Asymmetric hydrogenation of quinolines catalyzed by iridium complexes of BINOL-derived diphosphonites

Article abstract of DOI:10.1039/b602320g

A chiral diphosphonite, derived from BINOL and with an achiral diphenyl ether backbone, is an excellent ligand for the Ir-catalyzed asymmetric hydrogenation of quinolines; achiral P-ligands serving as possible additives (ee = 73-96%). The Royal Society of Chemistry 2006.

Full text of DOI:10.1039/b602320g

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Asymmetric hydrogenation of quinolines catalyzed by iridium
complexes of BINOL-derived diphosphonites
Manfred T. Reetz* and Xiaoguang Li
Received (in Cambridge, UK) 16th February 2006, Accepted 28th March 2006
First published as an Advance Article on the web 13th April 2006
DOI: 10.1039/b602320g
A chiral diphosphonite, derived from BINOL and with an
achiral diphenyl ether backbone, is an excellent ligand for the
Ir-catalyzed asymmetric hydrogenation of quinolines; achiral
P-ligands serving as possible additives (ee = 73–96%).
The asymmetric hydrogenation of quinoline derivatives constitutes
a convenient route to chiral tetrahydroquinolines, compounds
which are not only useful synthetic intermediates but also the
1
structural units of a number of alkaloids. Inspite of a fair amount
2
of effort, only four ligand systems are known to provide ee values
greater than 90%. Zhou et al. reported that Ir complexes generated
3
and (R)-MeO-Biphep or a ferrocenyl-
in situ from [Ir(COD)Cl]
2
4
oxazoline-derived P,N-ligand are effective in the asymmetric
hydrogenation of 2-substituted quinolines (maximum ee = 96 and
9
2%, respectively). Similar results were subsequently described by
5a
Chan using his previously prepared family of chiral dipyridyl-
6
phosphane ligands (P-Phos) (maximum ee = 92%) and more
5b
recently H8-BINAPO. In our own earlier work, we showed that
readily accessible and therefore cheap BINOL-derived dipho-
sphonites of the type 1–5 are highly efficient ligands in Rh-
7
catalyzed olefin hydrogenation, Rh-catalyzed conjugate addition
8
reactions of arylboronic acids and Ru-catalyzed transfer reduc-
9
tions of ketones. In each case, success depends upon the
appropriate choice of achiral backbone, i.e., among compounds
such as 1–5, there is no universal ligand that is most suited to all
reaction types. We now report that this class of chiral ligands is
also well suited to the asymmetric Ir-catalyzed hydrogenation of
quinoline derivatives, and that, once again, the nature of the
backbone is crucial.
Ligands 1–5, all prepared from (S)-BINOL, were first screened
in the asymmetric hydrogenation of 6a, with the formation of
the use of ligands 1, 2, 3, 4 and 5 were 45% (R), 50% (R), 16%
(R), 43% (S) and 88% (S), respectively. The reaction conditions
using the diphenyl ether-derived ligand 5 were then optimized
tetrahydroquinoline 7a under non-optimized conditions using I
2
as
10
an additive (substrate : [Ir(COD)Cl] : ligand : I = 100 : 1 : 2 : 20;
2
2
(substrate : [Ir(COD)Cl] : 5 : I = 200 : 1 : 2 : 2; 60 bar H ;
2 2 2
15 bar H ; toluene; 20 h). The ee values for 7a resulting from
2
toluene; 20 h), resulting in an ee value of 92% (>96% conversion).
At 0 uC, enantioselectivity increased to ee = 96% (>96%
conversion).
Max-Planck-Institut f u¨ r Kohlenforschung, D-45470 M u¨ lheim/Ruhr,
Germany.E-mail:reetz@mpi-muelheim.mpg.de;Fax:(+49)2083062985
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Chem. Commun., 2006, 2159–2160 | 2159

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Table 1 Ir-catalyzed asymmetric hydrogenation of quinoline deriva-
tives 6a–g using ligand (S)-5, with and without achiral P-additives
with 5. The ee values were determined by HPLC (OJ, AS-H or
3,4
OD-H columns), similar to Zhou’s procedure.
a
In summary, we have developed an efficient catalyst system for
the asymmetric Ir-catalyzed hydrogenation of quinoline deriva-
tives. The ligand comprises a diphosphonite derived from BINOL
and an achiral backbone originating from diphenyl ether. Due to
the ready accessibility of this ligand, the process is likely to attract
the interest of industrial chemists. Illuminating the source of the
enantioselectivity and the possible role of the achiral P-ligand (new
Entry
Quinoline
Achiral ligand
Conversion (%)
ee (%)
1
2
3
4
5
6
7
8
9
6a
6a
None
None
10
10
11
12
None
10
None
10
None
10
None
10
10
.96
.96
.96
.96
66
92(S)
96(S)
96(S)
94(S)
94(S)
94(S)
85(S)
91(S)
88(S)
91(S)
73(S)
80(S)
82(R)
90(R)
92(R)
b
b
6a
6a
6a
6a
c
c
c
73
6b
6b
6c
6c
.96
.96
.96
.96
42
.96
.96
.96
.96
Rh-complexes or O -scavengers?) are goals for the future.
2
We thank the Fonds der Chemischen Industrie for generous
support.
1
1
1
1
1
1
a
0
1
2
3
4
5
b
6d
6e
6f
6f
6g
Notes and references
1
(a) J. G. Keay, in Comprehensive Organic Synthesis, ed. B. M. Trost and
I. Fleming, Pergamon, Oxford, 1991, vol. 8, pp. 579–601; (b)
A. R. Katritzky, S. Rachwal and B. Rachwal, Tetrahedron, 1996, 52,
Substrate : [Ir(COD)Cl]
2
: (S)-5 : I
2 2
= 200 : 1 : 2 : 2; 60 bar H ;
c
b
toluene; 23 uC; 20 h. Substrate : Ir = 50 : 1 at 0 uC. 15 bar H
2
.
15031–15070; (c) Comprehensive Natural Products Chemistry, ed. D. H.
Barton, K. Nakanishi and O. Meth-Cohn, Elsevier, Oxford, 1999,
vol. 1–9.
Reviews of asymmetric hydrogenation of heteroaromatic compounds:
2
(a) H.-U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner and
M. Studer, Adv. Synth. Catal., 2003, 345, 103–151; (b) W. Tang and
X. Zhang, Chem. Rev., 2003, 103, 3029–3069; (c) Principles
and Applications of Asymmetric Synthesis, ed. G. Q. Lin, Y. M. Li
and A. S. C. Chan, Wiley-Interscience, New York, 2001. For some
recent publications, see: (d )J. P. Henschke, M. J. Burk, C. G. Malan,
D. Herzberg, J. A. Peterson, A. J. Wildsmith, C. J. Cobley and G. Casy,
Adv. Synth. Catal., 2003, 345, 300–307; (e) R. Kuwano, K. Kaneda,
T. Ito, K. Sato, T. Kurokawa and Y. Ito, Org. Lett., 2004, 6, 2213–2215;
(f) C. Y. Legault and A. B. Charette, J. Am. Chem. Soc., 2005, 127,
8966–8967; (g) F. Glorius, N. Spielkamp, S. Holle, R. Goddard and
C. W. Lehmann, Angew. Chem., 2004, 116, 2910–2913, (Angew. Chem.,
Int. Ed., 2004, 43, 2850–2852) and references cited therein.
Previously we have shown that monodentate BINOL-derived
phosphites and phosphonites are excellent ligands in a variety of
Rh-catalyzed olefin hydrogenation reactions, and that mixtures of
11
such ligands and achiral monodentate P-ligands can lead to
further improvements. So far, we have not been able to reach ee
values of >80% in the Ir-catalyzed hydrogenation of quinolines
using this strategy. Nevertheless, we decided to test possible effects
when using mixtures of ligand 5 and achiral P-ligands such as 8–12
3
W.-B. Wang, S.-M. Lu, P.-Y. Yang, X.-W. Han and Y.-G. Zhou, J. Am.
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4 S.-M. Lu, X.-W. Han and Y.-G. Zhou, Adv. Synth. Catal., 2004, 346,
09–912.
9
5
(a) L. Xu, K. H. Lam, J. Ji, J. Wu, Q.-H. Fan, W.-H. Lo and
A. S. C. Chan, Chem. Commun., 2005, 1390–1392; (b) K. H. Lam, L. Xu,
L. Feng, Q.-H. Fan, F. L. Lam, W.-H. Lo and A. S. C. Chan, Adv.
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W. T. Wong, J. Am. Chem. Soc., 2000, 122, 11513–11514; (b) J. Wu,
H. Chen, Z.-Y. Zhou, C. H. Yeung and A. S. C. Chan, Synlett, 2001,
(5 : achiral ligand = 1 : 2). Again, substrate 6a was used in the
model reaction. Generally, no positive effects resulted, but in some
cases small improvements were observed, depending upon the
nature of the achiral ligand (8, 92% ee; 9, 90% ee; 10, 94% ee; 11,
6
94% ee; 12, 94% ee).
1
050–1054; (c) J. Wu, H. Chen, W. H. Kwok, K. H. Lam, Z. Y. Zhou,
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(
A. S. C. Chan, J. Org. Chem., 2002, 67, 7908–7910; (e) J. Wu, X. Chen,
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7
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7
1, 1503–1509.
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8
9
4
1
0 (a) A. Togni, Angew. Chem., 1996, 108, 1581–1583, (Angew. Chem., Int.
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Following these exploratory experiments, the optimized proto-
col was applied to the other substrates. The results of the
hydrogenation experiments using compounds 6a–g are summar-
ized in Table 1. It can be seen that in all cases, with the exception
of 6d and 6e (Table 1, entries 11 and 12), enantioselectivities in the
range 90–96% ee were achieved, although in some cases this
required the use of an appropriate achiral ligand in combination
3
425–3428).
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Angew. Chem., Int. Ed., 2005, 44, 2959–2962); (b) R. Hoen, J. A.
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2
160 | Chem. Commun., 2006, 2159–2160
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