatic alkenes and the
hydroarylation becomes more favourable for styrene
derivatives. In the present studies, it was also found that

7644
Table 2. Study of the hydroamination reaction of various aniline and vinyl arene derivatives with the TPA catalysta
CH
N. Seshu Babu et al. / Tetrahedron Letters 48 (2007) 7642–7645
3
3
R
3
HN
R
NH CH
2
3
R
1
R
3
NH
2
TPA
+
+
Solvent free
o
80 C
1
2
R
R
2
1
2
R
R
R
1
2
3
4
Entry
R1
R3
Amine
Time (h)
(%) Yield 3b
(%) Yield 4b
Combined (%) Yield (3 + 4)b,e
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
H
H
H
H
H
H
4-BrÆC6H4NH2
4-BrÆC6H4NH2
4-BrÆC6H4NH2
4-ClÆC6H4NH2
4-ClÆC6H4NH2
4-ClÆC6H4NH2
4-FÆC6H4NH2
4-NO2ÆC6H4NH2
3-NO2ÆC6H4NH2
3-CF3ÆC6H4NH2
3-CF3ÆC6H4NH2
2-CH3ÆC6H4NH2
4-CH3OÆC6H4NH2
2-ClÆC6H4NH2
2,4-F2ÆC6H4NH2
2,4,6-Cl3ÆC6H4NH2
C6H5NHMe
1
12
6
75
66
25
62
52
70
48
96
93
55
Trace
35
28
60
45
—
Trace
30
70
33
42
25
50
Trace
Trace
25
85
54
62
25
40
—
89
95
75 (99:1)
96 (69:31)
95 (27:73)
95 (65:35)
94 (55:45)
95 (75:25)
98 (50:50)
96, 89c (99:1)
93 (99:1)
80 (69:31)
85 (1:99)f
89 (40:60)
90 (32:68)
85 (70:30)
85 (52:48)
—
4-Br
4-Me
H
4-Cl
4-Me
H
H
H
H
H
H
H
H
H
H
H
H
H
3
12
1.5
4
4
5
3
12
12
12
4
6
24
6
6
14
14
Trace
Trace
82d
78d
89, 82c (1:99)
95 (1:99)
82 (99:1)
78 (99:1)
1-Napthylamine
C6H5NHMe
1-Napthylamine
Trace
Trace
H
a Reaction conditions: alkene derivative (1 mmol); aniline derivative (2 mmol); temperature, 80 °C; catalyst, 30 mg.
b Isolated yields.
c Yields obtained after 4th cycle.
d Reaction temperature: 45 °C.
e Values in parentheses denotes the selectivity ratio of products 3 and 4.
f At a longer reaction time, the hydroarylation product 4 was formed as the major product.
(Table 2, entry 15) with styrene affording both hydro-
amination and hydroarylated products. However, the
di-ortho-substituted aniline derivative, 2,4,6-trichloro-
aniline did not react with styrene under the present
conditions (Table 2, entry 16).
To investigate the reusability of the TPA catalyst, recy-
cling was carried out for two examples where one gave a
high hydroamination yield and the other gave the
hydroarylation product. For both reactions, no appre-
ciable loss in activity was observed and analogous prod-
ucts were obtained (Table 2, entries 8 and 17).
On the other hand TPA catalyzed the reaction of an
aniline with an electron withdrawing group at the meta
position (Table 2, entry 10) with styrene affording both
hydroamination and hydroarylation products (Table 2).
3-Nitroaniline reacted with styrene to afford only the
hydroamination product (Table 2, entry 9). A similar
observation was noticed in the reaction of para-nitro-
aniline with styrene (Table 2, entry 8). Aniline deriva-
tives with electron donating substituents present at the
ortho and para positions also reacted with vinyl arene
derivatives. However, the rates of the reactions were
slow compared to reactions with anilines with electron
withdrawing substituents (Table 2, entries 12 and 13).
Styrene reacted rapidly with N-methylaniline and 1-nap-
thylamine to afford ortho-hydroarylation products in
high yields under the stated reaction conditions (Table
2, entries 17 and 18). However, when the reaction was
conducted at a lower temperature, hydroamination of
styrene was observed in high yield (Table 2, entries 19
and 20).
In summary, TPA catalyzes the hydroamination of sty-
rene derivatives with a variety of aryl amines. Control
experiments showed that facile N–H addition took place
quickly and at low temperatures, whereas C–H addition
(the Hofmann–Martius rearrangement) was favoured by
longer reaction times and elevated temperatures. The
catalyst can be recovered easily and reused four times
without any significant loss in activity.
3. Typical procedure for the hydroamination reaction
TPA (30 mg) was added to a mixture of styrene
(1 mmol) and 4-bromoaniline (2 mmol). The mixture
was stirred for 6 h at 80 °C under solvent-free
conditions. The progress of the reaction was monitored
by TLC and, on completion, the reaction mixture was
filtered and the filtrate concentrated under reduced
pressure to afford the crude product, which, after

N. Seshu Babu et al. / Tetrahedron Letters 48 (2007) 7642–7645
7645
Angew. Chem., Int. Ed. 2003, 42, 2708–2710; Beller, M.;
Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int. Ed.
2004, 43, 3368–3398.
chromatography on silica gel, gave 4-bromo-N-(1-(4-
methylphenyl)ethyl)aniline and 4-bromo-2-(1-(4-methyl-
phenyl)ethyl)aniline, eluent: n-hexane/ethyl acetate
(9.5:0.5 v/v).
2. Katwatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000,
122, 9546–9547.
3. (a) Kobayashi, S.; Komoto, I.; Matsuo, J.-I. Adv. Synth.
Catal. 2001, 343, 71–74; (b) Karshtedt, D.; Bell, A. T.;
Tilley, D. J. Am. Chem. Soc. 2005, 127, 12640–12646; (c)
Wang, X.; Widenhoefer, R. A. Organometallics 2004, 23,
1649–1651; (d) Hultzsch, K. C.; Hampel, F.; Wagner, T.
Organometallics 2004, 23, 2601–2612.
3.1. 4-Bromo-N-((1-phenyl)ethyl)aniline: (Table 2, entry
1, product 3)
CH3
4. Schlummer, B.; Hartwig, J. F. Org. Lett. 2002, 4, 1471–
1474.
Br
NH
5. Beller, M.; Thiel, O. R.; Trauthwein, H. Synlett 1999, 243–
245.
6. Anderson, L. L.; Arnold, J.; Bergman, R. G. J. Am. Chem.
Soc. 2005, 127, 14542–14543.
7. Kaspar, L. T.; Fingerhut, B.; Ackermann, L. Angew.
Chem. 2005, 44, 5972–5974.
8. (a) Casalnuovo, A. L.; Calabrese, J. C.; Milstein, D. J.
Am. Chem. Soc. 1988, 110, 6738; (b) Dorta, R.; Egli, P.;
Zurcher, F.; Togni, A. J. Am. Chem. Soc. 1997, 119,
10857–10858; (c) Zhao, J.; Goldman, A. S.; Hartwig, J. F.
Science 2005, 307, 1080–1082.
9. (a) Coulson, D. R. Tetrahedron Lett. 1971, 12, 429–430;
(b) Brunet, J.-J.; Commenges, G.; Neibecker, D.; Phlip-
pot, K. J. Organomet. Chem. 1994, 469, 221–228; (c)
Beller, M.; Thiel, O. R.; Trauthwein, H. Synlett 1999, 243–
245; (d) Beller, M.; Thiel, O. R.; Trauthwein, H.; Hartung,
C. G. Chem. Eur. J. 2000, 6, 2513–2522; (e) Utsunomiya,
M.; Kuwano, R.; Kawatsura, M.; Hartwig, J. F. J. Am.
Chem. Soc. 2003, 125, 5608–5609.
1H NMR (300 MHz, CDCl3): d 7.32–7.18 (m, 5H), 7.10
(dd, J = 8.3, 2.2 Hz, 2H), 6.34 (d, J = 8.9 Hz, 2H), 4.41
(q, J = 6.8 Hz, 1H), 3.90 (br s, 1H), 1.51 (d, J = 6.79 Hz,
3H); 13C NMR (75 MHz, DEPT, CDCl3): d 146.2 (Cq),
145.3 (Cq), 143.5 (Cq), 131.5 (CH), 128.2 (CH), 127.0
(CH), 125.0 (CH), 114.8 (CH), 53.0 (CH), 24.8 (CH3).
EI-MS: m/z (relative intensity) [M+] 276.15 (100). Anal.
Calcd for C14H14BrN: C, 60.89; H, 5.11; N, 5.07.
Found: C, 60.91; H, 5.05; N, 5.10.
3.2. 4-Bromo-N-(1-(4-bromophenyl)ethyl)aniline: (Table
2, entry 2, product 3)
CH3
NH
Br
Br
10. (a) Pawlas, J.; Nakao, Y.; Kawatsura, M.; Hartwig, J. F.
J. Am. Chem. Soc. 2002, 124, 3669–3679; (b) Fadini, L.;
Togni, A. Chem. Commun. 2003, 30–31.
1H NMR (300 MHz, CDCl3): d 7.48–7.12 (m, 4H), 6.31
(m, 4H), 4.38 (q, J = 6.8 Hz, 1H), 3.94 (br s, 1H), 1.51
(d, J = 6.8 Hz, 3H). 13C NMR (75 MHz, DEPT,
CDCl3): d 146.0 (Cq), 144.0 (Cq), 132.2 (CH), 130.5
(CH), 127.7 (CH), 120.8 (Cq), 115.2 (CH), 109.8 (Cq),
53.5 (CH), 24.9 (CH3). EI-MS: m/z (relative intensity)
[M+] 355.09 (100). Anal. Calcd for C14H13Br2N: C,
47.36; H, 3.69; N, 3.94. Found: C, 47.52; H, 3.55; N,
3.92.
11. (a) Kawatsura, M.; Hartwig, J. F. J. Am. Chem. Soc. 2000,
122, 9546–9547; (b) Minami, T.; Okamoto, H.; Ikeda, S.;
Tanaka, R.; Ozawa, F.; Yoshifuji, M. Angew. Chem., Int.
Ed. 2001, 40, 4501–4503; (c) Nettekoven, U.; Hartwig, J.
F. J. Am. Chem. Soc. 2002, 124, 1166–1167; (d) Uts-
unomiya, M.; Hartwig, J. F. J. Am. Chem. Soc. 2003, 125,
14286–14287.
12. (a) Brunet, J.-J.; Cadena, M.; Chu, N. C.; Diallo, O.;
Jacob, K.; Mothes, E. Organometallics 2004, 23, 1264–
1268; (b) Bender, C. F.; Widenhoefer, R. A. J. Am. Chem.
Soc. 2005, 127, 1070–1071.
13. (a) Utsunomiya, M.; Hartwig, J. F. J. Am. Chem. Soc.
2004, 126, 2702–2703; (b) Takaya, J.; Hartwig, J. F. J. Am.
Chem. Soc. 2005, 127, 5756–5757.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2007.08.120.
14. (a) Taylor, J. G.; Whittall, N.; Hii, K. K. Org. Lett. 2006,
8, 3561–3564; (b) Rosenfeld, D. C.; Shekhar, S.; Take-
miya, A.; Utsunomiya, M.; Hartwig, J. F. Org. Lett. 2006,
8, 4179–4182; (c) Motokura, K.; Nakagiri, N.; Mori, K.;
Mizugaki, T.; Ebitani, K.; Jitsukawa, K.; Kaneda, K. Org.
Lett. 2006, 8, 4617–4620.
15. Ackermann, L.; Born, R. Angew. Chem., Int. Ed. 2005, 44,
2444–2447.
16. Johns, A. M.; Sakai, N.; Ridder, A.; Hartwig, J. F. J. Am.
Chem. Soc. 2006, 126, 9306–9307.
References and notes
1. Muller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675–704;
Brunet, J. J.; Neibecker, D. In Catalytic Heterofunction-
alization; Togni, A., Grutzmacher, H., Eds.; Wiley-VCH:
Weinheim, 2001; pp 91–132; Roesky, P. W.; Muller, T. E.
17. Marcsekova, K.; Doye, S. Synthesis 2007, 1, 145–154.