Gold-catalyzed intramolecular hydroamination of allenes: a case of chirality transfer

Article abstract of DOI:10.1016/j.tetlet.2006.04.087

The hydroamination of allenes proceeded smoothly in the presence of gold catalysts to give the corresponding 2-vinyl pyrrolidines and piperidines in high yields. The reaction is very efficient and can be carried out with only 1-5 mol % catalyst at room te

Full text of DOI:10.1016/j.tetlet.2006.04.087

Tetrahedron Letters 47 (2006) 4749–4751
Gold-catalyzed intramolecular hydroamination of allenes: a case
of chirality transfer
Nitin T. Patil, L e´ opold Mpaka Lutete, Naoko Nishina and Yoshinori Yamamoto*
Department of Chemistry, Graduate School of Science, Tohoku University, Sendai 980-8578, Japan
Received 8 March 2006; revised 8 April 2006; accepted 20 April 2006
Available online 22 May 2006
Abstract—The hydroamination of allenes proceeded smoothly in the presence of gold catalysts to give the corresponding 2-vinyl
pyrrolidines and piperidines in high yields. The reaction is very efficient and can be carried out with only 1–5 mol % catalyst at room
temperature and under extremely mild conditions. As an example of chirality transfer, it is shown that aminoallene 1a (96% ee),
synthesized from (S)-(ꢀ)-1-octyn-3-ol, was converted into the corresponding pyrrolidine 2a (94% ee) in 99% yield.
ꢀ
2006 Elsevier Ltd. All rights reserved.
The synthesis of heterocycles via the metal-catalyzed
addition of nucleophiles to activated and non-activated
C–C bonds is one of the most important processes in
The use of gold catalysts in organic synthesis has re-
ceived much attention in recent years because of their
ability to co-ordinate with C–C bonds, thereby allowing
1
9
organic synthesis. Intramolecular cyclization of allenes
the attack of various nucleophiles. Taking into consid-
with tethered amines, formerly known as hydroamina-
tion,2 in the presence of a transition metal catalyst
represents the most common route for generating nitro-
gen-containing heterocycles (Eq. 1). Silver and mercury
eration the recent reports on allene activation by gold
catalysis, and more particularly a recent report by
10
Morita and Krause on the cyclization of a-amino allenes
1
0a
(Eq. 2), it occurred to us that it would be possible to
synthesize N-heterocycles in the presence of gold salts.
Herein, we report our preliminary results concerning
Au(I) and Au(III) catalyzed room temperature intra-
molecular hydroamination of allenes leading to pyrrol-
3
salts have been used for this purpose. However, the
Lewis acidity of the former catalyst and toxicity of the
latter catalyst restrict their use in the hydroamination.
An alternative strategy involves the use of organolanth-
4
5
11
anides and titanium as well as group four bis(sulfon-
idines and piperidines (Eq. 3).
6
amido) complexes. Our own interest on the palladium
catalyzed reactions of allenes encouraged us to examine
Me
2 mol%
AuCl3
Me
7
OR2
the possibility of the use of a palladium catalyst. In this
regard, we previously reported the cyclization of amino-
allenes in the presence of catalytic amounts of a palla-
dium complex under acidic conditions (0.15–1.0 equiv
R1
•
OR2
R1
ð2Þ
ð3Þ
N
NHX
CH Cl rt
2
2,
X
H
single diastereomer
high diastereoselectivity
8
C H
5 11
of acetic acid) (Eq. 1, TM = Pd). The use of a carbox-
Au(I) or Au(III),
rt, 3-24 h
•
ylic acid as an additive and high reaction temperature
n N
C5H11
(
70 ꢁC) were the drawbacks of the palladium catalyzed
R
NHR
53-99%
n = 1,2
hydroamination.
n
R
single enantiomer
high enantioselectivity
R
•
cat. TM
ð1Þ
Initial experiments were performed using aminoallene
NHR
NR
1
a as a model substrate, which was easily prepared
1
2
by the literature procedure.
The cyclization was
attempted in the presence of 5 mol % of commercially
Keywords: Allene; Gold catalyst; Hydroamination; Nitrogen hetero-
available AuBr in various solvents, and was found to
cycles; Chirality transfer.
3
*
Corresponding author. Tel.: +81 22 795 6581; fax: +81 22 795
784; e-mail: yoshi@mail.tains.tohoku.ac.jp
occur very smoothly in THF at room temperature in just
3 h. After an easy work-up that consisted of filtration of
6
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doi:10.1016/j.tetlet.2006.04.087

4750
N. T. Patil et al. / Tetrahedron Letters 47 (2006) 4749–4751
the reaction mixture on a short column of silica gel, the
corresponding pyrrolidine 2a was isolated in high purity
and in 99% yield as a single E-isomer. Further optimiza-
tion studies revealed that only 1 mol % of the catalyst
was required in order to obtain the product in quantita-
tive yield (Table 1, entry 1). Bearing in mind that the
gold catalyst coordinates the allene moiety through its
Lewis acidic character, we then examined the activity
of a variety of gold(I) and gold(III) salts. As shown in
starting material was recovered (entry 8). Thus, it
became clear that the use of –Ts, –COOEt, –Cbz or
–Bn as amine protecting groups was required for the
present reaction. An unprotected amine and an amine
bearing a strong electron withdrawing group did not
undergo reaction. To further examine the scope of this
process for the synthesis of piperidines, we synthesized
the substrates 1g and 1h and tested their reactivity.
The piperidines 2g and 2h were obtained in 53% and
80% yields, respectively.
entry 2, AuCl also gave an almost complete conversion
3
giving the product 2a in 98% yield. The use of gold(I)
chloride as a catalyst resulted in the formation of 2a in
It is clear that the scope and synthetic utility of this pro-
cess would be enhanced dramatically if the chirality was
transferred from the starting aminoallenes to the pro-
ducts. To check this possibility, we synthesized amino
allene 1a (96% ee) from (S)-(ꢀ)-1-octyn-3-ol, following
9
9% yield (entry 3). Although gold(I) or gold (III) salts
gave similar results, we preferred AuCl because of its air
stability compared to AuCl and AuBr . Further inves-
3
3
tigations on the protecting groups on the amine were
then pursued. The substrate 1b containing an ethoxycar-
bonyl group on the amine reacted smoothly in the pres-
ence of 1 mol % AuCl, giving the pyrrolidine 2b in 97%
yield (entry 4). The use of a benzyloxycarbonyl group,
which is used more frequently in organic synthesis, also
proved excellent for this hydroamination reaction (entry
1
3
the literature procedure. Treatment of enantiomeri-
cally pure aminoallene 1awith 1 mol % AuCl in THF
at rt gave pyrrolidine2a in excellent yield with 94% ee
25
{½aꢁ ꢀ39 (c 1.0, CHCl )} (Eq. 4).
D
3
C H
5
11
AuCl, THF
•
5
1
2
). However, in the case of the benzyl protected amine
d, 5 mol % of AuCl was necessary in order to obtain
d in 76% yield after stirring for 24 h (entry 6). As shown
N
R
C5H11
9
9%
ð4Þ
NHR
1
a 96% ee
2a 94% ee
in entry 7, the substrate 1e, wherein the amine was not
protected by any protecting group, did not give any de-
sired product; a complex mixture was obtained. The fail-
ure of this reaction can be explained on the basis of the
Lewis acidity of the gold catalyst. Presumably, the coor-
dination of the gold catalyst with the basic amine takes
place which in turn deactivates the catalyst. The use of a
very strong electron withdrawing group did not lead to a
reaction. When substrate 1f containing an –Nf protected
amine was subjected to gold catalysis under the standard
conditions, no desired product was obtained at all; the
In conclusion, we have found that Au(I) or Au(III) cat-
alysts promote a highly efficient intramolecular hydro-
amination of allenes under very mild conditions. The
method allowed the synthesis of five and six-membered
nitrogen heterocycles in high yields and in an atom eco-
nomical manner. The high catalyst activity of gold cata-
lysts associated with very mild conditions would allow
further applications towards the synthesis of natural
products.
a
Table 1. Au catalyzed cyclization of aminoallenes
b
Entry
Aminoallene 1
Product 2
Time (h)
Yield (%)
C H
5
11
•
N
C5H11
R
NHR
1
2
3
4
5
6
7
8
1a R = Ts
1a R = Ts
1a R = Ts
1b R = COOEt
1c R = Cbz
1d R = Bn
AuBr
3
2a R = Ts
2a R = Ts
2a R = Ts
2b R = COOEt
2c R = Cbz
2d R = Bn
2e R = NH
2f R = Nf
3
3
3
3
3
24
24
24
99
98
99
97
99
AuCl
AuCl
AuCl
AuCl
AuCl
AuCl
AuCl
3
c
76
c,d
1e R = NH
1f R = Nf
2
2
0
c,e
0
C H
5
11
•
N
R
C H
5 11
NHR
c
9
1g R = Ts
1h R = Cbz
AuCl
AuCl
2g R = Ts
2h R = Cbz
24
24
53
c
10
80
a
b
c
The reaction of 1 in the presence of 1 mol % of gold salts were carried out at rt in THF unless otherwise noted.
Isolated yields.
5
mol % of catalyst was used.
d
e
A complex mixture of products was obtained.
The starting material was recovered.

N. T. Patil et al. / Tetrahedron Letters 47 (2006) 4749–4751
4751
General procedure: The preparation of 2a is representa-
tive. 1a (100 mg, 0.3112 mmol) and AuCl (3.6 mg,
9. Reviews: (a) Dyker, G. Angew. Chem., Int. Ed. 2000, 39,
237–4239; (b) Hashmi, A. S. K. Gold Bull. 2003, 36, 3–9;
c) Hashmi, A. S. K. Gold Bull. 2004, 37, 51–65; (d)
Arcadi, A.; Giuseppe, S. D. Curr. Org. Chem. 2004, 8,
95–812; (e) Hoffmann-Roder, A.; Krause, N. Org.
4
(
0
.0156 mmol in THF (2 mL) were stirred at rt in a screw
capped vial for 3 h. The reaction mixture was directly
loaded on a silica gel column and eluted with 1:1 hex-
ane–ethyl acetate to afford pure 2a (99 mg, 99%).
7
Biomol. Chem. 2005, 3, 387–391; (f) Hashmi, A. S. K.
Angew. Chem., Int. Ed. 2005, 44, 6990–6993; (g) Ma, S.;
Yu, S.; Gu, Z. Angew. Chem., Int. Ed. 2006, 45, 200–203;
For some recent examples on the activation of C–C bond
by gold catalysts, see: (h) Zhang, J.; Yang, C.-G.; He, C.
J. Am. Chem. Soc. 2006, 128, 1798–1799; (i) Genin, E.;
Toullec, P. Y.; Antoniotti, S.; Brancour, C.; Genet, J.-P.;
Michelet, V. J. Am. Chem. Soc. 2006, 128, 3112–3113; (j)
Han, X.; Widenhoefer, R. A. Angew. Chem., Int. Ed. 2006,
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5
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3