The first rhodium-catalyzed anti-markovnikov hydroamination: Studies on hydroamination and oxidative amination of aromatic olefins

Article abstract of DOI:10.1002/(SICI)1521-3765(19990401)5:4<1306::AID-CHEM1306>3.0.CO;2-4

The first transition-metal-catalyzed regiospecific anti-Markovnikov hydroamination of aromatic olefins is reported. Styrene and substituted styrenes react with secondary aliphatic amines, especially morpholine and Narylpiperazines, in the presence of cationic rhodium complexes to give 2- aminoethenylbenzene and 2-aminoethylbenzene derivatives. Cationic [Rh(cod)₂]⁺BF₄^- and various phosphines (l:2-mixture) were employed as in situ catalysts. According to labeling experiments, there is no evidence that the hydroamination is a consecutive hydrogenation of a previously formed enamine. Hydroamination with simple secondary amines, for example piperidine, can also be achieved by the use of a higher olefin concentration and higher reaction temperatures than those given in previously published reaction procedures. Kinetic investigations of the major reaction pathway reveal that the reaction rate of the oxidative amination and the hydroamination is dependent on the styrene and on the catalyst concentration, and independent of the amine concentration. Experiments that employed deuterium-labeled amines (N-D) provided evidence that the mechanism involves an amine- activating pathway. The substituents on the styrene, the phosphine ligand, and the solvent influence the yield of the aminations and the enamine:alkylamine ratio.

Full text of DOI:10.1002/(SICI)1521-3765(19990401)5:4<1306::AID-CHEM1306>3.0.CO;2-4

FULL PAPER
Anti-Markovnikov Functionalizations of Unsaturated Compounds, Part 5[=]
The First Rhodium-Catalyzed Anti-Markovnikov Hydroamination:
Studies on Hydroamination and Oxidative Amination of Aromatic Olefins
²
M. Beller,*[a] H. Trauthwein,[b] M. Eichberger, C. Breindl,[b] J. Herwig,[c]
T. E. Müller,[b] and O. R. Thiel[b]
Abstract: The first transition-metal-cat-
alyzed regiospecific anti-Markovnikov
hydroamination of aromatic olefins is
reported. Styrene and substituted sty-
renes react with secondary aliphatic
amines, especially morpholine and N-
arylpiperazines, in the presence of cat-
ionic rhodium complexes to give 2-ami-
noethenylbenzene and 2-aminoethyl-
benzene derivatives. Cationic [Rh-
hydroamination is a consecutive hydro-
genation of a previously formed enam-
ine. Hydroamination with simple secon-
dary amines, for example piperidine, can
also be achieved by the use of a higher
olefin concentration and higher reaction
temperatures than those given in pre-
viously published reaction procedures.
Kinetic investigations of the major re-
action pathway reveal that the reaction
rate of the oxidative amination and the
hydroamination is dependent on the
styrene and on the catalyst concentra-
tion, and independent of the amine
concentration. Experiments that employ-
ed deuterium-labeled amines (N D)
provided evidence that the mechanism
involves an amine-activating pathway.
The substituents on the styrene, the
phosphine ligand, and the solvent influ-
ence the yield of the aminations and the
enamine:alkylamine ratio.
Keywords: aminations ´ anti-
Markovnikov reaction ´ catalysts ´
‡
(cod)2] BF4 and various phosphines
(1:2-mixture) were employed as in situ
catalysts. According to labeling experi-
ments, there is no evidence that the
reaction mechanisms
complexes
´
rhodium
particularly convenient method for the synthesis of amines
(Scheme 1).[2]
Introduction
Amines and their derivatives are of fundamental importance
as natural products, pharmacological agents, fine chemicals,
and dyes.[1] Hence, there is considerable interest in the
development of new efficient synthetic protocols for the
construction of carbon ± nitrogen bonds. In this respect, the
transition-metal-catalyzed hydroamination of olefins is a
Scheme 1. Hydroamination of olefins.
This environmentally friendly procedure is 100% atom
economic, that is, each atom from the starting material is
present in the product and no byproducts are formed.
Furthermore, olefins and amines are both inexpensive and
readily available feedstocks. Industrially important terminal
olefins provide, in principle, two regioisomeric amines, the
Markovnikov and the anti-Markovnikov product. The Mar-
kovnikov regioisomer is usually favored as a consequence of
the higher stability of the intermediate carbocation.
The negative entropy balance of the hydroamination
reaction does not permit the use of high reaction temper-
atures. Thus, a catalyst is required for successful transforma-
tions. Strong bases,[3] various acids,[4] and different types of
transition metal complexes[5±8] have been used as the catalyst
[a] Prof. M. Beller
Institut für Organische Katalyseforschung (IfOK)
an der Universität Rostock e. V.
Buchbinderstr. 5 ± 6, D-18055 Rostock (Germany)
Fax: (‡49)381-46693-24
E-mail: matthias.beller@ifok.uni-rostock.de
[b] Dr. H. Trauthwein, Dipl.-Chem. C. Breindl,
Dr. T. E. Müller, Dipl.-Chem. O. R. Thiel
Anorganisch-chemisches Institut, Technische Universität München,
Lichtenbergstr. 4, D-85747 Garching (Germany)
[c] Dr. J. Herwig
Celanese AG
Otto-Roelen-Str. 3, D-46147 Oberhausen (Germany)
[²] Dipl.-Chem. M. Eichberger (1969 ± 1997)
[=] Part 4: M. Beller, H. Trauthwein, M. Eichberger, C. Breindl,
T. E. Müller, A. Zapf, J. Organomet. Chem. 1998, 566, 277.
1306
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1306 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

1306±1319
for hydroamination reactions. Despite considerable progress
in recent years, a general hydroamination protocol for olefins
has not yet been developed. Since it is possible to change the
properties of the catalyst by simple ligand exchange reactions,
transition metal complexes probably offer the most promising
route for the development of a general and efficient catalytic
hydroamination process.
amination of a (nonactivated) aromatic olefin. We present
evidence that this kind of regioselective hydroamination
proceeds not through a hydrogenation of the enamine, but
rather by protolysis of an alkyl-rhodium intermediate. Herein
we describe in detail the scope, the reaction conditions,
labeling experiments, kinetic studies, and model complexes
for both the oxidative amination and the hydroamination
reactions.
The first transition metal catalysts for hydroamination were
rhodium salts, introduced by Du Pont for the reaction of
ethylene with secondary amines.[8i] Subsequently, Taube et al.
were able to elucidate the mechanism of this reaction and to
synthesize more-active rhodium catalysts.[8e±h] Interestingly,
Brunet and co-workers observed that a catalyst system
consisting of lithium anilide and rhodium[bis(triethylphos-
phine)]chloride [{Rh(PEt3)2Cl}2] catalyzes both the oxidative
amination and the hydroamination of styrene with aniline
(TON ˆ 21).[8c] The imine and the alkylamine are both formed
as the Markovnikov isomers. Hegedus et al. have shown that
palladium complexes can be employed in the intramolecular
oxidative amination of 2-aminostyrene derivatives.[9] Milstein
et al. showed that, in addition to rhodium complexes, iridium
complexes can also act as amination catalysts. Here, they
provided evidence for an oxidative N H addition pathway for
the reaction of aniline and norbornene.[7c] However, the
turnover numbers (TON ˆ 6) were low for this reaction. Very
recently, Togni et al. developed the first asymmetric hydro-
amination process. The turnover number of the reaction of
aniline and norbornene was significantly increased by the use
of chelating phosphine ligands and naked fluoride ions.[7a]
In addition to late transition metals, even early transition
metal complexes can serve as mediators for the amination of
olefins.[5] In particular, the introduction of organolanthanide
complexes by Marks and co-workers, mainly for the intra-
molecular hydroamination of aminoolefins or aminoalkynes,
constitutes an important breakthrough.[6] Even enantioselec-
tive intramolecular aminations have been performed by
means of chiral catalysts.[6d, g] Unfortunately, the intermolec-
ular hydroamination of olefins only proceeds with very low
turnover numbers (TON ˆ 2).[6c]
Results
Hydroamination of aromatic olefins: As demonstrated by our
previous investigations,[8a] cationic rhodium complexes, such
as [Rh(cod)2]BF4, catalyze the oxidative anti-Markovnikov
amination of aromatic olefins (Scheme 2).
Scheme 2. Rhodium-catalyzed oxidative anti-Markovnikov aminations of
aromatic olefins.
Secondary aliphatic amines proved to be good substrates
for this reaction, especially hexacyclic compounds, such as
piperidine. Unfortunately, bidentate amines, for example
thiomorpholine, piperazine, or N-methylpiperazine, react
very sluggishly or not at all.[14] These bidentate amines act as
chelating ligands at the rhodium center, so that free coordi-
nation sites are blocked. In order to investigate the factors
that govern the reactivity of amines more closely, we studied
the reaction of amines that contain a weak donating group, for
example, OR (R ˆ alkyl, aryl). Styrene and morpholine were
‡
combined in the presence of [Rh(cod)2] BF4 /2PPh3
(Scheme 3) to give the corresponding N-(2-phenylethenyl)-
morpholine (1a) and ethylbenzene in good yields, which
In all hydroamination reactions catalyzed by transition
metals to date, the Markovnikov product[10] is preferentially
formed when terminal olefins are used. The sole exception is
the intramolecular oxidative amination of o-aminostyrene;
only attack at the terminal position is possible here for reasons
of ring strain in the product.[11] However, the linear anti-
Markovnikov products are more important for industrial
applications. Hence, the development of a general catalytic
method for the functionalization of olefins with amines and
other nucleophiles in anti-Markovnikov regiochemistry has
been mentioned as one of the ten most important challenges
for new catalytic methods.[12]
Scheme 3. anti-Markovnikov oxidative amination and anti-Markovnikov
hydroamination of styrene with morpholine.
Publications on the anti-Markovnikov problem of simple
neutral olefins are rare.[13] An exception is the oxidative
amination of aromatic olefins to yield enamines, which we
have recently developed.[8a] Importantly, the products are
formed exclusively with anti-Markovnikov regiochemistry. In
this paper we present detailed studies on the mechanism of
this new reaction. Furthermore, we were able to observe, for
the first time, an intermolecular anti-Markovnikov hydro-
exceed all previously tested amines. Even more surprisingly
we observed, for the first time, the formation of the anti-
Markovnikov hydroamination product N-(2-phenylethyl)-
morpholine (1b) with a catalyst TON ˆ 5 and 14% yield.
The anti-Markovnikov regiochemistry of the product has
1
been unambiguously proved by H NMR, 13C NMR, DEPT-
13C NMR spectra, and GC/MS spectroscopy. The Markovni-
kov isomer was not detected.
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1307 $ 17.50+.50/0
1307

M. Beller et al.
FULL PAPER
To the best of our knowledge this is the first time that a
transition-metal-catalyzed anti-Markovnikov hydroamination
has been realized with olefins other than strongly activated
Michael systems, such as acrylonitrile or acrylic acid deriva-
tives.
In principle, two possibilities exist for the formation of the
hydroamination product: either a two-step mechanism with
subsequent hydrogenation of the initially built enamine, or an
independent direct process. In order to discover which of the
two mechanisms was operating, we investigated whether it
was possible for the rhodium hydride species to hydrogenate
the intermediate enamines under the reaction conditions
used. Thus, N-(2-phenylethenyl)morpholine and 2.5 mol% of
[Rh(cod)2]BF4/2PPh3 were combined under an atmosphere of
H2 (1 atm):[15] no N-(2-phenylethyl)morpholine was observed.
In addition, the rhodium-catalyzed reaction of styrene and
morpholine was performed in the presence of 1 atm H2: no
change in the enamine:alkylamine ratio was observed. These
are clear indications that the rhodium dihydride complex
formed in situ is not able to hydrogenate enamines under the
reaction conditions employed. Hence, N-(2-phenylethyl)mor-
pholine is not formed through the hydrogenation of enamine
N-(2-phenylethenyl)morpholine. Furthermore, no increase in
the hydrogenation of styrene was observed.
Scheme 4. Scrambling of deuterium in the rhodium-catalyzed amination
of styrene and morpholine in the presence of (E)-N-(1-deutero-2-phenyl-
ethenyl)morpholine.
nitrogen atom. We also detected a deuterium signal that can
be assigned to an aliphatic deuterium in the a-position of the
nitrogen (d ˆ 2.5); however, the magnitude of this aliphatic
deuterium signal was in the same order of magnitude as the
signals of the scrambled products.
A definite proof for a two-step oxidative amination ± hy-
drogenation pathway would be the reaction of styrene with
morpholine in the presence of a suitably deuterated enamine.
The olefinic a-H next to the nitrogen atom is the most suitable
position for deuterium. In contrast to the aromatic or benzylic
position, this olefinic position should be relatively stable
against H/D exchange. If hydrogenation of the deuterated
enamine occurred, then the olefinic deuterium would be
transformed into an aliphatic deuterium, which can easily be
detected by 2H NMR. Hence, we synthesized (E)-N-(1-
deutero-2-phenylethenyl)morpholine (18) by reaction of
1-deutero-2-phenylacetaldehydedimethylacetal (17) and mor-
pholine. The selectively labeled aldehyde was prepared from
unlabeled phenylacetaldehyde by means of the Corey ± See-
bach procedure.[16]
After we had isolated N-(2-phenylethyl)morpholine we
observed two resonances in the corresponding 2H NMR
spectrum that were both in the a-position to the amine atom.
We have assigned these signals to N-(1-deutero-2-phenyl-
ethyl)morpholine and to N-(2-phenylethyl)morpholine,
whereby incorporation of deuterium in the morpholine ring
has occurred. On account of the same intensity of the signals it
is very probable that N-(1-deutero-2-phenylethyl)morpholine
is produced through deuterium scrambling or by the hydro-
amination of deuterated styrenes produced in situ.
Because of the problems with deuterium scrambling, we
designed a chemical labeling experiment: we examined the
rhodium-catalyzed amination of 4-methylstyrene with mor-
pholine in the presence of 10 mol% N-(2-phenylethenyl)mor-
pholine (Scheme 5). On account of the similar reactivity
towards hydrogenation but differences in the structure of N-
[2-(4-tolyl)ethenyl]morpholine compared with N-(2-phenyl-
ethenyl)morpholine, it should be easy to detect whether a
hydrogenation of enamines occurs in situ.
When styrene and morpholine were combined in the
presence of 7.5 mol% (E)-N-(1-deutero-2-phenylethenyl)-
morpholine and 2.5 mol% of [Rh(cod)2]BF4/2PPh3, a non-
selective scrambling of the deuterium atom occurred
(Scheme 4). Apart from the
main peak of the deuterated
enamine (d ˆ 6.8), we detected
deuterium in the olefinic posi-
tions of the unreacted styrene
(d ˆ 6.7, 5.7, 5.2) as well as in the
methyl and methylene group of
ethylbenzene (d ˆ 2.6, 1.1). Sur-
prisingly, an intramolecular
scrambling of deuterium in the
enamine had also taken place
and the deuterium was attached
to the benzylic position of the
ethenyl group (d ˆ 5.3) and to
the methylene group (d ˆ 2.4)
Scheme 5. Reaction of 4-methylstyrene and morpholine in the presence of 10 mol% N-(2-phenylethenyl)-
morpholine.
within the ring next to the
1308
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1308 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Hydroamination
1306±1319
Under the typical reaction conditions of oxidative amina-
tion reactions ([Rh(cod)2]BF4/2PPh3 (2.5 mol%), THF, re-
flux), we obtained N-[2-(4-tolyl)ethyl]morpholine in 15%
yield and N-(2-phenylethyl)morpholine in 0.2% yield. Ob-
viously, there is a small hydrogenation activity responsible for
the formation of the 0.2% N-(2-phenylethyl)morpholine.
However, the ratio of enamine to alkylamine for the
unsubstituted enamine is ten times higher compared with that
of the methyl-substituted enamine! This clearly indicates that
a separate hydrogenation step of free enamine is negligible.
Thus, we conclude that N-(2-phenylethyl)morpholine is not
produced through hydrogenation of enamine N-(2-phenyl-
ethenyl)morpholine, but rather by an independent mecha-
nism. Therefore, this reaction constitutes the first example of
a transition metal-catalyzed anti-Markovnikov hydroamina-
tion of a neutral terminal olefin.
a methoxy group. 4-Methoxystyrene and 3,4-dimethoxystyr-
ene provided larger amounts of the alkylamine (5b, 6b), while
the yield of enamine (5a, 6a) was still comparably good (50 ±
60%). When styrenes substituted with electron-withdrawing
groups, such as chloride and trifluoromethyl, are employed,
alkylamines (8b, 9b) were still obtained as products. How-
ever, the amount of alkylamines was lower than that from
styrene. Surprisingly, 4-fluorostyrene also provided good yields
of both the enamine (7a) and the alkylamine(7b). Compared
with the reaction with piperidine as the amine, the amination
of 2-vinylnaphthalene with morpholine was disappointing.[8a]
Nevertheless, the conversion of morpholine with differently
substituted styrenes generally proceeded more efficiently
than the conversion with other secondary amines.
We were then interested in the amination of styrene with
other amines that contain a suitable second coordination site.
Piperazines are also hexacyclic amines; they bear a second
coordinating group in the para-position. As reported previ-
ously, piperazine and N-alkylpiperazines are strong chelating
ligands that can block coordination sites on the rhodium and
thus terminate catalysis.14 We thought that the attachment of
an aryl group on the nitrogen should reduce the electron
density and suppress the coordination ability of the second
nitrogen atom, both electronically and sterically. Indeed, by
the use of N-arylpiperazines with electron-withdrawing sub-
stituents, such as fluorine and CF3 on the aromatic ring, we
were able to observe oxidative amination as well as hydro-
amination (Scheme 7, Table 2). However, the corresponding
Scope and limitations: Next, we investigated the electronic
and steric influences of the aromatic olefin on this new type of
reaction (Scheme 6, Table 1). In all cases, enamine and alkyl-
amine are formed with anti-Markovnikov regiochemistry.
Scheme 6. Rhodium-catalyzed amination of styrenes and morpholine.
Table 1. Reaction of morpholine with substituted styrenes.[a]
Styrene
Enamine Alkylamine Ethylbenzene Enamine:
[%][b]
[%][c]
[%][c]
alkylamine
R ˆ H
74 (1a)
76 (2a)
62 (3a)
27 (4a)
50 (5a)
55 (6a)
60 (7a)
31 (8a)
21 (9a)
14 (1b)
15 (2b)
14 (3b)
6 (4b)
12 (5b)
26 (6b)
19 (7b)
7 (8b)
84
99
78
20
47
80
85
32
9
5.3
5.1
4.4
4.5
4.2
2.1
3.1
5.7
10.5
8.6
6.0
Scheme 7. Rhodium-catalyzed amination of styrene with N-arylpipera-
zines.
R ˆ 4-Me
R ˆ 3-Me
R ˆ 2-Me
R ˆ 4-MeO
R ˆ 3,4-MeO
R ˆ 4-F
N-aryl-N'-(arylethyl)piperazines were only produced in small
amounts with high enamine:alkylamine ratios. Interestingly,
electron-donating groups (e.g., methoxy and methyl) on the
phenyl ring of the piperazine prevent the formation of the
alkylamine.
R ˆ 4-Cl
R ˆ 3-CF3
2 (9b)
3 (10b)
2 (11b)
2-vinylnaphthalene 26 (10a)
38
21
R ˆ 4-Ph
12 (11a)
Table 2. Reaction of styrene with N-arylpiperazines.[a]
[a] Reaction conditions: styrene:amine ratio ˆ 4:1, 2.5 mol% [Rh(cod)2]-
BF4/2PPh3 relative to amine, reflux in THF 20 h. [b] The yield (referred to
amine) was determined by gas chromatography by the percentage area.
[c] The yield (referred to amine) was determined by gas chromatography
with an internal standard.
Amine
Enamine Alkylamine Ethylbenzene Enamine:
[%][b]
[%][c]
[%][c]
alkylamine
1-(4-fluorophenylpiperazine) 52 (12a)
1-(3-methylphenylpiperazine) 37 (13a) < 0.1
4 (12b)
69
54
80
13
±
16.5
1-(3-trifluoromethylphenyl-
piperazine)
33 (14a)
2 (14b)
Styrene substituted with a methyl group in the para or meta
position gave yields and product selectivities similar to those
of unsubstituted styrene. However, when the methyl group
was in the ortho position, the yield of the enamine (4a) and
the alkylamine (4b) decreased dramatically. Interestingly, the
enamine:alkylamine ratio was reduced by the introduction of
1-(2-methoxyphenylpiperazine) 31 (15a) < 0.1
45
±
[a] Reaction conditions: styrene:amine ratio ˆ 4:1, 2.5 mol% [Rh(cod)2]BF4/2PPh3
relative to amine, reflux in THF 20 h. [b] The yield (referred to amine) was
determined by gas chromatography by percentage area. [c] The yield (referred to
amine) was determined by gas chromatography with an internal standard.
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1309 $ 17.50+.50/0
1309

M. Beller et al.
FULL PAPER
Recently, we showed that olefin(bisamine)rhodium com-
plexes containing secondary amine ligands are precatalysts in
the oxidative amination of styrene, while rhodium complexes
with chelating amines, such as piperazine and thiomorpholine,
showed no catalytic activity at all.[14] Therefore, morpholine or
4-N-arylpiperazines do not behave as bidentate ligands in the
observed aminations. Indeed, the synthesis of cationic (cod)-
rhodium complexes with morpholine or 4-fluorophenylpiper-
azine as amine ligands proceeds from [{Rh(cod)Cl}2] and
morpholine or 4-fluorophenylpiperazine in the presence of
AgX (X ˆ CF3SO3 , BF4 ) in THF to yield the corresponding
bisamine complexes cyclooctadien-bis(morpholine)rhodi-
um(i) tetrafluoroborate (20) and cyclooctadien-bis[N-(N'-4-
fluorophenyl)piperazine]rhodium(i) tetrafluoroborate (21) in
excellent yield. After cooling to 08C, the complexes were
obtained as a yellow precipitate. According to spectroscopic
investigations and to elemental analyses, both amines form
olefin(bisamine)rhodium complexes. In the case of the
morpholine complex, we were able to obtain suitable crystals
for X-ray crystallographic analysis (Figure 1). The X-ray
Reaction conditions: Since we had proved that the hydro-
amination of styrenes is, in principle, possible in the presence
of cationic rhodium catalysts, we then studied in detail the
various reaction parameters in order to achieve hydroamina-
tion with other simple secondary amines, such as piperidine.
We achieved the first successful hydroamination of styrene
with piperidine (Table 3) in the presence of a transition metal
Table 3. Amination of styrene with piperidine.[a]
Reaction
Styrene:
Enamine Ethylbenzene Alkylamine (16)
conditions
piperidine [%]
[%]
[%]
THF, reflux
THF, reflux
4:1
10:1
4:1
4:1
4:1
4:1
4:1
4:1
55
70
52
19
23
3
57
76
> 99
21
40
12
±
< 0.1
7
5
< 0.1
< 0.1
< 0.1
< 0.1
< 0.1
toluene, reflux
dioxane, reflux
DMAc, 1508C
NMP, 1508C
DMSO, 1508C
CH3CN, reflux
±
±
±
[a] 2.5 mol% [Rh(cod)2]BF4/2PPh3 relative to amine, 20 h; yield referred
to amine.
catalyst: by the use of a large excess (tenfold) of styrene we
obtained N-(2-phenylethyl)piperidine in 7% yield (TON ˆ 3).
Although the yield is not useful on a preparative scale, this
result shows that anti-Markovnikov amination with simple
secondary amines can be achieved catalytically. In addition,
an increase in the reaction temperature in toluene as the
solvent also led to the formation of N-(2-phenylethyl)piper-
idine (16). In polar aprotic solvents the reaction rate is
reduced significantly or the amination does not take place at
all. This again shows the importance of vacant coordination
sites on the rhodium center. With 2-butanol as the solvent, we
observed the formation of a significant amount of styrene
dimers and of ethylbenzene, which was formed through
transfer hydrogenation.
Since the hydroamination mechanism implies a transfer of a
hydrogen atom from the nitrogen atom to the styrene, we in-
vestigated whether the addition of acid or base would change
the enamine:alkylamine ratio. Again, as a model reaction, we
studied the amination of styrene with morpholine (Table 4).
If the alkylamine is produced by protolysis of a rhodium ±
alkyl bond, then the presence of a protonating agent should
increase the formation of N-(2-phenylethyl)morpholine. To
test this hypothesis we varied the styrene:morpholine ratio,
which increased the concentration of the amine, which in turn
is believed to provide the proton. Although the total yield of
amination products is reduced, which is in agreement with the
results from kinetic studies (see below), the alkylamine:en-
amine ratio was increased significantly. We then investigated
whether the addition of an acid in combination with a
noncoordinating anion has the same effect. While the addition
of 10 mol% of HBF4 in refluxing THF caused only a small
increase in the hydroamination yield, under more harsh
conditions (pressure tube; toluene at 1408C in the presence of
20 mol% acid) the alkylamine became the major reaction
product for the first time. The yield of the enamine was
negligible under these reaction conditions (yield < 0.1%), so
that the anti-Markovnikov product was the main reaction
product. At present the yield (6%) and turnover numbers
‡
Figure 1. Molecular structure of the [Rh(cod)(morpholine)2] fragment in
20.
structure of 20 reveals the rhodium atom to have a square
planar coordination geometry and is coordinated to cod and
two amines, whereby the two morpholine molecules are
mutually cis. The rhodium ± nitrogen bond lengths
(Rh N11 ˆ 2.188(2) Š, Rh N21 ˆ 2.1740(17) Š) are of sim-
ilar length, as in the related piperidine complex [Rh(cod)(pi-
peridine)2]BF4 (between 2.159(4) Š and 2.186(4) Š).[14] The
angle between the two piperidine nitrogens N11-Rh-N21 in 20
is 85.39(7)8, which indicates that there is no steric strain
around rhodium. This angle is slightly smaller than the N-
Rh-N angle in the morpholine complex (90.1(1)8); this is
explained by the smaller steric demand of morpholine
compared to piperidine.
Thermogravimetric analysis revealed that complex 20
decomposes in two steps, namely at 2408C and at 2808C. As
can be seen by the mass balance, the cod ligand and one
morpholine ligand are simultaneously extruded first. This
indicates that, even in solid state, at least three coordination
sides are relatively labile.
1310
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1310 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Hydroamination
1306±1319
Table 4. Reaction of styrene and morpholine in the presence of an additive.[a]
Cocatalyst
[mol%]
Styrene:
morpholine
Reaction
conditions
Enamine (1a)
[%]
Alkylamine (1b)
[%]
Ethylbenzene
[%]
Enamine:
alkylamine
±
±
4:1
1:4
4:1
4:1
4:1
4:1
4:1
4:1
4:1
THF, reflux
THF, reflux
THF, reflux
Toluene, 1408C[c]
Toluene, 1408C[c]
THF, reflux
THF, reflux
THF, reflux
THF, reflux
74
38[b]
33
14
15[b]
7
6
6
< 0.1
11
5
84
35[b]
33
82
72
< 0.1
78
85
5.3
2.5
4.7
HBF4 (10)
HBF4 (10)
HBF4 (20)
KOtBu (25)
DIPEA (5)
DIPEA (100)
DIPEA (200)
5
0.8
< 0.1
< 0.1
75
77
73
< 0.2
< 0.1
6.8
15.4
12.1
6
83
[a] 2.5 mol% [Rh(cod)2]BF4/2PPh3 relative to amine, 20 h. [b] The yield is referred to styrene. [c] 2.5 mol% [Rh(cod)2]BF4/10PPh3 relative to amine, 20 h.
(TON ˆ 3) are not satisfying from a practical standpoint;
however, these experiments demonstrate that the anti-Mar-
kovnikov hydroamination of styrenes is possible.
used. Again, with sterically demanding phosphines, such as
tricyclohexylphosphine, no reaction occurred, while tri-(n-
butyl)phosphine led to good yields of N-(2-phenylethenyl)-
morpholine. The relatively low yield in the presence of
trimethylphosphine is ascribed to the instability of the
resulting complexes. Chelating phosphines, such as dppe and
1,1'-bisphenylferrocenylphosphine, inhibited the activity of
the catalyst.
In addition to phosphines, we examined a series of further
common ligands, such as phosphites, phosphine oxides,
pyridine, and acetonitrile. These ligands completely sup-
pressed the catalytic activity of the cationic rhodium complex.
In addition, no amination was observed in the presence of
triphenylarsane or triphenylstilbane. Thus, the tolerance of
the catalyst for the added ligand is very small.
As expected, the addition of another amine (DIPEA)
lowered the amount of hydroamination product as a result of
a competition for the proton that is needed for protolysis. The
addition of potassium tert-butylate as a base, which presum-
ably acts as an oxygen ligand, completely deactivated the
cationic rhodium catalyst and no catalysis was observed.
In order to investigate the influence of ligands on the
formation of hydroamination and oxidative amination prod-
ucts, several phosphines were tested for the reaction of
styrene with morpholine under standard conditions (Table 5).
The reaction was very sensitive to the type of phosphine. The
best yields of N-(2-phenylethyl)morpholine and N-(2-phenyl-
ethenyl)morpholine were obtained with PPh3. Electron-with-
drawing groups on the phenyl ring of the phosphine, such as
fluorine, lowered the yield. Electron-donating groups lead to
good results. Phosphines with large Tolman angles inhibited
the reaction, hence a good coordination of the phosphine to
the rhodium is a prerequisite for this amination reaction. In
addition to triarylphosphines, alkylphosphines can also be
Mechanism: In order to gain further insight into the
mechanism of the oxidative amination as well as the hydro-
amination reaction, additional deuterium labeling experi-
ments and kinetic investigations were performed. Firstly, we
examined the reaction of deuterated amines in the presence of
the catalyst [Rh(cod)2]BF4/2PPh3 without styrene. N-Deuter-
ated amines were synthesized
Table 5. Different ligands in the reaction of styrene and morpholine.
by the deprotonation of the
amine with n-butyllithium and
subsequent quenching of the
lithium amide with monodeu-
terated acetic acid. The N-deu-
terated morpholine and the cat-
ionic rhodium complex were
then refluxed in THF for 20 h
and the 2H NMR spectrum was
recorded (Figure 2).
In addition to the N D signal
of the starting material at d ˆ
2.0, a new resonance appeared
at d ˆ 2.7, which was assigned to
a deuterium atom bound at the
a-methylene group of the
amine. Thus, the deuterium
atom migrates from the nitro-
gen to the methylene group
(Scheme 8). This migration can
be explained by a dehydrogen-
ation ± hydrogenation mecha-
Ligand
Enamine (1a)
[%]
Alkylamine (1b) Ethylbenzene
Enamine:
alkylamine
[%]
[%]
[a]
PPh3
PPh3
74
24
29
13
±
< 0.1
2
53
< 0.1
46
56
46
22
< 0.1
56
< 0.1
17
14
3
84
22
5.3
8
±
±
±
±
±
10.6
±
7.7
9.3
6.5
5.5
±
±
±
±
±
[b]
[a]
[d]
P(p-C5H4F)3
P(p-C5H4F)3
P(C6F5)3
Ph2P(o-C6H4-OMe)[a]
Ph2P(o-C6H4-OEt)[a]
Ph2P(o-C6H4-OPh)[a]
Ph2P(o,o-C6H3-(OMe)2)[a]
Ph2P(p-C6H4-OMe)[a]
PhP(p-C6H4-OMe)2
P(p-C6H4-OMe)3
P(p-C6H4-OMe)3
Ph2P-pyridyl[b]
< 0.1
< 0.1
±
< 0.1
< 0.1
5
29
15
< 0.1
< 0.1
2
[a]
49
< 0.1
6
< 0.1
54
[a]
6
65
[c]
7
90
[d]
4
25
< 0.1
< 0.1
< 0.1
< 0.1
< 0.1
< 0.1
61
< 0.1
18
[a]
P(n-butyl)3
P(C6H11)3
P(CH3)3
dppe[a]
[a]
[a]
< 0.1
< 0.1
[a] Ratio of styrene:amine ˆ 4:1, 2.5 mol% [Rh(cod)2]BF4 /2PR3 relative to amine, 20 h reflux in THF. [b] Ratio
of styrene:amine ˆ 2:1, 1.0 mol% [Rh(cod)2]BF4/2PR3 relative to amine, 20 h reflux in THF. [c] Ratio of
styrene:amine ˆ 2:1, 1.0 mol% [Rh(nbd)2]BF4/2PR3 relative to amine, 20 h reflux in THF. [d] Ratio of
styrene:amine ˆ 2:1, 0.5 mol% [Rh(nbd)2]BF4/2PR3 relative to amine, 20 h reflux in THF.
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1311 $ 17.50+.50/0
1311

M. Beller et al.
FULL PAPER
4:1 in order to suppress the
hydroamination reaction and to
facilitate the analytical assign-
2
ment. The H NMR spectrum
obtained is shown in Figure 3.
The resonances at d ˆ 2.6 and
1.3 were assigned to deuterium
atoms, which are both bound to
carbon atoms in the ethyl group
of ethylbenzene. Surprisingly,
most of the deuterium is attach-
ed to all three sites of the vinyl
group of unconverted styrene
(d ˆ 6.8, 5.7 and 5.3). The minor
peaks at d ˆ 5.5 and 2.9 indicate
deuterium labeling of the en-
amine product, which was deu-
terated at the ethylene group
adjacent to the phenyl ring and
in a-position of the piperidine
ring.
Figure 2. 2H NMR of the reaction of [D1]morpholine with catalytic amounts of [Rh(cod)2]BF4/2PPh3 in refluxing
THF.
Figure 3. 2H NMR spectrum of the reaction of N-deuterated piperidine
and styrene.
In order to investigate this deuterium scrambling in more
detail, we also studied the reaction of [D1]di-iso-propylamine
with styrene and of a-methylstyrene with [D1]piperidine in
THF under reflux. In both rhodium-catalyzed reactions it is
known that no amination products are produced. Interest-
ingly, also no significant scrambling of deuterium was
observed. This clearly shows that deuterium scrambling
occurs only when the oxidative amination is successful. This
demonstrates the importance of a N H(D) activation for
successful catalysis.
In addition to labeling experiments, we sought to obtain
kinetic data of this reaction in order to gain an insight into the
time dependency of the reaction and to estimate the order of
the reactants in the amination of morpholine. The time-
dependent formation of enamine, ethylbenzene, and alkyl-
amine are depicted in Figure 4. Enamine and ethylbenzene
are formed concurrently and to a similar extent in a slightly
sigmoidal curve. The alkylamine graph has the same shape
and time-dependence, but to a smaller extent.
Scheme 8. Reaction of N-deuterated morpholine with [Rh(cod)2]BF4/
2PPh3.
nism. Similarly to transfer hydrogenation, a rhodium dihy-
dride species and an imine is formed by the oxidative addition
of the cationic rhodium into the N D bond and subsequent
elimination of the b-hydride. Presumably, the intermediate
hydride-rhodium-amide species is formed from the cationic
rhodium amine complex by deprotonation of N H bond and
protonation to give a Rh H bond. Insertion of the imine into
the rhodium ± hydrogen bond of the rhodium dihydride
complex and subsequent reductive elimination yields a
deuteration of the methylene group.
This experiment also offers an explanation for the greater
yield of ethylbenzene compared with the enamine as observed
in oxidative amination reactions. In the presence of styrene,
the rhodium dihydride, which is generated by the dissociation
of the RhH2 from the imine (Scheme 8), hydrogenates styrene
to ethylbenzene. The detection of imines would provide
evidence of this process. However, the imines formed are
difficult to detect because they readily undergo oligomeriza-
tion and polymerization reactions.
We then investigated how the reaction rate vi of the
products is influenced by the concentration of the compo-
nents. Hence, we varied the initial concentration of olefin,
amine and catalyst and determined the rate of reaction of
enamine and alkylamine ni (from the equation vi ꢀ cini) at the
beginning of the reaction (Table 6).
We then investigated the oxidative amination in the
presence of deuterated amines. Here, we used [D1]piperidine
instead of morpholine in THF with a styrene:amine ratio of
As shown in Table 6, the rate of enamine formation is first-
order in catalyst and olefin. The influence of the amine on the
1312
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1312 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Hydroamination
1306±1319
interactions of both electron-rich starting materials.[17] Since
the Gibbs free enthalpy of amination reactions becomes
unfavorable as the temperature increases because of the
entropy term, the activation of either the amine or the olefin
by means of a catalyst is necessary. The two limiting
mechanisms for the transition-metal-catalyzed oxidative ami-
nation are shown in Scheme 9. In the presence of cationic
Figure 4. Time ± yield diagram for the reaction of styrene and morpholine,
2.5 mol% [Rh(cod)2]BF4/2PPh3, styrene:morpholine ˆ 4:1. Insert: En-
largement of the alkylamine region.
Table 6. Order of the reaction rate n on the components of the reaction.
Olefin
Amine
Catalyst
enamine
alkylamine
0.95
0.85
0.18
0.14
0.99
1.05
reaction rate is almost negligible. The formation of alkylamine
exhibits the same rate behavior, namely nearly first-order in
olefin and catalyst, but almost independent of the amine.
Apart from the accelerating effect of an increased olefin
concentration, the olefin also has a stabilizing effect on the
catalyst (Figure 5). Here, we studied the amination of styrene
Scheme 9. Possible mechanisms for the oxidative amination of styrene.
rhodium complexes, both reaction pathways (amine versus
olefin activation) seem to be possible.
In the amine-activation pathway, the rhodium center inserts
into the nitrogen ± hydrogen bond by oxidative addition. The
H-Rh-NR2 species could also be formed by the coordination
of the amine followed by deprotonation at the coordinated
nitrogen and reprotonation at the rhodium center. The
resulting amido-hydrido complex inserts into the olefin and
forms an alkyl-rhodium species. In the case of oxidative
amination, this alkyl-rhodium species eliminates the enamine
by b-H elimination to yield a rhodium dihydride species. This
rhodium(iii) species is regenerated to the catalytically active
rhodium(i) complex by the hydrogenation of a second styrene
molecule. In the olefin-activation pathway, a rhodium olefin
complex is formed, which leads to an umpolung of the double
bond. Subsequent nucleophilic attack of the amine on the
olefin rhodium moiety also yields the corresponding alkyl
rhodium complex.
The 1,2-deuterium shift of N-deuterated amines demon-
strates that an activation of the N H bond is very reasonable
in the presence of the catalyst. Thus, we prefer the amine-
activation route to explain the observed activity of the
cationic rhodium system. Kinetic investigations revealed that
the rate-determining step of the oxidative amination is
dependent on the concentration of the olefin. Hence, the
insertion of the olefin into the rhodium ± nitrogen bond is
likely to be the rate-determining step. This assumption is
reasonable, because the olefin coordinates much more weakly
to the metal center compared with the amine[18] and the
coordination of the olefin is a prerequisite for the following
insertion step.
Figure 5. Dependence of the reaction rate and enamine yield (based on
amine) with respect to the styrene:piperidine ratio, 2.5 mol %
[Rh(cod)2]BF4/2PPh3, THF, reflux.
with piperidine in order to emphasize this effect. It is evident
that the productivity of the catalyst system is increased for the
enamine as the concentration of styrene increases. This
observation implies that the actual catalyst becomes deacti-
vated during the reaction. However, this deactivation can be
suppressed by an excess of olefin. Moreover, this result has an
important implication on preparative aminations. It is evident
that the increase of the styrene:amine ratio leads to a drastic
increase in the yield of amination products. So far our
standard procedure used a styrene:amine ratio of 4:1;
however, it is clear that the yield of the desired oxidative
amination products is easily increased by the use of a higher
olefin concentration.
Discussion
The amination of olefins is hindered by a high kinetic
activation barrier caused by unfavorable intermolecular
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1313 $ 17.50+.50/0
1313

M. Beller et al.
FULL PAPER
The existence of rhodium dihydride species in the reaction
mixture is most probable. The scrambling of deuterium atoms
from the N D group to styrene is easily explained by the
insertion of styrene into the rhodium ± deuterium bond and
subsequent b-hydride elimination to give a rhodium hydride
complex. However, as shown by studies of the reaction of
[D1]di-iso-propylamine with styrene and of a-methylstyrene
with [D1]piperidine, this insertion ± elimination sequence only
takes place if rhodium dihydride species are formed as a
consequence of a preceding amination reaction.
As a result of our investigations on the new oxidative
amination reaction, the first transition-metal-catalyzed anti-
Markovnikov hydroamination of an aromatic olefin was
observed with morpholine and N-arylpiperazines. On the
basis of various labeling studies, we conclude that the major
part of the hydroamination product (2-aminoethylbenzene) is
not formed by a subsequent enamine hydrogenation. Thus,
the formation of the alkylamine proceeds through an inde-
pendent catalytic amination cycle. We propose that this cycle
is strongly related to the formation of the enamine. Alter-
natively to the b-hydride elimination, protolysis of the
2-aminoalkylrhodium complex generates the alkylamine
(Scheme 10).
with secondary amines was observed with morpholine as the
amine. The amount of the hydroamination product is
positively influenced by an increase in the olefin concentra-
tion and at elevated reaction temperatures.
The alkylamine is probably formed by the protolysis of the
corresponding alkyl rhodium complex. Labeling experiments
show that the hydroamination product is not formed by a
hydrogenation of the previously formed enamine. Experi-
ments with N-deuterated amines in the presence of a cationic
rhodium catalyst provide evidence for the occurrence of an
amine-activation mechanism. The use of N-deuterated amines
in the rhodium-catalyzed reaction with styrene led to a
scrambling of deuterium. The major part of the deuterium is
incorporated in all olefinic positions of the styrene. For this
reason, it can be concluded that rhodium ± hydrogen com-
plexes are present in the catalytic cycle. Kinetic investigations
revealed that the olefin concentration and the catalyst
concentration are important, thus leading to a mechanism
whereby the olefin reacts with a rhodium species as the rate-
limiting step.
It is obvious from a preparative point of view that the
hydroamination yields are at present not satisfactory. How-
ever, we have unambiguously shown for the first time that
metal-catalyzed anti-Markovni-
kov hydroamination reactions
with simple olefins are possible,
and have thus demonstrated
that this important type of re-
Scheme 10. Possible routes for the reaction of rhodium-alkyl species.
action can be achieved in prin-
Interestingly, morpholine generated a comparatively high
yield of the hydroamination product compared with other
amines that we studied. One possibility is that the hemilabile
oxygen atom of morpholine
ciple. Further work to develop this methodology to a
synthetically useful level is in progress.
coordinates to the rhodium cen-
ter and stabilizes the alkylrho-
dium complex, thus decreasing
Experimental Section
the possibility of b-hydride
elimination (Scheme 11).
The proposed protolysis step
is supported by the fact that an
increase in the concentration of
Scheme 11. Hypothetical coor-
Materials and methods: All reactions involving organometallic compounds
were carried out with the use of vacuum line, Schlenk, and syringe
techniques. All solvents were dried and distilled prior to use, according to
standard procedures. Amines were distilled from CaH2, silver salts and
dination of the rhodium-alkyl
species with morpholine to sup-
press b-hydride elimination.
other chemicals were purchased from Fluka and Aldrich and used as
[20]
received. [{Rh(cod)Cl}2][19] and [Rh(cod)2]BF4
reported procedures.
were prepared by the
the amine or of protons also increases the amount of the
hydroamination product. In addition, the formation of the
alkylamine is dependent on the styrene concentration. An
excess of styrene also promotes the formation of the hydro-
amination product. This is in agreement with an independent
hydroamination cycle, because at higher concentrations of
styrene a hydrogenation of enamine by a rhodium-dihydride
species is unlikely.
Physical and analytical methods: 1H and 13C spectra were recorded on a
Bruker AT360 and a Jeol-GX400 spectrometer. 1H and 13C chemical shifts
are reported in ppm relative to tetramethylsilane. 2H NMR spectra were
recorded on a JEOL-GX270 spectrometer. Infrared spectra were obtained
on a Perkin ± Elmer1600 spectrometer. Mass spectroscopic analyses were
performed on a Finnigan MAT311A with Fast Atom Bombardment (FAB)
or Field Desorption (FD). The elemental analyses were carried out by the
Microanalytical Laboratory of the Technische Universität München
(Germany). GC spectra for the analysis of the catalytic reactions were
recorded with a HP6890 gas chromatograph equipped with a HP-1
capillary column. Yields were determined with hexadecane as an internal
standard. GC/MS-studies were conducted on a HP5890 with 70 eVelectron
impact ionization (detector: HP5970B).
Conclusion
General procedure for the amination of styrene and morpholine: Catalytic
reactions: the catalyst (0.11 mmol) and the phosphine (0.22 mmol) were
suspended in the corresponding solvent (10 mL). Subsequently, morpho-
line (4.40 mmol) and styrene (17.6 mmol) were added at room temperature.
The mixture was refluxed for 20 h. The yield was determined by gas
chromatography with hexadecane as an internal standard.
The regioselective anti-Markovnikov amination is one of the
great challenges in modern catalysis. By means of cationic
rhodium catalysts, oxidative amination of styrene was ach-
ieved with unfunctionalized secondary amines, such as
piperidine, in refluxing THF and with a small olefin:amine
ratio. For the first time hydroamination of aromatic olefins
Alternatively, the reaction mixture was heated in a pressure tube for 20 h.
1314
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1314 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Hydroamination
1306±1319
Most enamines were identified by GC/MS because the enamines are very
sensitive towards hydrolysis and have a very high boiling point.
(m, 4H, N CH2), 2.33 (s, 3H, CH3); 13C{1H} NMR (91 MHz, 258C, CDCl3):
d ˆ 140.0 (C1), 137.9 (C3), 129.4 (C2), 128.2 (C5), 126.8 (C4), 125.6 (C6),
66.9 (C O), 60.9 (Ph-C-C), 53.7 (N C), 33.2 (Ph C), 21.3 (CH3); MS: m/z:
Subsequently, the enamine was hydrogenated to the corresponding alkyl-
amine. For this, Pd/C (0.5 g, 5%) was added to the enamine and the
reaction mixture was stirred for 48 h in a hydrogen atmosphere (1 atm).
After filtration the solvent was removed by evaporation. The residue was
dissolved in dichloromethane (20 mL) and extracted three times with HCl
(5%). The combined aqueous phases were neutralized by the addition of
NaOH up to pH ˆ 9 and then extracted three times with dichloromethane.
The combined organic layers were dried over MgSO4 and the solvent was
removed by distillation.
‡
‡
205 [M ], 100 [CH2N(C2H4)2O ].
Reaction of morpholine with 2-methylstyrene: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 2-methylstyrene (2.08 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
(E)-N-[2-(2-Methylphenyl)ethenyl]morpholine (4a): GC yield: 27%; MS:
‡
‡
‡
‡
m/z: 203 [M ], 188 [M
CH3], 144 [M
C3H7O], 130 [M
C4H10O],
‡
118 [(CH3C6H4C2H4) ].
Reaction of morpholine with styrene: According to the general procedure,
morpholine (0.38 mL, 4.4 mmol), styrene (2 mL, 17.6 mmol), [Rh(cod)2]-
BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg, 0.22 mmol) were allowed to
react in THF (10 mL) and the solution was then refluxed for 20 h.
N-[2-(2-Methylphenyl)ethyl]morpholine (4b): The isolation was per-
formed according to the general procedure, and the product was purified
by column chromatography (hexane/ethyl acetate 10:1). GC yield (before
hydrogenation): 6%; GC yield (after hydrogenation): 33%; isolated yield:
15% (135 mg); 1H NMR (360 MHz, 258C, CDCl3): d ˆ 7.14 (m, 4H, arom.
H), 3.76 (t, 3J(H,H) ˆ 4.4 Hz, 4H, CH2 O), 2.81 (m, 2H, Ph CH2CH2),
2.55 (m, 6H, PhCH2, N CH2), 2.33 (s, 3H, CH3); 13C{1H} NMR (91 MHz,
258C, CDCl3): d ˆ 138.2 (C1), 135.9 (C2), 130.2 (C3), 129.2 (C6), 126.2
(C4), 126.0 (C5), 66.9 (C O), 59.6 (Ph-C-C), 53.7 (N C), 30.5 (Ph C), 19.3
(E)-N-(2-Phenylethenyl)morpholine (1a): This compound was isolated by
distillation (1488C, 0.1 mbar); GC yield: 74%; 1H NMR (360 MHz, 258C,
CDCl3): d ˆ 7.27 (m, 2H, H2), 7.24 (m, 2H, H3), 7.10 (m, 1H, H4), 6.53 (d,
3
3J(H,H) ˆ 14.0 Hz, 1H, CH N), 5.36 (d, J(H,H) ˆ 14.0 Hz, 1H, Ph CH),
3.68 (t, 3J(H,H) ˆ 4.7 Hz, 4H, O CH2), 2.95 (t, 3J(H,H) ˆ 4.8 Hz, 4H,
N CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ 139.8 (CH N), 138.6
(C1), 128.5 (C2), 124.4 (C4), 124.2 (C3), 101.5 (Ph C), 66.5 (O C), 49.1
‡
‡
(CH3); MS: m/z: 205 [M ], 100 [CH2N(C2H4)2O ].
Reaction of morpholine with 4-methoxystyrene: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 4-methoxystyrene (2.36 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
‡
‡
‡
(N C); MS: m/z: 189 [M ], 158 [M
CH3O], 130 [C6H5 C2H2NCH ], 104
‡
‡
‡
[(C6H5 C2H3) ], 91 [(C6H5 CH2) ], 77 [(C6H5) ].
N-(2-Phenylethyl)morpholine (1b): In order to isolate the alkylamine 1b,
the enamine was hydrolyzed in a stirred biphasic mixture of HCl (5%) and
CH2Cl2. The phases were separated and the organic layer was washed twice
with HCl (5%). The combined aqueous phases were neutralized by the
addition of NaOH up to pH ˆ 9 and extracted three times with dichloro-
methane. The combined organic layers were dried with MgSO4, and the
solvent was removed by distillation. GC yield: 14%; isolated yield: 6%
(50 mg); 1H NMR (360 MHz, 258C, CDCl3): d ˆ 7.20 (m, 2H, H3), 7.13 (m,
(E)-N-[2-(4-Methoxyphenyl)ethenyl]morpholine (5a): GC yield: 50%;
‡
‡
‡
‡
MS: m/z: 219 [M ], 204 [M
CH3], 174 [M
C2H5O], 160 [M
‡
‡
C3H7O], 135 [(CH3O C6H4 C2H4) ], 121 [(CH3O C6H4 CH2) ], 100
[(OC4H8N CH2) ].
‡
N-[2-(4-Methoxyphenyl)ethyl]morpholine (5b): The isolation was per-
formed according to the general procedure, and the product was purified by
column chromatography (hexane/ethyl acetate 10:1). GC yield (before
hydrogenation): 12%; GC yield (after hydrogenation): 62%; isolated yield:
3
2H, H2), 7.11 (m, 1H, H4), 3.66 (t, J(H,H) ˆ 4.58 Hz, 4H, O CH2), 2.72
3
(m, 2H, Ph CH2CH2), 2.53 (m, 2H, Ph CH2), 2.44 (t, J(H,H) ˆ 4.58 Hz,
3
33% (321 mg); 1H NMR (360 MHz, 258C, CDCl3): d ˆ 7.08 (d, J(H,H) ˆ
4H, N CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ 140.1 (C1), 128.6
(C3), 128.5 (C2), 126.1 (C4), 66.9 (O C), 60.8 (Ph-C-C), 53.7 (N C), 33.3
7.8 Hz, 2H, H2), 6.79 (d, 3J(H,H) ˆ 7.8 Hz, 2H, H3), 3.73 (s, 3H, OCH3),
3.70 (t, 3J(H,H) ˆ 4.4 Hz, 4H, CH2 O), 2.70 (m, 2H, Ph CH2CH2), 2.52
(m, 2H, PhCH2), 2.48 (m, 4H, N CH2); 13C{1H} NMR (91 MHz, 258C,
CDCl3): d ˆ 157.9 (C1), 132.1 (C4), 129.5 (C2), 113.7 (C3), 66.9 (C O), 61.0
(PhCH2CH2N), 55.1 (O CH3), 53.6 (N C), 32.3 (Ph CH2).
‡
‡
‡
(Ph C); MS: m/z: 191 [M ], 160 [M
100 [M
CH3O], 130 [C6H5 C2H2NCH ],
‡
‡
‡
C6H5 CH2], 91 [(C6H5 CH2) ], 77 [(C6H5) ].
Reaction of morpholine with 4-methylstyrene: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 4-methylstyrene (2.08 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
Reaction of morpholine with 3,4-dimethoxystyrene: According to the
general procedure, morpholine (0.38 mL, 4.4 mmol), 3,4-dimethoxystyrene
(2.89 g, 17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
(E)-N-[2-(4-Methylphenyl)ethenyl]morpholine (2a): GC yield: 76%; MS:
‡
‡
‡
‡
203 [M ], 188 [M
CH3], 144 [M
C3H7N], 130 [M
C4H9N], 118
(E)-N-[2-(3,4-Dimethoxyphenyl)ethenyl]morpholine (6a): GC yield:
‡
‡
‡
‡
[(CH3 C6H4 C2H3) ].
55%; MS: m/z: 249 [M ], 234 [M
CH3], 218 [M
OCH3].
N-[2-(4-Methylphenyl)ethyl]morpholine (2b): The isolation was per-
formed according to the general procedure, and the product was purified
by column chromatography (hexane/ethyl acetate 10:1). GC yield (before
hydrogenation): 15%; GC yield (after hydrogenation): 91%; isolated yield:
N-[2-(3,4-Dimethoxyphenyl)ethyl]morpholine (6b): The isolation was
performed according to the general procedure, and the product was
purified by column chromatography (hexane/ethyl acetate 10:1). GC yield
(before hydrogenation): 26%; GC yield (after hydrogenation): 81%;
isolated yield: 32% (353 mg); 1H NMR (360 MHz, 258C, CDCl3): d ˆ 6.75
(m, 3H, arom. H), 3.83 (s, 3H, OCH3), 3.82 (s, 3H, C4 OCH3), 3.71 (t,
3J(H,H) ˆ 4.4 Hz, 4H, CH2 O), 2.72 (m, 2H, PhCH2CH2), 2.55 (m, 2H,
PhCH2CH2), 2.50 (m, 4H, N CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3):
d ˆ 148.8 (C3), 147.3 (C4), 132.7 (C1), 120.4 (C6), 112.0 (C5), 111.3 (C2),
66.9 (C O), 60.9 (Ph-C-C), 55.8 (OCH3), 55.7 (OCH3), 53.6 (N C), 32.8
1
59% (532 mg); H NMR (360 MHz, 258C, CDCl3): d ˆ 7.09 (s, 4H, arom.
H), 3.74 (t, 3J(H,H) ˆ 4.4 Hz, 4H, CH2 O), 2.76 (m, 2H, PhCH2CH2), 2.57
(m, 2H, PhCH2), 2.52 (m, 4H, N CH2), 2.31 (s, 3H, CH3); 13C{1H} NMR
(91 MHz, 258C, CDCl3): d ˆ 137.0 (C1), 135.5 (C4), 129.0 (C3), 128.5 (C2),
66.9 (C O), 60.9 (PhCH2CH2), 53.7 (N C), 32.8 (PhCH2), 20.9 (CH3); MS:
‡
‡
m/z: 205 [M ], 100 [(O(CH2)4NCH2) ].
‡
‡
(Ph C); MS: m/z: 251 [M ], 100 [(O(CH2CH2)2NCH2) ].
Reaction of morpholine with 3-methylstyrene: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 3-methylstyrene (2.08 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
Reaction of morpholine with 2-vinylnaphthalene: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 2-vinylnaphthaline (2.71 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
(E)-N-[2-(3-Methylphenyl)ethenyl]morpholine (3a): GC yield: 62%; MS:
‡
‡
‡
‡
m/z: 203 [M ], 188 [M
CH3], 144 [M
C3H7O], 130 [M
C4H10O],
(E)-N-[2-(2-Naphthyl)ethenyl]morpholine (10a): GC yield: 26%; MS: m/
‡
‡
‡
‡
118 [(CH3C6H4C2H4) ].
z: 239 [M ], 180 [M
CH2CH2OCH3], 154 [(C10H7CHCH2) ], 141
‡
‡
[(C10H7CH2) ], 127 [(C10H7) ].
N-[2-(3-Methylphenyl)ethyl]morpholine (3b): The isolation of 3b was
performed according to the general procedure, and the product was
purified by column chromatography (hexane/ethyl acetate 10:1). GC yield
(before hydrogenation): 14%; GC yield (after hydrogenation): 76%;
isolated yield: 40% (361 mg); 1H NMR (360 MHz, 258C, CDCl3): d ˆ 7.17
(t, 3J(H,H) ˆ 7.7 Hz, 1H, H5), 7.02 (m, 3H, H2, H4, H6), 3.75 (t, 3J(H,H) ˆ
4.4 Hz, 4H, CH2 O), 2.77 (m, 2H, PhCH2CH2), 2.59 (m, 2H, PhCH2), 2.54
N-[2-(2-Naphthyl)ethyl]morpholine (10b): The isolation was performed
according to the general procedure, and the product was purified by
column chromatography (hexane/ethyl acetate 10:1). GC yield (before
hydrogenation): 2%; GC yield (after hydrogenation): 28%; isolated yield:
1
17% (180 mg); H NMR (360 MHz, 258C, CDCl3): d ˆ 7.89 ± 7.81 (m, 3H,
3
3
H4, H5, H8), 7.73 (s, 1H, H1), 7.47 (quint d, J(H,H) ˆ 7.0 Hz, J(H,H) ˆ
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1315 $ 17.50+.50/0
1315

M. Beller et al.
FULL PAPER
1.5 Hz, 2H, H6, H7), 7.36 (dd, 3J(H,H) ˆ 8.0 Hz, 3J(H,H) ˆ 1.5 Hz, 1H,
H3), 3.78 (m, 4H, C O), 2.71 (m, 2H, Ph CH2CH2), 2.99 (m, 4H, N CH2),
2.58 (m, 2H, Ph CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ 133.5
(C2). 132.0 (C8a), 130.8 (C4a), 127.5 (C3), 127.3 (C5, C8), 127.3 (C4), 126.8
(C1), 125.9 (C7), 125.2 (C6), 66.9 (C O), 60.6 (s, Ph-C-C), 53.65 (N C),
(before hydrogenation): 2%; GC yield (after hydrogenation): 23%;
isolated yield: 7% (79 mg); 1H NMR (360 MHz, 258C, CDCl3): d ˆ 7.47
(m, 2H, H4, H2), 7.40 (m, 2H, arom. H5, H6), 3.76 (t, 3J(H,H) ˆ 4.4 Hz,
4H, CH2 O), 2.87 (m, 2H, Ph CH2CH2), 2.61 (m, 2H, PhCH2), 2.54 (m,
4H, N CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ 141.2 (C1), 132.1
‡
‡
33.32 (Ph C); MS: m/z: 241 [M ], 155 [(C10H7CH2CH2) ], 141
(arom. C6), 130.9 (C3), 128.8 (C5), 125.3 (C2), 123.0 (C4), 66.9 (CH) O),
‡
‡
‡
‡
[(C10H7CH2) ], 127 [(C10H7) ], 100 [(O(CH2CH2)2NCH2) ].
60.2 (Ph CH2CH2), 53.6 (PhCH2), 33.3 (N CH2); MS: m/z: 258 [M
100 [(CH2N(C2H4)2O) ].
H],
‡
Reaction of morpholine with 4-vinylbiphenyl: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 4-vinylbiphenyl (3.19 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
Reaction of N-(4-fluorophenyl)-piperazine with styrene: According to the
general procedure, 1-(4-fluorophenyl)piperazine (792 mg, 4.4 mmol), styr-
ene (2.0 mL, 17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3
(58 mg, 0.22 mmol) were allowed to react in THF (10 mL) in a pressure
tube at 1208C.
(E)-N-[2-(4-Biphenyl)ethenyl]morpholine (11a): GC yield: 12%; MS: 265
‡
‡
‡
[M ], 206 [M
CH2CH2OCH3], 180 [C6H5C6H4CH2CH ].
1-(4-Fluorophenyl)-4-(2-phenyl-1-ethenyl)piperazine (12a): GC yield:
N-[2-(4-Biphenyl)ethyl]morpholine (11b): The isolation was performed
according to the general procedure, and the product was purified by
column chromatography (hexane/ethyl acetate/NEt3 1:1:0.01). GC yield
(before hydrogenation): 2%; GC yield (after hydrogenation): 14%;
‡
‡
‡
52%; MS: m/z: 282 [M ], 191 [M
CH Ph], 150 [M
CH2
N
CHCH Ph], 122, 70.
1-(4-Fluorophenyl)-4-(2-phenyl-1-ethyl)piperazine (12b): The isolation
was performed according to the general procedure, and the product was
purified by column chromatography (hexane/ethyl acetate 3:1). GC yield
(before hydrogenation): 4%; GC yield (after hydrogenation): 56%;
1H NMR (400 MHz, CDCl3, 258C): d ˆ 7.10 ± 7.25 (m, 5H, arom. H1, H2,
H3), 6.80 ± 6.95 (m, 4H, FC6H4) 2.55 ± 3.30 (m, 12H, Ph CH2CH2 ,
N CH2); 13C{1H} NMR (100 MHz, CDCl3, 258C): d ˆ 157.6 (d, 1J(C,F) ˆ
239 Hz, F C), 148.3 (arom. C4), 140.5 (arom. C1), 129.1 (arom. C4), 128.8
1
isolated yield: 6% (70 mg); H NMR (360 MHz, 258C, CDCl3): d ˆ 7.81 ±
7.77 (m, 1H, H8), 7.71 ± 7.44 (m, 6H, H3, H6, H7), 7.36 (m, 2H, H2), 3.80 (t,
3J(H,H) ˆ 4.4 Hz, 4H, CH2 O), 2.89 (m, 2H, Ph-C-C), 2.68 (m, 2H,
Ph CH2), 2.54 (m, 4H, N C); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ
141.0 (C1), 139.3 (C5), 139.07 (C4), 129.11 (C7), 128.74 (C2), 127.14 (C8),
127.10 (C6), 126.98 (C3), 66.98 (C O), 60.79 (Ph-C-C), 53.72 (N C), 32.94
(Ph C).
3
Reaction of morpholine with 4-fluorostyrene: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 4-fluorostyrene (2.15 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
(arom. C3), 126.5 (arom. C2), 118.3 (d, J(C,F) ˆ 8 Hz, FC-C-C), 115.9 (d,
2J(C,F) ˆ 22 Hz, FC C), 60.8 (Ph CH2CH2), 53.6 (N CH2), 50.6 (PhCH2),
‡
‡
‡
34.0 (N CH2); MS: m/z: 284 [M ], 207 [M
Ph], 193 [M
CH2 Ph],
150, 122, 70.
(E)-N-[2-(4-Fluorophenyl)ethenyl]morpholine (7a): GC yield: 60%; MS:
Reaction of N-(3-trifluoromethylphenyl)piperazine with styrene: Accord-
ing to the general procedure, 1-(3-trifluoromethylphenyl)piperazine
(1.01 g, 4.4 mmol), styrene (2.0 mL, 17.6 mmol), [Rh(cod)2]BF4 (45 mg,
0.11 mmol), and PPh3 (58 mg, 0.22 mmol) were allowed to react in THF
(10 mL) in a pressure tube at 1208C.
‡
‡
‡
m/z: 207 [M ], 176[M
[(FC6H4C2H2NCH2) ], 122 [(FC6H4C2H2) ].
CH3O], 149 [(FC6H4C2H2N(CH2)2) ], 135
‡
‡
N-[2-(4-Fluorophenyl)ethyl]morpholine (7b): The isolation was performed
according to the general procedure, and the product was purified by
column chromatography (hexane/ethyl acetate 5:1). GC yield (before
hydrogenation): 19%; GC yield (after hydrogenation): 79%; isolated yield:
1-(3-Trifluoromethylphenyl)-4-(2-phenyl-1-ethenyl)piperazine (14a): GC
‡
‡
‡
yield: 33 %; MS: m/z:332 [M ], 241 [M
CH Ph], 200 [M
1
55% (506 mg); H NMR (360 MHz, 258C, CDCl3): d ˆ 7.15 (m, 2H, H3),
CH2 N CHCH Ph], 130, 117.
6.96 (t, 3J(H,H) ˆ 3J(H,F) ˆ 8.9 Hz, 2H, H2), 3.74 (t, 3J(H,H) ˆ 4.4 Hz, 4H,
CH2 O), 2.77 (m, 2H, PhCH2CH2), 2.57 (m, 2H, PhCH2), 2.51 (m, 4H,
N CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ 161.5 (d, 1J(C,F) ˆ
242.6 Hz, C1), 135.8 (C4), 130.0 (d, 3J(C,F) ˆ 10.1 Hz, C3), 115.23 (d,
2J(C,F) ˆ 21.2 Hz, C2), 67.0 (C O), 60.8 (Ph-C-C), 53.7 (N CH2), 32.5
1-(3-Trifluoromethylphenyl)-4-(2-phenyl-1-ethyl)piperazine (14b): The
isolation was performed according to the general procedure, and the
product was purified by column chromatography (hexane/ethyl acetate
1:1). GC yield (before hydrogenation): 2%; GC yield (after hydrogena-
tion): 35%; 1H NMR (400 MHz, CDCl3, 258C): d ˆ 7.41 ± 7.08 (m, 9H,
arom. H), 3.38 ± 3.26 (m, 4H, N CH2), 2.96 ± 2.85 (m, 2H, Ph CH2CH2),
2.78 ± 2.62 (m, 6H, PhCH2, N CH2); 13C{1H} NMR (100 MHz, CDCl3,
258C): d ˆ 151.9 (arom. C1, arom C N), 140.6 (arom. C), 132.6 ± 131.4 (q,
2J(C,F) ˆ 19 Hz, CF3 C), 130.1 (arom. C), 129.2 (arom. C3), 129.0(arom.
C2), 126.7 (arom. C4), 128.9 ± 120.8 (q, 1J(C,F) ˆ 273 Hz, CF3), 119.1 (arom.
C), 115.4 (q, 3J(C,F) ˆ 4 Hz, CF3-C-C), 112.6 (q, 3J(C,F) ˆ 4 Hz, CF3-C-C),
60.1 (Ph CH2CH2), 53.6 (N CH2), 34.1 (N CH2), 49.2 (PhCH2); MS (CI,
‡
‡
(PhCH2); MS: m/z: 209 [M ], 100 [(O(CH2CH2)2NCH2) ].
Reaction of 4-chlorostyrene with morpholine: According to the general
procedure, morpholine (0.38 mL, 4.4 mmol), 4-chlorostyrene (2.44 g,
17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
(E)-N-[2-(4-Chlorophenyl)ethenyl]morpholine (8a): GC yield: 31%; MS:
‡
‡
‡
‡
m/z: 223 [M ], 192 [M
CH3O], 164 [M
C3H7O], 130 [M
Cl
‡
‡
‡
C3H7O].
70 eV): m/z: 334 [M ], 243 [M
CH2 Ph], 200, 172, 145 [Ph CF3 ], 105,
91, 70.
(E)-N-[2-(4-chlorophenyl)ethyl]morpholine (8b): The isolation was per-
formed according to the general procedure, and the product was purified by
column chromatography (hexane/ethyl acetate 10:1). GC yield (before
hydrogenation): 7%; GC yield (after hydrogenation): 38%; isolated yield:
Reaction of N-(2-methoxyphenyl)piperazine with styrene: According to
the general procedure, 1-(2-methoxyphenyl)piperazine (845 mg,
4.4 mmol), styrene (2.0 mL, 17.6 mmol), [Rh(cod)2]BF4 (45 mg,
0.11 mmol), and PPh3 (58 mg, 0.22 mmol) were allowed to react in THF
(10 mL) in a pressure tube at 1208C.
1
3
20% (198 mg); H NMR (360 MHz, 258C, CDCl3): d ˆ 7.31 (d, J(H,H) ˆ
3
3
8.35 Hz, 2H, H2), 7.20 (d, J(H,H) ˆ 8.35 Hz, 2H, H3), 3.80 (t, J(H,H) ˆ
4.9 Hz, 4H, O CH2), 2.83 (m, 2H, PhCH2CH2N), 2.65 (m, 2H, Ph CH2),
2.58 (m, 4H, N CH2); 13C{1H} NMR (91 MHz, 258C, CDCl3): d ˆ 167.9
(C4), 132.9 (C1), 129.7 (C2), 114.2 (C3), 67.4 (C O), 61.4 (Ph-C-C), 53.9
1-(2-Methoxyphenyl)-4-(2-phenyl-1-ethenyl)piperazine (15a): GC yield:
31%; MS: m/z: 294 [M ], 203 [M
CHCH Ph], 130, 117.
‡
‡
‡
CH Ph], 162 [M
CH2
N
‡
(C N), 32.5 (Ph C); MS: m/z: 225 [M ], 207, 164, 130.
1-(2-Methoxyphenyl)-4-(2-phenyl-1-ethyl)piperazine (15b): The isolation
was performed according to the general procedure, and the product was
purified by column chromatography (hexane/ethyl acetate 3:1). GC yield
(before hydrogenation): <0.1%; GC yield (after hydrogenation): 31%;
1H NMR (400 MHz, CDCl3, 258C): d ˆ 7.17 ± 7.33 (m, 5H, arom. H), 6.83 ±
7.03 (m, 4H, arom. H), 3.37 (s, 3H, CH3), 3.07 ± 3.19 (m, 4H, N CH2),
2.80 ± 2.89 (m, 2H, Ph-CH2-CH2), 2.62 ± 2.72 (Ph CH2, N CH2); 13C{1H}
NMR (100 MHz, CDCl3, 258C): d ˆ 152.7 (arom. C OMe), 141.7 (arom.
C N), 140.7 (arom. C CH2), 129.1 (arom. C3), 128.8 (arom. C2), 126.5
(arom. C4), 123.3 (arom. C), 121.4 (arom. C), 118.6 (arom. C), 111.6 (arom.
C), 61.0 (Ph-C-C), 55.7 (CH3), 53.8 (N C), 51.5 (N C), 34.0 (Ph C); MS:
Reaction of morpholine with 3-trifluoromethylstyrene: According to the
general procedure, morpholine (0.38 mL, 4.4 mmol), 3-trifluoromethylstyr-
ene (3.0 g, 7.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3 (58 mg,
0.22 mmol) were refluxed in THF (10 mL).
(E)-N-[2-(3-Trifluoromethylphenyl)ethenyl]morpholine (9a): GC yield:
‡
‡
‡
‡
21%; MS: m/z: 257 [M ], 238 [M
F] 198 [M
C3H7O], 185 [M
‡
‡
CH2CH2OCH2CH2], 172 [(CF3PhC2H5) ], 151 [(CF2PhC2H5) ].
N-[2-(3-Trifluoromethylphenyl)ethyl]morpholine (9b): The isolation was
performed according to the general procedure, and the product was
purified by column chromatography (hexane/ethyl acetate 10:1). GC yield
1316
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1316 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Hydroamination
1306±1319
‡
‡
‡
m/z: 296 [M ], 205 [M
105, 91, 70.
CH2 Ph], 190 [M
CH3 CH2 Ph], 162, 120,
0.41 mmol) were dissolved in THF (2 mL) and stirred for 10 min. AgCl
was filtered off from the clear orange solution which was then cooled to
08C. Morpholine (78 mg, 0.90 mmol) was added and the solution was
stirred for several min at 08C. The yellow precipitate which had formed was
washed with THF (2 Â 1 mL) and pentane (3 Â 1 mL). Finally, the product
was dried in vacuo. Yield: 151 mg (80%); 1H NMR (400 MHz, CD2Cl2,
258C): d ˆ 4.02 (s, 4H, CH(cod)), 3.75 (s, 8H, CH2 O), 3.43 (s, 2H, NH),
2.87 (s, 8H, CH2 N), 2.44 (d, 3J(H,H) ˆ 8.5 Hz, 4H, CH2(cod)), 1.83 (d,
3J(H,H) ˆ 8.5 Hz, 4H, CH2(cod)); 13C{1H } NMR (100 MHz, CD2Cl2,
258C): d ˆ 83.0 (d, 1J(Rh,C) ˆ 12.9 Hz, C(cod)), 68.2 (C O), 49.9 (C N),
31.6 (CH2(cod)); IR (KBr): nÄ ˆ 3266 (m), 3190 (s), 3016 (w), 2953 (s), 2934
Reaction of N-(3-methylphenyl)piperazine with styrene: According to the
general procedure, 1-(3-methylphenyl)piperazine (774 mg, 4.4 mmol),
styrene (2.0 mL, 17.6 mmol), [Rh(cod)2]BF4 (45 mg, 0.11 mmol), and PPh3
(58 mg, 0.22 mmol) were allowed to react in THF (10 mL) in a pressure
tube at 1208C.
1-(3-Methylphenyl)-4-(2-phenyl-1-ethenyl)piperazine (13a): GC yield:
37%; MS: m/z: 278 [M ], 207 [M
CHCH Ph], 117.
‡
‡
‡
CH Ph], 146 [M
CH2
N
1-(3-Methylphenyl)-4-(2-phenyl-1-ethyl)piperazine (13b): The isolation
was performed according to the general procedure, and the product was
purified by column chromatography (hexane/ethyl acetate 3:1). GC yield
(before hydrogenation): <0.1%; GC yield (after hydrogenation): 37%;
1H NMR (400 MHz, CDCl3, 258C): d ˆ 7.25 ± 7.10 (m, 5H, arom. H), 7.08 (t,
3J(H,H) ˆ 8.0 Hz, 1H), 6.60 (s, 1H, arom. H), 6.71 (d, 3J(H,H) ˆ 8.0 Hz,
2H, arom. H), 3.20 ± 3.13 (m, 4H, N CH2), 2.83 ± 2.76 (m, 2H, Ph-C-CH2),
2.66 ± 2.57 (m, 6H, N CH2, Ph CH2), 2.24 (s, 3H, CH3); 13C{1H} NMR
(100 MHz, CDCl3, 258C): d ˆ 151.7 (arom. C N), 140.6 (arom. C CH2),
139.2 (arom. C CH3), 129.3 (arom. N-C-CH2), 129.1 (arom. Cmeta), 128.8
(arom. Cortho), 126.5 (arom. Cpara), 121.1 (arom. C), 117.3 (arom. C), 113.6
(arom. C), (arom. C), 61.0 (Ph-C-C), 53.8 (N C), 49.6 (N C), 34.0 (Ph C),
(s), 2860 (s), 2829 (m), 1452 (m), 1438 (m), 1250 (m), 1202 (m), 1114 (ss),
1
1069 (ss), 1037 (ss), 880 cm
(s); MS (FD, CD2Cl2): m/z: 383
‡
‡
[Rh(cod){(morpholine)2 } ] , 298 [Rh(cod)(morpholine) ] ;
C16H30BF4N2O2Rh (472.14): calcd C 40.7, H 6.4, N 5.9; found C 40.3, H
6.6, N 6.2.
[(1,2,5,6-h)-1,5-Cyclooctadien]bis[N-(N'-4-fluorophenyl)piperazine]rho-
dium(i) tetrafluoroborate (21): [{Rh(cod)Cl}2] (100 mg, 0.20 mmol) and
AgSO3CF3 (104 mg, 0.41 mmol) were dissolved in THF (2 mL) and stirred
for 10 min. AgCl was filtered off from the clear orange solution which was
then cooled to 08C. 4-Fluorophenylpiperazine (81 mg, 0.45 mmol) was
added and the solution was stirred for several min at 08C. The yellow
precipitate which had formed was washed with THF (2 Â 1 mL) and
pentane (3 Â 1 mL). Finally, the product was dried in vacuo. Yield: 224 mg
(85%); 1H NMR (400 MHz, 258C, CDCl3): d ˆ 6.94 (t, 3J(H,H) ˆ 8.6 Hz,
4H, arom. H3), 6.83 (m, 4H, arom. H2), 3.94 (brs, 4H, CH(cod)), 3.10 (brs,
16H, N-CH2-CH2-N), 2.4 (s, 4H, CH2(cod)), 1.74 (d, 3J(H,H) ˆ 5.2 Hz, 4H,
CH2(cod)); 13C{1H} NMR (100.6 MHz, 258C, CDCl3): d ˆ 157.9 (d,
1J(C,F) ˆ 241.1 Hz, arom. C F), 115.7 (d, 2J(C,F) ˆ 22.3 Hz, arom. C2),
118.7 (d, 3J(C,F) ˆ 7.8 Hz, arom. C3), 146.9 (arom. C4), 88.7 (br, CH(cod)),
50.4 (br, Ph NCH2), 45.9 (br, HNCH2), 30.4 (br, CH2(cod)); IR (KBr): nÄ ˆ
3252 (m), 3179 (s), 2934 (s), 2878 (m), 2823 (s), 1512 (ss), 1448 (s), 1235 (ss),
‡
‡
22.2 (CH3); MS: m/z: 280 [M ], 189 [M
CH2 Ph], 146, 70.
Reaction of piperidine with styrene: [Rh(cod)2]BF4 (45 mg, 0.11 mmol) and
PPh3 (58 mg, 0.22 mmol) were suspended in 10.0 mL toluene. Subsequent-
ly, piperidine (4.4 mmol) was added and a clear yellow solution was
obtained. Styrene (5.0 mL, 44.0 mmol) was added and the reaction mixture
was refluxed for 20 h.
N-(2-Phenylethyl)piperidine (16): The isolation is analogous to that of 1b;
GC yield 5%; 1H NMR (360 MHz, 258C, CDCl3): d ˆ 7.1 (m, 5H, arom. H),
2.7 (m, 2H, PhCH2CH2N), 2.5 (m, 2H, PhCH2), 2.4 (s, 4H, N CH2), 1.5 (s,
6H, N-CH2-CH2-CH2); 13C NMR (91 MHz, 258C, CDCl3): d ˆ 140.2 (C1),
128.4 (C3), 126.8 (C2), 125.6 (C4), 61.1 (Ph-C-C), 54.2 (N C), 33.3 (Ph C),
1
‡
‡
1162 (s), 1062 (ss), 825 cm (ss); MS (FAB): m/z: 571 [M ], 391 [M
‡
F Ph N(CH2)4NH], 211 [Rh(cod) ]; C28H38BF6N4Rh (658.34): calcd C
52.6, H 6.4, N 7.8; found C 52.4, H 6.3, N 8.4.
‡
‡
26.6 (N-C-C), 24.5 (N-C-C-C); MS: m/z: 187 [M ], 98 [(CH2N(CH2)5) ].
1-Deutero-phenylacetaldehydedimethylacetal (17): 1-Deutero-phenyl-
acetaldehydedimethylacetal was prepared from 2-benzyl-1,3-dithian
(3.58 g, 17 mmol), which was synthesized according to ref. [21], n-butyl-
lithium (12 mL, 1.6m), D2O (0.33 mL, 18 mmol), HgCl2 (4.34 g, 17 mmol),
and HgO (1.73 g, 9 mmol) in methanol (100 mL). 1H NMR (270 MHz,
258C, CDCl3): d ˆ 7.41 ± 7.21(m, 5H, arom. H), 3.35 (s, 6H, OCH3), 2.93 (s,
2H, Ph CH2); 13C{1H} NMR (67.9 MHz, 258C, CDCl3): d ˆ 137.0 (arom.
Cipso), 129.0 (arom. Cortho), 128.3 (arom. Cmeta), 126.3 (arom. Cpara), 104.8 (t,
3J(C,D) ˆ 26.4 Hz), 53.2 (OCH3), 39.5 (Ph CH2).
Kinetic studies: In a typical experiment, the catalyst, consisting of
[Rh(cod)2]BF4 and PPh3, was suspended in THF (30 mL) under argon.
Subsequently, morpholine (0.38 mL, 4.4 mmol) and hexadecane (0.1 mL)
were added at room temperature. The mixture was stirred and heated to
reflux. Styrene was added to the hot mixture, which indicated the beginning
of the experiment.
Variation of the olefin: [Rh(cod)2]BF4 (45 mg, 0.11 mmol), PPh3 (58 mg,
0.22 mmol), morpholine (0.38 mL, 4.4 mmol), and THF (25 mL) were used.
The amount of styrene was varied (35, 44, 53, or 62 mmol).
N-(1-Deutero-2-phenylethenyl)morpholine (18): 1-Deutero-phenylacetal-
dehydedimethylacetal (1.28 g, 8 mmol) was stirred in dioxane (10 mL) and
HCl (5%, 10 mL) for 1 h. Subsequently, the phases were separated, and the
aqueous phase was washed two times with dichloromethane (5 mL). The
combined organic phases were dried over MgSO4, and the solvent was
removed in vacuo. The aldehyde product was immediately converted to the
enamine (18) by the addition of morpholine (0.70 mL, 80 mmol)[22] in
toluene (50 mL) and p-toluenesulfonic acid (5 mg). The enamine was
distilled in vacuo (1488C, 0.1 mbar). Yield: 53% (0.81 mg); 1H NMR
(270 MHz, 258C, CDCl3): d ˆ 7.26 ± 7.20 (m, 4H, arom. H), 7.06 (m, 1H,
Variation of the amine: [Rh(cod)2]BF4 (45 mg, 0.11 mmol), PPh3 (58 mg,
0.22 mmol), styrene (5.0 mL, 44 mmol) and THF (25 mL) were used. The
amount of morpholine was varied (1.1, 2.2, 3.3, or 4.4 mmol).
Variation of the catalyst: Morpholine (0.38 mL, 4.4 mmol), styrene (5.0 mL,
44 mmol), and THF (25 mL) were used. The catalyst was varied:
[Rh(cod)2]BF4 (18 mg, 0.04 mmol), PPh3 (23 mg, 0.08 mmol) or
[Rh(cod)2]BF4 (45 mg, 0.11 mmol), PPh3 (58 mg, 0.22 mmol), or
[Rh(cod)2]BF4 (180 mg, 0.44 mmol), PPh3 (232 mg, 0.88 mmol).
The reaction samples (0.1 mL) were removed from the refluxing reaction
mixture with a syringe through a septum. The yields were determined by
GC analysis with hexadecane as an internal standard. All the data collected
could be convincingly fit over approximately three half-lives (R > 0.98) by
least-squares to 1 equiv, where c is the concentration at time t of the
alkylamine, enamine, and ethylbenzene respectively. The order of the
reaction ni is determined by a logarithmic plot according to Equation (2), in
which cj0 is the initial concentration of the component j (j ˆ styrene,
morpholine, catalyst).
3
arom. Hpara), 5.43 (s, 1H, Ph CH), 3.77 (t, J(H,H) ˆ 4.8 Hz, 4H, OCH2),
3.03 (t, 3J(H,H) ˆ 4.8 Hz, 4H, NCH2); 2H{1H} NMR (41.5 MHz, 258C,
CHCl3): d ˆ 6.66 (CD N).
N-Deuterated amines: [D1]piperidine (19a), [D1]morpholine (19b),
[D1]di-iso-propylamine (19c): The amine (piperidine, morpholine, or di-
iso-propylamine; 160 mmol) was dissolved in pentane (100 mL) and cooled
to
788C. n-Butyllithium (100 mL, 1.2 equiv) in hexane was added
dropwise. The mixture was warmed to room temperature, the lithium
amide was then filtered off and washed with pentane (2 Â 30 mL).
Subsequently, the lithium amide was dissolved in a mixture of diethylether
(10 mL) and pentane (10 mL) and cooled to 08C. [D1]Acidic acid (8 mL,
140 mmol) was added dropwise. Distillation afforded the N-deuterated
products: [D1]piperidine (19a): 74 mmol; [D1]morpholine (19b): 86 mmol;
[D1]di-iso-propylamine (19c): 69 mmol. The degree of deuteration
vi t ˆ ci
(1)
(2)
ni
vi ꢀ c
j0
Crystallography: Crystals were grown by the slow diffusion of Et2O into a
solution of 20 in CH2Cl2. A yellow needle of dimensions 0.76 Â 0.13 Â
0.08 mm was mounted on the tip of a glass fiber. Cell constants were
determined by least-squares refinement of 1998 reflections in the range
27.28 < 2q < 51.78 with the program CELL.[23] Crystal data: orthorhombic
1
2
(>98%) was checked by H and H NMR spectroscopy.
[(1,2,5,6-h)-1,5-Cyclooctadien]bis(morpholine)rhodium(i)-tetrafluorobo-
rate (20): [{Rh(cod)Cl}2] (100 mg, 0.20 mmol) and AgBF4 (80 mg,
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1317 $ 17.50+.50/0
1317

M. Beller et al.
FULL PAPER
P212121; a ˆ 6.6940(4), b ˆ 15.0855(10), c ˆ 18.7192(14) Š; V ˆ
1890.3(2) Š3; formula unit ˆ C16H30BF4N2O2Rh with Z ˆ 4; FWˆ 472.14;
Faraday Trans. I 1993, 89, 3513; e) P. Fink, J. Datka, J. Chem. Soc.
Faraday Trans. I 1989, 85, 3079; f) M. Deeba, M. E. Ford, T. A.
Johnson, J. Chem. Soc. Chem. Commun. 1987, 8, 562.
F(000) ˆ 968; m(MoKa) ˆ 9.54 cm 1; l(MoKa) ˆ 0.71073 Š; 1calcd
ˆ
1.659 gcm 3. Preliminary examination and data collection were carried
out on an imaging plate diffraction system (IPDS; Stoe & Cie) equipped
with a rotating anode (NONIUS FR591; 50 kV; 80 mA) and graphite
monochromator. The data were collected at 163(1) K with the use of liquid
nitrogen cold stream low-temperature apparatus and with an exposure time
of 6.0 min per image (rotation scan modus from f ˆ 0.0 ± 1608 with Df ˆ
18). 11316 Reflections were collected (2.918 < q < 25.618) of which 11274
were observed. Final full-matrix least-squares refinement (on F 2) based on
3491 unique reflections of which 3488 were used converged with 325
variable parameters and 1 restraint. Non-hydrogen atoms were refined
anisotropically, hydrogen atoms were refined isotropically with U(H) ˆ
1.2Ueq(parent atom). R1 ˆ 0.0187, for F 2 > 2s(F 2); wR2 ˆ 0.0459;[24] GoF
[5] For hydroamination mediated by early transition metals, see: a) P. L.
McGrane, T. Livinghouse, J. Am. Chem. Soc. 1993, 115, 11485;
b) A. M. Baranger, P. J. Walsh, R. G. Bergman, J. Am. Chem. Soc.
1993, 115, 2753; c) P. J. Walsh, F. J. Hollander, R. G. Bergman,
Organometallics 1993, 12, 3705; d) P. L. McGrane, T. Livinghouse, J.
Org. Chem. 1992, 57, 1323; e) P. L. McGrane, M. Jensen, T. Living-
house, J. Am. Chem. Soc. 1992, 114, 5459; f) P. J. Walsh, A. M.
Baranger, R. G. Bergman, J. Am. Chem. Soc. 1992, 114, 1708; g) P. J.
Walsh, F. J. Hollander, R. G. Bergman, J. Am. Chem. Soc. 1988, 110,
8729.
[6] For hydroamination catalyzed by lanthanoid complexes, see: a) Y. Li,
T. J. Marks, J. Am. Chem. Soc. 1998, 120, 1757; b) Y. Li, T. J. Marks, J.
Am. Chem. Soc. 1996, 118, 9295; c) Y. Li, T. J. Marks, J. Am. Chem.
Soc. 1996, 118, 707; d) Y. W. Li, T. J. Marks, Organometallics 1996, 15,
3770; e) C. M. Haar, C. L. Stern, T. J. Marks, Organometallics 1996, 15,
1765; f) E. L. Eliel, S. H. Wilen, L. N. Mander, Stereochemistry of
Organic Compounds, Wiley, New York, 1994, p.682; g) M. A.
(F 2) ˆ 1.051; D1max ˆ 0.44, D1min
ˆ
0.37 eŠ 3. The data analysis and the
drawing were performed with the programs STRUX-V[25], SIR-92[26]
,
SHELXL-93[27] and SCHAKAL-97[28].Crystallographic data (excluding
structure factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC-112071 and 112072. Copies of the data can
be obtained free of charge on application to CCDC, 12 Union Road,
Cambridge CB21EZ, UK (fax: (‡44)1223-336-033; e-mail: depos-
it@ccdc.cam.ac.uk).
Â
Giardell, V. P. Conticello, L. Brard, M. R. Gagne, T. J. Marks, J. Am.
Chem. Soc. 1994, 116, 10241; h) M. A. Giardello, V. P. Conticello, L.
Brard, M. Sabat, A. L. Rheingold, C. L. Stern, T. J. Marks, J. Am.
Chem. Soc. 1994, 116, 10212; i) Y. Li, P. F. Fu, T. J. Marks, Organo-
Â
metallics 1994, 13, 439; j) M. R. Gagne, C. L. Stern, T. J. Marks, J. Am.
Â
Chem. Soc. 1992, 114, 275; k) M. R. Gagne, S. P. Nolan, T. J. Marks,
Â
Organometallics 1990, 9, 1716; l) M. R. Gagne, T. J. Marks, J. Am.
Chem. Soc. 1989, 111, 4108.
Acknowledgements
[7] For hydroamination by middle and late transition metals, see: a) R.
Dorta, P. Egli, F. Zürcher, A. Togni, J. Am. Chem. Soc. 1997, 119,
10857; b) Y. Tamaru, M. Hojo, H. Higashimura, Z.-I. Yoshida, J. Am.
Chem. Soc. 1988, 110, 3994; c) A. L. Casalnuovo, J. L. Calabrese, D.
Milstein, J. Am. Chem. Soc. 1988, 110, 6738; d) Y. Fukuda, K.
Utimoto, H. Nozaki, Heterocycles 1987, 25, 297; e) D. M. Gardener,
R. T. Clark, USP 4.454.321, 1984; Chem. Abstr. 1984, 101, 130217r;
f) L. S. Hegedus, J. M. McKearin, J. Am. Chem. Soc. 1982, 104, 2444;
g) B. Pugin, L. M. Venanzi, J. Organomet. Chem. 1981, 214, 125, and
references therein; h) J. Barluenga, F. Azar, R. Liz, R. J. Rodes, J.
Chem. Soc. Perkin Trans. 1980, 2732.
We thank Prof. Dr. K. Kühlein (Hoechst AG), Dr. G. Stark, and Dr. A.
Zapf (Institute for Catalysis, Rostock) for general discussions. Degussa AG,
Hoechst AG, and Heraeus are thanked for loans of precious metals. H.T.
acknowledges funding from the Fonds der Chemischen Industrie. We also
thank the Deutsche Forschungsgemeinschaft (BE 1931/3-1) for financial
support. We thank Dr. E. Herdtweck for the X-ray structure and Dr. W.
Wachter for the thermogravimetric analysis.
[8] For hydroamination by rhodium catalysts, see: a) M. Beller, M.
Eichberger, H. Trauthwein, Angew. Chem. 1997, 109, 2306; Angew.
Chem. Int. Ed. Engl. 1997, 36, 2225; b) J.-J. Brunet, G. Commenges, D.
Neibecker, K. Philippot, J. Organomet. Chem. 1994, 469, 221; c) J.-J.
Brunet, D. Neibecker, K. Philippot, Tetrahedron Lett. 1993, 34, 3877;
d) J.-J. Brunet, D. Neibecker, K. Philippot, J. Chem. Soc. Chem.
Commun. 1992, 1215; e) E. Krukowa, R. Taube, D. Steinborn,
DDP 296.909.A5, 1991; Chem. Abstr. 1992, 116, 213993b; f) D. Selent,
D. Scharfenberg-Pfeiffer, G. Reck, R. Taube, J. Organomet. Chem.
1991, 415, 417; g) D. Steinborn, B. Dies, I. Wagner, R. Taube, Z. Chem.
1989, 29, 333; h) D. Steinborn, R. Taube, Z. Chem. 1986, 26, 349;
i) D. R. Coulson, Tetrahedron Lett. 1971, 12, 429.
[1] For general references, see: a) J. March, Advanced Organic Chemistry,
4th ed., Wiley, New York, 1992, p. 768, and references therein; b) J.-J.
Brunet, D. Neibecker, F. Niedercorn, J. Mol. Catal. 1989, 49, 235;
c) J. P. Collman, L. S. Hegedus, J. R. Norton, R. G. Finke, Principles
and Applications of Organotransition Metal Chemistry, University
Sciences Books, Mill Valley, 1987, chapters 7.4 and 17.1; d) B. M. Trost,
T. R. Verhoeven in Comprehensive Organometallic Chemistry (Eds.:
G. Wilkinson, F. G. A. Stone, E. W. Abel), Pergamon, Oxford, 1982,
Vol. 8, p. 892, and references therein; e) M. S. Gibson, in The
Chemistry of the Amino Group (Ed.: S. Patai), Interscience, New
York, 1968, p. 61.
[2] For leading reviews of hydroamination, see: a) M. Beller, T. E. Müller,
Chem. Rev. 1998, 98, 675; b) R. Taube, in Applied Homogenous
Catalysis with Organometallic Compounds (Eds.: B. Cornils, W. A.
Herrmann), VCH, Weinheim, 1996, p. 507; c) D. M. Roundhill, Chem.
Rev. 1992, 92, 1; d) L. S. Hegedus, Angew. Chem. 1988, 100, 1147;
Angew. Chem. Int. Ed. Engl. 1988, 27, 1113; e) M. B. Gasc, A. Lattes,
J. J. Perie, Tetrahedron 1983, 39, 703; f) J.-E. Bäckvall, Acc. Chem. Res.
1983, 16, 335; g) V. Jäger, H. G. Viehe, Houben ± Weyl, Methoden der
Organischen Chemie, Thieme, Stuttgart, 1977, Vol 5/2a, p. 713; h) S. I.
Suminov, A. N. Kost, Russ. Chem. Rev. 1969, 38, 884; i) I. A.
Chekulaeva, I. A. Kondratꢁeva, Russ. Chem. Rev. 1965, 34, 669.
[3] For alkalimetal and base-catalyzed hydroamination, see: a) G. P. Pez,
J. E. Galle, Pure Appl. Chem. 1985, 57, 1917; b) J. Wollensak, R. D.
Closson, Org. Synth. 1963, 43, 45; c) R. Stroh, J. Ebersberger, H.
Haberland, W. Hahn, Angew. Chem. 1957, 69, 124; d) B. W. Howk,
E. L. Little, S. L. Scott, G. M. Whitman, J. Am. Chem. Soc. 1954, 76,
1899.
[9] a) L. S. Hegedus, Angew. Chem. 1988, 100, 1147; Angew. Chem. Int.
Ed. Engl. 1988, 27, 1113; b) L. S. Hegedus, J. M. McKearin, J. Am.
Chem. Soc. 1982, 104, 2444; c) L. S. Hegedus, G. F. Allen, J. J. Bozell,
E. L. Waterman, J. Am. Chem. Soc. 1978, 100, 5800; d) B. Škermark,
Â
J. E. Bäckvall, L. S. Hegedus, K. Zetterberg, K. Siirala-Hansen, K.
Sjöberg, J. Organomet. Chem. 1974, 72, 127.
[10] V. Markovnikov, C. R. Acad. Sci. 1875, 85, 668.
[11] R. C. Larock, T. R. Hightower, L. A. Hasvold, K. P. Peterson, J. Org.
Chem. 1996, 61, 3584.
[12] J. Haggin, Chem. Eng. News. 1993, 17(22), 23.
[13] C. M. Jensen, W. C. Trogler, Science 1986, 233, 1069.
[14] M. Beller, H. Trauthwein, M. Eichberger, C. Breindl, T. E. Müller, A.
Zapf, J. Organomet. Chem. 1998, 566, 277.
[15] a) G. K. Anderson, R. Kumar, Inorg. Chim. Acta 1988, 146, 89;
b) J. M. Brown, P. A. Chaloner, A. G. Kent, B. A. Murrer, P. N.
Nicholson, D. Parker, P. J. Sidebottom, J. Organomet. Chem. 1981, 216,
263; c) R. R. Schrock, J. A. Osborn, J. Am. Chem. Soc. 1971, 93, 2397.
[16] a) D. Seebach, E. J. Corey, J. Org. Chem. 1975, 40, 231; b) E. J. Corey,
D. Seebach, Angew. Chem. 1965, 77, 1134; Angew. Chem. Int. Ed.
Engl. 1965, 4, 1075.
[4] For hydroamination by acid catalysts, see: a) M. Lequitte, F. Figueras,
C. Moreau, S. Hub, J. Cat. 1996, 255; b) A. Cermona, A. Corma, M.
Â
Â
Iglesias, A. San Jose, F. Sanchez, J. Organomet. Chem. 1995, 492, 11;
c) N. Mizuno, M. Tabata, T. Uematsu, M. Iwamoto, J. Cat. 1994, 146,
249; d) N. Mizuno, M. Tabata, T. Uematsu, M. Iwamoto, J. Chem. Soc.
[17] D. Steinborn, R. Taube, Z. Chem. 1986, 26, 349.
1318
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1318 $ 17.50+.50/0
Chem. Eur. J. 1999, 5, No. 4

Hydroamination
1306±1319
[18] B. Denise, G. Pannetier, J. Organomet. Chem. 1978, 161, 171.
[19] G. Giordano, R. H. Crabtree, Inorg. Synth. 1979, 19, 218.
[20] R. R. Schrock, J. A. Osborn, J. Am. Chem. Soc. 1971, 93, 3089.
[21] D. Seebach, Synthesis 1969, 17.
[22] P. W. Hickmott, in The Chemistry of Enamines (Ed.: Z. Rappoport),
Wiley, 1994, p. 727.
[25] G. Artus, W. Scherer, T. Priermeier, E. Herdtweck, STRUX-V, A Pro-
gram System to Handle X-ray Data, TU München (Germany), 1994.
[26] A. Altomare, G. Cascarano, C. Giacovazzo, A. Guagliardi, M. C.
Burla, G. Polidori, M. Camalli, SIR-92, University of Bari (Italy),
1992.
[27] G. M. Sheldrick, SHELXL-93. Program for the Refinement of Crystal
Structrures, University of Göttingen (Germany), 1993.
[28] E. Keller, SCHAKAL-97, Albert-Ludwigs-Universität Freiburg (Ger-
many), 1997.
[23] IPDS Operating System, Version 2. 7. Stoe
& Cie, Darmstadt
(Germany), 1996.
2
[24] R1 ˆ S(jjF0 j j Fc jj)/S j F0 j ); wR2 ˆ [S[w(F0 F2c)2]/S[w(Fo2)2]]1/2
Received: October 23, 1998 [F1411]
Chem. Eur. J. 1999, 5, No. 4
ꢀ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1999
0947-6539/99/0504-1319 $ 17.50+.50/0
1319