N-H activation vs. C-H activation: Ruthenium-catalysed regioselective hydroamination of alkynes and hydroarylation of an alkene with N-methylaniline

Article abstract of DOI:10.1039/a902240f

Phenylacetylene and its derivatives undergo regioselective insertion into the N-H bond of N-methylaniline in the presence of Ru₃(CO)₁₂ catalyst to afford N-methyl-N-(α-styryl)anilines in high yields, whereas styrene reacts with the ortho C-H bond of N-methylaniline giving 2-(1-phenylethyl)-N-methylaniline.

Full text of DOI:10.1039/a902240f

N–H activation vs. C–H activation: ruthenium-catalysed regioselective
hydroamination of alkynes and hydroarylation of an alkene with
N-methylaniline
Yuko Uchimaru
National Institute of Materials and Chemical Research, Tsukuba, Ibaraki 305, Japan.
E-mail: y_uchimaru@home.nimc.go.jp
Received (in Cambridge, UK) 22nd March 1999, Accepted 12th May 1999
Phenylacetylene and its derivatives undergo regioselective
catalyst Ru
Ru (CO)12, 69% with [RuCl
was more selectively transformed to 3a with Ru
selectivity based on the amount of 2a consumed) than with
3
(CO)12 was more effective; 85% yield of 3a with
(CO) . In addition, the amine 2a
(CO)12 (96%
insertion into the N–H bond of N-methylaniline in the
3
2
3 2
]
presence of Ru
3
(CO)12 catalyst to afford N-methyl-N-(a-
3
styryl)anilines in high yields, whereas styrene reacts with the
ortho C–H bond of N-methylaniline giving 2-(1-phenyl-
ethyl)-N-methylaniline.
[RuCl
2
(CO)
(p-cymene)]
, Fe(CO)
were ineffective. Thus, Ru
effective among the complexes examined.
3 2
] (74%). Other transition metal complexes such as
[RuCl
2
2
,
RuCl
2
(PPh
3
)
4
3
,
[RuCl
2
(cod)]
(PPh
n
[CpRu(CO)
2
]
2
5
, Co (CO)
2
8
, Co
(CO)12, PdCl
2
3
)
2
Transition metal complex-catalysed hydroamination of carbon–
carbon double or triple bonds with non-tertiary amines is an
attractive method for carbon–nitrogen bond formation. Indeed,
various intramolecular hydroamination reactions of aminoalk-
and Cp ZrMe
2
2
3
(CO)12 was the most
Table 1 summarises the results of the reactions of alkynes 1a–
d with p-substituted N-methylanilines 2a,b. In all cases, the
corresponding enamines 3a–e were obtained in high yields. The
results of p-substituted phenylacetylenes 1a–c (runs 1–3)
suggest that an electron-withdrawing substituent at the para-
position increases the yield of 3. The tendency was more clearly
observed when the reactions were carried out under the retarded
reaction conditions (1:2a = 1:1 mol/mol, in toluene, 70 °C, 18
h); the yields of products: 3c (26%) > 3a (13%) > 3b (4%).§
A conjugated enyne, 1-ethynylcyclohexene (1d) also underwent
hydroamination with 2a to give enamine 3e under similar
conditions (run 5).
1
,2a
enes and aminoalkynes have been reported to date.
Although
–5
several examples of intermolecular reactions2 have been also
reported, the substrates for these reactions are usually limited to
4
highly reactive or strained carbon unsaturated compounds. We
have found that ordinary alkynes undergo hydroamination with
aromatic amines in the presence of a catalytic amount of
Ru (CO)12. This is the first example of ruthenium-catalysed
3
intermolecular hydroamination. In addition, the same ruthe-
nium complex catalyses regioselective hydroarylation reaction
of an alkene with an aromatic amine via ortho C–H bond
activation. We report here these ruthenium complex-catalysed
reactions.
Surprisingly, when styrene (4) was used instead of alkynes,
the reaction course was completely different. As shown in
Scheme 1, the hydroarylation product, 2-(1-phenylethyl)-N-
methylaniline (5), was selectively obtained in 83% yield after
A mixture of phenylacetylene (1a, 0.25 mmol), N-methylani-
line (2a, 2.5 mmol), and Ru (CO)12 (0.0125 mmol Ru) was
3
heated at 70 °C in a sealed glass tube under nitrogen. After 18
h, 1a was completely consumed and N-methyl-N-(a-styryl)ani-
line (3a) was regioselectively formed in 85% GLC yield (based
on the amount of 1a charged) (Table 1, run 1). GLC and GC-MS
analyses indicated that isomers of 3a were less than 2% yield.†
A similar result was obtained under milder conditions (50 °C, 3
d). In a separate four-fold scale reaction, 3a was isolated in 61%
yield by Kugelrohr distillation and was fully characterised by
3
heating a mixture of 4 (0.25 mmol), 2a (0.25 mmol), Ru (CO)12
(0.0125 mmol Ru) and toluene (0.2 ml) at 150 °C for 19 h.‡ The
hydroamination product was not detected at all. Treatment of
the same mixture at 70–100 °C reaction temperature resulted in
complete recovery of both starting materials 2a and 4.
Previously a [RhCl(PEt
ported to promote hydroarylation of norbornene with aniline.
3 2 2
) ] –lithium amide system was re-
4
d
In this system, however, not only hydroarylation, but also
hydroamination proceeded at the same time, and the combined
yields for both reactions were not high. Therefore we believe
that our present reaction is the first successful example of
transition-metal complex-catalysed hydroarylation of an alkene
with an aromatic amine.6
1
13
H and C NMR, IR and GC-MS analyses.‡
The catalytic activity of several transition metal complexes
was also examined for the present reaction (1a: 2a:catalyst =
:10:0.05 mol ratio, 70 °C, 18 h). A ruthenium complex
RuCl (CO) was found to promote the reaction. However, the
1
[
2
3 2
]
A plausible mechanism for hydroamination of alkyne is
shown in Scheme 2, which involves (i) oxidative addition of the
N–H bond of amine 2 to a coordinatively unsaturated ruthe-
Table 1 Hydroamination of alkynes catalysed by Ru
3
(CO)12a
Me
N
Me
N
7
,8
nium(0) centre giving the (amido)ruthenium hydride 6, (ii)
coordination of alkyne 1 to the ruthenium centre to form
complex 7, followed by (iii) intramolecular nucleophilic attack
of the nitrogen lone pair of 7 on the coordinated carbon–carbon
triple bond,4 and (iv) reductive elimination of enamine 3 from
the vinyl ruthenium species 8 to reproduce the coordinatively
unsaturated ruthenium(0) centre.¶ The trend of the relative
R
Ru3(CO)12
0 °C, 18 h
cat.
H
R
+
7
R'
R'
a,d
1
2
3
Run
1
R
2
RA
3
Yield (%)b
1
2
3
4
5
1a
1b
1c
1a
1d
Ph
p-MeC
p-FC
Ph
2a
2a
2a
2b
H
H
H
Me
H
3a
3b
3c
3d
3e
85
78
88
76
77
Me
N
Me
N
6
H
4
4
6
H
Ru3(CO)12 cat.
50 °C, 19 h
H
H
+
Ph
1
Me
Cyclohex-1-enyl 2a
a
1
3
0.25 mmol; 2 2.5 mmol; Ru (CO)12 0.0125 mmol/Ru; 70 °C for 18 h.
4
2a
5
Ph
b
GLC yields based on the charged amount of alkyne 1.‡
Scheme 1
Chem. Commun., 1999, 1133–1134
1133

Me
N
the unsaturated substrate. Studies on other substrates and the
mechanism are in progress.
R
Ph
R
3
Me
Ph
Notes and references
N
iii
[Ru]
†
Trimers of 1a, such as 1,2,4-triphenylbenzene and 1,3,5-triphenylbenzene,
iv
Me
N
were detected in 5 and 2% yields, respectively.
‡ All the products in this study were known and were identified by H and
13C NMR, IR and GC-MS analyses or by comparison with authentic
samples. For synthesis of authentic samples of the enamines, see J.
Barluenga, F. Aznar, R. Liz and R. Rodes, J. Chem. Soc., Perkin Trans. 1,
Ru
H
1
8
Ph
H
i
2
a
1
980, 2732. For an authentic sample of 2-(1-phenylethyl)-N-methylaniline,
Me
N
see M. M. Aly, M. Z. Badr, A. M. Fahmy and S. A. Mahgoub, Acta Chim.
Hung., 1985, 120, 15.
Me
N
R
ii
Ph
Ph
§
Recoveries of the starting materials are as follows; for the reaction of 1c
1c 69%, 2a 72%), for the reaction of 1a (1a 85%, 2a 86%), for the reaction
of 1b (1b 94%, 2a 96%).
3
Since activation of an N–H bond of aniline by Ru (CO)12 was reported to
Ru
Ru
(
H
H
6
7
¶
R
1
take place under reaction conditions similar to those in the present reaction
Scheme 2
[see ref. 7(a)], we propose a mechanism with the (amido)ruthenium hydride
6
involved as an intermediate [step (i)]. However, because of the relatively
high coordination ability of the carbon–carbon triple bond with the metal
centre, we cannot completely exclude the possibility of another mechanism
which includes alkyne coordination to the Ru metal centre followed by
nucleophilic attack of an amine nitrogen at the activated carbon–carbon
triple bond.
Me
N
H
Me
Me
H
5
N
H
Ph
1
2
See for a review of intramolecular hydroamination, L. S. Hegedus,
Angew. Chem., Int. Ed. Engl., 1988, 27, 1113.
See for reviews of intermolecular hydroamination: (a) T. E. Müller and
M. Beller, Chem. Rev., 1998, 98, 675; (b) J.-J. Brunet, Gazz. Chim. Ital.,
1997, 127, 111; (c) J.-J. Brunet, D. Neibecker and F. Niedercorn, J. Mol.
Catal., 1989, 49, 235.
Ru
[
Ru]
Me
N
Ph
H
Ph 10
2
a
3
A. M. Baranger, P. J. Walsh and R. G. Bergman, J. Am. Chem. Soc., 1993,
Ph
1
15, 2753; Y. Li and T. J. Marks, Organometallics, 1996, 15, 3770; A.
Me
H
N
Me
N
4
Haskel, T. Straub and M. S. Eisen, Organometallics, 1996, 15, 3773; M.
S. Eisen, T. Straub and A. Haskel, J. Alloys Compd., 1998, 271–273,
116.
Ph
Ru
Ru
H
4 (a) A. L. Casalnuovo, J. C. Calabrese and D. Milstein, J. Am. Chem. Soc.,
988, 110, 6738; (b) P. J. Walsh, A. M. Baranger and R. G. Bergman, J.
Am. Chem. Soc., 1992, 114, 1708; (c) A. L. Seligson and W. C. Trogler,
Organometallics, 1993, 12, 744; (d) J.-J. Brunet, G. Commenges, D.
Neibecker and K. Philippot, J. Organomet. Chem., 1994, 469, 221; (e) R.
Dorta, P. Egli, F. Zürcher and A. Togni, J. Am. Chem. Soc., 1997, 119,
1
H
9
6
Scheme 3
1
1
0857; (f) I. Nakamura, H. Itagaki and Y. Yamamoto, J. Org. Chem.,
998, 63, 6458 and references cited therein.
reactivities of para-substituted phenylacetylenes 1a–c toward
a (vide supra) is consistent with step (iii). On the other hand,
the striking difference in the reaction course for styrene
hydroarylation) may be explained by a mechanism depicted in
2
5
6
Rhodium-catalysed hydroamination of styrene and hex-1-ene has
recently been reported as a side reaction of oxidative amination, see ref.
2
Murai et al. reported several examples of ruthenium-catalysed hydro-
arylation of alkenes and alkynes with aromatic ketones, imines, and
esters: S. Murai, N. Chatani and F. Kakiuchi, Pure. Appl. Chem., 1997,
69, 589 and references cited therein.
7 (a) E. Sappa and L. Milone, J. Organomet. Chem., 1973, 61, 383; (b)
G. C. Hsu, W. P. Kosar and W. D. Jones, Organometallics, 1994, 13,
(
(b).
Scheme 3. Probably because of the lower coordination ability of
8
the carbon–carbon double bond to the metal centre, the styrene
analogue of complex 7 might not be produced from the
(
amido)ruthenium hydride complex 6. Instead, if ortho C–H
9
bond activation takes place to form complex 9, hydroarylation
product 5 could be formed via a ring expansion reaction of the
strained four-membered ruthenacycle 9 with styrene followed
by reductive elimination from the resulting six-membered
ruthenacycle 10.
3
85.
8
9
J. P. Collmann, L. S. Hegedus, J. R. Norton and R. G. Finke, Principles
and Applications of Organotransition Metal Chemistry, University
Science Books, Hill Valley, CA, 1987.
To summarize, we have found the first examples of
ruthenium-complex catalysed regioselective hydroamination
and hydroarylation of carbon–carbon multiple bonds with N-
methylaniline. The reaction course depends on the structure of
J. F. Hartwig, R. G. Bergman and R. A. Andersen, J. Am. Chem. Soc.,
1
991, 113, 3404.
Communication 9/02240F
1134
Chem. Commun., 1999, 1133–1134