Asymmetric hydrogenation of quinolines catalyzed by iridium with chiral ferrocenyloxazoline derived N,P ligands

Article abstract of DOI:10.1002/adsc.200404017

Chiral ferrocenyloxazoline derived N,P ligands are used in the iridium-catalyzed asymmetric hydrogenation of quinolines, and up to 92% ee was obtained. The role of the planar chirality is also studied.

Full text of DOI:10.1002/adsc.200404017

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Asymmetric Hydrogenation of Quinolines Catalyzed by Iridium
with Chiral Ferrocenyloxazoline Derived N,PLigands
Sheng-Mei Lu, Xiu-Wen Han, Yong-Gui Zhou*
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, the Chinese Academy of Sciences, Dalian
116023, P. R. China
Fax: (þ86)-411-4684746, e-mail: ygzhou@dicp.ac.cn
Received: January 18, 2004; Accepted: May 25, 2004
Abstract: Chiral ferrocenyloxazoline derived N,P li-
gands are used in the iridium-catalyzed asymmetric
hydrogenation of quinolines, and up to 92% ee was
obtained. The role of the planar chirality is also stud-
ied.
N,P ligands, which can be easily synthesized fromamino
acids, have been successfully used in the hydrogenation
of aromatic and heteroaromatic compounds with practi-
cal optical yields. Indeed, in a patent, N,P ligands have
been claimed to be used, but no detailed information
[
10]
was given. Intrigued by the importance of chiral tetra-
[11]
Keywords: asymmetric hydrogenation; homogeneous
catalysis; N,P ligands; planar chirality; quinolines
hydroquinolines as useful synthetic intermediates and
as structural subunits existing in alkaloids and other bio-
[
12]
logically active compounds, and the success in the hy-
drogenation of unfunctionalized olefins and imines with
[
13]
N,P ligand-iridiumcomplexes,
we decided to explore
the application of ferrocene derived phosphino-oxazo-
Asymmetric hydrogenation of aromatic and heteroaro- line ligands in the hydrogenation of quinolines and to
matic compounds is a very useful reaction as it provides study the role of planar chirality in this reaction.
a convenient access to numerous saturated or partially
The chiral ligands (Figure 1) used in our study were
saturated chiral cyclic compounds, whose synthesis by conveniently prepared according to known methods
[
1]
direct cyclization is often difficult. Recently, some starting fromco mme rcially available optically active
[
14]
progress has been made in this challenging field. Ito amino acids.
and co-workers reported a highly effective hydrogena- To assess the effectiveness of ligands and the impact of
tion of N-Boc- or N-Ac-substituted indoles using the other factors, we chose the hydrogenation of 2-methyl-
Rh/Trap/Cs CO catalytic system, and up to 95% ees quinoline as the model reaction. Chiral iridium com-
2
3
[
2]
were obtained. Bianchini realized an asymmetric hy- plexes prepared in situ from[Ir(COD)Cl] 2 and chiral
drogenation of 2-methylquinoxaline with ees up to N,P ligands were employed as catalysts, and the reac-
9
0% employing an orthometalated dihydride-iridium tions were carried out in toluene at roomtemperature
[3]
complex. Two other systems, i.e., [Ir(COD)/(R,R)- under 600 psi of hydrogen with a substrate:[Ir]:ligand:
BDPBzP]OTf and [Rh(NBD)/(R,R)-BDPBzP]OTf, de- I2 ratio of 100:0.5:1.1:5. First, we investigated the ef-
veloped by the same group showed low enantioselectiv- fect of substituents in the oxazoline ring on the conver-
ities. Studer and co-workers× [Rh(NBD)(DIOP)]BF4 sion and enantioselectivities. The results are summar-
catalyst gave only 24±27% ee in the hydrogenation of ized in Table 1. The chiral N,P ligands of ferrocenyloxa-
monosubstituted pyridines and furans. 2-Methylqui- zolines derived fromdifferent amino alcohols show var-
noxaline was hydrogenated with Rh(DIOP)H in ied effectiveness for the enantioselectivity. The results
[4]
[
5]
[6]
3% ee. In 2003, Henschke investigated the application
of Noyori×s RuCl (diphosphine)(diamine)/base catalyst
2
systemin the hydrogenation of 2-methylquinoxaline, up
[
7]
to 73% ee was obtained. Some heterogeneous chirally
modified catalysts and chiral auxiliary-based methods
were also developed for asymmetric hydrogenation of
[
8]
aromatic and heteroaromatic compounds. More re-
cently, our group reported the first catalytic asymmetric
hydrogenation of quinolines with high enantioselectivi-
ties using [Ir(COD)Cl] /MeO-Biphep/I as the catalyst
2
2
[9]
system. Among the above homogenous catalytic sys-
tems, bidentate biphosphines are the more effective Figure 1. Chiral phosphino-oxazoline ligands derived from
and widely used ligands. As far as we know, no effective amino acids.
Adv. Synth. Catal. 2004, 346, 909±912
DOI: 10.1002/adsc.200404017
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
909

COMMUNICATIONS
Sheng-Mei Lu et al.
showed that the t-Bu-substituted ligand 1b (entry 2) is have no clear effect on the conversion and the enantio-
superior to 1a (R¼i-Pr, entry 1), 1c (R¼Bn, entry 3) selectivities (entries 7±10). Therefore, the optimized
and 1d (R¼Ph, entry 4). For the corresponding non-pla- conditions for asymmetric hydrogenation of quinolines
nar chiral phenyloxazoline ligands, 2b with t-Bu on the with Ir complexes of chiral N,P ligands in the presence
oxazoline ring also shows a higher enantioselectivity of I are [Ir(COD)Cl] /(S,S )-1b/I /toluene/H 600 psi/
2
2
P
2
2
than 2a with i-Pr (75% vs. 63%, entries 6 and 7). Ligands 258C.
without the planar chirality (2a and 2b) showed lower
Under the optimized conditions, a variety of substitut-
enantioselectivities than the corresponding (oxazolinyl- ed quinoline derivatives were hydrogenated using the
ferrocenyl)phosphine ligands (1a and 1b) (63% in en- [Ir(COD)Cl] /(S,S )-1b/toluene/I catalyst system. The
2
P
2
try 6 vs. 77% in entry 1 and 75% in entry 7 vs. 90% in en- results are shown in Table 3. Several 2-alkyl-substituted
try 2). To investigate the effect of planar chirality on the quinolines were hydrogenated with high enantioselec-
enantioselectivity and absolute configuration of the tivities (x90% ee) regardless of the length of the chain
[15]
products, 1e with the same central chirality and oppo- (entries 1±4). 2-Arenethyl-substituted quinolines also
site planar chirality to 1b was synthesized and used in the gave good asymmetric induction (entries 6 and 8). For
hydrogenation of 2-methylquinoline. Under the same 2-aryl-substituted quinolines (entry 7), however only
conditions, lower enantioselectivity and the same abso- 3% enantioselectivity was obtained and the reason is
lute configuration were observed with (S,R ) ligand 1e not clear. It is noted that a hydroxy group can be tolerat-
P
(
77% in entry 5 vs. 90% in entry 2). It seems that the ab- ed in this catalytic system. For example, both high yields
solute configuration of the product is mainly controlled and ees were achieved for substrates 3i and 3j with hy-
by the central chirality of the oxazoline ring. The lower droxy groups (entries 9 and 10).
ee with 1e suggests the mismatched nature of the (R)
To evaluate further the catalytic efficiency of the
planar chirality with the (S) central chirality on the oxa- [Ir(COD)Cl] /(S,S )-1b/I systemin asymmetric hydro-
2
P
2
zolinyl ring. Compound (S,S )-1b is the matched case in genation, we investigated the effect of the substrate-
P
terms of planar and central chiralities. The ligand (S,S )- to-catalyst (S/C) molar ratio on the conversion and
P
1
b was therefore used throughout the rest of the studies. enantioselectivity of this reaction. 2-Methylquinoline
The effects of the solvents, hydrogen pressure, and was selected as substrate, the results (Figure 2) show
temperature on the reaction conversion and enantiose- that the reaction can proceed smoothly at an S/C of
lectivity were also investigated using Iridiumcomplexes
of 1b as the catalyst. The results are summarized in Ta-
ble 2. Greater than 95% conversions were achieved in
all solvents examined, either protic or aprotic, in 12 h.
But the ees of the product are highly solvent-dependent.
Non-polar solvents (entries 1, 6, 7) tend to give higher
enantioselectivities than polar solvents (entries 2±5).
Change in hydrogen pressure and reaction temperature
500/1 or 1000/1 with complete conversion, the ee de-
[a]
Table 2. Asymmetric hydrogenation of 2-methylquinoline.
[a]
Table 1. Asymmetric hydrogenation of 2-methylquinoline.
[
b]
Entry
H [psi]; T [ 8C]
Solvent
CH Cl
ee [%]
2
1
2
3
4
5
6
7
8
9
600; 25
600; 25
600; 25
600; 25
600; 25
600; 25
600; 25
600; 0
87
14
44
18
51
88
90
90
89
90
2
2
[
b]
[c]
[d]
THF
Entry Ligand Conversion [%] ee [%] Configuration
EtOAc
MeOH
i-PrOH
benzene
toluene
toluene
toluene
toluene
1
2
3
4
5
7
1a
1b
1c
1d
1e
2b
>95
>95
>95
>95
85
77
90
73
73
77
75
(R)
(R)
(R)
(R)
(R)
(R)
>95
300; 25
100; 25
1
0
[
a]
Reaction conditions: 1 mmol scale, quinoline/[Ir(COD)
[
a]
Cl] /chiral ligand/I ¼100/0.5/1.1/5, 5 mL toluene, 600 psi
Reaction conditions: 1 mmol scale, quinoline/[Ir(COD)
2
2
H
2
Cl] /chiral ligand/I ¼100/0.5/1.1/5, 5 mL solvent, H , the
2
2
2
[
[
b]
c]
1
Determined by H NMR analysis of the crude products.
Determined by HPLC analysis with a Chiralpak OJ-H
column.
absolute configuration of product is R; conversion is deter-
1
mined by H NMR analysis of the crude products and is
>95% in all cases.
Determined by HPLC analysis with a Chiralpak OJ-H
column.
[
d]
[b]
The absolute configuration of product is assigned by com-
parison of rotation sign with literature data.
910
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Adv. Synth. Catal. 2004, 346, 909±912

Asymmetric Hydrogenation of Quinolines
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[a]
Table 3. Iridium-catalyzed asymmetric hydrogenation of quinolines 3.
[
b]
[c]
[d]
Entry
R/R’ of 3
Yield [%]
ee [%]
Configuration
1
2
3
4
5
6
7
H/Me (3a)
H/Et (3b)
H/n-Pentyl (3c)
Me/Me (3d)
F/Me (3e)
95 (4a)
95 (4b)
94 (4c)
93 (4d)
86 (4e)
92 (4f)
45 (4g)
90
91
92
92
89
72
3
R
R
R
R
R
R
S
H/Phenethyl (3f)
[e]
H/Ph (3g)
8
9
(3h)
82 (4h)
89 (4i)
87
80
R
S
(3i)
10
(3j)
82 (4j)
79
S
[
[
[
[
[
a]
Reaction conditions: 1 mmol scale, quinoline/[Ir(COD)Cl] /chiral ligand/I ¼100/0.5/1.1/5, 5 mL toluene, 600 psi H
2
2
2
b]
Yield of isolated product based on the quinolines by column chromatography
Determined by HPLC analysis with Chiral column (see experimental section).
Determined by comparison of rotation sign with literature data or by analogue.
The conversion is 50%.
c]
d]
e]
creased slightly (90% ee vs. 88% ee, 86% ee). But when
the S/C is 2000/1, the conversion is only 67%, although
the ee is 82%.
In conclusion, Ir complexes with chiral N,P ligands are
effective catalysts for the asymmetric hydrogenation of
heteroaromatic compounds such as quinolines, and up
to 92% ees were obtained. Central chirality dominates
the absolute configuration of the products in iridium-
ferrocenyloxazoline catalytic systems with planar chiral-
ity. The method described provides an effective, mild
and convenient route to synthesize chiral tetrahydroqui-
noline derivatives.
Figure 2. Effect of the S/C on the conversion and enantiose-
lectivity.
were dried over sodiumsulfate and concentrated to afford
the crude product. Purification was performed on a silica gel
column eluted with hexane/EtOAc to give pure product. The
enantiomeric excesses were determined by HPLC with chiral
columns (OJ-H, OD-H, or AS-H). 4a: OJ-H, elute: hexane/i-
PrOH¼95/5, flow rate: 1.0 mL/min, (S) t1¼12.1 min, (R)
t2¼13.5 min; 4b: HPLC OJ-H, elute: hexane/i-PrOH¼95/5,
flow rate: 1.0 mL/min, (S) t1¼10.2 min, (R) t2¼11.4 min; 4c:
HPLC OJ-H, elute: hexane/i-PrOH¼95/5, flow rate 0.5 mL/
min), (S) t1¼14.7 min, (R) t2¼16.2 min; 4d: HPLC OJ-H,
elute: hexane/i-PrOH¼90/10, flow rate: 1.0 mL/min, (S) t1¼
Experimental Section
General Experimental Procedure for Hydrogenation
A mixture of [Ir(COD)Cl] (3.4 mg, 0.005 mmol) and (S,S )-1b
2
P
(
5.5 mg, 0.011 mmol) in toluene (5 mL) was stirred at room
temperature for 30 min in a glove-box. The mixture was trans-
ferred by a syringe to a stainless steel autoclave in which I2
1
5.1 min, (R) t2¼19.2 min; 4e: HPLC OD-H, elute: hexane/i-
PrOH¼94/6, flow rate: 1.0 mL/min, (S) t1¼5.3 min, (R) t2¼
(
12.7 mg, 0.05 mmol) and substrate (1.0 mmol) were placed be-
6
.6 min; 4f: HPLC AS-H, elute: hexane/i-PrOH¼94/6, flow
forehand. The hydrogenation was performed at room temper-
rate 1.0 mL/min, (S) t1¼5.2 min, (R) t2¼5.6 min; 4g: HPLC
ature under H (600 psi) for 12±16 h. After carefully releasing
2
AS-H, elute: hexane/i-PrOH¼94/6, flow rate 1.0 mL/min,
the hydrogen, the reaction mixture was diluted with dichloro-
methane (20 mL). Saturated sodium carbonate solution
(
S) t1¼5.5 min, (R) t2¼14.7 min; 4h: HPLC AS-H, elute: hex-
(
5 mL) was added and the mixture was stirred for 15 min. Lay-
ane/i-PrOH¼94/6, flow rate: 1.0 mL/min, (S) t1¼11.3 min,
(R) t2¼12.4 min; 4i: HPLC OD-H, elute: hexanes/i-PrOH¼
94/6, flow rate: 1.0 mL/min), (S) t1¼1.8 min, (R) t2¼
ers were separated and the aqueous layer was extracted with di-
chloromethane (3ꢀ15 mL). The combined organic layers
Adv. Synth. Catal. 2004, 346, 909±912
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¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Sheng-Mei Lu et al.
1
4.1 min; 4j: HPLC OD-H, elute: hexane/i-PrOH¼97/3, flow
[11] J. D. Keay, in: Comprehensive Organic Synthesis, (Eds.:
B. M. Trost, I. Fleming), Pergamon Press, Oxford, 1991,
Vol. 8, pp. 579±601.
rate: 0.5 mL/min, (S) t1¼25.5 min, (R) t2¼26.9 min.
[
12] a) D. H. R. Barton, K. Nakanishi, O. Meth-Cohn, (Eds.),
Comprehensive Natural Product Chemistry, Elsevier, Ox-
ford, 1999, Vols. 1±9; b) I. Jacquemond-Collet, S. Hanne-
douche, N. Fabre, I. Fouraste, C. Moulis, Phytochemistry
1999, 51, 1167±1169; c) J. H. Rokotoson, N. Fabre, I. Jac-
quemond-Collet, S. Hannedouche, I. Fouraste, C. Moulis,
Planta Med. 1998, 64, 762±763; d) P. J. Houghton, T. Z.
Woldemariam, Y. Watanabe, J. M. Yates, Planta Med.
1999, 65, 250±254; e) I. Jacquemond-Collet, J. M. Bas-
siere, S. Hannedouche, C. Bertand, I. Fouraste, C. Mou-
lis, Phytochem. Anal. 2001, 12, 312±319.
Acknowledgements
We are grateful for the financial support fromNational Science
Foundation of China (20302005) and Talent Scientist Program,
the Chinese Academy of Sciences.
References and Notes
[
[
[
[
[
[
[
1] P. N. Rylander, Catalytic Hydrogenation in Organic Syn-
thesis, Academic Press, New York, 1979, p. 175.
2] R. Kuwano, K. Sato, T. Kurokawa, D. Karube, Y. Ito, J.
Am. Chem. Soc. 2000, 122, 7614±7615.
3] C. Bianchini, P. Barbaro, G. Scapacci, E. Farnetti, M.
Graziani, Organometallics 1998, 17, 3308±3310.
4] C. Bianchini, P. Barbaro, G. Scapacci, J. Organomet.
Chem. 2001, 621, 26±33.
[13] A. Pfaltz, J. Blankenstein, R. Hilgraf, E. Hormann, S.
McIntyre, F. Menges, M. Schonleber, S. P. Smidt, B. Wus-
tenberg, N. Zimmermann, Adv. Synth. Catal. 2003, 345,
33±43, and references cited therein.
[14] a) C. J. Richards, A. W. Mulvaney, Tetrahedron: Asym-
metry, 1996, 7, 1419±1430; b) G. J. Dawson, C. G. Frost,
J. M. J. Williams, Tetrahedron Lett. 1993, 34, 3149±
3150; c) P. V. Matt, A. Pfaltz, Angew. Chem. Int. Ed.
Engl. 1993, 32, 566±568; d) T. Sammakia, E. L. Stange-
land, J. Org. Chem. 1997, 62, 6104±6105; e) J. Sprinz,
G. Helmchen, Tetrahedron Lett. 1993, 34, 1769±1772;
f) K. H. Ahn, C-W. Cho, H.-H. Baek, J. Park, S. Lee, J.
Org. Chem. 1996, 61, 4937±4943.
5] M. Studer, C. Wedemeyer-Exl, F. Spindler, H. U. Blaser,
Monatsh. Chem. 2000, 131, 1335±1343.
6] S. Murata, T. Sugomoto, S. Matsuura, Heterocycles 1987,
2
6, 763±766.
7] a) C. J. Cobley, J. P. Henschke, Adv. Synth. Catal. 2003,
45, 195±201; b) J. P. Henschke, M. J. Burk, C. G. Malan,
3
D. Herzberg, J. A. Peterson, A. J. Wildsmith, C. J. Cob-
ley, G. Casy, Adv. Synth. Catal. 2003, 345, 300±307.
8] Using heterogeneous chirally modified catalysts: a) M.
Maris, W. R. Huck, T. Mallat, A. Baiker, J. Catal. 2003,
[15] For recent papers on the role of planar chirality, see:
a) C. Bolm, K. Mu nƒ iz-Fern a¬ ndez, A. Seger, G. Raabe,
K. Gunther, J. Org. Chem. 1998, 63, 7860±7867; b) C.
Bolm, K. Mu nƒ iz-Fern a¬ ndez, J. P. Hildebrand, Org. Lett.
1999, 1, 991±994; c) K. Mu nƒ iz-Fern a¬ ndez, C. Bolm,
Chem. Eur. J. 2000, 6, 2309±2316; d) Y. Donde, L. E.
Overman, J. Am. Chem. Soc. 1999, 121, 2933±2934;
e) S. L. You, Y. G. Zhou, X. L. Hou, L. X. Dai, Chem.
Commun. 1998, 2765±2766; f) S. L. You, X. L. Hou,
L. X. Dai, Y. H. Yu, W. Xia, J. Org. Chem. 2002, 67,
4684±4695; g) W. P. Deng, X. L. Hou, L. X. Dai, Y. H.
Yu, W. Xia, Chem. Commun. 2000, 285±286; h) W. P.
Deng, X. L. Hou, L. X. Dai, X. W. Dong, Chem. Com-
mun. 2000, 1483±1484; i) W. P. Deng, X. L. Hou, L. X.
Dai, Y. H. Yu, W. Xia, J. Am. Chem. Soc. 2001, 123,
6508±6519; j) W. Zhang, T. Shimanuki, T. Kida, Y. Naka-
tusuji, I. Ikeda, J. Org. Chem. 1999, 64, 6247±6251; k) R.
Shintani, M. M. C. Lo, G. C. Fu, Org. Lett. 2000, 2, 3695±
3697; l) A. Togni, S. D. Pastor, J. Org. Chem. 1990, 55,
1649±1664; m) T. Hayashi, M. Konoshi, M. Fukushima,
T. Mise, M. Kagotani, M. Tajika, M. Kumada, J. Am.
Chem. Soc. 1982, 104, 180±186.
[
2
19, 52±58; b) H. -U. Blaser, H. Honig, M. Studer, C.
Wedemeyer-Exl, J. Mol. Catal. A: Chemical, 1999, 139,
2
1
53±257; c) H. Brunner, C. Huber, Chem. Ber. 1992,
25, 2085±2093; d) H. Brunner, P. Bublak, M. Helget,
Chem. Ber. 1997, 130, 55±61; e) S. A. Raynor, J. M. Tho-
mas, R. Raja, B. F. G. Johnson, R. G. Bell, M. D. Mantle,
Chem. Commun. 2000, 1925±1926; using auxiliary-based
methods: f) N. Douja, R. Malacea, M. Banciu, M. Bes-
son, C. Pinel, Tetrahedron Lett. 2003, 44, 6991±6993;
g) N. Douja, M. Besson, P. Gallezot, C. Pinel, J Mol. Cat-
al. A: Chemical 2002, 186, 145±151; h) M. Besson, B.
Blanc, M. Champelet, P. Gallezot, K. Nasar, C. Pinel, J.
Catal. 1997, 170, 254±264; i) M. Besson, P. Gallezot, S.
Neto, C. Pinel, Chem. Commun. 1998, 1431±1432; j) F.
Glorius, N. Spielkamp, S. Holle, R. Goddard, C. W. Leh-
mann, Angew. Chem. Int. Ed. 2004, 43, 2850±2852.
9] W. B. Wang, S. M. Lu, P. Y. Yang, X. W. Han, Y. G. Zhou,
J. Am. Chem. Soc. 2003, 125, 10536±10537.
[
[10] R. Fuchs, (assigned to Lonza AG), U. S. Patent 5,945,534,
1
999.
912
¹ 2004 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 909±912