Catalytic asymmetric hydrogenation of heteroaromatic compounds, indoles [12]

Full text of DOI:10.1021/ja001271c

7614
J. Am. Chem. Soc. 2000, 122, 7614-7615
Catalytic Asymmetric Hydrogenation of
Heteroaromatic Compounds, Indoles
Ryoichi Kuwano,* Koji Sato, Takashi Kurokawa,
Daisuke Karube, and Yoshihiko Ito*
Department of Synthetic Chemistry and
Biological Chemistry, Graduate School of Engineering
Kyoto UniVersity, Sakyo-ku, Kyoto 606-8501, Japan
ReceiVed April 12, 2000
Catalytic asymmetric hydrogenations of prochiral unsaturated
1
2
3
4
compounds, olefin, ketone, and imine, have been intensively
studied and are considered as a versatile method of creating a
chiral carbon center.5 However, no highly enantioselective
hydrogenation of heteroaromatic groups has so far been reported
doline (2a) with 85% ee (77% conversion). No reduction of the
fused aromatic ring of 1a was observed.
On further investigation into the asymmetric hydrogenation,
6
except that of 2-methylquinoxaline to our knowledge. Resonance
[
Rh(nbd)
2 6
]SbF was found to be superior to Rh(acac)(cod) as
stability of heteroaromatic compounds might impede the enan-
catalyst precursor (Table 1). It is noted that addition of base is
7
tioselective hydrogenation, which may find potentially wide
applicability in stereoselective organic synthesis.8 Herein, we
describe the highly enantioselective hydrogenation of heteroaro-
matic compounds, indoles.
,9
a
Table 1. Catalytic Asymmetric Hydrogenation of 1a
b
c
entry
base
none
Et
Cs
CO
pyridine
Cs CO
Cs CO3
2
P(H ), MPa temp °C convn, % ee, %
1
2
3
4
5
6
5.0
60
60
60
60
60
60
60
trace
100
100
44
7 (S)
We recently disclosed that the rhodium complex generated from
3
N
5.0
5.0
5.0
5.0
1.0
94 (R)
94 (R)
76 (R)
3
Rh(acac)(cod) and PPh is a good catalyst for the hydrogenation
2
CO
3
10
of five-membered heteroaromatic compounds. Thus chiral
rhodium complexes prepared in situ from Rh(acac)(cod) and
various commercially available chiral bisphosphines (1 mol %)
were examined for asymmetric hydrogenation of N-acetyl-2-
K
2
3
0
100
2
3
92 (R)
93 (R)
d
100e
7
2
10.0
2
butylindole (1a) at 60 °C for 2 h with 5.0 MPa of H in 2-propanol
a
Reactions were carried out in 2-propanol (2.0 mL) for 2 h. 1a (0.5
]SbF /(S,S)-(R,R)-PhTRAP/base was 100/1.0/1.05/10
(
eq 1), resulting in non-enantioselective hydrogenation (0-1%
mmol)/[Rh(nbd)
2
6
11
ee). Fortunately, the successful asymmetric hydrogenation has
b
1
unless otherwise noted. Determined by H NMR analysis of crude
been achieved by use of a trans-chelating chiral bisphosphine
product. c Determined by HPLC analysis with CHIRALPAK AD. d 1a/
[Rh(nbd) ]SbF /(S,S)-(R,R)-PhTRAP/Cs CO was 1000/1.0/1.1/10. The
ligand, (S,S)-(R,R)-PhTRAP,1
2,13
giving (R)-N-acetyl-2-butylin-
2
6
2
3
e
reaction was carried out for 20 h. 92% isolated yield.
(
1) For reviews, see: (a) Takaya, H.; Ohta, T.; Noyori, R. In Catalytic
Asymmetric Synthesis; Ojima, I., Ed.; VCH Publishers: New York, 1994; pp
-39. (b) Noyori, R. In Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994; pp 16-94.
2) For reviews, see: (a) Pfaltz, A. In StereoselectiVe Synthesis; Helmchen,
G., Hofmann, R. W., Mulzer, J., Schaumann, E., Eds.; Theime: Stuttgart,
996; Vol. 7, pp 4334-4359. (b) Brown, J. M. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
999; Vol. 1, pp 121-182. (c) Halterman, R. L. In ComprehensiVe Asymmetric
Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
999; Vol. 1, pp 183-195.
necessary for achievement of high enantioselectivity as well as
high catalytic activity. The [Rh(nbd) ]SbF -(S,S)-(R,R)-PhTRAP
2 6
catalyst scarcely promoted the hydrogenation in the absence of
base, giving a trace of 2a with only 7% ee (S) (entry 1). Addition
3 2 3
of 10 mol % of Et N or Cs CO brought remarkable improvement
1
(
1
of the enantioselectivity and catalytic activity (100% conversion,
1
94% ee (R)) (entries 2 and 3).14 Both the enantioselectivity and
1
catalytic activity were significantly dependent upon base: K
CO gave (R)-2a with 76% ee, and pyridine did not activate the
cationic PhTRAP-rhodium complex at all (entries 4 and 5). The
amount of Cs CO did not affect the selectivity: 20 mol %, 94%
ee; 1 mol %, 93% ee. It is possible to carry out the asymmetric
hydrogenation at lower pressure (1.0 MPa) without significant
decrease of the selectivity and reaction rate (entry 6). The amount
of PhTRAP-rhodium complex can be reduced to 0.1 mol %,
and the reaction was completed within 20 h to give (R)-2a of
2
-
(
3) For reviews, see: (a) Brunner, H. In StereoselectiVe Synthesis;
Helmchen, G., Hofmann, R. W., Mulzer, J., Schaumann, E., Eds.; Theime:
Stuttgart, 1996; Vol. 7, pp 3945-3966. (b) Ohkuma, T.; Noyori, R. In
ComprehensiVe Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto,
H., Eds.; Springer: Berlin, 1999; Vol. 1, pp 199-246.
3
2
3
(4) For reviews, see: (a) Martens, J. In StereoselectiVe Synthesis; Helmchen,
G., Hofmann, R. W., Mulzer, J., Schaumann, E., Eds.; Theime: Stuttgart,
1
996; Vol. 7, pp 4199-4219. (b) Blaser, H.-U.; Springer, F. In ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer: Berlin, 1999; Vol. 1, pp 247-265.
(5) For examples, see: (a) Schreiber, S. L.; Kelly, S. E.; Porco, J. A., Jr.;
Sammakia, T.; Suh, E. M. J. Am. Chem. Soc. 1988, 110, 6210-6218. (b)
9
3% ee in 92% isolated yield (entry 7).
Although 2-propanol has frequently been used as a hydrogen
source in the transfer hydrogenation of unsaturated compounds
Kitamura, M.; Nagai, K.; Hsiao, Y.; Noyori, R. Tetrahedron Lett. 1990, 31,
5
49-542. (c) Taber, D. F.; Wang, Y. J. Am. Chem. Soc. 1997, 119, 22-26.
(
6) Bianchini, C.; Barbaro, P.; Scapacci, G.; Farnetti, E.; Graziani, M.
Organometallics 1998, 17, 3308-3310.
7) For resonance energy of heteroaromatic compounds, see: Bird, C. W.
Tetrahedron Lett. 1992, 48, 335-340.
8) For reviews of the hydrogenation of heteroaromatic compounds, see:
(
(11) Representative results of using commercially available chiral bisphos-
phines were as follows: (R)-BINAP, 1% ee (S); (R)-(S)-BPPFA, 0% ee;
(2S,3S)-Chiraphos, 1% ee (S); (-)-(2R, 3R)-DIOP, 0% ee; (2S, 4S)-BPPM,
0% ee; (R,R)-Me-DuPHOS, 0% ee.
(12) (S,S)-(R,R)-PhTRAP ) (R,R)-2,2′′-bis[(S)-(diphenylphosphino)ethyl]-
1,1′′-biferrocene.
(13) (a) Sawamura, M.; Hamashima, H.; Ito, Y. Tetrahedron: Asymmetry
1991, 2, 593-596. (b) Sawamura, M.; Hamashima, H.; Sugawara, M.;
Kuwano, R.; Ito, Y. Organometallics 1995, 14, 4549-4558.
(14) We presume that a Rh(I)H complex is an active species for the
asymmetric hydrogenation (see ref 10). The base additive possibly deprotonates
from a cationic Rh(III)H
See: Schrock, R. R.; Osborn, J. A. J. Am. Chem. Soc. 1976, 98, 2134-2143.
(
(
a) Keay, J. G. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I. Eds.; Pergamon: Oxford, 1991; Vol. 8, pp 579-602. (b) Gribble, G. W. In
ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Perga-
mon: Oxford, 1991; Vol. 8, pp 603-633. (c) Katritzky, A. R.; Rachwal, S.;
Rachwal, B. Tetrahedron 1996, 52, 15031-15070.
(9) For examples, see: (a) Rossen, K.; Weissman, S. A.; Sager, J.; Reamer,
R. A.; Askin, D.; Volante, R. P.; Reider, P. J. Tetrahedron Lett. 1995, 36,
6419-6422. (b) Gilchrist, T. L.; Graham, K.; Coulton, S. Tetrahedron Lett.
1
995, 36, 8693-8696.
(
2
complex, generating a neutral Rh(I)H complex.
10) Kuwano, R.; Sato, K.; Ito, Y. Chem. Lett. 2000, 428-429.
1
0.1021/ja001271c CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/20/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 31, 2000 7615
Table 2. Catalytic Asymmetric Hydrogenations of 2-Substituted
a
Indoles
hydrogenation of 1d (83% ee). Use of Et
improved the enantioselectivity remarkably, providing (S)-2d with
5% ee (entry 3). The enantiomeric excess of 2 was little affected
3 2 3
N instead of Cs CO
9
by the steric and electronic properties of the substituent on the
fused aromatic ring of 1 (entries 4-7). The protective group on
the nitrogen atom may play an important role in the enantiose-
lection. N-Boc derivative 3 was converted into (S)-4 with lower
enantiomeric excess (entry 8).18 Optically active 3-substituted
indoline 6 could be obtained by use of the [Rh(nbd)
PhTRAP-Cs CO catalyst, but the hydrogenation competed with
the undesirable alcoholysis of 5 significantly (eq 3).
2 6
]SbF -
2
3
In summary, the catalytic asymmetric hydrogenation of indoles
has been accomplished by use of the [Rh(nbd) ]SbF -PhTRAP-
2
6
base catalyst, providing a variety of optically active indolines with
up to 95% ee. This is the first example of highly enantioselective
hydrogenation of five-membered heteroaromatic compounds using
asymmetric catalysis. Future work will be directed toward the
development of highly enantioselective hydrogenation of other
heteroaromatic compounds, pyrrole, furan, pyridine, etc.
a
2
Reactions were carried out at 60 °C and 5.0 MPa of H in
Acknowledgment. This work was supported by a Grant-in-Aid for
Scientific Research from the Ministry of Education, Science, and Culture,
Japan.
2
[
-propanol (2.0 mL) unless otherwise noted. 1 or 3 (0.5 mmol)/
Rh(nbd) ]SbF /(S,S)-(R,R)-PhTRAP/Cs CO
lated yield. Determined by HPLC analysis with CHIRALPAK AD
unless otherwise noted. Determined by HPLC analysis with CHIRAL-
was 100/1.0/1.05/10. b Iso-
2
6
2
3
c
d
Supporting Information Available: Experimental procedures and
compound characterization data (PDF). This material is available free of
charge via the Internet at http://pubs.acs.org.
e
CEL OD-H. The reaction was carried out at 100 °C and 10.0 MPa.
f
Et
3
N was used instead of Cs
2
CO
3
. Determined by HPLC analysis with
CHIRALPAK AS.
JA001271C
using a transition metal complex,15 such a possibility is ruled out
by the experiment using H and Rh(acac)(cod)-PhTRAP catalyst
in 2-propanol-d . No product resulting from D addition was
detected in GC-MS analysis.1
A variety of 2-substituted indoles were hydrogenated into the
corresponding indolines with high enantiomeric excesses in high
yields (eq 2, Table 2). The hydrogenations of 2-isobutyl- and
(15) (a) Spogliarich, R.; Tencich, A.; Kaspar, J.; Graziani, M. J. Organomet.
2
Chem. 1982, 240, 453-459. (b) Saburi, M.; Ohnuki, M.; Ogasawara, M.;
Takahashi, T.; Uchida, Y. Tetrahedron Lett. 1992, 33, 5783-5786. (c) Haack,
K.-J.; Hashiguchi, S.; Fujii, A.; Ikariya, T.; Noyori, R. Angew. Chem., Int.
Ed. Engl. 1997, 36, 285-288. (d) Alonso, D. A.; Brandt, P.; Nordin, S. J.
M.; Andersson, P. G. J. Am. Chem. Soc. 1999, 121, 9580-9588.
8
2
6,17
(
16) The hydrogenation in 2-propanol-d
PhTRAP-Cs CO catalyst also gave the product resulting from H
confirmed by H NMR analysis). However, the exchange of hydrogen for
deuterium on the N-acetyl group was observed in this case.
8
using the [Rh(nbd)
2
]SbF
6
-
2
3
2
addition
1
(
2-phenylindole, 1b and 1c, proceeded with 91% ee and 87% ee,
respectively (entries 1 and 2). With indole-2-carboxylate 1d, the
PhTRAP-rhodium complex failed in high asymmetric induction
(17) The reactions in other solvents also proceeded with high enantiose-
lectivity and good catalyst activity: 92% conversion, 91% ee in toluene; 53%
conversion, 87% ee in 1,2-dichloroethane; 52% conversion, 84% ee in THF.
2
(79% ee) under the above conditions (60 °C, 5.0 MPa of H ).
(18) The hydrogenation of 3 proceeded with 46% ee (S) under the best
Higher temperature and hydrogen pressure (100 °C, 10.0 MPa
of H ) were, however, favorable to the highly enantioselective
conditions for the reduction of 1d ([Rh(nbd)
100 °C, 10.0 MPa, 0.5 h).
2
]SbF
6
3
-PhTRAP-Et N catalyst,
2