An enantioselective approach to 2,3-disubstituted indolines through consecutive Bronsted acid/Pd-complex-promoted tandem reactions

Article abstract of DOI:10.1002/chem.201100576

In tandem: A divergent and enantioselective approach to 2,3-disubstituted indolines was developed through consecutive Bronsted acid/Pd-complex- promoted tandem reactions from simple 2-substituted indoles and aldehydes in one operation to give up to 98 % ee (see scheme; R¹=H, F, or Me; R ²=alkyl; R³=aryl or alkyl). Three Bronsted acid promoted steps and two Pd-catalyzed hydrogenation steps were involved in this process. Copyright

Full text of DOI:10.1002/chem.201100576

COMMUNICATION
DOI: 10.1002/chem.201100576
An Enantioselective Approach to 2,3-Disubstituted Indolines through
Consecutive Brønsted Acid/Pd-Complex-Promoted Tandem Reactions
Ying Duan, Mu-Wang Chen, Zhi-Shi Ye, Duo-Sheng Wang, Qing-An Chen, and
Yong-Gui Zhou*[a]
Tandem reactions and consecutive catalysis (or relay cat-
alysis) have been receiving considerable attention in organic
synthesis due to their abilities of constructing multiple new
chemical bonds to build complex chiral molecules in a single
operation.[1,2] Transition-metal-catalyzed asymmetric hydro-
genation is one of the most widely used and reliable catalyt-
ic methods for preparation of chiral molecules.[3] The combi-
nation of Brønsted acid/transition-metal-catalyzed tandem
reactions involving asymmetric hydrogenation as key step
remains rare,[4] although Krische and co-workers reported
2,3-disubstituted indolines (Scheme 1).[12] Herein, we de-
scribe the enantioselective access to chiral 2,3-disubstituted
indolines through consecutive Brønsted acid/Pd-complex-
À
the C C bond formation with metal hydride as the catalytic
species.[2c,5]
Chiral 2,3-disubstituted indolines are significant building
blocks in biologically active natural products and pharma-
ceutically active compounds.[6] Generally, these compounds
are synthesized from either dynamic resolution or multiple-
step reactions.[7] The most straightforward and atom eco-
nomic means towards chiral indolines may be the asymmet-
ric hydrogenation of substituted indole derivatives. Recently,
some significant progress has been achieved by us and other
groups for the highly enantioselective hydrogenation of sub-
stituted indoles using chiral Pd, Rh, Ru, and Ir complexes as
catalysts.[8] Very recently, we developed a facile approach to
chiral 2,3-disubstituted indolines through dehydration-trig-
gered asymmetric hydrogenation of 3-(a-hydroxyalkyl)in-
doles.[9] Despite these contributions, the tedious procedure
for the preparation of the substrates limits its synthetic ap-
plications. So, the search for a rapid, simple, and divergent
method for synthesizing chiral 2,3-disubstituted indolines is
still highly desirable.
Scheme 1. The process for synthesis of 2,3-disubstituted indolines Brøn-
sted acid (HX)-promoted three-step reaction and Pd-catalyzed two-step
reaction.
promoted reductive alkylation/hydrogenation reactions with
up to 98% ee (Scheme 1). Three steps are promoted by a
Brønsted acid and two hydrogenation steps are catalyzed by
a Pd complex. Furthermore, the asymmetric hydrogenation
should drive the equilibrium of the Friedel–Crafts reaction
by converting the Friedel–Crafts product into a hydrogena-
tion product.
The reaction process was proposed as shown in Scheme 1.
The Brønsted-acid-promoted Friedel–Crafts reaction of 2-
methylindole and aldehyde afforded 3-(a-hydroxyalkyl)in-
dole 4; then, 4 was dehydrated to give the important inter-
mediate vinylogous iminium I,[13] followed by two asymmet-
ric hydrogenation steps to accomplish this process. For the
above process, several issues should be addressed. Firstly, 2-
substituted indole 1a might be preferentially hydrogenated
(Scheme 2, reaction 1).[8e] Secondly, bisindoles 6 is always
the byproduct of indole and aldehyde with Brønsted acid as
the catalyst (Scheme 2, reaction 2).[10e,14] Thirdly, both strong
Brønsted acid and water existed in the reaction, so the rele-
vant hydrogenation catalyst must be compatible with them.
Therefore, several experiments were designed to assess the
feasibility of this process. To our delight, after mixing 2-
methylindole, benzaldehyde, and para-toluenesulfonic acid
monohydrate (TsOH·H2O) in CDCl3 and stirring for 5 min,
the peaks of 2-methylindole and benzaldehyde almost disap-
peared, as observed by 1H NMR analysis. This result sug-
gested that the Friedel–Crafts reaction between 2-methyl
Considering reductive alkylation (Friedel–Crafts/dehydra-
tion/reduction) of 2-substituted indoles and aldehydes can
rapidly lead to 2,3-disubstituted indoles,[10] we envisioned
that combination of reductive alkylation of 2-substituted in-
doles and asymmetric hydrogenation[11] of 2,3-disubstituted
indoles can lead to a rapid and divergent approach to chiral
[a] Y. Duan, M.-W. Chen, Z.-S. Ye, D.-S. Wang, Q.-A. Chen,
Prof. Y.-G. Zhou
Dalian Institute of Chemical Physics
Chinese Academy of Sciences (CAS)
457 Zhongshan Road, Dalian 116023 (P.R. China)
Fax : (+86)411-84379220
E-mail: ygzhou@dicp.ac.cn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201100576.
Chem. Eur. J. 2011, 17, 7193 – 7197
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
7193

contrast to strong acid, a weak acid such as benzoic acid was
ineffective, and TsOH·H2O showed the best result in terms
of enantioselectivity and reactivity (Table 1, entries 7–13).
Finally, several commercially available chiral bisphosphine
ligands were investigated; (R)-H8-BINAP was found to be
superior to other ligands (91% ee in Table 1, entry 14). Con-
sequently, the optimal conditions were established; Pd-
AHCTNUGRTEG(NNNU OCOCF3)2/(R)-H8-BINAP/TsOH·H2O/H2 (600 psi) in
CH2Cl2/TFE (2:1) at 508C.
Next, to explore the scope of this reaction, various 2-sub-
stituted indoles and aldehydes were subjected to the optimal
conditions and the results are summarized in Table 2. Gen-
erally, this reaction displayed good functional group toler-
ance. It was found that electron-deficient groups on indoles
or on aldehydes gave indolines with slightly lower ee values
(Table 2, entries 3, 10 and 11). An increase of enantioselec-
tivity was observed in response to the employment of alkyl
aldehydes instead of aromatic aldehydes. The investigation
of aromatic aldehydes with variation in their steric features
revealed that the reaction proceeded smoothly to give the
desirable products with high ee values and slightly decreased
yields (Table 2, entries 15–17). Notably, excellent 97–
98% ees were achieved with substrates 2,7-dimethylindole
1e (Table 2, entries 12–17), and this may be ascribed to the
steric effect of the 7-methyl group.
Scheme 2. Possible side reactions.
indole and benzaldehyde was very fast (Scheme 1). More-
over, bisindole 6 could be reversibly transformed to vinylo-
gous iminium I (Scheme 2, reaction 3) in the presence of
strong Brønsted acid and aldehyde (see further).[10c,15] Re-
cently, palladium complexes have been successfully applied
to the enantioselective hydrogenation of unprotected in-
doles, activated imines, and ketones by us and other
groups.[8e,9,16] Our preliminary mechanistic study found that
the palladium hydrogenation
catalyst was not sensitive to
Table 1. Optimization for tandem reaction of 1a and 2a.[a]
Brønsted acid and water.
Therefore, we foresaw that the
Pd catalyst system might work
well in this tandem reac-
tion.[8e,9,16]
Entry
Solvent
Acid
Ligand
Yield
[%][b]
ee
To explore the possibility of
the proposed reductive alkyla-
tion/hydrogenation tandem pro-
cess, we began with the reaction
of 2-methylindole and benzal-
dehyde using by TsOH·H2O
[%][c]
1
2
3
4
5
6
7
8
toluene
THF
CH2Cl2
TFE
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
TsOH·H2O
MeSO3H
TFA
PhCO2H
l-CSA
d-CSA
TsOH·H2O
TsOH·H2O
TsOH·H2O
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
–
–
–
–
83
75
91
86
88
88
63
–
84
75
91
93
88
63
75
84
85
87
84
41
–
86
80
91
89
84
CH2Cl2/TFE (1:2)
CH2Cl2/TFE (1:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
CH2Cl2/TFE (2:1)
and PdACHTUNGTRENNUNG(OCOCF3)2/(R)-BINAP
as the catalyst. In our initial in-
vestigations, we found that the
solvent played a crucial role in
the transformation (Table 1, en-
tries 1–7). No reaction was ob-
served in toluene or THF
(Table 1, entries 1 and 2). Mod-
erate yields and ee values were
obtained in dichloromethane
and trifluoroethanol (TFE), re-
spectively (Table 1, entries 3
and 4). Fortunately, the mixed
solvent of dichloromethane and
TFE (CH2Cl2/TFE=2:1) pro-
vided enhanced yields and the
best enantioselectivity. Next,
9
10[d]
11
12
13
14
15
[a] Conditions: 1a (0.25 mmol), 2a (0.275 mmol), PdACTHNUGTRNEUNG(OCOCF3)2 (0.005 mmol), ligand (0.006 mmol), acid
(0.25 mmol), and 3 mL solvent at 508C for 3–20 h. [b] Yield of isolated product. [c] Determined by HPLC.
[d] With full conversion of 1a and 2-methyl-3-benzylindole 5 was obtained as byproduct. TsOH=toluenesul-
various acids were tested: in fonic acid, CSA=10-camphorsulfonic acid, TFA=trifluoroacetic acid.
7194
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 7193 – 7197

An Enantioselective Approach to 2,3-Disubstituted Indolines
COMMUNICATION
Table 2. The synthesis of 2,3-disubstituted indoline derivatives 3.[a]
Entry
R1
R2
R3
Product
Yield
[%][b]
ee
[%][c]
1
2
3
4
5
6
7
8
H
H
H
H
H
H
H
H
Me
Me
Me
Me
Ph
3aa
3ab
3ac
3ad
3ae
3ba
3bd
3ca
3 cd
3da
3dd
3ea
3ed
3ee
3ef
91
83
87
91
94
92
85
73
91
80
74
82
82
84
77
81
73
91
90
87
93
92
94
96
93
91
87
91
97
97
98
97
97
98
4-MeOC6H4
4-FC6H4
Cy
iPr
Ph
Cy
Ph
Cy
Ph
Cy
Ph
Cy
Scheme 3. Hydrogenation of 5 and 6 by using the chiral palladium.
Me
nBu
nBu
phenethyl
phenethyl
Me
Me
Me
Me
Me
nylogous iminium I in the presence of Brønsted acid and
benzaldehyde.
9
H
10
11
12
13
14
15
16
17
5-F
5-F
7-Me
7-Me
7-Me
7-Me
7-Me
7-Me
To obtain more evidence to clarify the mechanism, we
performed three isotopic labeling experiments with deuter-
ated solvent and deuterium gas, respectively (Scheme 4),
and the results were identical to our previous reports.[8e,9]
When the hydrogenation was carried out in deuterated TFE
for 18 h, 3aa was obtained as the product with complete
conversion. 1H NMR analysis showed that one deuterium
atom took up the 3 position with 87% incorporation
[Eq. (6)]. When the hydrogenation reaction was stopped at
iPr
Me
Me
Me
4-MeC6H4
3-MeC6H4
2-MeC6H4
3eg
3eh
[a] Conditions:
1
(0.25 mmol),
2
(0.275 mmol), PdACHTNGUTERNNU(G OCOCF3)2
(0.005 mmol), (R)-H8-BINAP (0.006 mmol), TsOH·H2O (0.25 mmol),
and solvent (3 mL) at 508C for 3–20 h. [b] Yield of isolated product.
[c] Determined by HPLC. Cy=cyclohexyl, iPr=isopropyl, nBu=n-butyl.
1
3 h, 3aa and 5 were obtained at a ratio of 10:90; H NMR
analysis of the isolated indole 5 showed that no deuterium
atom was incorporated at the benzylic position (Scheme 4,
reaction 7). When 1a was treated with D2, 3aa was obtained
with 91 and 93% incorporation of deuterium at the 2- and
benzylic position, respectively (Scheme 4, reaction 8). The
To gain insights into the mechanism information of the
transformation, a series of experiments were conducted.
Electrospray ionization mass spectroscopic analysis of the
solution of 2-methylindole,
benzaldehyde and TsOH·H2O
in TFE/CH2Cl2 (1:2) after stir-
ring for 5 min at room temper-
ature showed peaks at m/z +
220.1085 and m/zÀ 171.0168,
which were consistent with the
intermediacy of I in Scheme 1.
In another experiment, 2-
methyl-3-benzylindole 5 can be
isolated from the reaction mix-
tures performed at room tem-
perature to shorten the reac-
tion time to 3 h under the stan-
dard conditions.[9,15] When we
subjected 5 to hydrogenation
using the chiral palladium
complex as a catalyst, full con-
version and a similar 89% ee
were obtained (Scheme 3, reac-
Scheme 4. Deuterium-labeling studies.
tion 4 vs. entry 13, Table 1). This result suggested that the re-
action proceeded stepwise with 5 as the intermediate. When
the mixture of bisindole 6 and benzaldehyde 2a was subject-
ed to hydrogenation under standard conditions, a similar
90% ee was obtained with full conversion (Scheme 3, reac-
tion 5 vs. entry 13, Table 1), which suggested that the reac-
tion is reversible between bisindole 6 and intermediate vi-
above experiments clearly indicated that vinylogous iminium
I, indole 5, and bisindole 6 were probably the intermediates
and all of them could be finally transformed to the desired
product, which was the key factor for the successful tandem
reactions.
In summary, we have developed an efficient tandem reac-
tion through a consecutive Brønsted acid/Pd complex to
Chem. Eur. J. 2011, 17, 7193 – 7197
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7195

Y.-G. Zhou et al.
[3] a) The Handbook of Homogeneous Hydrogenation (Eds.: J. G. de V-
ries, C. J. Elsevier), Wiley-VCH, Weinheim, 2007; b) W. Tang, X.
Zhang, Chem. Rev. 2003, 103, 3029.
[4] a) Y. Chi, Y.-G. Zhou, X. Zhang, J. Org. Chem. 2003, 68, 4120; b) C.
Li, B. Villa-Marcos, J. Xiao, J. Am. Chem. Soc. 2009, 131, 6967.
[5] a) J. F. Bower, I. S. Kim, R. L. Patman, M. J. Krische, Angew. Chem.
2008, 121, 36; Angew. Chem. Int. Ed. 2008, 48, 34; b) S. B. Han, H.
Han, M. J. Krische, J. Am. Chem. Soc. 2010, 132, 1760; c) B.
Bechem, R. L. Patman, A. S. K. Hashmi, M. J. Krische, J. Org.
Chem. 2010, 75, 1795.
afford chiral 2,3-disubstituted indolines. Commercially avail-
able starting materials (2-substituted indoles and aldehydes),
simple operation procedures, high yields, and high stereose-
lectivity make this method useful for rapid and divergent
synthesis of chiral 2,3-disubstituted indolines in one single
operation. Further investigations to extend the reaction
scope and illustrate applications of this process in organic
synthesis are underway.
[6] For some reviews, see: a) I. W. Southon, J. Buckingham in Diction-
ary of Alkaloids, Chapman and Hall, New York, 1989; b) N. Neuss,
M. N. Neuss in The Alkaloids (Eds.: A. Brossi, M. Suffness), Aca-
demic Press, San Diego, 1990, p. 229; c) F. Gueritte, J. Fahy in Anti-
cancer Agents from Natural Products (Eds.: G. M. Cragg, D. G. I.
Kingstom, D. J. Newman), CRC Press, Boca Raton, 2005, p. 123;
d) Modern Alkaloids (Eds.: E. Fattorusso, O. Taglialatela-Scafati),
Wiley-VCH, Weinheim, 2008, and references therein.
[7] a) F. O. Arp, G. C. Fu, J. Am. Chem. Soc. 2006, 128, 14264; b) X.-L
Hou, B.-H. Zheng, Org. Lett. 2009, 11, 1789; c) S. Anas, H. B.
Kagan, Tetrahedron: Asymmetry 2009, 20, 2193, and references
therein.
[8] a) R. Kuwano, K. Sato, T. Kurokawa, D. Karube, Y. Ito, J. Am.
Chem. Soc. 2000, 122, 7614; b) R. Kuwano, K. Kaneda, T. Ito, K.
Sato, T. Kurokawa, Y. Ito, Org. Lett. 2004, 6, 2213; c) R. Kuwano,
M. Kashiwabara, Org. Lett. 2006, 8, 2653; d) R. Kuwano, M. Kashi-
wabara, K. Sato, T. Ito, K. Kanedaa, Y. Ito, Tetrahedron: Asymmetry
2006, 17, 521; e) D.-S. Wang, Q.-A. Chen, W. Li, C.-B. Yu, Y.-G.
Experimental Section
General Procedure: Ligand (0.006 mmol) and PdACTHNUGTRNEUNG(OCOCF3)2 (1.7 mg,
0.005 mmol) were placed in a dried Schlenk tube under nitrogen atmos-
phere, and degassed anhydrous acetone was added. The mixture was
stirred at RT for 1 h, then solvent was removed under vacuum to give the
catalyst. In a glovebox, acid (0.25 mmol) and indole (0.25 mmol) were
stirred in 1 mL solvent at room temperature for 1 min. Subsequently, al-
dehyde (0.275 mmol) was added slowly to the solution. Finally, the above
catalyst together with solvent (2 mL) was added to the reaction mixture.
The hydrogenation was performed at 508C under H2 (600 psi) in a stain-
less steel autoclave for 16 h. After carefully releasing the hydrogen, the
resulting mixture was concentrated under vacuum and dissolved in satu-
rated aqueous NaHCO3 (5 mL). After stirring for 10 min, the mixture
was extracted with CH2Cl2 (3ꢁ5 mL) and dried over Na2SO4. After pu-
rification by silica gel chromatography using petroleum ether/EtOAc
(10:1) as eluent, the enantiomeric excess of the products were deter-
mined by HPLC with chiral column.
ˇ ´
Zhou, X. Zhang, J. Am. Chem. Soc. 2010, 132, 8909; f) N. Mrsic, T.
Jerphagnon, A. J. Minnaard, B. L. Feringa, J. G. de Vries, Tetrahe-
dron: Asymmetry 2010, 21, 7; g) A. Baeza, A. Pfaltz, Chem. Eur. J.
2010, 16, 2036.
[9] D.-S. Wang, J. Tang, Y.-G. Zhou, M.-W. Chen, C.-B. Yu, Y. Duan,
G.-F. Jiang, Chem. Sci. 2011, 2, 803.
[10] a) J. E. Appleton, K. N. Dack, A. D. Green, J. Steele, Tetrahedron
Lett. 1993, 34, 1529; b) P. Zhou, Y. Li, K. L. Meagher, R. G. Mew-
shaw, B. L. Harrison, Tetrahedron Lett. 2001, 42, 7333; c) A. Maha-
devan, H. Sard, M. Gonzalez, J. C. McKew, Tetrahedron Lett. 2003,
44, 4589; d) J. A. Campbell, V. Bordunov, C. A. Broka, J. Dank-
wardt, R. T. Hendricks, J. M. Kress, K. A. M. Walker J.-H. Wang,
Tetrahedron Lett. 2004, 45, 3793; e) J. R. Rizzo, C. A. Alt, T. Y.
Zhang, Tetrahedron Lett. 2008, 49, 6749.
Acknowledgements
We are grateful to financial support from National Natural Science Foun-
dation of China (21032003), National Basic Research Program of China
(2010CB833300) and Dalian Institute of Chemical Physics (K2010F1).
The authors thank Prof. Xumu Zhang for helpful discussion.
[11] For selected examples of our groupꢃs work on asymmetric hydroge-
nation, 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) Y.-J. Zhao, Y.-Q.
Wang, Y.-G. Zhou, Chin. J. Catal. 2005, 26, 737; c) S.-M. Lu, X.-W.
Han, Y.-G. Zhou, Chin. J. Org. Chem. 2005, 25, 634; d) Y.-G. Zhou,
P.-Y. Yang, X.-W. Han, J. Org. Chem. 2005, 70, 1679; e) S.-M. Lu,
Y.-Q. Wang, X.-W. Han, Y.-G. Zhou, Angew. Chem. 2006, 118, 2318;
Angew. Chem. Int. Ed. 2006, 45, 2260; f) Y.-G. Zhou, Acc. Chem.
Res. 2007, 40, 1357; g) D.-W. Wang, W. Zeng, Y.-G. Zhou, Tetrahe-
dron: Asymmetry 2007, 18, 1103; h) D.-S. Wang, Y.-G. Zhou, Tetra-
hedron Lett. 2010, 51, 3014; i) D.-S. Wang, J. Zhou, D.-W. Wang, Y.-
L. Guo, Y.-G. Zhou, Tetrahedron Lett. 2010, 51, 525.
[12] a) K. D. Camm, N. M. Castro, Y. Liu, P. Czechura, J. L. Snelgrove,
D. E. Fogg, J. Am. Chem. Soc. 2007, 129, 4168; b) J. Elaridi, J. Patel,
W. R. Jackson, A. J. Robinson, J. Org. Chem. 2006, 71, 7538.
[13] a) N. A. Kogan, G. N. Kulbitskii, Chem. Heterocycl. Compd. 1978,
14, 46; b) J.-H. Sheu, Y.-K. Chen, Y.-L. V. Hongt, J. Org. Chem.
1993, 58, 5784; c) R. Ballini, A. Palmieri, M. Petrini, E. Torregiani,
Org. Lett. 2006, 8, 4093; d) M. Rueping, B. J. Nachtsheim, S. A.
Moreth, M. Bolte, Angew. Chem. 2008, 120, 603; Angew. Chem. Int.
Ed. 2008, 47, 593; e) P. G. Cozzi, F. Benfatti, L. Zoli, Angew. Chem.
2009, 121, 1339; Angew. Chem. Int. Ed. 2009, 48, 1313; f) D. Enders,
A. A. Narine, F. Toulgoat, T. Bisschops, Angew. Chem. 2008, 120,
5744; Angew. Chem. Int. Ed. 2008, 47, 5661; g) F.-L. Sun, M. Zeng,
Q. Gu, S.-L. You, Chem. Eur. J. 2009, 15, 8709; h) Q.-X. Guo, Y.-G.
Peng, J.-W. Zhang, L. Song, Z. Feng, L.-Z. Gong, Org. Lett. 2009,
11, 4620; i) C. Guo, J. Song, S.-W. Luo, L.-Z. Gong, Angew. Chem.
Keywords: asymmetric catalysis
hydrogenation · palladium · tandem reaction
·
Brønsted acid
·
[1] a) R. A. Bunce, Tetrahedron 1995, 51, 13103; b) I. Ryu, N. Sonoda,
Chem. Rev. 1996, 96, 177; c) P. J. Parsons, C. S. Penkett, A. J. Shell,
Chem. Rev. 1996, 96, 195; d) P. Eilbracht, L. Bꢂrfacker, C. Buss, C.
Hollmann, B. E. Kitsos-Rzychon, C. L. Kranemann, T. Rische, R.
Roggenbuck, A. Schmidt, Chem. Rev. 1999, 99, 3329; e) J.-C. Wa-
silke, S. J. Obrey, R. T. Baker, G. C. Bazan, Chem. Rev. 2005, 105,
1001; f) P. J. Walsh, M. M. Hussain, Acc. Chem. Res. 2008, 41, 883.
[2] a) Q. Cai, C. Zheng, S.-L. You, Angew. Chem. 2010, 122, 8848;
Angew. Chem. Int. Ed. 2010, 49, 8666; b) Q. Cai, Z.-A. Zhao, S.-L.
You, Angew. Chem. 2009, 121, 7564; Angew. Chem. Int. Ed. 2009,
48, 7428; c) X.-Y. Liu, C.-M. Che, Org. Lett. 2009, 11, 4204; d) Z.-Y.
Han, H. Xiao, X.-H. Chen, L.-Z. Gong, J. Am. Chem. Soc. 2009,
131, 9182; e) E. Skucas, M. Y. Ngal, V. Komanduri, M. J. Krische,
Acc. Chem. Res. 2007, 40, 1394; f) K. Sorimachi, M. Terada, J. Am.
Chem. Soc. 2008, 130, 14452; g) Y. J. Park, J.-W. Park, C.-H. Jun,
Acc. Chem. Res. 2008, 41, 222; h) V. Komanduri, M. J. Krische, J.
Am. Chem. Soc. 2006, 128, 16448; i) W. Hu, X. Xu, J. Zhou, W.-J.
Liu, H. Huang, J. Hu, L. Yang, L.-Z. Gong, J. Am. Chem. Soc. 2008,
130, 7782; j) Y. Huang, A. M. Walji, C. H. Larsen, D. W. C. MacMil-
lan, J. Am. Chem. Soc. 2005, 127, 15051; k) Y. Hamashima, S.
Suzuki, T. Tamura, H. Somei, M. Sodeoka, Chem. Asian J. 2011, 6,
658–668.
7196
www.chemeurj.org
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2011, 17, 7193 – 7197

An Enantioselective Approach to 2,3-Disubstituted Indolines
COMMUNICATION
2010, 122, 5690; Angew. Chem. Int. Ed. 2010, 49, 5558; selected ex-
amples on transformations involved vinylogous imine intermediates,
see: j) R. Ballini, A. Palmieri, M. Petrini, R. R. Shaikha, Adv. Synth.
Catal. 2008, 350, 129; k) Y. Li, F.-Q. Shi, Q.-L. He, S.-L. You, Org.
Lett. 2009, 11, 3182; l) B.-H. Zheng, C.-H. Ding, X.-L. Hou, L.-X.
Dai, Org. Lett. 2010, 12, 1688; m) L. Jing, J. Wei, L. Zhou, Z.
Huang, Z. Li, D. Wu, H. Xiang, X. Zhou, Chem. Eur. J. 2010, 16,
10955.
Yu, D.-W. Wang, X.-B. Wang, Y.-G. Zhou, Org. Lett. 2008, 10, 2071;
e) C.-B. Yu, D.-W. Wang, Y.-G. Zhou, J. Org. Chem. 2009, 74, 5633;
f) M.-W. Chen, Y. Duan, Q.-A. Chen, D.-S. Wang, C.-B. Yu, Y.-G.
Zhou, Org. Lett. 2010, 12, 5075; g) X.-Y. Zhou, M. Bao, Y.-G. Zhou,
Adv. Synth. Catal. 2010, 352, 84. For other groupsꢃ work on Pd-cata-
lyzed asymmetric hydrogenation, see: h) H. Abe, H. Amii, K. Un-
eyama, Org. Lett. 2001, 3, 313; i) P. Nanayakkara, H. Alper, Chem.
Commun. 2003, 2384; j) A. Suzuki, M. Mae, H. Amii, K. Uneyama,
J. Org. Chem. 2004, 69, 5132; k) Q. Yang, G. Shang, W. Gao, J.
Deng, X. Zhang, Angew. Chem. 2006, 118, 3916; Angew. Chem. Int.
Ed. 2006, 45, 3832; l) L. Rubio-Pꢄrez, F. J. Pꢄrez-Flores, P. Sharma,
L. Velasco, A. Cabrera, Org. Lett. 2009, 11, 265; m) N. S. Gouliouki-
na, G. N. Bondarenko, A. V. Bogdanov, K. N. Gavrilov, I. P. Belet-
skaya, Eur. J. Org. Chem. 2009, 510.
[14] a) E. Fisher, Liebigs Ann. 1886, 236, 162; b) W. E. Noland, D. Rob-
inson, Tetrahedron 1958, 3, 68; c) W. E. Noland, M. R. Venkiteswar-
an, R. A. Lovald, J. Org. Chem. 1961, 26, 4249.
[15] M. Shiri, M. A. Zolfigol, H. G. Kruger, Z. Tanbakouchian, Chem.
Rev. 2010, 110, 2250.
[16] For our groupꢃs work on Pd-catalyzed asymmetric hydrogenation,
see: a) Y.-Q. Wang, S.-M. Lu, Y.-G. Zhou, Org. Lett. 2005, 7, 3235;
b) Y.-Q. Wang, Y.-G. Zhou, Synlett 2006, 1189; c) Y.-Q. Wang, S.-M.
Lu, Y.-G. Zhou, J. Org. Chem. 2007, 72, 3729; d) Y.-Q. Wang, C.-B.
Received: February 21, 2011
Published online: May 12, 2011
Chem. Eur. J. 2011, 17, 7193 – 7197
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
7197