Rhenium-catalyzed addition of trimethylsilylacetylene to aldimines

Article abstract of DOI:10.1246/cl.2006.1376

A rhenium complex, [ReBr(CO)₃(thf)]₂, catalyzes reactions of aldimines with trimethylsilylacetylene to give propargylamines in excellent yields. The reactions proceed at room temperature under solvent-free conditions. Copyright

Full text of DOI:10.1246/cl.2006.1376

1376
Chemistry Letters Vol.35, No.12 (2006)
Rhenium-catalyzed Addition of Trimethylsilylacetylene to Aldimines
Yoichiro Kuninobu,Ã Yuichi Inoue, and Kazuhiko TakaiÃ
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology,
Okayama University, Tsushima, Okayama 700-8530
(Received September 6, 2006; CL-061030; E-mail: kuninobu@cc.okayama-u.ac.jp, ktakai@cc.okayama-u.ac.jp)
A rhenium complex, [ReBr(CO)3(thf)]2, catalyzes reactions
smoothly by using both aldimines having an electron-donating
and an electron-withdrawing group at the para-position of the
aromatic ring of aldimines 1d and 1e (Entries 4 and 5). Aldimine
1f gave the corresponding propargylamine 3f quantitatively
without losing a bromo group (Entry 6). This result is in contrast
to a report that an aldimine having a bromo group gave the
corresponding propargylamine in moderate yield.6a Alkenyl al-
dimine 1g afforded enyne 3g in 80% yield (Entry 7). Similar
to aromatic aldimines, aliphatic aldimines 1h, 1i, and 1j also pro-
vided propargylamine 3h, 3i, and 3j, in good to quantitative
yields (Entries 8–10). A hetero-aromatic aldimine, furyl aldi-
mine 1k, also gave the corresponding propargylamine 3k in
46% yield (Entry 11).
Next, we investigated the role of the rhenium complex. One
of the possible functions of the rhenium catalyst is the activation
of acetylene 2a by coordination. As a result, the deprotonation of
2a by aldimines or propargylamines might be promoted and the
nucleophilicity of 2a would be increased. However, the propar-
gylamines were not formed by using platinum dichloride or gal-
lium trichloride, which are well known as reagents that coordi-
nate to acetylenes and increase the acidity of the alkynes. Anoth-
er possibility is that the rhenium catalyst acted as a Lewis acid
and activated the aldimines. However, other Lewis acids, scan-
dium triflate, lanthanum triflate, ytterbium triflate, and indium
triflate, did not promote the reaction.11 These results indicate that
of aldimines with trimethylsilylacetylene to give propargyl-
amines in excellent yields. The reactions proceed at room tem-
perature under solvent-free conditions.
Propargylamines are important intermediates and building
blocks for organic synthesis, especially of biologically active
compounds.1 Although there have been many methods for syn-
thesizing propargylamines, most of these need the activation
of starting materials. Some well- known methods are the nucleo-
philic attack of alkynylides to imines,2 alkynylzinc additions to
acyl iminiums,3 and the addition of terminal alkynes to nitro-
nes.4,5 There have recently been some reports on the transition
metal-catalyzed synthesis of propargylamines without activating
starting materials.6 These reactions do not need any bases and/or
activation of imines to promote the reactions. However, in most
cases, they need a solvent and/or harsh reaction conditions. In
addition, the yields of propargylamines are sometimes decreased
when imines having functional groups, such as methoxy,7
chloro,7 or bromo6a groups, are used. We report herein that a rhe-
nium catalyst8 promoted the reactions between aldimines and tri-
methylsilylacetylene under mild and solvent-free conditions,
and gave propargylamines efficiently.
By the treatment of aldimine 1a (0.50 mmol) with trimethyl-
silylacetylene (2a) (0.55 mmol) in the presence of a rhenium cat-
alyst, [ReBr(CO)3(thf)]2 (2.5 mol %), in toluene (0.20 mL) at
25 ꢀC for 24 h, the addition of the terminal acetylene to the imine
moiety of the aldimine occurred, and propargylamine 3a was ob-
tained in 56% yield. To improve the yield of 3a, several solvents
were investigated. The yield of 3a decreased to 21% in hexane, a
nonpolar solvent. When the rather polar solvents dichloro-
methane and THF were used, the yields were improved and
propargylamine 3a was formed in 62% and 57% yields, respec-
tively. However, more polar N,N-dimethylformamide provided
3a in only 7% yield. Interestingly, 3a was obtained in 89% yield
by performing the reaction of 1a with 2a under solvent-free con-
ditions (Table 1, Entry 1).9,10 The fact that this reaction proceed-
ed without any solvent and even at room temperature (25 ꢀC)
deserves special mention. However, the addition reactions did
not proceed at higher temperatures by using other terminal
acetylenes, such as phenylacetylene, 1-ethynylcyclohexene,
1-octyne, and ethyl propiolate. Aldimines 1b and 1c bearing a
benzyl or phenyl group on the nitrogen atom of the imine moie-
ty, also gave the corresponding propargylamines in quantitative
yields (Entries 2 and 3). In particular, aldimine 1c has high
reactivity and the reaction completed within 3 h. However, an
aldimine having a tosyl group on the nitrogen atom of the imine
moiety did not provide the corresponding propargylamine, even
though the imine moiety must be activated by the tosyl group.
The reactions between aldimines and acetylene 2a proceeded
Table 1. Reactions of several aldimines with trimethyl-
silylacetylenea
R'
R'
HN
[ReBr(CO)3(thf)]2 (2.5 mol %)
neat, Temp, Time
N
+
SiMe3
2a
Temp/°C Time/h Yield/%b
R
R
H
SiMe3
3
1
Yield/%b
Temp/°C Time/h
Entry
1
Imine
Entry
Imine
tBu
N
Ph
H
3a:
3b:
89 (92)
25
24
N
H
7c
80
24 3g: 80 (86)
24 3h: 81 (85)
1a
1g
Ph
N
H
94 (>99)
2
3
4
25
25
25
24
3
tBu
H
N
1b
8d
80
50
nC10H21
Ph
N
1h
N
3c: 95 (>99)
3d: 93 (>99)
H
tBu
H
N
1c
95 (>99)
24 3i:
9
1i
Ph
H
3
Ph
1d
MeO
N
10
11
25
50
24 3j: 94 (>99)
Ph
H
1j
N
H
3e:
96 (>99)
5
6
25
25
3
3
1e
Ph
CF3
Br
N
Ph
46 (53)
48 3k:
O
N
H
1k
3f: 95 (>99)
H
1f
a2a (1.1 equiv.) bIsolated yield. The yield determined by
1H NMR is reported in parentheses. cDichloromethane was used
as a solvent. [ReBr(CO)3(thf)]2 (5.0 mol %), 2a (3.0 equiv.).
d
Copyright Ó 2006 The Chemical Society of Japan

Chemistry Letters Vol.35, No.12 (2006)
1377
Financial support by a Grant-in-Aid for Scientific Research
on Priority Areas (No. 18037049, ‘‘Advanced Molecular Trans-
formations of Carbon Resources’’), and for Young Scientists (B)
(No. 18750088) from the Ministry of Education, Culture, Sports,
Science and Technology of Japan.
Ph
HN
ReI
H
SiMe3
R
SiMe3
H
ReIII
Ph
H ReIII
SiMe3
N
References and Notes
Ph
N
R
1
a) J. A. Porco, Jr., F. J. Schoenen, T. J. Stout, J. Clardy,
S. L. Schreiber, J. Am. Chem. Soc. 1990, 112, 7410. b) M. A.
Huffman, N. Yasuda, A. E. DeCamp, E. J. J. Grabowski, J.
Org. Chem. 1995, 60, 1590.
SiMe3
R
H
Scheme 1. Proposed mechanism of the formation of propargyl-
amines.
2
a) L. M. Harwood, K. J. Vines, M. G. B. Drew, Synlett 1996,
1051. b) J. Cossy, C. Poitevin, D. G. Pardo, Synlett 1998, 251.
c) S. Florio, L. Troisi, V. Capriati, G. Suppa, Eur. J. Org.
Chem. 2000, 200, 3793.
the role of the rhenium catalyst is not only as a Lewis acid.
The proposed reaction mechanism is as follows (Scheme
1):12 (1) Oxidative addition of trimethylsilylacetylene to a
rhenium(I) center;13 (2) nucleophilic addition of an alkynyl-
rhenium(III) species to an aldimine; (3) reductive elimination.
As a result, a propargylamine is formed and the rhenium(I)
catalyst is regenerated.
Although a reaction between phenylacetylene (2b) and
aldimine 1c did not occur with [ReBr(CO)3(thf)]2, the reaction
proceeded to give the corresponding adduct 4 quantitatively by
using both the rhenium complex and copper(I) chloride (eq 1).14
3
4
C. Fischer, E. M. Carreira, Org. Lett. 2004, 6, 1497.
For the zinc(II), triethylamine and 2-dimethylaminoethanol-
promoted reaction of terminal acetylene with nitrones, see:
R. Fassler, D. E. Frantz, J. Oetiker, E. M. Carreira, Angew.
¨
Chem., Int. Ed. 2002, 41, 3054.
5
6
For the dialkylzinc-assisted alkynylation of nitrones, see: S.
Pinet, S. U. Pandya, P. Y. Chavant, A. Ayling, Y. Vallee,
Org. Lett. 2002, 4, 1463.
a) C. Fischer, E. M. Carreira, Org. Lett. 2001, 3, 4319. b) C.-J.
Li, C. Wei, Chem. Commun. 2002, 268. c) S. B. Park, H.
Alper, Chem. Commun. 2005, 1315. For the transition metal-
catalyzed enantioselective synthesis of propargylamines, see:
d) C. Koradin, K. Polborn, P. Knochel, Angew. Chem., Int.
Ed. 2002, 41, 2535. e) C. Wei, C.-J. Li, J. Am. Chem. Soc.
2002, 124, 5638. f) C. Wei, Z. Li, C.-J. Li, Synlett 2004,
1472. g) M. Benaglia, D. Negri, G. Dell’Anna, Tetrahedron
Lett. 2004, 45, 8705.
Ph
[ReBr(CO)3(thf)]2 (2.5 mol %)
Ph
HN
N
CuCl (5.0 mol %)
+
(1)
Ph
Ph
Ph
H
neat, 25 °C, 24 h
1c
2b
4
96%
Ph
Next, we investigated three-component coupling reactions.
Initially, the reaction of benzaldehyde, aniline, and trimethyl-
silylacetylene was carried out. However, the corresponding
propargylamine was not obtained, regardless of the quantitative
formation of an aldimine, which was derived from benzaldehyde
and aniline. Addition of molecular sieves to remove water did
not produce the propargylamine but still the aldimine was
obtained. Therefore, we carried out the reaction in two steps to
avoid the influence of aniline on the rhenium-catalyzed addition
of trimethylsilylacetylene (2a) to aldimine 1c. Treatment of
benzaldehyde with aniline in the presence of molecular sieves
at 25 ꢀC for 3 h, followed by the addition of a catalytic amount
of the rhenium complex, [ReBr(CO)3(thf)]2, and trimethyl-
silylacetylene (2a) gave the desired three-component coupling
product, propargylamine 3c, in 95% yield (eq 2). In this reaction,
aromatic aldimine 1c was formed in situ by the reaction of
benzaldehyde with aniline, followed by the addition of tri-
methylsilylacetylene to 1c in a similar way to the reaction in
Table 1, Entry 3.
7
8
S. Orlandi, F. Colombo, M. Benaglia, Synthesis 2005, 1689.
a) Y. Kuninobu, A. Kawata, K. Takai, J. Am. Chem. Soc.
2005, 127, 13498. b) Y. Kuninobu, Y. Tokunaga, A. Kawata,
K. Takai, J. Am. Chem. Soc. 2006, 128, 202. c) Y. Kuninobu,
Y. Nishina, M. Shouho, K. Takai, Angew. Chem., Int. Ed.
2006, 45, 2766. d) Y. Kuninobu, Y. Nishina, C. Nakagawa,
K. Takai, J. Am. Chem. Soc. 2006, 128, 12376. e) Y.
Kuninobu, A. Kawata, K. Takai, Org. Lett. 2005, 7, 4823.
f) Y. Kuninobu, A. Kawata, K. Takai, J. Am. Chem. Soc.
2006, 128, 11368.
1
9
The H NMR yields were determined by using 1,1,2,2-tetra-
chloroethane as an internal standard.
10 A ketimine, which was derived from the reaction between
acetophenone and aniline, did not give the corresponding
propargylamine even at 80 ꢀC.
11 For reports that those triflates act as a Lewis acid and activate
aldimines, see: S. Kobayashi, Top. Organomet. Chem. 1999,
2, 63.
12 The reaction did not proceed in the presence of triethylamine
or N-methylaniline instead of a rhenium complex, [ReBr-
(CO)3(thf)]2. The result indicates that aldimines or propargyl
amines did not increase the nucleophilicity of trimethyl-
silylacetylene (2a) by deprotonation.
13 For examples of hydride-alkynyl-rhenium complexes, see:
a) K.-W. Lee, W. T. Pennington, A. W. Cordes, T. L. Brown,
J. Am. Chem. Soc. 1985, 107, 631. b) K.-W. Lee, T. L. Brown,
Organometallics 1985, 4, 1025.
Ph
1) molecular sieves (4A)
HN
Ph
O
neat, 25 °C, 3 h
+
PhNH2
(2)
2) [ReBr(CO)3(thf)]2 (2.5 mol %)
SiMe3 (2a, 1.1 equiv.)
neat, 50 °C, 24 h
Ph
H
SiMe3
(1.1 equiv.) (1.0 equiv.)
3c
95%
In summary, we have succeeded in the rhenium-catalyzed
synthesis of propargylamines by the reactions of aromatic aldi-
mines with trimethylsilylacetylene in excellent yields under mild
reaction conditions. Another merit of these reactions is that they
proceed in the absence of a solvent. A propargylamine could also
be obtained quantitatively by the stepwise treatment of benzal-
dehyde with aniline, and trimethylsilylacetylene, and the rheni-
um catalyst.
14 Although the reaction proceeded with only 5.0 mol % of
copper(I) chloride, the yield of propargylamine (4) was low
(62%).
Published on the web (Advance View) November 11, 2006; doi:10.1246/cl.2006.1376