A convenient rhodium-catalyzed intermolecular hydroamination procedure for terminal alkynes

Article abstract of DOI:10.1021/jo010444t

The first rhodium-catalyzed intermolecular hydroamination of alkynes is presented. Terminal alkynes react efficiently with anilines in the presence of cationic rhodium(I) catalysts under very mild reaction conditions (e.g., base and acid free at room temperature) to yield up to 99% of the corresponding imines. An easy one-pot protocol for the synthesis of secondary amines was developed by combining this alkyne amination reaction with in situ addition of organolithium reagents.

Full text of DOI:10.1021/jo010444t

J . Org. Chem. 2001, 66, 6339-6343
6339
A Con ven ien t Rh od iu m -Ca ta lyzed In ter m olecu la r Hyd r oa m in a tion
P r oced u r e for Ter m in a l Alk yn es
Christian G. Hartung,† Annegret Tillack,† Harald Trauthwein,‡ and Matthias Beller*,†
Institut fu¨r Organische Katalyseforschung an der Universita¨t Rostock e.V., Buchbinderstrasse 5-6,
18055 Rostock, Germany, and Aventis R&T, Industriepark Ho¨chst,
65926 Frankfurt am Main-Ho¨chst, Germany
matthias.beller@ifok.uni-rostock.de
Received April 30, 2001
The first rhodium-catalyzed intermolecular hydroamination of alkynes is presented. Terminal
alkynes react efficiently with anilines in the presence of cationic rhodium(I) catalysts under very
mild reaction conditions (e.g., base and acid free at room temperature) to yield up to 99% of the
corresponding imines. An easy one-pot protocol for the synthesis of secondary amines was developed
by combining this alkyne amination reaction with in situ addition of organolithium reagents.
Sch em e 1. Hyd r oa m in a tion of Alk en es a n d
Alk yn es
New C-N bond forming reactions are of considerable
interest in both synthetic organic and industrial chem-
istry due to the importance of amines and their deriva-
tives in almost all areas of chemistry. The most atom
economic process for the synthesis of amines is the
hydroamination reaction, in which the C-N bond is
formed directly by the addition of NH3, a primary, or
secondary amine to a multiple bond, without generating
any waste products.1 The catalytic hydroamination of
C-C double bonds (Scheme 1) has been investigated only
rarely.2 Hence, a generally applicable procedure has yet
to be reported. In particular the efficient hydroamination
of aliphatic alkenes is not yet possible and remains one
of the most important challenges for catalysis research.
In contrast to alkenes, alkynes are better π-donors and
have a sterically less hindered, cylindrical π-system as
well as more nucleophilic sp-hybridized C-atoms.3 Thus
alkynes are in general more reactive in amination
reactions, which is illustrated by the more exothermic
(∼70 kJ /mol) addition of NH3 to acetylene compared to
the equivalent reaction with ethylene.4 Even though the
hydroamination of alkynes is thermodynamically more
favorable, a high activation barrier nevertheless exists.
Catalytic procedures are indispensable in overcoming
these activation barriers.1
A variety of catalysts have successfully been employed
in catalytic cyclization of aminoalkynes to give nitrogen-
containing heterocycles.1,5 Intermolecular amination re-
actions with alkynes are, however, much more difficult,
and only a few examples have been reported. Further-
more these reactions are generally limited to specific
substrates. Pioneering work was done by J . Barluenga
et al. who employed mercury and thallium salts for the
Markovnikov hydroamination of alkynes with anilines.6
Only moderate yields of the imine or enamine products
were obtained using 2-5 mol % of the toxic metal
catalysts. Later on, the intermolecular hydroamination
of alkynes was also realized with catalysts of the alkali
metals (Cs),7 early transition metals (Zr),8 lanthanides
* To whom correspondence should be addressed. Phone: +49-381/
466930; Fax: +49-381/4669324.
† Institut fu¨r Organische Katalyseforschung an der Universita¨t
Rostock e.V.
‡ Aventis R&T.
(1) Mu¨ller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675. (b) Mu¨ller,
T. E.; Beller, M. In Transition Metals for Organic Synthesis; Beller,
M.; Bolm, C., Eds.; Wiley-VCH: Weinheim, 1998; Vol. 2, pp 316-330.
(c) Taube, R. In Homogeneous Catalysis with Organometallic Com-
pounds; Cornils, B.; Herrmann, W. A., Eds.; VCH: Weinheim, 1996;
pp 507-520. (d) J a¨ger, V.; Viehe, H. G. In Houben-Weyl, Methoden
der Organischen Chemie, Thieme Verlag: Stuttgart, 1977; Vol. 5/2a,
713. (e) Haak, E.; Doye, S. Chem. Unserer Zeit 1999, 33, 296.
(2) For selected recent publications, see: (a) Kawatsura, M.; Hartwig,
J . F. Organometallics 2001, 20, 1960. (b) Beller, M.; Breindl, C.;
Riermeier, T. H.; Tillack, A. J . Org. Chem. 2001, 66, 1403. (c)
Kawatsura, M.; Hartwig, J . F. J . Am. Chem. Soc. 2000, 122, 9546. (d)
Senn, H. M.; Blochl, P. E.; Togni, A. J . Am. Chem. Soc. 2000, 122,
4098. (e) Hartung, C. G.; Breindl, C.; Tillack, A.; Beller, M. Tetrahedron
2000, 56, 5157. (f) Beller, M.; Breindl, C.; Riermeier, T. H.; Eichberger,
M.; Trauthwein, H. Angew. Chem. 1998, 110, 3571; Angew. Chem., Int.
Ed. 1998, 37, 3389. (g) Beller, M.; Breindl, C. Tetrahedron 1998, 54,
6359. (h) Brunet, J . J . Gazz. Chim. Ital. 1997, 127, 111.
(3) Lowry, T. H.; Richardson, K. S. Mechanism and Theory in
Organic Chemistry, 3rd ed.; Harper & Row: New York, 1987; chapter
7.
(5) Hegedus, L. S. Angew. Chem., Int. Ed. Engl. 1988, 27, 1113. (b)
Bu¨rgstein, M. R.; Berberich, H.; Roesky, P. W. Organometallics 1998,
17, 1452. (c) Li, Y.; Marks, T. J . J . Am. Chem. Soc. 1998, 120, 1757.
(d) Arredondo, V. M.; Tian, S.; McDonald, F. E..; Marks, T. J . Am.
Chem. Soc. 1999, 121, 3633. (e) Mu¨ller, T. E.; Pleier, A.-K. J . Chem.
Soc., Dalton Trans. 1999, 583. (f) Mu¨ller, T. E.; Grosche, M.; Herdtweck,
E.; Pleier, A.-K.; Walter, E.; Yan, Y.-K. Organometallics 2000, 19, 170.
(g) Penzien, J .; Mu¨ller, T. E.; Lercher, J . A. Chem. Commun. 2000,
1753. (h) Burling, S.; Field, L. D.; Messerle, B. A. Organometallics
2000, 19, 87. (i) Kondo, T.; Okada, T.; Suzuki, T.; Mitsudo, T. J .
Organomet. Chem. 2001, 622, 149. (j) Kim, Y. K.; Livinghouse, T.;
Bercaw, J . E. Tetrahedron Lett. 2001, 42, 2933.
(6) Barluenga, J .; Aznar, F. Synthesis 1975, 704. (b) Barluenga, J .;
Aznar, F. Synthesis 1977, 195. (c) Barluenga, J .; Aznar, F.; Liz, R.;
Rodes, R. J . Chem. Soc., Perkin Trans. 1 1980, 2732.
(7) Tzalis, D.; Koradin, C.; Knochel, P. Tetrahedron Lett. 1999, 40,
6193.
(4) Li, Y.; Marks, T. J . J . Am. Chem. Soc. 1996, 118, 9295. (b) Pedley,
J . B.; Naylor, R. D.; Kirby, S. P. Thermochemical Data of Organic
Compounds; Chapman and Hall: London, 1986; Appendix tables 1, 3.
(8) Baranger, A. M.; Walsh, P. J .; Bergman, R. G. J . Am. Chem.
Soc. 1993, 115, 2753. (b) Walsh, P. J .; Baranger, A. M.; Bergman, R.
G. J . Am. Chem. Soc. 1992, 114, 1708.
10.1021/jo010444t CCC: $20.00 © 2001 American Chemical Society
Published on Web 08/23/2001

6340 J . Org. Chem., Vol. 66, No. 19, 2001
Hartung et al.
(Nd),9 and actinides (U, Th).10 The applicability and
efficiency of these various types of catalysts are still
limited, due to sensitivity to air, humidity, and functional
groups.
Ta ble 1. Rh od iu m -Ca ta lyzed Hyd r oa m in a tion of
1-Octyn e w ith An ilin ea
Two recent publications describe distinct improvement
in the hydroamination of alkynes. Y. Wakatsuki et al.
introduced a Ru3(CO)12/acid catalyst system permitting
predominantly the high-yielding conversion of anilines
with terminal phenyl acetylenes to give the corresponding
branched imines.11,12 However, only one example is given
for the hydroamination of aliphatic 1-octyne with aniline
which gives the corresponding product in 63% yield.
Advantageously, the reactions can be run under an air
atmosphere and often without a solvent.
An alternative method employing titanocene catalysts
was developed by S. Doye et al.13 The best results were
obtained with aromatic, disubstituted alkynes, which can
be aminated with a series of aryl and alkylamines to yield
the corresponding products with high regioselectivity. It
is noteworthy that both the Doye and Wakatsuki groups
employed reaction temperatures of about 100 °C, and
nonactivated aliphatic alkynes have only given low to
moderate yields so far.
temp
1-octyne/
mol %
cat.
yield of
entry [°C] aniline ratio
catalyst system
3a [%]
1b
2
3
4
5
6
7
8
9
100
50
4:1
2:1
2:1
2:1
2:1
4:1
1.2:1
1:2
1:4
2:1
2:1
2.5
1.5
1.0
1.5
2.0
1.5
1.5
1.5
1.5
1.5
1.5
[Rh(cod)2]BF4/2PPh3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
[Rh(cod)2]BF4/3PCy3
26
>99
63
79
>99
77
67
70
91
46
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
0
10
11c
0
73
a
20 h reaction time in toluene. Yields and mol % catalyst refer
to the limiting reagent. Yields were determined by GC analysis
with an internal standard (hexadecane). bReaction in an ACE
c
pressure tube with THF as the solvent. 44 h reaction time.
all. Hence, the cationic character of the catalyst seemed
to be a necessary requirement for a successful reaction.
We assume that the alkyne is activated by the cationic
metal center to rate-determining nucleophilic attack of
the amine, in agreement with kinetic measurements
which reveal that the initial reaction rate is first order
in catalyst and amine concentration and zero order in
alkyne concentration. However, an amine activation
pathway cannot be excluded. The addition of a phosphine
is essential, since without phosphine the product is only
formed in very low yields (<5%). A screening of several
phosphine ligands showed that the best results were
obtained in the presence of 3 equiv (refers to rhodium)
of the basic tricyclohexylphosphine (PCy3) (Table 1, entry
2). PPh3, P(o-tolyl)3, and P(n-Bu)3 were also active as
ligands but proved to be less suitable than PCy3. In the
presence of chelating phosphines, however, no reaction
was observed.
Toluene, THF, and dioxane used as solvents showed
similar results in the reaction. In CH2Cl2 the reaction
proceeds initially very rapidly, but soon stops probably
due to acid impurities inhibiting the cationic catalyst.
Strongly coordinating solvents such as acetonitrile or
DMSO are unsuitable. A variation of the reaction tem-
perature revealed that the reaction runs smoothly at
room temperature (Table 1, entries 3-9). Hence, in the
presence of 2 mol % of Rh catalyst and 6 mol % of PCy3,
the desired product N-(2-octylidene)aniline 3a is obtained
in 99% yield. Even at 0 °C, high yields of the imine
product can be obtained; however, the reaction is some-
what slower (Table 1, entries 10, 11). An important
advantage of using lower reaction temperatures is that
only small amounts of alkyne oligomers are produced.
At higher reaction temperatures (e.g., 50 °C, Table 1,
entry 2) quantitative yield is obtained after 20 h using
1.5 mol % rhodium catalyst. With respect to the alkyne/
amine ratio, the yields are increased by using an excess
of either amine or alkyne.
Resu lts a n d Discu ssion
To improve and extend our previously reported rhodium-
catalyzed amination reactions,14 we became interested in
the amination of aliphatic alkynes. We describe herein
an efficient and mild conversion of aliphatic alkynes with
anilines by means of a commercially available rhodium
catalyst.
The initial experiments for the hydroamination of
alkynes were performed under our previously described
standard reaction conditions. 1-Octyne 1a was reacted
with aniline 2a in the presence of 2.5 mol % Rh(cod)2BF4/2
PPh3 in THF in a pressure tube at 100 °C giving N-(2-
octylidene)aniline 3a regioselectively in 26% yield (Table
1, entry 1) via hydroamination of the alkyne followed by
tautomerization of the resultant enamine to the more
stable imine. Oligomerization and polymerization of the
alkyne are observed as side reactions.
Other rhodium complexes ([Rh(cod)Cl]2, [Rh(cod)(acac)],
[Rh(PPh3)3Cl], RhCl3‚xH2O) also in combination with
phosphine ligands show no hydroamination reactivity at
(9) Li, Y.; Marks, T. J . Organometallics 1996, 15, 3370.
(10) Haskel, A.; Straub, T.; Eisen, M. S. Organometallics 1996, 15,
3773. (b) Eisen, M. S.; Straub, T.; Haskel, A. J . Alloys Compd. 1998,
271-273, 116.
(11) Tokunaga, M.; Eckert, M.; Wakatsuki, Y. Angew. Chem. 1999,
111, 3416; Angew. Chem., Int. Ed. 1999, 38, 3222. (b) Tokunaga, M.;
Wakatsuki, Y. J . Synth. Org. Chem. J pn. 2000, 58, 587.
(12) See also: (a) Heider, M.; Henkelmann, J .; Ruehl, T. Eur. Pat.
Appl. EP 646 571, 1995; Chem. Abstr. 1995, 123, 229254s. (b)
Uchimaru, Y. Chem. Commun. 1999, 1133. (c) Kadota, I.; Shibuya, A.;
Mpaka Lutete, L.; Yamamoto, Y. J . Org. Chem. 1999, 64, 4570.
(13) Haak, E.; Bytschkov, I.; Doye, S. Angew. Chem. 1999, 111, 3584;
Angew. Chem., Int. Ed. 1999, 38, 3389. (b) Haak, E.; Siebeneicher, H.;
Doye, S. Org. Lett. 2000, 2, 1935.
(14) Beller, M.; Eichberger, M.; Trauthwein, H. Angew. Chem. 1997,
109, 2306; Angew. Chem., Int. Ed. Engl. 1997, 36, 2225. (b) Beller,
M.; Trauthwein, H.; Eichberger, M.; Breindl, C.; Mu¨ller, T. E.; Zapf,
A. J . Organomet. Chem. 1998, 566, 277. (c) Beller, M.; Trauthwein,
H.; Eichberger, M.; Breindl, C.; Mu¨ller, T. E. Eur. J . Inorg. Chem. 1999,
1121. (d) Beller, M.; Trauthwein, H.; Eichberger, M.; Breindl, C.;
Herwig, J .; Mu¨ller, T. E.; Thiel, O. R. Chem. Eur. J . 1999, 5, 1306. (e)
Trauthwein, H.; Tillack, A.; Beller, M. Chem. Commun. 1999, 2029.
(f) Beller, M.; Thiel, O. R.; Trauthwein, H.; Hartung, C. G. Chem. Eur.
J . 2000, 6, 2513. (g) Tillack, A.; Trauthwein, H.; Hartung, C. G.;
Eichberger, M.; Pitter, S.; J ansen, A.; Beller, M. Monatsh. Chem. 2000,
131, 1327.
The present scope and limitations of the new rhodium-
catalyzed hydroamination of alkynes are shown in Table
2. 1-Octyne and 1-hexyne react well (Table 2, entries
1-7), while in the case of phenylacetylene rapid oligo-
merization occurs, thus leading to lower product yields

Hydroamination Procedure for Terminal Alkynes
J . Org. Chem., Vol. 66, No. 19, 2001 6341
Ta ble 2. Rh od iu m -Ca ta lyzed Hyd r oa m in a tion of
1-Alk yn es w ith An ilin esa
Ta ble 3. On e-P ot P r otocol for th e Syn th esis of
Secon d a r y Am in es by Nu cleop h ilic Ad d ition of
Or ga n olith iu m Com p ou n d sa
entry
alkyne R
aniline R1
C6H5
mol % catalyst
yield [%]
1
2
3b
4
5
6
7
8
n-hexyl
n-butyl
n-butyl
n-hexyl
n-hexyl
n-hexyl
n-hexyl
Ph
1.5
1.5
1.5
1.5
1.5
1.5
1.0
2.5
79 (3a )
83 (3b)
55 (3c)
73 (3d )
63 (3e)
80 (3f)
C6H5
2-Me-C6H4
4-Me-C6H4
4-MeO-C6H4
3-F-C6H4
4-Cl-C6H4
C6H5
entry alkyne R aniline R1 R2-Li (equiv) overall yield [%]
>99 (3g)
10c (3h )
1
2
3
4
5
n-hexyl
n-hexyl
n-hexyl
n-hexyl
n-butyl
H
H
H
Cl
H
MeLi (1.1)
n-BuLi (1.1)
PhLi (2.2)
n-BuLi (1.1)
n-BuLi (1.1)
45 (5a )
60 (5b)
42 (5c)
55 (5d )
56 (5e)
a
20 h reaction time at room temperature in toluene with
[Rh(cod)2]BF4/3 PCy3 as the catalytic system, alkyne/amine ratio
2:1. Yields and mol % catalyst refer to the aniline. Yields were
determined by GC analysis with an internal standard (hexade-
cane). b44 h reaction time. cConversion of aniline; product identified
by GC/MS analysis.
a
Step 1: 1.5 mol % [Rh(cod)2]BF4/3 PCy3, 20 h, room temper-
ature, toluene, alkyne/aniline ratio 2:1. Step 2: 0.5 h at -70 °C,
then 2 h at room temperature. Yields were determined by GC
analysis with an internal standard (hexadecane) and refer to the
aniline.
Sch em e 2. Rea ction of P h en yla cetylen e a n d
Mor p h olin e
and phenyllithium reagents as nucleophiles to our reac-
tion mixtures, the corresponding secondary amines were
obtained in reasonable yields (not optimized). The results
of this convenient one-pot protocol are summarized in
Table 3. It is clear that this procedure can be easily
extended to other nucleophilic alkyl and aryl reagents,
making amines with a number of different substitution
patterns accessible.
In conclusion we have established that the cationic
rhodium catalyst system [Rh(cod)2]BF4/PR3 is active and
practical for the intermolecular hydroamination of
1-alkynes with anilines under mild reaction conditions.
For the first time, efficient catalytic hydroamination of
alkynes is possible at room temperature. This methodol-
ogy constitutes an easy route to the corresponding imines
in high yields, which can subsequently be used in situ
for the preparation of secondary amines by addition of
nucleophiles. Apart from the Ru3(CO)12-catalyzed method,
it is the only intermolecular amination reaction of
alkynes using late transition metals. Clearly the sub-
strate scope of the procedure has still to be improved,
but compared to previously reported methods, our cata-
lytic system has also some advantages (weakly oxophilic,
nontoxic, easy to handle).
(Table 2, entry 8). Using anilines as the amine component
of the reaction furnishes the products in good to very good
yield. Substituents at the aniline core are tolerated with
respect to both electronic as well as steric properties,
whereby electron-withdrawing substituents react faster,
electron-donating slower. Higher yields and faster reac-
tions can be achieved either using reaction temperatures
of about 50 °C or higher catalyst amounts. In a kinetic
experiment the reaction of 1-octyne with 4-chloroaniline
in the presence of 5.5 mol % [Rh(cod)2]BF4/3PCy3 gave
the corresponding imine in 59% yield after only 20 min.
TON’s of up to 100 in 20 h and TOF’s of up to 35 mol/
(mol‚h) (initial rate to an extend of 50% yield) were
reached at room temperature.
The products of the conversion of 1-octyne with N-
methylaniline or with aliphatic or alicyclic amines
were only formed in low yields (identified by GC/MS
analysis). Interestingly, under our previously reported
reaction conditions,14 the conversion of phenylacetylene
with morpholine furnished the anti-Markovnikov hy-
droamination product 4 in 15% yield (nonoptimized)
(Scheme 2).
Since we had a convenient procedure for the ambient
amination of aliphatic alkynes in hand, we were inter-
ested in the further functionalization of the imine prod-
ucts. Advantageously, compared to the general prepara-
tion of imines via amination of carbonyl compounds the
hydroamination of alkynes does not produce any water
as byproduct. Hence, we envisaged a one-pot protocol for
the synthesis of branched amines directly from alkynes
by in situ addition of organometallic compounds.
Unfortunately, enolizable ketimines are known to show
poor reactivity toward nucleophilic 1,2-addition, mainly
due to enolization on addition of organometallic re-
agents.15 Thus only poor yields of amines are obtained
in these reactions. Nevertheless, by simply adding alkyl
Exp er im en ta l Section
Chemicals were obtained from Aldrich, Fluka, Acros, and
Strem and unless otherwise noted were used without further
purification. Liquid amines were distilled from CaH2. Alkynes
were degassed, flushed with argon, and stored over molecular
sieves (4 Å). Absolute solvents were purchased from Fluka.
All operations were carried out under an argon atmosphere.
The [Rh(cod)2]BF4 catalyst was synthesized according to a
literature procedure.16
Gen er a l P r oced u r e for th e Con ver sion of Alk yn es
w ith Am in es. The alkyne was added slowly using a syringe
to a solution or suspension of the [Rh(cod)2]BF4/PR3 catalyst
(15) Stork, G.; Dowd, S. R. J . Am. Chem. Soc. 1963, 85, 2178. (b)
Bloch, R. Chem. Rev. 1998, 98, 1407. (c) Enders, D.; Reinhold, U.
Tetrahedron: Asymmetry 1997, 8, 1895. (d) Hemmer, R.; Lu¨rken, W.
In Houben-Weyl, Methoden der Organischen Chemie; Thieme Verlag:
Stuttgart, 1990; Vol. E 14b/2, p 1029.
(16) Schrock, R. R.; Osborn, J . A. J . Am. Chem. Soc. 1971, 93, 3089.

6342 J . Org. Chem., Vol. 66, No. 19, 2001
Hartung et al.
and the amine (5.0 mmol) in toluene (10 mL) under argon at
room temperature. The mixture was stirred at the given
temperature for the specified time. Isolation of the product was
done by fractional distillation in vacuo. The products were
stored under argon at -20 °C. The purity of the products
(>99.5%) was verified by GC analysis. The imine products
were isolated as a mixture of the E- and Z-isomers; thus, some
NMR resonances were present as two signals (indicated below
by “+”), representing both isomers.
N-(2-Octylid en e)a n ilin e (3a ). According to the general
procedure, aniline (0.46 mL, 5.0 mmol) and 1-octyne (1.48 mL,
10.0 mmol) were reacted in the presence of 1.5 mol % [Rh(cod)2]-
BF4 (30.5 mg, 0.075 mmol) and 4.5 mol % PCy3 (63.1 mg, 0.225
mmol) at room temperature for 20 h. Fractional distillation
afforded 3a as a colorless oil. Yield: 79% (GC); bp 65-66 °C/
0.1 mbar. 1H NMR (CDCl3, 400 MHz) δ: 7.27 (m, 2H), 7.01
(m, 1H), 6.67 (m, 2H), 2.39 + 2.10 (m, 2H), 2.14 + 1.76 (s,
3H), 1.66 + 1.42 (m, 2H), 1.41-1.15 (m, 6H), 0.91 + 0.83 (t, J
) 7.1 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ: 172.7 + 172.2,
151.6 + 151.1, 128.8 + 128.7, 122.9 + 122.8, 119.5, 41.7 +
34.1, 31.7 + 31.4, 29.1 + 29.0, 26.8 + 26.3, 25.9 + 19.4, 22.6
+ 22.4, 14.1 + 14.0. GC/MS (EI, 70 eV) m/z: 203 (M+), 188
(M+ - CH3), 174 (M+ - CH2CH3), 160 (M+ - (CH2)2CH3), 146
(M+ - (CH2)3CH3), 132 (M+ - (CH2)4CH3), 118 (M+ - (CH2)5-
CH3), 92, 77.
% PCy3 (63.1 mg, 0.225 mmol) at room temperature for 20 h.
Fractional distillation afforded 3e as a colorless oil. Yield: 63%
(GC); bp 109-113 °C/0.1-0.2 mbar. 1H NMR (CD2Cl2, 400
MHz) δ: 6.83 (m, 2H), 6.59 (m, 2H), 3.77 (s, 3H), 2.37 + 2.12
(m, 2H), 2.10 + 1.75 (s, 3H), 1.65 + 1.47 (m, 2H), 1.42-1.14
(m, 6H), 0.91 + 0.85 (t, J ) 7.0 Hz, 3H). 13C NMR (CD2Cl2,
100 MHz) δ: 173.0 + 172.3, 156.0 + 155.9, 145.5 + 145.1, 120.8
+ 120.7, 114.4 + 114.4, 55.7, 42.0 + 34.1, 32.1 + 31.8, 29.6 +
29.4, 27.2 + 26.6, 26.0 + 19.4, 23.0 + 22.8, 14.2 + 14.1. GC/
MS (EI, 70 eV) m/z: 233 (M+), 218 (M+ - CH3), 204 (M+
-
CH2CH3), 190 (M+ - (CH2)2CH3), 176 (M+ - (CH2)3CH3), 163,
162 (M+ - (CH2)4CH3), 148 (M+ - (CH2)5CH3), 122, 107, 92,
77.
N-(2-Octylid en e)-3-flu or oa n ilin e (3f). According to the
general procedure, 3-fluoroaniline (0.48 mL, 5.0 mmol) and
1-octyne (1.48 mL, 10.0 mmol) were reacted in the presence
of 1.5 mol % [Rh(cod)2]BF4 (30.5 mg, 0.075 mmol) and 4.5 mol
% PCy3 (63.1 mg, 0.225 mmol) at room temperature for 20 h.
Fractional distillation afforded 3f as a colorless oil. Yield: 80%
1
(GC); bp 83 °C/0.2 mbar. H NMR (CD2Cl2, 400 MHz) δ: 7.24
(m, 1H), 6.72 (m, 1H), 6.44 (m, 1H), 6.39 (m, 1H), 2.38 + 2.11
(m, 2H), 2.11 + 1.76 (s, 3H), 1.65 + 1.47 (m, 2H), 1.43-1.08
(m, 6H), 0.91 + 0.84 (t, J ) 7.1 Hz, 3H). 13C NMR (CD2Cl2,
100 MHz) δ: 173.2 + 172.7, 163.3 + 163.2 (d, J ) 245 Hz),
153.9 + 153.4 (d, J ) 9 Hz), 130.1 + 130.0 (d, J ) 10 Hz),
115.1 + 115.0, 109.1 + 109.0 (d, J ) 21 Hz), 106.4 + 106.3 (d,
J ) 21 Hz), 41.4 + 34.2, 31.7 + 31.3, 29.1 + 28.9, 26.7 + 26.0,
25.5 + 19.3, 22.6 + 22.4, 13.8 + 13.7. GC/MS (EI, 70 eV) m/z:
N-(2-H exylid en e)a n ilin e (3b ). According to the
general procedure, aniline (0.46 mL, 5.0 mmol) and 1-hexyne
(1.15 mL, 10.0 mmol) were reacted in the presence of 1.5 mol
% [Rh(cod)2]BF4 (30.5 mg, 0.075 mmol) and 4.5 mol % PCy3
(63.1 mg, 0.225 mmol) at room temperature for 20 h. Fractional
distillation afforded 3b as a colorless oil. Yield: 83% (GC); bp
221 (M+), 206 (M+ - CH3), 192 (M+ - CH2CH3), 178 (M+
-
(CH2)2CH3), 164 (M+ - (CH2)3CH3), 151, 150 (M+ - (CH2)4-
CH3), 136 (M+ - (CH2)5CH3), 110, 95, 75.
1
52 °C/0.2 mbar. H NMR (CD2Cl2, 400 MHz) δ: 7.28 (m, 2H),
N-(2-Octylid en e)-4-ch lor oa n ilin e (3 g). According to the
general procedure, 4-chloroaniline (638 mg, 5.0 mmol) and
1-octyne (1.48 mL, 10.0 mmol) were reacted in the presence
of 1.0 mol % [Rh(cod)2]BF4 (20.3 mg, 0.05 mmol) and 3.0 mol
% PCy3 (42.1 mg, 0.15 mmol) at room temperature for 20 h.
Fractional distillation afforded 3g as a colorless oil. Yield: 99%
(GC); bp 110-113 °C/0.1-0.2 mbar. 1H NMR (CD2Cl2, 400
MHz) δ: 7.24 (m, 2H), 6.60 (m, 2H), 2.37 + 2.09 (m, 2H), 2.10
+ 1.74 (s, 3H), 1.64 + 1.45 (m, 2H), 1.43-1.13 (m, 6H), 0.90 +
0.84 (t, J ) 7.1 Hz, 3H). 13C NMR (CD2Cl2, 100 MHz) δ: 173.4
+ 172.8, 150.8 + 150.2, 128.9 + 128.8, 127.8 + 127.8, 120.9,
41.6 + 34.2, 31.8 + 31.5, 29.2 + 29.1, 26.9 + 26.2, 25.7 + 19.3,
22.7 + 22.5, 13.9 + 13.8. GC/MS (EI, 70 eV) m/z: 239, 237
(M+), 224, 222 (M+ - CH3), 210, 208 (M+ - CH2CH3), 196, 194
(M+ - (CH2)2CH3), 182, 180 (M+ - (CH2)3CH3), 169, 168, 167,
166 (M+ - (CH2)4CH3), 154, 152 (M+ - (CH2)5CH3), 126, 111,
91, 75.
(E)-N-(2-P h en yleth en yl)m or p h olin e (4). According to
the general procedure, morpholine (0.44 mL, 5.0 mmol) and
phenylacetylene (2.20 mL, 20.0 mmol) were reacted in the
presence of 2.5 mol % [Rh(cod)2]BF4 (50.8 mg, 0.125 mmol)
and 5.0 mol % PPh3 (65.6 mg, 0.250 mmol) in 10 mL of THF
under reflux for 20 h. Fractional distillation afforded 4 as a
pale yellow oil, that crystallizes under cooling. Yield: 15%
(GC). 1H NMR (CDCl3, 360 MHz) δ: 7.27 (m, 2H), 7.24 (m,
2H), 7.10 (m, 1H), 6.53 (d, J ) 14.0 Hz, 1H), 5.36 (d, J ) 14.0
Hz, 1H), 3.68 (t, J ) 4.7 Hz, 4H), 2.95 (t, J ) 4.7 Hz, 4H). 13C
NMR (CDCl3, 91 MHz) δ: 139.8, 138.6, 128.5, 124.4, 124.2,
101.5, 66.5, 49.1. GC/MS (EI, 70 eV) m/z: 189 (M+), 158 (M+
- OCH3), 130 (C6H5C2H2NCH+), 104 (C6H5C2H3+), 91 (C6H5-
CH2+), 77 (C6H5+).
7.02 (m, 1H), 6.66 (m, 2H), 2.39 + 2.11 (m, 2H), 2.12 + 1.75
(s, 3H), 1.65 + 1.46 (m, 2H), 1.43 + 1.20 (sext, J ) 7.3 Hz,
2H), 0.97 + 0.81 (t, J ) 7.3 Hz, 3H). 13C NMR (CD2Cl2, 100
MHz) δ: 172.1 + 171.6, 152.0 + 151.5, 128.8 + 128.7, 122.6 +
122.5, 119.3, 41.2 + 33.7, 29.0 + 28.3, 25.5 + 19.1, 22.6 + 22.4,
13.8 + 13.5. GC/MS (EI, 70 eV) m/z: 175 (M+), 160 (M+ - CH3),
146 (M+ - CH2CH3), 133, 132 (M+ - (CH2)2CH3), 118 (M+
(CH2)3CH3), 92, 77.
-
N-(2-Hexylid en e)-2-m eth yla n ilin e (3c). According to the
general procedure, o-toluidine (0.54 mL, 5.0 mmol) and 1-hex-
yne (1.15 mL, 10.0 mmol) were reacted in the presence of 1.5
mol % [Rh(cod)2]BF4 (30.5 mg, 0.075 mmol) and 4.5 mol % PCy3
(63.1 mg, 0.225 mmol) at room temperature for 44 h. Fractional
distillation afforded 3c as a colorless oil. Yield: 55% (GC); bp
43 °C/0.1 mbar. 1H NMR (CD2Cl2, 400 MHz) δ: 7.18-7.06 (m,
2H), 6.93 (m, 1H), 6.52 (m, 1H), 2.42 + 2.03 (m, 2H), 2.15 +
1.68 (s, 3H), 2.01 (s, 3H), 1.67 + 1.46 (m, 2H), 1.44 + 1.19 (m,
2H), 0.98 + 0.80 (t, J ) 7.3 Hz, 3H). 13C NMR (CD2Cl2, 100
MHz) δ: 171.7 + 171.3, 150.7 + 150.1, 130.2 + 130.1, 127.0,
126.3 + 126.2, 122.7, 118.7 + 118.5, 41.0 + 34.0, 28.8 + 28.6,
25.3 + 19.4, 22.8 + 22.6, 17.5 + 17.4, 13.9 + 13.6. GC/MS (EI,
70 eV) m/z: 189 (M+), 174 (M+ - CH3), 160 (M+ - CH2CH3),
147, 146 (M+ - (CH2)2CH3), 132 (M+ - (CH2)3CH3), 91, 65.
N-(2-Octylid en e)-4-m eth yla n ilin e (3d ). According to the
general procedure, p-toluidine (536 mg, 5.0 mmol) and 1-octyne
(1.48 mL, 10.0 mmol) were reacted in the presence of 1.5 mol
% [Rh(cod)2]BF4 (30.5 mg, 0.075 mmol) and 4.5 mol % PCy3
(63.1 mg, 0.225 mmol) at room temperature for 20 h. Fractional
distillation afforded 3d as a colorless oil. Yield: 73% (GC); bp
1
74-75 °C/0.1 mbar. H NMR (CD2Cl2, 400 MHz) δ: 7.08 (m,
2H), 6.94 (m, 2H), 2.36 + 2.09 (m, 2H), 2.30 (s, 3H), 2.10 +
1.73 (s, 3H), 1.64 + 1.46 (m, 2H), 1.43-1.14 (m, 6H), 0.91 +
0.84 (t, J ) 7.1 Hz, 3H). 13C NMR (CD2Cl2, 100 MHz) δ: 172.2
+ 171.6, 149.4 + 148.9, 132.0 + 131.9, 129.3 + 129.2, 119.2,
41.6 + 33.8, 31.7 + 31.4, 29.1 + 29.0, 26.8 + 26.2, 25.6 + 19.0,
22.6 + 22.4, 20.4, 13.8 + 13.7. GC/MS (EI, 70 eV) m/z: 217
(M+), 202 (M+ - CH3), 188 (M+ - CH2CH3), 174 (M+ - (CH2)2-
CH3), 160 (M+ - (CH2)3CH3), 147, 146 (M+ - (CH2)4CH3), 132
(M+ - (CH2)5CH3), 106, 91, 65.
N-(2-Octylid en e)-4-m eth oxya n ilin e (3e). According to
the general procedure, p-anisidine (616 mg, 5.0 mmol) and
1-octyne (1.48 mL, 10.0 mmol) were reacted in the presence
of 1.5 mol % [Rh(cod)2]BF4 (30.5 mg, 0.075 mmol) and 4.5 mol
In Situ Con ver sion of th e Bu ilt Im in es w ith Or ga n o-
lith iu m Com p ou n d s. A solution of the organolithium com-
pound (1.1 or 2.2 equiv based to the amine) was added slowly
by a syringe at -70 °C to the reaction mixture of the
conversion of the alkyne and the aniline. The solution was
stirred for 30 min at -70 °C, allowed to warm to room
temperature for 2 h, diluted with dichloromethane, and
quenched with methanol. The mixture was washed with water
and dried over MgSO4. After removal of the solvents in vacuo,
the product was isolated by column chromatography.
N-2-(2-Meth yloctyl)a n ilin e (5a ). A solution of methyl-
lithium (1.6 M in diethyl ether, 3.44 mL, 5.5 mmol) was added
to the reaction mixture as described for compound 3a . The

Hydroamination Procedure for Terminal Alkynes
J . Org. Chem., Vol. 66, No. 19, 2001 6343
residue was purified by column chromatography (n-hexane/
ethyl acetate ) 30:1) to afford 5a as a pale yellow oil. Yield:
N-5-(5-Meth ylu n d eca n yl)-4-ch lor oa n ilin e (5d ). A solu-
tion of n-butyllithium (1.6 M in hexane, 3.44 mL, 5.5 mmol)
was added to the reaction mixture as described for compound
3g. The residue was purified by column chromatography (n-
hexane/ethyl acetate ) 50:1) to afford 5d as a pale yellow oil.
1
45% (GC). H NMR (CDCl3, 400 MHz) δ: 7.12 (m, 2H), 6.74-
6.68 (m, 3H), 2.98 (br s, 1H), 1.59 (m, 2H), 1.36-1.18 (m, 14H),
0.86 (t, J ) 6.9 Hz, 3H). 13C NMR (CDCl3, 100 MHz) δ: 146.9,
128.9, 117.8, 116.8, 53.7, 41.9, 31.8, 29.8, 28.3, 24.0, 22.6, 14.1.
1
Yield: 55% (GC). H NMR (CDCl3, 400 MHz) δ: 7.04 (d, J )
GC/MS (EI, 70 eV) m/z: 219 (M+), 204 (M+ - CH3), 134 (M+
-
8.9 Hz, 2H), 6.57 (d, J ) 8.9 Hz, 2H), 3.17 (br s, 1H), 1.64-
1.46 (m, 4H), 1.32-1.20 (m, 12H), 1.19 (s, 3H), 0.85 (m, 6H).
13C NMR (CDCl3, 100 MHz) δ: 145.6, 128.8, 122.0, 117.0, 56.2,
39.7, 39.4, 31.8, 29.8, 26.0, 25.8, 23.5, 23.2, 22.6, 14.1, 14.1.
GC/MS (EI, 70 eV) m/z: 297, 295 (M+), 282, 280 (M+ - CH3),
240, 238 (M+ - (CH2)3CH3), 212, 210 (M+ - (CH2)5CH3), 127
(H2NC6H4Cl+). Anal. Calcd for C18H30ClN: C, 73.07; H, 10.22;
N, 4.73. Found: C, 73.34; H, 10.40; N, 4.67.
(CH2)5CH3), 93 (H2NPh+). Anal. Calcd for C15H25N: C, 82.13;
H, 11.49; N, 6.39. Found: C, 81.99; H, 11.43; N, 6.32.
N-5-(5-Meth ylu n d eca n yl)a n ilin e (5b). A solution of n-
butyllithium (1.6 M in hexane, 3.44 mL, 5.5 mmol) was added
to the reaction mixture as described for compound 3a . The
residue was purified by column chromatography (n-hexane/
ethyl acetate ) 50:1) to afford 5b as a pale yellow oil. Yield:
1
60% (GC). H NMR (CDCl3, 400 MHz) δ: 7.10 (m, 2H), 6.68
N-5-(5-Meth yln on yl)a n ilin e (5e). A solution of n-butyl-
lithium (1.6 M in hexane, 3.44 mL, 5.5 mmol) was added to
the reaction mixture as described for compound 3b. The
residue was purified by column chromatography (n-hexane/
ethyl acetate ) 40:1) to afford 5e as a pale yellow oil. Yield:
56% (GC). 1H NMR (CDCl3, 400 MHz) δ: 7.11 (m, 2H), 6.68
(m, 3H), 3.38 (br s, 1H), 1.58 (m, 4H), 1.33-1.23 (m, 8H), 1.22
(s, 3H), 0.87 (t, J ) 7.0 Hz, 6H). 13C NMR (CDCl3, 100 MHz)
δ: 147.0, 128.9, 117.4, 116.2, 56.0, 39.5, 26.1, 25.9, 23.2, 14.1.
(m, 3H), 3.25 (br s, 1H), 1.58 (m, 4H), 1.34-1.18 (m, 15H),
0.86 (m, 6H). 13C NMR (CDCl3, 100 MHz) δ: 147.0, 128.9,
117.4, 116.2, 56.0, 39.8, 39.5, 31.8, 29.8, 26.1, 25.9, 23.6, 23.2,
22.6, 14.1, 14.1. GC/MS (EI, 70 eV) m/z: 261 (M+), 246 (M+
-
CH3), 204 (M+ - (CH2)3CH3), 176 (M+ - (CH2)5CH3), 93
(H2NPh+). Anal. Calcd for C18H31N: C, 82.69; H, 11.95; N, 5.36.
Found: C, 82.62; H, 12.00; N, 5.23.
N-2-(2-P h en yloctyl)a n ilin e (5c). A solution of phenyl-
lithium (1.8 M in cyclohexane/ether (70/30), 6.11 mL, 11.0
mmol) was added to the reaction mixture as described for
compound 3a . The residue was purified by column chroma-
tography (n-hexane/ethyl acetate ) 70:1) to afford 5c as a pale
yellow oil. Yield: 42% (GC). 1H NMR (CDCl3, 400 MHz) δ: 7.47
(m, 2H), 7.33 (m, 2H), 7.23 (m, 1H), 6.99 (m, 2H), 6.60 (m,
1H), 6.33 (m, 2H), 4.01 (br s, 1H), 1.83 (m, 2H), 1.65 (s, 3H),
1.35-1.16 (m, 8H), 0.85 (t, J ) 6.9 Hz, 3H). 13C NMR (CDCl3,
100 MHz) δ: 146.7, 146.1, 128.6, 128.3, 126.2, 126.2, 116.9,
115.2, 58.3, 44.6, 31.7, 29.6, 25.6, 23.6, 22.6, 14.0. GC/MS (EI,
70 eV) m/z: 281 (M+), 266 (M+ - CH3), 196 (M+ - (CH2)5CH3),
131, 118, 105, 93, 77. Anal. Calcd for C20H27N: C, 85.35; H,
9.67; N, 4.98. Found: C, 85.24; H, 9.70; N, 4.91.
GC/MS (EI, 70 eV) m/z: 233 (M+), 218 (M+ - CH3), 176 (M+
-
(CH2)3CH3), 132, 120, 93 (H2NPh+). Anal. Calcd for C16H27N:
C, 82.34; H, 11.66; N, 6.00. Found: C, 82.42; H, 11.60; N, 5.89.
Ack n ow led gm en t. This work was supported by
grants from the Deutsche Forschungsgemeinschaft (DFG
1931/3-2). The Max-Buchner-Forschungsstiftung is
thanked for a grant to C.G.H. The help rendered by Dr.
M. Hateley (IfOK) is greatly appreciated.
J O010444T