Novel Ir-SYNPHOS and Ir-DIFLUORPHOS catalysts for asymmetric hydrogenation of quinolines

Article abstract of DOI:10.1055/s-2007-991076

Novel Ir-SYNPHOS and Ir-DIFLUORPHOS catalysts were synthesized and used for the synthesis of tetrahydroquinolines via asymmetric hydrogenation of the corresponding quinoline derivatives. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-991076

LETTER
2743
Novel Ir–SYNPHOS® and Ir–DIFLUORPHOS® Catalysts for Asymmetric
Hydrogenation of Quinolines
Catalysts for Asy
o
mmetric Hyd
r
rogenat
a
ion of Quin
l
olines ie Deport,a Marie Buchotte,a Keren Abecassis,a Hiroshi Tadaoka,b Tahar Ayad,a Takashi Ohshima,b
Jean-Pierre Genet,*a Kazushi Mashima,*b Virginie Ratovelomanana-Vidal*a
a
Laboratoire de Synthèse Sélective Organique et Produits Naturels, UMR 7573 C.N.R.S, Ecole Nationale Supérieure de Chimie de Paris,
11, Rue P. et M. Curie, 75231 Paris Cedex 05, France
Fax +33(1)44071062; E-mail: jean-pierre-genet@enscp.fr; E-mail: virginie-vidal@enscp.fr
b
Department of Chemistry, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan
Fax +81(6)68506245; E-mail: mashima@chem.es.osaka-u.ac.jp
Received 10 August 2007
Abstract: Novel Ir–SYNPHOS and Ir–DIFLUORPHOS catalysts
were synthesized and used for the synthesis of tetrahydroquinolines
via asymmetric hydrogenation of the corresponding quinoline
derivatives.
R'
N
R
H
1
Key words: catalysts, iridium, hydrogenation, enantioselectivity
Me
NH
Me
O
N
N
H
N
H
H2N
O
Over the last few years, tetrahydroquinoline derivatives 1
have stimulated greatest interest due to their biological
activities. Many simple synthetic 1,2,3,4-tetrahydro-
quinolines are used as potential drugs.1 Among them, the
2,4,6-trisubstituted tetrahydroquinoline 22 exhibited
activity as a bradykinin antagonist with muscarinic re-
ceptors, L-689,560 (3)3 is a potent NMDA antagonist and
(–)-galipeine (4)4 can be used against fevers (Figure 1).
Because the synthetic utility of this family of compounds
is well established, synthetic methods for the enantio-
selective synthesis of 2-substituted tetrahydroquinolines
were reported1 including intramolecular aza-Diels–Alder
reactions.5
H
N
Me
Me
NH
Me
O
( )3
N
H
NH
2
Cl HN
N
H
OH
N
Cl
N
H
CO2H
Me
OMe
(–)-galipeine (4)
L-689,560 (3)
Figure 1
The direct asymmetric hydrogenation of aromatic
compounds6 and more particularly of 2-substituted quino-
lines derivatives is a convenient route to synthesize opti-
cally active 2-substituted tetrahydroquinoline derivatives
1. Recently, Zhou and co-workers reported the first
In previous communications, we have described the syn-
thesis of new atropisomeric diphosphines (Figure 2)
named SYNPHOS10 and DIFLUORPHOS.11
Our studies have demonstrated both their relevant steric
and electronic properties and their catalytic performance12
in ruthenium-promoted hydrogenation reactions.13 We
have recently reported the preparation of a new generation
of Ir–SYNPHOS catalysts14a which were fully character-
ized. Since the tetrahydroquinoline is an extremely impor-
tant unit that can be found in many synthetic and bioactive
compounds and as part of our continuing interest in
expanding the catalytic properties of our ligands in homo-
geneous hydrogenation reactions,13 we wish to report
the synthesis and a new application of novel chiral Ir–
catalytic asymmetric hydrogenation of quinolines using
7a
[IrCl(cod)]2/MeO-Biphep/I2
and chiral ferrocenyl-
oxazoline-derived N,P ligands7b as catalysts with good
yields and high enantioselectivities. They described a new
strategy for the asymmetric hydrogenation of quinolines
by using chloroformate7c as an activating reagent. Good
results were also obtained with the air-stable Ir(P-PHOS)
complex and their immobilization in poly(ethylenegly-
col)dimethyl ether (DMPEG)8a together with chiral phos-
phinite H8-BINAPO8b and chiral diphosphinite ligand
derived from (R)-1,1¢spirobiindane-7,7¢-diol at a high
substrate/catalyst ratio.8c A chiral diphosphonite, derived
from BINOL with an achiral diphenylether backbone9a
and Ir(BINAP)-cored dendrimers9b were also used.
O
O
F
F
O
O
O
PPh2
PPh2
PPh2
PPh2
O
O
F
F
O
SYNLETT 2007, No. 17, pp 2743–2747
Advanced online publication: 25.09.2007
1
6
.1
0
.
2
0
0
7
(S)-SYNPHOS
(S)-DIFLUORPHOS
DOI: 10.1055/s-2007-991076; Art ID: G25607ST
© Georg Thieme Verlag Stuttgart · New York
Figure 2

2744
C. Deport et al.
LETTER
SYNPHOS and Ir–DIFLUORPHOS catalysts for the
asymmetric hydrogenation of quinoline derivatives.
Table 1 Optimization of the Asymmetric Hydrogenation of
2-Methylquinoline (5)
We first examined the Ir–SYNPHOS-promoted hydro-
genation reaction of 2-methylquinoline (5, Scheme 1).
Chiral iridium complexes were prepared in situ by stirring
the [IrCl(cod)]2 together with (S)-SYNPHOS at room
temperature in toluene for 1 hour followed by the addition
of 10 equivalents of aqueous HI for 45 minutes. The cata-
lytic tests were performed at 30 °C under 50 bar of hydro-
gen pressure with a substrate/catalyst ratio (S/C) of 100
(Scheme 1) in the presence of a catalytic amount of
iodine. Preliminary studies were carried out by varying
both the solvent of the hydrogenation reaction and the
hydrogen pressure (Table 1). Under these experimental
conditions, the hydrogenation of 2-methylquinoline (5) to
10 demonstrated to be highly solvent dependent. In alco-
holic solvents such as MeOH and i-PrOH, 2-methyl-
1,2,3,4-tetrahydroquinoline 10 was obtained with both
moderate conversions and enantioselectivities (entries 1
and 2, 40% and 20% conv., 27% and 47% ee, respective-
ly). When an aprotic solvent such as CH2Cl2 was used
(entry 3), an increased conversion and selectivity were
reached (entry 3, 70% conv., 87% ee). Using a mixture of
THF–MeOH (9:1) led to the formation of 10 with excel-
lent conversion and good enantioselectivity (entry 4, 98%
conv., 87% ee). Similar results were achieved when the
hydrogenation of 5 was performed in toluene–THF (9:1,
entry 5, 100% conv., 86% ee). Finally, the optimal condi-
tions were achieved when 2-methylquinoline (5) was hy-
drogenated in THF with quantitative conversion and 90%
of enantioselectivity (entry 6) although no improvement
was observed in lowering either the temperature to 10 °C
(entry 7) or the pressure from 30 to 5 bar which resulted
in decreased conversions and ee (entries 8 and 9).
Entry
P (bar)
50
Solvent
Conv. (%)a ee (%)b
1
2
3
4
5
6
7
8
9
MeOH
40
20
27
47
87
87
86
90
88
73
64
50
i-PrOH
50
CH2Cl2
70
50
THF–MeOH (9:1)
Toluene–THF (9:1)
THF
98
50
100
100
100
97
50
50
THF/10 °C
THF
30
5
THF
96
a Conversions were determined by 1H NMR analysis of the crude
product.
b The ee values were determined by HPLC analysis (chiralcel OD-H
column).
O
Ph2
Me
X
P
O
O
O
Ir
aq HI (10 equiv)
O
P
H
Ph2
or HBr (2.2 equiv)
30–45 min
r.t.
O
15, X = I
16, X = Cl
+
X
H
Ph2
P
H
Ph2
P
X
[X]–
O
Ir
O
Ir
X
P
P
Ph2
O
O
Ph2
O
O
[IrCl(cod)]2, (S)-SYNPHOS,
O
aq HI
O
17, X = I
18, X = Br
H
2 (50 bar), 30 °C, 24 h, I2
N
N
H
solvent
Scheme 2
5
10
Scheme 1
The screening tests were carried out on a 1 mmol scale in
THF under 50 bar of hydrogen pressure at 30 °C by using
both 1 mol% of the Ir–SYNPHOS complexes [Ir2I3H2(S)-
synphos2]+I– [(S)-17], [Ir2Br3H2(S)-synphos2]+Br– [(S)-18]
(Scheme 2) and the in situ generated Ir catalyst
[IrCl(cod)]2/(S)-SYNPHOS/HI. As illustrated in Table 2,
all hydrogenations exhibited good levels of both conver-
sion (up to 100%) and enantioselectivity (up to 91%). The
hydrogenation of 2-methylquinoline (5) to 10 proceeded
smoothly with quantitative conversion and 85% ee with
IrI(H)(O2CMe)[(S)-synphos] [(S)-15] and 10 equivalents
of aqueous HI (entry 1) although a better 91% ee was
reached using IrI(H)(O2CMe)[(S)-synphos] [(S)-15] with
2.2 equivalents of methanolic HBr (entry 2). Fully compa-
rable conversions and enantioselectivities were obtained
with both IrCl(H)(O2CMe)[(S)-synphos] [(S)-16] with 2.2
equivalents of methanolic HBr and the in situ generated
[IrCl(cod)]2/(S)-SYNPHOS/HI (entries 3 and 4, 90% ee).
Next, a comparative study was carried out using these
optimized conditions with a new generation of Ir–(S)-
SYNPHOS catalysts (Scheme 2) recently synthesized14a
in our group and this study was extended to a series of
quinoline derivatives 5–9 (Scheme 3). The mononuclear
Ir catalysts IrI(H)(O2CMe)[(S)-synphos] [(S)-15] and
IrCl(H)(O2CMe)[(S)-synphos] [(S)-16] were prepared
from [IrX(cod)]2 (X = I, Cl) according to our convenient
one-pot procedure14a (Scheme 2). The effect of halide
variation was studied by adding either aqueous HI or
methanolic HBr to the mononuclear catalysts (S)-15 and
(S)-16 to generate the corresponding cationic triply
halogen-bridged dinuclear iridium(III) complexes of
SYNPHOS (S)-17 and (S)-18 which were tested as cata-
lysts for the asymmetric hydrogenation of quinolines 5–9
(Table 2).
Synlett 2007, No. 17, 2743–2747 © Thieme Stuttgart · New York

LETTER
Catalysts for Asymmetric Hydrogenation of Quinolines
2745
These results compare favorably with the asymmetric hy- and 12, up to 88% ee). Finally, the Ir-catalyzed hydroge-
drogenation of 2-methylquinoline (5) with benzylchloro- nation of 2-phenylquinoline 9 to 14 was performed with
formate as an activating agent (83% ee).7c Afterwards, 2- lower conversions and ee values up to 66% (entries 13–
substituted quinolines 6–9 were hydrogenated with the Ir– 15, conv. 70–92%, ee 56–66%, respectively).
SYNPHOS-based catalytic systems. As previously out-
R'
lined for 5, the best results for asymmetric hydrogenation
of 6 to 11 were obtained by using IrCl(H)(O2CMe)[(S)-
R'
[Ir-(S)-SYNPHOS]
H2 (50 bar), 30 °C, 24 h, I2
R
N
H
synphos] [(S)-16] with 2.2 equivalents of methanolic HBr
and the in situ generated [IrCl(cod)]2/(S)-SYNPHOS/HI
with ee up to 88% (entries 7 and 8) although a lower ee
was attained by using IrI(H)(O2CMe)[(S)-synphos] [(S)-
15] with 2.2 equivalents HBr (entries 5 and 6, 80% ee).
Iridium-promoted hydrogenation reaction of 7 with (S)-15
and 2.2 equivalens HBr and with (S)-16 and 2.2 equiva-
lents HBr furnished the corresponding tetrahydroquino-
line 12, respectively, with 87% and 80% ee (entries 9 and
10). Comparable ee were observed for the asymmetric hy-
drogenation of 8 to 13 both with (S)-15 and 2.2 equiva-
lents HBr and (S)-16 and 2.2 equivalents HBr (entries 11
N
R
THF
5, R = Me, R' = H
6, R = Me, R' = Me
7, R = Me, R' = OMe
8, R = Me, R' = F
9, R = Ph, R' = H
10, R = Me, R' = H
11, R = Me, R' = Me
12, R = Me, R' = OMe
13, R = Me, R' = F
14, R = Ph, R' = H
Scheme 3
Afterwards, this study was extended to novel iridium cat-
alysts based upon DIFLUORPHOS ligand. The Ir–DIF-
LUORPHOS complexes were prepared in situ by mixing
[IrCl(cod)]2 with (S)-DIFLUORPHOS and in a simple
Table 2 Asymmetric Hydrogenation of Quinolines 5–9 with Ir–(S)-SYNPHOS Catalysts
Entry
1
Substrate
[Ir–(S)-SYNPHOS] catalyst
Conv. (%)a
100
Product
ee (%, conf.)b
5
IrI(H)(O2CMe)[(S)-synphos] (15)/HI
85 (S)
N
H
2
3
4
5
5
5
5
6
IrI(H)(O2CMe)[(S)-synphos] (15)/HBr
IrCl(H)(O2CMe)[(S)-synphos] (16)/HBr
in situ [IrCl(cod)]2/(S)-synphos/HI
IrI(H)(O2CMe)[(S)-synphos] (15)/HI
100
100
100
>95
10
10
10
91 (S)
90 (S)
90 (S)
80 (S)
N
H
6
7
8
9
6
6
6
7
IrI(H)(O2CMe)[(S)-synphos] (15)/HBr
IrCl(H)(O2CMe)[(S)-synphos] (16)/HBr
in situ [IrCl(cod)]2/(S)-synphos/HI
100
100
100
92
11
80 (S)
88 (S)
88 (S)
87 (S)
11
11
IrI(H)(O2CMe)[(S)-synphos] (15)/HBr
MeO
N
H
10
11
7
8
IrCl(H)(O2CMe)[(S)-synphos] (16)/HBr
IrI(H)(O2CMe)[(S)-synphos] (15)/HBr
100
100
12
80 (S)
88 (S)
F
N
H
12
13
8
9
IrCl(H)(O2CMe[(S)-synphos] (16)/HBr
IrI(H)(O2CMe)[(S)-synphos] (15)/HBr
99
70
13
82 (S)
58 (R)
Ph
N
H
14
15
9
9
IrCl(H)(O2CMe)[(S)-synphos] (16)/HBr
in situ [IrCl(cod)]2/(S)-synphosc
80
92
14
14
56 (R)
66 (R)
a Conversions were determined by 1H NMR analysis of the crude product.
b The ee values were determined by HPLC analysis using Chiralcel OD-H or Chiralcel OJ column.
c Hydrogenation was carried out in toluene.
Synlett 2007, No. 17, 2743–2747 © Thieme Stuttgart · New York

2746
C. Deport et al.
LETTER
R'
one-pot reaction of [IrX(cod)]2 (X = I, Cl) with 2 equiva-
lents of (S)-DIFLUORPHOS and 10 equivalents of acetic
R'
[Ir-(S)-DIFLUORPHOS]
H2 (50 bar), 30 °C, 24 h, I2
THF
acid
affording
mononuclear
complexes
and
N
R
R
N
H
IrI(H)(O2CMe)[(S)-difluorphos]
[(S)-19]
5, R = Me, R' = H
6, R = Me, R' = Me
8, R = Me, R' = F
9, R = Ph, R' = H
10, R = Me, R' = H
11, R = Me, R' = Me
13, R = Me, R' = F
14, R = Ph, R' = H
IrCl(H)(O2CMe)[(S)-difluorphos] [(S)-20]. The corre-
sponding cationic complex (S)-21 was synthesized by
adding 2.2 equivalents of methanolic HBr to (S)-19 and
(S)-20 (Scheme 4).
Scheme 5
O
F
Table 3 Asymmetric Hydrogenation of Quinolines 5, 6, 8, and 9
with Ir–(S)-DIFLUORPHOS Catalysts
Ph2
P
O
Me
F
O
O
X
Ir
No Ir–(S)-DIFLUORPHOS catalyst
Conv. Product ee
(S)-DIFLUORPHOS
(%)a
(%)b
[IrX(cod)]2
X = I, Cl
F
F
O
H
P
Ph2
AcOH
O
1
2
IrI(H)(O2CMe)[(S)-difluorphos]
(19)/HBr
100
10
10
90
19, X = I
20, X = Cl
HBr
+
IrCl(H)(O2CMe)[(S)-difluorphos]
(20)/HBr
100
90
X
H
H
Ph2
Ph2
P
X
P
Ir
Ir
[X]–
O
O
F
3
4
[IrCl(cod)]2/(S)-difluorphosc
90
10
11
91
88
X
F
P
Ph2
P
Ph2
O
O
IrI(H)(O2CMe)[(S)-difluorphos]
(19)/HBr
100
F
F
O
O
F
F
O
O
5
6
7
IrCl(H)(O2CMe)[(S)-difluorphos]
(20)/HBr
100
100
100
11
13
13
85
90
88
21, X = Br
F
F
Scheme 4
IrI(H)(O2CMe)[(S)-difluorphos]
(19)/HBr
Once prepared, these Ir catalysts were screened for the
asymmetric hydrogenation of quinolines derivatives 5, 6,
8, and 9. The catalytic tests were performed on a 1 mmol
scale in THF under 50 bar of hydrogen pressure at 30 °C
by using 1 mol% of the Ir–DIFLUORPHOS complexes
(Scheme 5). We were pleased to find that homogeneous
systems based on Ir–DIFLUORPHOS catalysts gave
good results with excellent conversions up to 100% and
ee up to 92% (Table 3). Asymmetric hydrogenation of
IrCl(H)(O2CMe)[(S)-difluorphos]
(20)/HBr
8
9
[IrCl(cod)]2/(S)-difluorphosc
95
13
14
92
58
IrI(H)(O2CMe)[(S)-difluorphos]
(19)/HBr
100
10 IrCl(H)(O2CMe)[(S)-difluorphos]
(20)/HBr
100
14
57
2-methylquinoline
IrI(H)(O2CMe)[(S)-difluorphos]
(5)
conducted
with
both
and
a Conversions were determined by 1H NMR analysis of the crude
product.
[(S)-19]
b The ee values were determined by HPLC analysis (chiralcel OD-H
or chiralcel OJ).
IrCl(H)(O2CMe)[(S)-difluorphos] [(S)-20] treated, re-
spectively, with 2.2 equivalents of methanolic HBr
together with [IrCl(cod)]2/(S)-difluorphos led to the for-
mation of 10 with complete conversion and up to 91% ee
(entries 1–3). In most cases, comparable conversions (up
to 100%) and enantioselectivities were achieved, respec-
tively, for the formation of tetrahydroquinolines deriva-
tives 11 (entries 4 and 5, up to 88% ee), 13 (entries 6–8,
up to 92% ee), and 14 (entries 9 and 10, up to 58%) and
thus whatever the Ir–DIFLUORPHOS complexes con-
sidered.
c Hydrogenation was carried out in toluene.
In conclusion, we have synthesized novel Ir catalysts
based upon SYNPHOS and DIFLUORPHOS that are use-
ful for producing enantiomerically enriched tetrahydro-
quinoline derivatives. In this work, we have demonstrated
that the new Ir–SYNPHOS and Ir–DIFLUORPHOS com-
plexes can be efficiently used in these transformations15
with good conversions (up to 100%) and enantioselec-
tivities (up to 92%) by using different counterions. We are
currently investigating the scope of these new Ir–
SYNPHOS and Ir–DIFLUORPHOS complexes for
transition-metal catalysis.
The absolute configurations of the chiral tetrahydro-
quinoline derivatives 11–14 were assigned from [a]D
value by comparison with known compounds.7a
Acknowledgment
We would like to thank the CNRS and the Japan Society for the
Promotion of Sciences for financial support (2007–2008).
Synlett 2007, No. 17, 2743–2747 © Thieme Stuttgart · New York

LETTER
Catalysts for Asymmetric Hydrogenation of Quinolines
2747
(11) (a) Jeulin, S.; Duprat de Paule, S.; Ratovelomanana-Vidal,
V.; Genet, J.-P.; Champion, N. Angew. Chem. Int. Ed. 2004,
43, 320. (b) Jeulin, S.; Duprat de Paule, S.;
References and Notes
(1) (a) Katritzky, A. R.; Rachwal, S.; Rachwal, B. Tetrahedron
1996, 52, 15031. (b) See also Scott, J. D.; Williams, R. M.
Chem. Rev. 2002, 102, 1669.
Ratovelomanana-Vidal, V.; Genet, J.-P.; Champion, N.
Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 5799.
(2) Witherup, K. M.; Ransom, R. W.; Varga, S. L.; Pitzenberger,
S. M.; Lotti, V. J.; Lumma, V. J. US 5 288 725, 1994.
(3) (a) Leeson, P. D.; Carling, R. W.; Moore, K. W.; Moseley,
A. M.; Smith, J. D.; Stevenson, G.; Chan, T.; Baker, R.;
Foster, A. C.; Grimwood, S.; Kemp, J. A.; Marshall, G. R.;
Hoogsteen, K. J. Med. Chem. 1992, 35, 1954. (b) Yoneda,
Y.; Suzuki, T.; Ogita, K.; Han, D. J. Neurochem. 1993, 60,
634. (c) Mager, P. P. Drug Des. Discovery 1994, 11, 185.
(4) Yang, P. Y.; Zhou, Y. G. Tetrahedron: Asymmetry 2004, 15,
1145.
(12) (a) Mordant, C.; Dünkelmann, P.; Ratovelomanana-Vidal,
V.; Genet, J.-P. Chem. Commun. 2004, 1296. (b) Mordant,
C.; Dünkelmann, P.; Ratovelomanana-Vidal, V.; Genet,
J.-P. Eur. J. Org. Chem. 2004, 3017. (c) Mordant, C.;
Reymond, S.; Tone, H.; Lavergne, D.; Touati, R.;
Ben Hassine, B.; Ratovelomanana-Vidal, V.; Genet, J.-P.
Tetrahedron 2007, 343, 1592. (d) Jeulin, S.; Ayad, T.;
Ratovelomanana-Vidal, V.; Genet, J.-P. Adv. Synth. Catal.
2007, 63, 6115.
(13) (a) Noyori, R. In Asymmetric Catalysis in Organic
Synthesis; Wiley: New York, 1994, 16. (b) Noyori, R.
Angew. Chem. Int. Ed. 2002, 41, 2008.
(5) Avemaria, F.; Vanderheiden, S.; Bräse, S. Tetrahedron
2003, 59, 6785.
(6) (a) For a recent review, see: Glorius, F. Org. Biomol. Chem.
2005, 3, 4171; and references cited therein. (b) Legault, C.
Y.; Charette, A. B. J. Am. Chem. Soc. 2005, 127, 8966.
(c) Bianchini, C.; Barbaro, P.; Scapacci, G.; Farnetti, E.;
Graziani, M. Organometallics 1998, 17, 3308.
(d) Henschke, J. P.; Burk, M. J.; Malan, C. G.; Herzberg, D.;
Peterson, J. A.; Wildsmith, A. J.; Cobley, C. J.; Casy, G.
Adv. Synth. Catal. 2003, 345, 300. (e) Kuwano, R.; Sato,
K.; Kurokawa, T.; Karube, D.; Ito, Y. J. Am. Chem. Soc.
2000, 122, 7614. (f) Kuwano, R.; Kaneda, K.; Ito, T.; Sato,
K.; Kurokawa, T.; Ito, Y. Org. Lett. 2004, 6, 2213.
(7) (a) Wang, W. B.; Lu, S. M.; Yang, P. Y.; Han, X. W.; Zhou,
Y. G. J. Am. Chem. Soc. 2003, 125, 10536. (b) Lu, S. M.;
Han, X. W.; Zhou, Y. G. Adv. Synth. Catal. 2004, 346, 909.
(c) Lu, S.; Wang, Y.; Han, X. W.; Zhou, Y. G. Angew. Chem.
Int. Ed. 2006, 45, 2260.
(8) (a) Xu, L.; Lam, K. H.; Ji, J.; Wu, J.; Fan, Q. H.; Lo, W. H.;
Chan, A. S. C. Chem. Commun. 2005, 1390. (b) Lam, K.
H.; Xu, L.; Feng, L.; Fan, Q. H.; Lam, F. L.; Lo, W. H.;
Chan, A. S. C. Adv. Synth. Catal. 2005, 347, 1755.
(c) Tang, W. J.; Zhu, S. F.; Xu, L. J.; Zhou, Q. L.; Fan, Q.
H.; Zhou, H. F.; Lam, K.; Chan, A. S. C. Chem. Commun.
2007, 613.
(9) (a) Reetz, M. T.; Li, X. Chem. Commun. 2006, 2159.
(b) Wang, Z. J.; Deng, G. J.; Li, Y.; He, Y. M.; Tang, W. J.;
Fan, Q. H. Org. Lett. 2007, 9, 1243.
(c) Ratovelomanana-Vidal, V.; Genet, J. P. J. Organomet.
Chem. 1998, 567, 163. (d) Ratovelomanana-Vidal, V.;
Genet, J.-P. Can. J. Chem. 2000, 78, 846. (e) Genet, J.-P.
Acc. Chem. Res. 2003, 36, 908.
(14) (a) Yamagata, T.; Tadaoka, H.; Nagata, M.; Hirao, T.;
Kataoka, Y.; Ratovelomanana-Vidal, V.; Genet, J.-P.;
Mashima, K. Organometallics 2006, 25, 2505. See also:
(b) Mashima, K.; Nakamura, T.; Matsuo, Y.; Tani, K.
J. Organomet. Chem. 2000, 607, 51. (c) Mashima, K.;
Kusano, K.; Sato, N.; Matsumura, Y.; Nozaki, K.;
Kumobayashi, H.; Sayo, N.; Hori, Y.; Ishizaki, T.;
Akutagawa, S.; Takaya, H. J. Org. Chem. 1994, 59, 3064.
(15) General Hydrogenation Procedure
The Ir complex (0.01 mmol) was placed in a dry 10 mL
Schlenk tube which was equipped with a magnetic bar, a
stopper, and connected to a supply of vacuum/argon.
Degassed anhydrous acetone (2 mL) was introduced via a
syringe under a stream of argon. The mixture was degassed
with three vacuum/argon cycles. Methanolic HBr (2.2
equiv) was added dropwise to the solution and stirred for 30
min at r.t. The precipitate was concentrated under vacuum
and anhydrous THF (2 mL) was introduced via syringe
under a stream of argon. Then, the solution was degassed
again with three vacuum/argon cycles. The mixture was
transferred by a syringe to a dry 10 mL Schlenk tube, in
which I2 (0.1 mmol) and quinoline (1 mmol) were placed
beforehand. This Schlenk tube was equipped with a
magnetic bar, a stopper, and connected to a supply of
vacuum/argon. The mixture was degassed with three
vacuum/argon cycles. The hydrogenation was performed
under H2 (50 bar) at 30 °C for 24 h. After releasing the
hydrogen, the reaction mixture was concentrated and the
crude product was purified by a short silica gel column
eluted with cyclohexane–EtOAc.
(10) (a) Duprat de Paule, S.; Champion, N.; Ratovelomanana-
Vidal, V.; Genet, J.-P.; Dellis, P. FR 2830254, 2001.
(b) Duprat de Paule, S.; Champion, N.; Ratovelomanana-
Vidal, V.; Genet, J.-P.; Dellis, P. WO 03029259, 2003.
(c) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal,
V.; Genet, J.-P.; Champion, N.; Dellis, P. Tetrahedron Lett.
2003, 44, 823. (d) Duprat de Paule, S.; Jeulin, S.;
Ratovelomanana-Vidal, V.; Genet, J.-P.; Champion, N.;
Dellis, P. Eur. J. Org. Chem. 2003, 1931.
(e) Duprat de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal,
V.; Genet, J.-P.; Champion, N.; Deschaux, G.; Dellis, P.
Org. Process Res. Dev. 2003, 7, 399.
Synlett 2007, No. 17, 2743–2747 © Thieme Stuttgart · New York