Iridium-catalyzed asymmetric hydrogenation of 3-substituted 2H-1,4-benzoxazines

Article abstract of DOI:10.1002/adsc.201100568

The highly enantioselective hydrogenation of 3-aryl-2H-1,4-benzoxazines was achieved using the (cyclooctadiene)iridium chloride dimer/(S)-SegPhos/iodine {[Ir(COD)Cl]₂/(S)-SegPhos/I₂} system as catalyst with up to 92% ee. The 3-styryl

Full text of DOI:10.1002/adsc.201100568

FULL PAPERS
DOI: 10.1002/adsc.201100568
Iridium-Catalyzed Asymmetric Hydrogenation of 3-Substituted
2H-1,4-Benzoxazines
Kai Gao,a Chang-Bin Yu,a Duo-Sheng Wang,a and Yong-Gui Zhoua,b,*
a
State Key Laboratory of Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan
Road, Dalian 116023, Peopleꢀs Republic of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Sciences, Shanghai 200032, Peopleꢀs Republic of China
Fax : (+86)-411-8437-9220; phone: (+86)-411-8437-9220; e-mail: ygzhou@dicp.ac.cn
Received: July 18, 2011; Revised: October 1, 2011; Published online: January 20, 2012
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201100568.
Abstract: The highly enantioselective hydrogenation iridium catalyst and Pd/C in two consecutive steps
of 3-aryl-2H-1,4-benzoxazines was achieved using whereby 93–95% ee values were obtained.
the (cyclooctadiene)iridium chloride dimer/(S)-Seg-
Phos/iodine {[IrACHTUNGTRENNUNG(COD)Cl]2/(S)-SegPhos/I2} system as
catalyst with up to 92% ee. The 3-styryl-2H-1,4-ben- Keywords: asymmetric hydrogenation; benzoxazines;
zoxazine derivatives were also hydrogenated by the chiral amines; cyclic imines; iridium
Introduction
finally 1,2-hydride addition to obtain the tetrahydro-
quinoline product [Scheme 1, Eq. (1)].[12h,13h,i] Due to
The synthesis of chiral amines is very important both the similarity in the structures of benzoxazine and the
in academic and pharmaceutical research and indus- imine intermediate B, we envisioned that the direct
try.[1] Although great progress has been made in the asymmetric hydrogenation of benzoxazines would be
transition metal-catalyzed asymmetric hydrogenation an appropriate access to the chiral cyclic amines by
of imines,[2–5] the continuing demand for chiral amines using the Ir/diphosphine/I2 catalyst system developed
is urgent. 3-Substituted-3,4-dihydro-2H-1,4-benzoxa- by us [Scheme 1, Eq. (2)]. Herein, we present our
zines represent the structural motifs of many chiral findings on the Ir-catalyzed enantioselective hydroge-
drugs, and are also employed as building blocks for nation of 3-substituted 2H-1,4-benzoxazines.
the synthesis of some natural products,[6,7] therefore,
their synthesis has attracted much attention in recent
years. Examples including the Ru-BINAP-catalyzed
hydrogenation of acetol as key intermediate for the
synthesis of levofloxacin,[8a] as well as the Rh/Me-
Duphos-catalyzed asymmetric hydrogenation of exo-
cyclic enamides have been reported by our group.[9]
In 2006, Rueping and co-workers developed a highly
enantioselective reduction of 3-aryl-2H-1,4-benzoxa-
zines catalyzed by chiral Brønsted acids using a
Hantzsch dihydropyridine as hydrogen source.[10a]
However, few reports have been concerned with the
direct asymmetric hydrogenation of cyclic imines to
obtain these important compounds.[11b]
In 2009, our group disclosed the mechanism of the
Ir-catalyzed asymmetric hydrogenation of quinolines
in the presence of I2, which was a cascade reaction in-
volving 1,4-hydride addition to form enamine inter-
mediate A, then isomerization to cyclic imine B, and hydrogenation of quinolines.
Scheme 1. Mechanism for the iridium-catalyzed asymmetric
Adv. Synth. Catal. 2012, 354, 483 – 488
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
483

Kai Gao et al.
FULL PAPERS
Table 1. Asymmetric hydrogenation of 3-phenyl-2H-1,4-
entries 2–8), and benzene was the best choice in terms
of conversion and enantioselectivity (87% ee, Table 1,
entry 8).
benzACHTUNGTRENNUNG
oxazine (1a).[a]
Subsequently, some commercially available chiral
ligands were screened (Figure 1, Table 2). The reac-
tion with WalPhos ligand gave full conversion, but
moderate ee was obtained (Table 2, entry 2). Me-
DuPhos and PHOX ligands gave both low reactivity
and poor enantioselectivity (Table 2, entries 3 and 4).
SynPhos and its analogues such as C4-TunPhos and
MeO-BiPhep exhibited good enantioselectivities
Entry
Solvent
Conversion [%][b]
ee [%][c,d]
1
2
3
4
5
6
7
8
CH2Cl2
CHCl3
EtOAc
MeOH
THF
1,4-dioxane
toluene
benzene
>95
>95
>95
>95
>95
>95
>95
>95
80 (S)
79 (S)
77 (S)
60 (S)
75 (S)
80 (S)
85 (S)
87 (S)
Table 2. Screening of ligands for the hydrogenation of 3-
phenyl-2H-1,4-benzoxazine (1a).[a]
[a]
Reaction conditions: [IrACHTNUTRGENNG(U COD)Cl]2 (1 mol%), (S)-Seg-
Phos (2.2 mol%), I2 (10 mol%), 3 mL solvent, H2
(600 psi), room temperature, 15 h.
Conversions were determined by H NMR analysis of the
crude products.
Determined by HPLC analysis with chiral OD-H
[b]
[c]
[d]
1
Entry Ligand
Conversion [%][b] ee [%][c]
1
2
3
(S)-SegPhos
(R,Rp)-WalPhos
(R,R)-Me-DuPhos
>95
>95
45
87 (S)
56 (S)
4 (S)
column.
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
The absolute configuration of 2a was assigned by com-
parison of the observed optical rotation with reported
data.
4
5
6
7
8
9
(S)-iPr-PHOX
(R)-SynPhos
(R)-C4-TunePhos
(R)-MeO-BiPhep
(S)-BINAP
(R)-DTBM-SegPhos >95
(S)-MeO-MOP
(S)-SegPhos
32
38 (R)
85 (R)
77 (R)
81 (R)
16 (S)
31 (R)
6 (S)
>95
>95
>95
>95
Results and Discussion
Based on our previous work,[12] the hydrogenation of
3-phenyl-2H-1,4-benzoxazine (1a) was initially per-
formed in CH2Cl2 under 600 psi of H2 at room tem-
perature in the presence of 1 mol% iridium catalyst
10
70
>95
11[d]
88 (S)
[a]
Reaction conditions: [IrACHTNUTRGNENG(U COD)Cl]2 (1 mol%), ligand
(2.2 mol%), I2 (10 mol%), 3 mL benzene, H2 (600 psi),
room temperature, 15 h.
generated in situ from [IrACHTNUTRGNENG(U COD)Cl]2, (S)-SegPhos and
additive I2. To our delight, the reaction ran smoothly
and with moderate enantioselectivity (80% ee,
Table 1, entry 1). Encouraged by this result, the effect
of solvents was investigated as shown in Table 1. Full
conversions were achieved for all solvents (Table 1,
[b]
[c]
[d]
1
Conversions were determined by H NMR analysis of the
crude products.
Determined by HPLC analysis with a chiral OD-H
column.
Run under 400 psi of H2.
Figure 1. Structures of the examined chiral phosphine ligands.
484
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 483 – 488

Iridium-Catalyzed Asymmetric Hydrogenation of 3-Substituted 2H-1,4-Benzoxazines
Table 3. Asymmetric hydrogenation of 3-aryl-2H-1,4-benz-
oxazines 1.[a]
Table 4. Hydrogenation of 3-styryl-2H-1,4-benzoxazine de-
rivatives 3.[a]
ACHTUNGTRENNUNG
Entry
R’/R
Yield [%][b]
ee [%][c,d]
Entry
R
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
H/Ph (1a)
91 (2a)
95 (2b)
97 (2c)
91 (2d)
98 (2e)
93 (2f)
95 (2g)
96 (2h)
98 (2i)
97 (2j)
96 (2k)
96 (2l)
98 (2m)
97 (2n)
93 (2o)
88 (S)
85 (S)
87 (S)
86 (S)
85 (S)
84 (S)
85 (S)
88 (S)
88 (S)
90 (S)
88 (S)
89 (S)
89 (S)
92 (S)
79 (S)
1
2
3
4
5
Ph (3a)
80 (4a)
73 (4b)
77 (4c)
71 (4d)
66 (4e)
94 (–)
93 (–)
94 (–)
95 (–)
95 (–)
H/3-Me-C6H4 (1b)
H/3-MeO-C6H4 (1c)
H/4-Me-C6H4 (1d)
H/4-C6H5-C6H4 (1e)
H/2-F-C6H4 (1f)
H/3-F-C6H4 (1g)
H/4-F-C6H4 (1h)
H/3-Cl-C6H4 (1i)
H/4-Cl-C6H4 (1j)
H/3-Br-C6H4 (1k)
H/4-Br-C6H4 (1l)
H/4-CF3-C6H4 (1m)
H/3,4-Cl2-C6H3 (1n)
t-Bu/Ph (1o)
4-Me-C6H4 (3b)
4-F-C6H4 (3c)
4-Cl-C6H4 (3d)
4-CF3- C6H4 (3e)
[a]
Reaction conditions: i) [IrACHTNUTRGNENG(U COD)Cl]2 (1 mol%), (S)-Seg-
Phos (2.2 mol%), I2 (2 mol%), 3 mL toluene, H2
(400 psi), room temperature, 15 h; ii) Pd/C, H2 (400 psi),
THF, room temperature.
Isolated yields.
Determined by HPLC analysis with a chiral column.
9
10
11
12
13
14
15
[b]
[c]
After establishing the successful asymmetric hydro-
genation of 3-aryl-substituted benzoxazines, we ap-
plied this catalyst system to hydrogenate the interest-
ing 3-styryl-2H-1,4-benzoxazine derivatives (Table 4).
The reaction gave full conversions, but with mixtures
of partially and completely hydrogenated products.
For example, for the hydrogenation of 3-styryl-2H-
1,4-benzoxazine (3a), the ratio of the corresponding
products was 1:4 (determined by NMR). Next, we
tried to optimize the ratio of hydrogenation products
by varying the solvents, hydrogen pressure and reac-
tion time, however, the results were unsatisfactory.
[a]
Reaction conditions: [IrACHTNUTRGENNG(U COD)Cl]2 (1 mol%), (S)-Seg-
Phos (2.2 mol%), I2 (10 mol%), 3 mL benzene, H2
(400 psi), room temperature, 15 h.
[b]
[c]
[d]
Isolated yields.
Determined by HPLC analysis with chiral column.
The absolute configuration of 2a was assigned by com-
parison of the observed optical rotation with the report-
ed data. The absolute configurations of the other prod-
ucts were deduced by analogy to 2a.
(Table 2, entries 5–7), while, BINAP showed lower ee Therefore, Pd/C was added after the completion of
(Table 2, entry 8). Although the sterically demanding the iridium hydrogenation to reduce the remaining
DTBM-SegPhos provided high ees in the asymmetric C=C bond of the partially hydrogenated product. For-
hydrogenation of quinolines,[14] low enantiocontrol tunately, high yields (66–80%) and excellent ee values
was observed for benzoxazines (Table 2, entry 9). The (93–95%) were achieved for the hydrogenation of 3-
monodentate ligand MeO-MOP was also tested and styryl-2H-1,4-benzoxazine derivatives. Substrates with
yielded poor results (Table 2, entry 10). Eventually, both electron-donating and electron-withdrawing sub-
(S)-SegPhos gave the highest ee (87% ee, Table 2, stituents on the phenyl group can be tolerated
entry 1). On lowering the hydrogen pressure, the (Table 4).
enantioselectivity increased slightly (88% ee, Table 2,
entry 11). Thus, the optimal conditions were estab-
lished as: [Ir
(400 psi).
N
With the optimized conditions in hand, a variety of In summary, the asymmetric hydrogenation of 3-aryl-
benzoxazines was evaluated to examine the substrate 2H-1,4-benzoxazines utilizing the [Ir(COD)Cl]2/(S)-
AHCTUNGTRENNUNG
scope. As shown in Table 3, all the 3-aryl substituted SegPhos/I2 catalyst system was achieved with up to
benzoxazines were completely converted to the corre- 92% ee. Furthermore, the intriguing 3-styryl-2H-1,4-
sponding amines with high enantioselectivities regard- benzoxazine derivatives were also hydrogenated by
less of the position and electronic effects of substitu- iridium catalyst and Pd/C in two consecutive steps
ents R on the benzene ring (84–92% ees, Table 3, en- whereby 93–95% ee values were obtained. This
tries 1–14). The substrate with a tert-butyl group at method provides an atom economical access to phar-
the 6-position revealed a negative effect the on enan- maceutically relevant chiral amines. Further work will
tioselectivity which may be ascribed to steric effects be directed to the asymmetric hydrogenation of other
(Table 3, entry 15).
heterocyclic compounds.
Adv. Synth. Catal. 2012, 354, 483 – 488
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
485

Kai Gao et al.
FULL PAPERS
enantiomer};[10a] 1H NMR (400 MHz, CDCl3): d=3.98–4.03
(m, 2H), 4.27–4.31 (m, 1H), 4.52 (dd, J=8.5, 3.0 Hz, 1H),
6.67–6.73 (m, 2H), 6.80–6.87 (m, 2H), 7.33–7.43 (m, 5H);
13C NMR (100 MHz, CDCl3): d=54.4, 71.2, 115.6, 116.8,
119.1, 121.7, 127.4, 128.5, 129.0, 134.1, 139.3, 143.7; HPLC
(OD-H, eluent: hexanes/i-PrOH=70/30, detector: 254 nm,
flow rate: 0.7 mLminÀ1): t1 =10.6 min (minor), t2 =13.9 min
(major).
Experimental Section
General Remarks
All reactions were carried out under an atmosphere of nitro-
gen using standard Schlenk techniques, unless otherwise
noted. 1H NMR and 13C NMR spectra were recorded at
room temperature in CDCl3 on a 400 MHz instrument with
tetramethylsilane (TMS) as internal standard. Enantiomeric
excesses were determined by HPLC analysis. Optical rota-
tions were measured by a polarimeter. Flash column chro-
matography was performed on silica gel (200–300 mesh).
All reactions were monitored by TLC analysis. 3-Substituted
2H-1,4-benzoxazines were synthesized according to the liter-
ature procedure.[15]
General Procedure for Hydrogenation of 3
In a nitrogen-filled glovebox, a mixture of [Ir
(1.7 mg, 0.0025 mmol) and (S)-SegPhos
ACHTUNGTRENNUNG
0.0055 mmol) was stirred in toluene (1 mL) at room temper-
ature for 5 min, then I2 (1.3 mg, 0.005 mmol) was added.
The mixture was stirred for another 5 min and then imine
substrate (0.25 mmol) together with 2 mL toluene were
added. The resulting solution was transferred from the glo-
vebox to an autoclave. Then the autoclave was charged with
400 psi of H2. The hydrogenation was performed at room
temperature for 15 h. After carefully releasing the hydrogen
gas, the solvent was removed under vacuum, then the Pd/C
reduction was conducted in THF to hydrogenate the re-
maining C=C bond of the partially hydrogenated product.
After that, the reaction mixture was concentrated and the
residue was purified by column chromatography to furnish
the corresponding hydrogenation product, which was then
analyzed by chiral HPLC on a column (OJ-H) to determine
the enantiomeric excess.
3-Phenethyl-3,4-dihydro-2H-1,4-benzoxazine (4a): yield:
80%; 94% ee; [a]Dr:t:: À18.8 (c 1.20, CHCl3); 1H NMR
(400 MHz, CDCl3): d=1.82–1.88 (m, 2H), 2.78 (dd, J=8.7,
1.9 Hz, 2H), 3.41–3.44 (m, 1H), 3.71 (br, 1H), 3.92 (dd, J=
10.5, 7.3 Hz, 1H), 4.23 (dd, J=10.5, 2.7 Hz, 1H), 6.58 (dd,
J=7.7, 1.4 Hz, 1H), 6.67 (td, J=7.7, 1.5 Hz, 1H), 6.79–6.82
(m, 2H), 7.24 (t, J=7.1 Hz, 3H), 7.31–7.35 (m, 2H);
13C NMR (100 MHz, CDCl3): d=32.1, 34.0, 49.4, 69.4, 115.7,
116.7, 118.9, 121.6, 126.4, 128.5, 128.8, 133.4, 141.3, 144.0;
HPLC (OJ-H, eluent: hexanes/i-PrOH=60/40, detector:
254 nm, flow rate: 0.8 mLminÀ1), t1 =18.5 min (major), t2 =
21.1 min (minor); HR-MS: m/z=262.1206, calculated for
C16H17NONa [M+Na]+: 262.1208.
General Procedure for the Synthesis of 3-Substituted
2H-1,4-Benzoxazines
To a round-bottom flask were added the appropriate 2-ami-
nophenol (3 mmol) and CH2Cl2 (20 mL), then 20% aqueous
K2CO3 solution (20 mL) and (n-Bu)4NHSO4 (1 mg) was
added. The substituted 2-bromoacetophenone or (E)-1-
bromo-4-phenylbut-3-en-2-one (3 mmol) was dissolved in
5 mL CH2Cl2 and added dropwise to the reaction mixture
which was then stirred at room temperature and monitored
by TLC. After the consumption of the starting materials, the
organic layer was washed with water (30 mL) and brine
(20 mL), then dried by anhydrous Na2SO4. The solvent was
removed under vacuum and the crude product was purified
by column chromatography using petroleum ether and
EtOAc as eluent to obtain the corresponding benzoxazines.
3-(3-Methylphenyl)-2H-1,4-benzoxazine (1b): yield: 86%;
1H NMR (400 MHz, CDCl3): d=2.42 (s, 3H), 5.04 (s, 2H),
6.90 (d, J=8.0 Hz, 1H), 7.01 (t, J=7.5 Hz, 1H), 7.13 (t, J=
7.6 Hz, 1H), 7.38–7.26 (m, 2H), 7.43 (d, J=7.7 Hz, 1H),
7.65 (d, J=7.6 Hz, 1H), 7.77 (s, 1H); 13C NMR (100 MHz,
CDCl3): d=21.7, 63.2, 115.7, 122.5, 123.8, 127.2, 128.0, 128.7,
128.8, 132.2, 135.6, 138.7, 146.6, 159.1; HR-MS: m/z=
224.1081, calculated for C15H14NO [M+H]+: 224.1075.
General Procedure for Asymmetric Hydrogenation of
1
In a nitrogen-filled glovebox, a mixture of [Ir
(1.7 mg, 0.0025 mmol) and (S)-SegPhos
ACHTUNGTRENNUNG
Acknowledgements
0.0055 mmol) was stirred in benzene (1 mL) at room tem-
perature for 5 min, then I2 (6.4 mg, 0.025 mmol) was added.
The mixture stirred for another 5 min and then the imine
substrate (0.25 mmol) together with 2 mL benzene were
added. The resulting solution was transferred from the glo-
vebox to an autoclave. Then the autoclave was charged with
400 psi of H2. The hydrogenation was performed at room
We are grateful to the financial support from National Natu-
ral Science Foundation of China (21032003 and 20921092),
and National Basic Research Program of China
(2010CB833300).
temperature for 15 h. After carefully releasing the hydrogen References
gas, the reaction mixture was concentrated to afford the
crude product which was purified by silica gel column with
petroleum ether and EtOAc as eluent to furnish the corre-
sponding hydrogenation product. The enantiomeric excesses
were determined by chiral HPLC with chiral columns (OD-
H or AD-H).
3-Phenyl-3,4-dihydro-2H-1,4-benzoxazine (2a): known
compound;[10a] yield: 91%; 88% ee; [a]rD:t:: +102.0 (c 1.08,
CHCl3), {Lit. [a]rD:t:: À118.1 (c 1.0, CHCl3) for 98% ee of (R)-
[1] a) D.-W. Wang, Y.-G. Zhou, Q.-A. Chen, D.-S. Wang,
in: Chiral Amine Synthesis: Methods, Developments
and Applications, 1st edn., (Ed.: T. C. Nugent), Wiley-
VCH, Weinheim, 2010, pp 299–339; b) T. Ohkuma, M.
Kitamura, R. Noyori, in: Catalytical Asymmetric Syn-
thesis, 2nd edn., (Ed.: I. Ojima), Wiley, New York, 2000,
pp 410–421; c) H.-U. Blaser, C. Malan, B. Pugin, F.
Spindler, H. Steiner, M. Studer, Adv. Synth. Catal.
486
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 483 – 488

Iridium-Catalyzed Asymmetric Hydrogenation of 3-Substituted 2H-1,4-Benzoxazines
2003, 345, 1031; d) S. Kobayashi, H. Ishitani, Chem.
Rev. 1999, 99, 1069.
[2] For reviews, see: a) W. Tang, X. Zhang, Chem. Rev.
2003, 103, 3029; b) N. Fleury-Brꢂgeot, V. de La Fuente,
S. Castillꢃn, C. Claver, ChemCatChem 2010, 2, 1346;
c) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou, Chem. Rev. 2011,
111, 1713.
B. L. Feringa, J. G. de Vries, J. Am. Chem. Soc. 2009,
131, 8358; n) M. Chang, W. Li, G. Hou, X. Zhang, Adv.
Synth. Catal. 2010, 352, 3121; o) K. Kutlescha, T. Irr-
gang, R. Kempe, Adv. Synth. Catal. 2010, 352, 3126;
p) K. Gao, C.-B. Yu, W. Li, Y.-G. Zhou, X. Zhang,
Chem. Commun. 2011, 47, 7845.
[6] a) K. S. Brown, C. Djerassi, J. Am. Chem. Soc. 1964,
86, 2451; b) S. D. McAllister, G. Rizvi, S. Anavi-Goffer,
D. P. Hurst, J. Barnett-Norris, D. L. Lynch, P. H.
Reggio, M. E. Abood, J. Med. Chem. 2003, 46, 5139;
c) J. IIas, P. S. Anderluh, M. S. Dolene, D. Kikelj, Tetra-
hedron 2005, 61, 7325; d) A. Belattar, J. E. Saxton, J.
Chem. Soc. Perkin Trans. 1 1992, 679; e) J. Y. Shim,
E. R. Collantes, W. J. Welsh, J. Med. Chem. 1998, 41,
4521; f) S. Daiichi, Drugs Future 1992, 17, 559.
[7] a) V. P. Krasnov, G. L. Levit, I. M. Bukrina, I. N. An-
dreeva, L. S. Sadretdinova, M. A. Korolyova, M. I.
Kodess, V. N. Charushin, O. N. Chupakhin, Tetrahe-
dron: Asymmetry 2003, 14, 1985; b) V. N. Charushin,
V. P. Krasnov, G. L. Levit, M. A. Korolyova, M. I.
Kodess, O. N. Chupakhin, M. H. Kim, H. S. Lee, Y. J.
Park, K. C. Kim, Tetrahedron: Asymmetry 1999, 10,
2691; c) V. P. Krasnov, G. L. Levit, M. I. Kodess, V. N.
Charushin, O. N. Chupakhin, Tetrahedron: Asymmetry
2004, 15, 859; d) V. A. Potemkin, V. P. Krasnov, G. L.
Levit, E. V. Bartashevich, I. N. Andreeva, M. B. Kuz-
minsky, N. A. Anikin, V. N. Charushin, O. N. Chupa-
khin, Mendeleev Commun. 2004, 14, 69.
[3] a) C. A. Willoughby, S. L. Buchwald, J. Am. Chem. Soc.
1994, 116, 8952; b) J. Campora, S. L. Buchwald, E. Gu-
tierrez-Puebla, A. Monge, Organometallics 1995, 14,
2039; c) M. Ringwald, R. Sturmer, H. H. Brintzinger, J.
Am. Chem. Soc. 1999, 121, 1524; d) H. B. Kagan, N.
Langlois, T. P. Dang, J. Organomet. Chem. 1975, 90,
353; e) M. J. Burk, J. E. Feaster, J. Am. Chem. Soc.
1992, 114, 6266; f) V. I. Tararov, R. Kadyrov, T. H. Rier-
meier, C. Fischer, A. Bçrner, Adv. Synth. Catal. 2004,
346, 561; g) G. Shang, Q. Yang, X. Zhang, Angew.
Chem. 2006, 118, 6508; Angew. Chem. Int. Ed. 2006, 45,
6360; h) C. Q. Li, J. L. Xiao, J. Am. Chem. Soc. 2008,
130, 13208; i) C. Botteghi, M. Bianchi, E. Benedetti, U.
Matteoli, Chimia 1975, 29, 256; j) W. Oppolzer, M.
Wills, C. Starkemann, G. Bernardinelli, Tetrahedron
Lett. 1990, 31, 4117; k) J. C. Cobley, J. P. Henschke,
Adv. Synth. Catal. 2003, 345, 195; l) J. C. Cobley, E.
Foucher, J.-P. Lecouve, I. C. Lennon, J. A. Ramsden, G.
Thominot, Tetrahedron: Asymmetry 2003, 14, 3431;
m) P. Cheruku, T. L. Church, P. G. Andersson, Chem.
Asian J. 2008, 3, 1390; n) F. Chen, T. Wang, Y. He, Z.
Ding, Z. Li, L. Xu, Q.-H. Fan, Chem. Eur. J. 2011, 17,
1109; o) F. Chen, Z. Ding, J. Qin, T. Wang, Y. He, Q.-
H. Fan, Org. Lett. 2011, 13, 4348.
[4] a) Y.-Q. Wang, Y.-G. Zhou, Synlett 2006, 1189; b) Q.
Yang, G. Shang, W. Gao, J. Deng, X. Zhang, Angew.
Chem. 2006, 118, 3916; Angew. Chem. Int. Ed. 2006, 45,
3832; c) Y.-Q. Wang, S.-M. Lu, Y.-G. Zhou, J. Org.
Chem. 2007, 72, 3729; d) C.-B. Yu, D.-W. Wang, Y.-G.
Zhou, J. Org. Chem. 2009, 74, 5633; e) M.-W. Chen, Y.
Duan, Q.-A. Chen, D.-S. Wang, C.-B. Yu, Y.-G. Zhou,
Org. Lett. 2010, 12, 507; f) C.-B. Yu, K. Gao, D.-S.
Wang, L. Shi, Y.-G. Zhou, Chem. Commun. 2011, 47,
5052.
[5] Selected examples for Ir-catalyzed asymmetric hydro-
genation of imines, see: a) Y. N. C. Chan, J. A. Osborn,
J. Am. Chem. Soc. 1990, 112, 9400; b) P. Schbider, G.
Koch, R. Prꢂtꢄt, G. Wang, F. M. Bohnen, C. Krꢅger, A.
Pfaltz, Chem. Eur. J. 1997, 3, 887; c) D. Xiao, X. Zhang,
Angew. Chem. 2001, 113, 3533; Angew. Chem. Int. Ed.
2001, 40, 3425; d) B. Pugin, H. Landert, F. Spindler, H.-
U. Blaser, Adv. Synth. Catal. 2002, 344, 974; e) C.
Moessner, C. Bolm, Angew. Chem. 2005, 117, 7736;
Angew. Chem. Int. Ed. 2005, 44, 7564; f) A. Trifonova,
J. S. Diesen, P. G. Andersson, Chem. Eur. J. 2006, 12,
2318; g) S.-F. Zhu, J.-B. Xie, Y.-Z. Zhang, S. Li, Q.-L.
Zhou, J. Am. Chem. Soc. 2006, 128, 12886; h) T. Ima-
moto, N. Iwadate, K. Yoshida, Org. Lett. 2006, 8, 2289;
i) M. N. Cheemala, P. Knochel, Org. Lett. 2007, 9, 3089;
j) M. T. Reetz, O. Bondarev, Angew. Chem. 2007, 119,
4607; Angew. Chem. Int. Ed. 2007, 46, 4523; k) C. Li, C.
Wang, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc.
2008, 130, 14450; l) Z. Han, Z. Wang, X. Zhang, K.
Ding, Angew. Chem. 2009, 121, 5449; Angew. Chem.
[8] a) R. Noyori, Acta Chem. Scand. 1996, 50, 380; b) A.
Miyadera, A. Imura, Tetrahedron: Asymmetry 1999, 10,
119; c) K. Sakano, S. Yokohama, I. Hayakawa, S. Atar-
ashi, S. Kadoya, Agric. Biol. Chem. 1987, 51, 1265;
d) M. Imamura, I. Hayakawa, Chem. Pharm. Bull.
1987, 35, 1896; e) R. Noyori, T. Ohkuma, Angew.
Chem. 2001, 113, 40; Angew. Chem. Int. Ed. 2001, 40,
40.
[9] Y.-G. Zhou, P.-Y. Yang, X.-W. Han, J. Org. Chem. 2005,
70, 1679–1683.
[10] a) M. Rueping, A. P. Antonchick, T. Theissmann,
Angew. Chem. 2006, 118, 6903; Angew. Chem. Int. Ed.
2006, 45, 6751; b) R. I. Storer, D. E. Carrera, Y. Ni,
D. W. C. MacMillan, J. Am. Chem. Soc. 2006, 128, 84;
c) M. Rueping, F. Tato, F. R. Schoepke, Chem. Eur. J.
2010, 16, 2688; d) M. Rueping, E. Sugiono, F. R.
Schoepke, Synlett 2010, 852; e) M. Rueping, E. Sugio-
no, A. Steck, T. Theissmann, Adv. Synth. Catal. 2010,
352, 281; f) M. Rueping, E. Merino, R. M. Koenigs,
Adv. Synth. Catal. 2010, 352, 2629; g) A. V. Malkov, K.
ˇ
ˇ
´
Vrankovꢆ, S. Stoncius, P. Kocovsky, J. Org. Chem. 2009,
74, 5839; h) M. Rueping, M. Stoeckel, E. Sugiono, T.
Theissmann, Tetrahedron 2010, 66, 6565; i) Z.-Y. Xue,
Y. Jiang, X.-Z. Peng, W.-C. Yuan, X.-M. Zhang, Adv.
Synth. Catal. 2010, 352, 2132; j) M. Rueping, C. Brink-
mann, A. P. Antonchick, L. Atodiresei, Org. Lett. 2010,
12, 4604; k) Z.-Y. Xue, Y. Jiang, W.-C. Yuan, X.-M.
Zhang, Eur. J. Org. Chem. 2010, 616.
[11] a) S. Atarashi, H. Tsurumi, T. Fujiwara, I. Hayakawa, J.
Heterocycl. Chem. 1991, 28, 329; b) K. Satoh, M. Inena-
ga, K. Kanai, Tetrahedron: Asymmetry 1998, 9, 2657;
c) L. Xie, J. Chin. Chem. Lett. 1995, 6, 857; d) J. Adrio,
J. C. Carretero, J. L. G. Ruano, A. Pallarꢂs, M. Vicioso,
Heterocycles 1999, 51, 1563.
ˇ ´
Int. Ed. 2009, 48, 5345; m) N. Mrsic, A. J. Minnaard,
Adv. Synth. Catal. 2012, 354, 483 – 488
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
487

Kai Gao et al.
FULL PAPERS
[12] For our groupꢀs work on the asymmetric reduction of
quinolines, see: a) W.-B. Wang, S.-M. Lu, P.-Y. Yang,
X.-W. Han, Y.-G. Zhou, J. Am. Chem. Soc. 2003, 125,
10536; b) S.-M. Lu, X.-W. Han, Y.-G. Zhou, Adv.
Synth. Catal. 2004, 346, 909; c) Y.-J. Zhao, Y.-Q. Wang,
Y.-G. Zhou, Chin. J. Catal. 2005, 26, 737; d) S.-M. Lu,
Y.-Q. Wang, X.-W. Han, Y.-G. Zhou, Angew. Chem.
2006, 118, 2318; Angew. Chem. Int. Ed. 2006, 45, 2260;
e) D.-W. Wang, W. Zeng, Y.-G. Zhou, Tetrahedron:
Asymmetry 2007, 18, 1103; f) Y.-G. Zhou, Acc. Chem.
Res. 2007, 40, 1357; g) X.-B. Wang, Y.-G. Zhou, J. Org.
Chem. 2008, 73, 5640; h) D.-W. Wang, X.-B. Wang, D.-
S. Wang, S.-M. Lu, Y.-G. Zhou, Y.-X. Li, J. Org. Chem.
2009, 74, 2780; i) D.-W. Wang, D.-S. Wang, Q.-A. Chen,
Y.-G. Zhou, Chem. Eur. J. 2010, 16, 1133; j) D.-S.
Wang, Y.-G. Zhou, Tetrahedron Lett. 2010, 51, 3014.
[13] Recent examples on asymmetric hydrogenation of qui-
nolines by other groups, see: a) H. Zhou, Z. Li, Z.
Wang, T. Wang, L. Xu, Y. He, Q.-H. Fan, J. Pan, L. Gu,
A. S. C. Chan, Angew. Chem. 2008, 120, 8592; Angew.
daoka, D. Cartigny, T. Nagano, T. Gosavi, T. Ayad, J.-P.
GenÞt, T. Oshima, V. Ratovelomanana-Vidal, K. Ma-
shima, Chem. Eur. J. 2009, 15, 9990; d) S.-M. Lu, C.
Bolm, Adv. Synth. Catal. 2008, 350, 1101; e) Z. Li, T.
Wang, Y. He, Z. Wang, Q.-H. Fan, J. Pan, L.-J. Xu,
Org. Lett. 2008, 10, 5265; f) M. T. Reetz, X. Li, Chem.
Commun. 2006, 42, 2159; g) J. L. NfflÇez-Rico, H.
Fernꢆndez-Pꢂrez, J. Benet-Buchholz, A. Vidal-Ferran,
Organometallics 2010, 29, 6627; h) G. E. Dobereiner,
A. Nova, N. D. Schley, N. Hazari, S. J. Miller, O. Eisen-
stein, R. H. Crabtree, J. Am. Chem. Soc. 2011, 133,
7547; i) T. Wang, L.-G. Zhuo, Z. Li, F. Chen, Z. Ding,
Y. He, Q.-H. Fan, J. Xiang, Z.-X. Yu, A. S. C. Chan, J.
Am. Chem. Soc. 2011, 133, 9878.
[14] D.-S. Wang, J. Zhou, D.-W. Wang, Y.-L. Guo, Y.-G.
Zhou, Tetrahedron Lett. 2010, 51, 525.
[15] a) G. Sabitha, A. V. S. Rao, Synth. Commun. 1987, 17,
341; b) M. Ju Young, J. H. Ahn, H. M. Kim, N. M.
Yoon, K. W. Kim, J. H. Kang, S. J. Lee, J. Heterocycl.
Chem. 2002, 39, 1065; c) Y. Ma, Y. Zhang, J. Chem.
Res. 2000, 388; d) C. Banzatti, F. Heidempergher, P.
Melloni, J. Heterocycl. Chem. 1983, 20, 259.
ˇ ´
Chem. Int. Ed. 2008, 47, 8464; b) N. Mrsic, L. Lefort,
J. A. F. Boogers, A. J. Minnaard, B. L. Feringa, J. G.
de Vries, Adv. Synth. Catal. 2008, 350, 1081; c) H. Ta-
488
asc.wiley-vch.de
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2012, 354, 483 – 488