Highly Enantioselective Synthesis of Indolines: Asymmetric Hydrogenation at Ambient Temperature and Pressure with Cationic Ruthenium Diamine Catalysts

Article abstract of DOI:10.1002/anie.201607890

A highly enantioselective synthesis of indolines by asymmetric hydrogenation of 1H-indoles and 3H-indoles at ambient temperature and pressure, catalyzed by chiral phosphine-free cationic ruthenium complexes, has been developed. Excellent enantio- and diastereoselectivities (up to >99 % ee, >20:1 d.r.) were obtained for a wide range of indole derivatives, including unprotected 2-substituted and 2,3-disubstituted 1H-indoles, as well as 2-alkyl- and 2-aryl-substituted 3H-indoles.

Full text of DOI:10.1002/anie.201607890

Angewandte
Communications
Chemie
International Edition: DOI: 10.1002/anie.201607890
German Edition: DOI: 10.1002/ange.201607890
Heterocycles
Highly Enantioselective Synthesis of Indolines: Asymmetric
Hydrogenation at Ambient Temperature and Pressure with Cationic
Ruthenium Diamine Catalysts
Zhusheng Yang, Fei Chen,* Yanmei He, Nianfa Yang, and Qing-Hua Fan*
Abstract: A highly enantioselective synthesis of indolines by
asymmetric hydrogenation of 1H-indoles and 3H-indoles at
ambient temperature and pressure, catalyzed by chiral phos-
phine-free cationic ruthenium complexes, has been developed.
Excellent enantio- and diastereoselectivities (up to > 99% ee,
> 20:1 d.r.) were obtained for a wide range of indole
derivatives, including unprotected 2-substituted and 2,3-disub-
stituted 1H-indoles, as well as 2-alkyl- and 2-aryl-substituted
3H-indoles.
O
ptically active indoline derivatives are ubiquitous struc-
tural moieties in chiral pharmaceuticals and biologically
interesting natural alkaloids.[1] In addition, optically active
indolines serving as either organocatalysts or chiral auxiliaries
have been successfully used in a number of asymmetric
transformations.[2] Consequently, a variety of protocols have
been devoted to the asymmetric synthesis of enantioenriched
indolines by both the synthetic and medicinal chemistry
communities.[1e,3]
Among the various reported methods,[4–7] the direct
asymmetric hydrogenation (AH) of the corresponding readily
available indoles represents one of the most straightforward,
efficient, and atom-economic approaches for attaining opti-
cally active indolines.[6,7] However, because of the inherent
aromatic stability and the poisoning effects of indoles and/or
indolines on metal catalysts, this transformation still repre-
sents a challenge.[8] In 2000, Kuwano and co-workers devel-
oped the first highly effective hydrogenation of N-protected
indoles catalyzed by a Rh/PhTRAP complex in the presence
of a base.[6a] Since this pioneering work, a few transition
metal/chiral phosphine catalysts have been successfully
employed in the AH of N-protected indoles (Scheme 1a).[6]
Most recently, Zhou and co-workers demonstrated that the
simple unprotected indoles (1H-indoles) could be reduced via
[*] Z. Yang, F. Chen, Y.-M. He, Prof. Dr. Q.-H. Fan
CAS Key Laboratory of Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences (CAS)
University of Chinese Academy of Sciences
Beijing 100190 (P. R. China)
Scheme 1. Enantioselective synthesis of indolines by AH. Boc=tert-
butoxycarbonyl, Tf=trifluoromethanesulfonyl, Ts=4-toluenesulfonyl.
and
iminium salt intermediates generated in situ by addition of
a stoichiometric amount of a Brønsted acid (Scheme 1b).[7]
Despite the significant progress achieved, these catalytic
systems still suffer from some drawbacks, such as high
hydrogen pressure, need of a protecting group, or use of
basic or acidic additives. Moreover, only monosubstituted or
2,3-disubstituted indolines could be synthesized by these
protocols (Scheme 1a,b), and asymmetric synthesis of 2,3,3-
trisubstituted indolines by AH has been less developed.
Collaborative Innovation Center of Chemical Science and Engineer-
ing, Tianjin 300072 (P. R. China)
E-mail: chenfei211@iccas.ac.cn
fanqh@iccas.ac.cn
Z. Yang, Prof. N. Yang
College of Chemistry, Xiangtan University
Xiangtan, Hunan 411105 (P.R. China)
Supporting information for this article can be found under:
http://dx.doi.org/10.1002/anie.201607890.
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1
These are not the final page numbers!

Angewandte
Communications
Chemie
Table 1: AH of 1H-indoles catalyzed by (R,R)-6a.[a]
Although a number of iridium and ruthenium complexes with
different chiral phosphine ligands have been employed in the
AH of trisubstituted 3H-indoles over the past two decades,[9]
only one substrate, 2,3,3-trimethyl 3H-indole, was reported in
all cases (Scheme 1c). So far, there is limited success in the
AH of unprotected indoles, and to the best of our knowledge,
the AH of racemic 3,3-disubstituted 3H-indoles has not been
documented yet.
Most recently, we have found that the cationic ruthenium
complexes of chiral monosufonylated diamines[10] are very
efficient catalysts for the AH of several types of N-containing
heteroaromatic compounds and ketimines with excellent
enantioselectivity.[11] Further mechanism study indicated
that dihydrogen could be activated by the cationic ruthenium
Entry
R1/R2
R3
Yield [%][b]
ee [%][c]
1
2
3
4
5
6
7
8
9
10
11
12[d]
13[d]
14[d]
15[d]
16[d]
17[e,f]
18[g]
19[g]
Me/H
nPr/H
nBu/H
n-Pentyl/H
C6H5CH2/H
4-FC6H4CH2/H
4-MeC6H4CH2/H
3-MeC6H4CH2/H
Me/H
Me/H
Me/H
-(CH2)3-
-(CH2)4-
-(CH2)4-
-(CH2)4-
-(CH2)5-
Me/Me
H
H
H
H
H
H
H
H
Me
OMe
F
H
H
CH3
F
H
H
Me
H
94 (2a)
88 (2b)
92 (2c)
89 (2d)
93 (2e)
92 (2 f)
90 (2g)
93 (2h)
93 (2i)
93 (2j)
94 (2k)
92 (2l)
91 (2m)
94 (2n)
92 (2o)
73 (2p)
95 (2q)
85 (2r)
53 (2s)
96 (R)
96 (R)
97 (R)
96 (R)
97 (R)
97 (R)
96 (R)
97 (R)
95 (R)
95 (R)
94 (R)
89 (R,R)
95 (R,R)
90 (R,R)
94 (R,R)
99 (R,R)
97 (R,R)
40 (R)
À
complex with the aid of substrate to generate the Ru H active
species and the iminium salt, and the in situ activated
substrate was then reduced by a stepwise H+/HÀ transfer
process.[11b] We thus envisioned that such cationic ruthenium
complex could be used to hydrogenate 1H-indoles and 3H-
indoles, via iminium salts, without the addition of acid
(Scheme 1d,e). Herein, we communicate the highly effective
AH of a wide range of 1H-indoles and 3H-indoles under very
mild reaction conditions. A kinetic resolution was also
observed when racemic 3,3-disubstituted 3H-indoles were
hydrogenated.
H/Me
Ph/H
42 (S)
[a] Reaction conditions: substrates 1a–s (0.2 mmol) and (R,R)-6a in
HFIP, and H2 (1 atm). Stirred at RT for 24 h. [b] Yield of isolated product.
[c] The ee values were determined by HPLC with a chiral-phase column.
[d] cis/trans isomer >20:1. [e] (R,R)-6a (2.0 mol %) and H2 (50 atm).
Stirred at 508C for 24 h. [f] cis/trans isomer=8:1. [g] (R,R)-6a
(5.0 mol%), H2 (50 atm), stirred at 508C for 24 h.
In our initial study, the AH of 2-methyl-indole (1a) with
the catalyst (R,R)-5a (see Scheme 1) was chosen as the model
reaction for the optimization of the reaction conditions (see
Table S1 in the Supporting Information). The solvent influ-
neced the catalytic performance significantly, and full con-
version and high enantioselectivity were observed in hexa-
fluoroisopropanol (HFIP).[12] Upon the screening of a variety
of catalysts, (R,R)-6a was found to be optimal in terms of both
reactivity and enantioselectivity. In addition, the enantiose-
lectivity was insensitive to hydrogen pressure and temper-
ature. Remarkably, even if the reaction was conducted at
ambient temperature and pressure,[13] full conversion and the
same ee value were obtained within 3 hours. To the best of our
knowledge, this is the first example for AH of heteroaromatic
compounds at ambient temperature and pressure. Further-
more, when the substrate to catalyst ratio was increased to
1000, only very slight erosion of the ee value was observed
(see entry 27 in Table S1).
Under the optimized reaction conditions, the AH of
a variety of 1H-indoles was examined, and good to excellent
enantioselectivities were obtained (Table 1). 2-Alkyl-substi-
tuted indoles were hydrogenated in very good yields with
excellent enantioselectivities (entries 1–11), regardless of
either the length of side chain or the position of substituents
at the phenyl ring. Notably, excellent results were also
achieved with 2,3-disubstituted fused ring indolines
(entries 12–16). It was found that the enantiomeric excess
increased from 89 to 99% when increasing the ring size from
five- to six- and seven-membered rings. In addition, the
hydrogenation of 2,3-dimethylindole could be carried out
under harsh reaction conditions (entry 17). More difficult
substrates such as 3-methyl and 2-phenyl indoles were also
tested, and moderate ee values were obtained (entries 18 and
19).
Encouraged by the above excellent results, we then
extended this catalytic system to the synthesis of chiral
2,3,3-trisubsituted indolines, which are more commonly found
in alkaloids and other natural products. So far, the AH of 3H-
indoles is still limited to only one substrate.[9] A quick survey
with 3a as the model substrate revealed that (R,R)-7a was the
optimal catalyst (see Table S2). As shown in Table 2, a series
of 2-alkyl-substituted 3H-indole derivatives (3a–f) were
hydrogenated at ambient temperature and pressure in HFIP
with excellent reactivity and enantioselectivity (93–98% ee).
This catalytic system was further applied to the AH of 2-
aryl-substituted 3H-indoles (Table 2), which are much more
difficult substrates for hydrogenation, and transition-metal-
catalyzed AH of this class of substrates has not been reported
yet.[5a] In contrast to 2-alkyl-substituted 3H-indoles, the AH of
3g proceeded smoothly in THF instead of HFIP (see
À
Table S3). Interestingly, (R,R)-7g with a (PhO)2PO2 anion
was found to be optimal catalyst, thus indicating that the
counteranion played an important role on catalytic perform-
ance.[11e–f,14] Under the optimized reaction conditions, high
yields and excellent enantioselectivities (97– > 99% ee) were
obtained for a range of 2-aryl-substituted 3H-indoles (3g–r).
Finally, the AH of a range of racemic 3H-indoles bearing
different substituents at C3 was carried out. Interestingly,
a kinetic resolution of 3H-indoles by AH was observed for the
first time.[15,16] After optimizing the reaction conditions,
several substrates were resolved with high selectivity
(Table 3), thus providing the reduced products with very
2
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
These are not the final page numbers!

Angewandte
Communications
Chemie
Table 2: AH of 2-alkyl- and 2-aryl-substituted 3H-indoles.
were obtained with higher enantioselectivity (see Table S4).
Notably, both the products and recovered starting materials
are valuable chiral compounds bearing C3 quaternary chiral
centers of indoline and indole cores, respectively.
An isotope-labeling experiment was carried out (see
Scheme S3). When 1a was subjected to hydrogenation with
D2, the incorporation of deuterium was observed only at the
2-position. All results indicate that the reaction proceeds
through the generation of an iminium salt, by C3 protonation
with the in situ generated TfOH acid, which was subsequently
reduced by the ruthenium complex to afford the desired
indolines.
In summary, we have developed a highly enantioselective
synthesis of indolines, by AH of unprotected 1H-indoles and
3H-indoles catalyzed by chiral ruthenium diamine complexes
at ambient temperature and pressure. Excellent enantio- and
diastereoselectivities were obtained for a wide range of indole
derivatives. Moreover, a kinetic resolution of racemic 3,3-
disubstituted 3H-indoles was achieved with high selectivity
for the first time. The unique features of this protocol,
including broad substrate scope, excellent enantioselectivity
and diastereoselectivity, mild reaction conditions, and opera-
tional simplicity, make it very useful and practical for both
academic and industrial applications.
Reaction conditions. For substrates 3a–e (0.2 mmol): (R,R)-7a in HFIP,
and H2 (1 atm). Stirred at RT for specifed time. For 3 f: H2 (50 atm),
stirred at 508C. For substrates 3g–n and 3p–r (0.2 mmol): (R,R)-7g in
THF, and H2 (1 atm). Stirred at RT for 24 h. For 4o: H2 (50 atm), stirred
at 508C for 24 h. Yields of isolated products are given in all cases.
Acknowledgments
We thank the National Natural Science Foundation of China
(Nos. 21232008, 21473216 and 21521002) and CAS (QYZDJ-
SSW-SLH023) for financial support.
Table 3: Kinetic resolution of racemic 3,3-disubstituted 3H-indoles by
AH.
Keywords: heterocycles · hydrogenation · indoles · N ligands ·
ruthenium
[1] For reviews, see: a) I. W. Southon, J. Buckingham, Dictionary of
Alkaloids, Chapman and Hall, New York, 1989; b) N. Neuss,
M. N. Neuss, The Alkaloids (Eds.: H. A. Brossi, M. Suffness),
Academic Press, San Diego, 1990, p. 229; c) F. Gueritte, J. Fahy,
Anticancer Agents from Natural Products (Eds.: G. M. Cragg,
D. G. I. Kingstom, D. J. Newman), CRC Press, Boca Raton, FL,
2005, p. 123; d) Modern Alkaloids (Eds.: E. Fattorusso, O.
Taglialatela-Scafati), Wiley-VCH, Weinheim, 2008; e) D.
Zhang, H. Song, Y. Qin, Acc. Chem. Res. 2011, 44, 447. For
some examples, see: f) J. Dunlop, K. L. Marquis, H. K. Lim, L.
Leung, J. Kao, C. Cheesman, S. Rosenzweig-Lipson, CNS Drug
Rev. 2006, 12, 167; g) H. Zhao, A. Thurkauf, X. He, K. Hodgetts,
X. Zhang, S. Rachwal, R. X. Kover, A. Hutchison, J. Peterson,
A. Kieltyka, R. Brodbeck, R. Primus, J. W. F. Wasley, Bioorg.
Med. Chem. Lett. 2002, 12, 3105; h) D. Ramanitrahasimbola, P.
Rasoanaivo, S. Ratsimamanga, H. Vial, Mol. Biochem. Parasitol.
2006, 146, 58; i) J. P. Marino, M. B. Rubio, G. Cao, A. de Dios, J.
Am. Chem. Soc. 2002, 124, 13398; j) D. Kato, Y. Sasaki, D. L.
Boger, J. Am. Chem. Soc. 2010, 132, 3685.
Reaction conditions: Substrates 3s–y (0.2 mmol) and (R,R)-7a in HFIP
(1 mL), and H2 (1 atm). Stirred at RT. Substrate 3z and (R,R)-7g in
toluene, and H2 (50 atm). Stirred at 508C. Conversions were determined
by 1H NMR spectroscopy.
[2] For selected examples, see: a) R. K. Kunz, D. W. C. MacMillan,
J. Am. Chem. Soc. 2005, 127, 3240; b) F. Andersson, E.
Hedenstrçm, Tetrahedron: Asymmetry 2006, 17, 1952; c) A.
Hartikka, P. I. Arvidsson, J. Org. Chem. 2007, 72, 5874; d) J.
Pietruszka, R. C. Simon, ChemCatChem 2010, 2, 505.
good enantioselectivities (64–88% ee) and the recovered
substrates with excellent enantioselectivities (93– > 99% ee).
When the reaction was stopped at lower conversion, indolines
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

Angewandte
Communications
Chemie
[3] a) D. Liu, G. Zhao, L. Xiang, Eur. J. Org. Chem. 2010, 3975; b) S.
Anas, H. B. Kagan, Tetrahedron: Asymmetry 2009, 20, 2193, and
references therein.
Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996,
118, 4916; c) R. Noyori, S. Hashiguchi, Acc. Chem. Res. 1997, 30,
97; d) T. Ikariya, A. J. Blacker, Acc. Chem. Res. 2007, 40, 1300;
For a pioneering work on AH of ketones, see: e) M. Ito, M.
Hirakawa, K. Murata, T. Ikariya, Organometallics 2001, 20, 379;
f) T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, C. Sandoval,
R. Noyori, J. Am. Chem. Soc. 2006, 128, 8724.
[4] For selected examples, see: 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) K. Saito, Y. Shibata, M. Yamanaka, T. Akiyama, J.
Am. Chem. Soc. 2013, 135, 11740; d) M. Lꢀpez-Iglesias, E. Busto,
V. Gotor, V. Gotor-Fernꢁndez, J. Org. Chem. 2012, 77, 8049;
e) G. S. Gil, U. M. Groth, J. Am. Chem. Soc. 2000, 122, 6789;
f) K.-T. Yip, M. Yang, K.-L. Law, N.-Y. Zhu, D. Yang, J. Am.
Chem. Soc. 2006, 128, 3130; g) M. Nakanishi, D. Katayev, C.
Besnard, E. P. Kꢂndig, Angew. Chem. Int. Ed. 2011, 50, 7438;
Angew. Chem. 2011, 123, 7576; h) T. Saget, S. J. Lemouzy, N.
Cramer, Angew. Chem. Int. Ed. 2012, 51, 2238; Angew. Chem.
2012, 124, 2281; i) E. E. Maciver, S. Thompson, M. D. Smith,
Angew. Chem. Int. Ed. 2009, 48, 9979; Angew. Chem. 2009, 121,
10164; j) E. Ascic, S. L. Buchwald, J. Am. Chem. Soc. 2015, 137,
4666; k) A. Martꢃnez, M. J. Webber, S. Mꢂller, B. List, Angew.
Chem. Int. Ed. 2013, 52, 9486; Angew. Chem. 2013, 125, 9664;
l) Y.-C. Xiao, C. Wang, Y. Yao, J. Sun, Y.-C. Chen, Angew. Chem.
Int. Ed. 2011, 50, 10661; Angew. Chem. 2011, 123, 10849.
[5] a) M. Rueping, C. Brinkmann, A. P. Antonchick, I. Atodiresei,
Org. Lett. 2010, 12, 4604; b) A. D. Lackner, A. V. Samant, F. D.
Toste, J. Am. Chem. Soc. 2013, 135, 14090.
[11] a) H. Zhou, Z. Li, Z. Wang, T. Wang, L. Xu, Y.-M. He, Q.-H. Fan,
J. Pan, L. Gu, A. S. C. Chan, Angew. Chem. Int. Ed. 2008, 47,
8464; Angew. Chem. 2008, 120, 8592; b) T. Wang, L.-G. Zhuo, Z.
Li, F. Chen, Z. Ding, Y.-M. He, Q.-H. Fan, J. Xiang, Z.-X. Yu,
A. S. C. Chan, J. Am. Chem. Soc. 2011, 133, 9878; c) T. Wang, F.
Chen, J. Qin, Y.-M. He, Q.-H. Fan, Angew. Chem. Int. Ed. 2013,
52, 7172; Angew. Chem. 2013, 125, 7313; d) J. Zhang, F. Chen, Y.-
M. He, Q.-H. Fan, Angew. Chem. Int. Ed. 2015, 54, 4622; Angew.
Chem. 2015, 127, 4705; e) F. Chen, T. Wang, Y.-M. He, Z. Ding,
Z. Li, L. Xu, Q.-H. Fan, Chem. Eur. J. 2011, 17, 1109; f) Z.-Y.
Ding, F. Chen, J. Qin, Y.-M. He, Q.-H. Fan, Angew. Chem. Int.
Ed. 2012, 51, 5706; Angew. Chem. 2012, 124, 5804.
[12] For recent reviews, see: a) T. Sugiishi, M. Matsugi, H. Hama-
moto, H. Amii, RSC Adv. 2015, 5, 17269. For dramatic improve-
ments in both product yield and enantioselectivity in the AH of
imines in fluorinated solvents, b) H. Abe, H. Amii, K. Uneyama,
Org. Lett. 2001, 3, 313; c) M.-W. Chen, Y. Duan, Q.-A. Chen, D.-
S. Wang, C.-B. Yu, Y.-G. Zhou, Org. Lett. 2010, 12, 5075; d) L.
Pauli, R. Tannert, R. Scheil, A. Pfaltz, Chem. Eur. J. 2015, 21,
1482.
[6] 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,
ˇ ´
M. Kashiwabara, Org. Lett. 2006, 8, 2653; d) N. Mrsic, T.
[13] Few examples of AH of imines at ambient pressure, see: a) S.-F.
Zhu, J.-B. Xie, Y.-Z. Zhang, S. Li, Q.-L. Zhou, J. Am. Chem. Soc.
2006, 128, 12886; b) A. Dervisi, C. Carcedo, L. Ooi, Adv. Synth.
Catal. 2006, 348, 175; c) T. Imamoto, N. Iwadate, K. Yoshida,
Org. Lett. 2006, 8, 2289.
[14] a) F. Chen, Z. Ding, J. Qin, T. Wang, Y.-M. He, Q.-H. Fan, Org.
Lett. 2011, 13, 4348; b) F. Chen, Z. Ding, Y.-M. He, J. Qin, T.
Wang, Q.-H. Fan, Tetrahedron 2012, 68, 5248; c) J. Qin, F. Chen,
Z. Ding, Y.-M. He, L. Xu, Q.-H. Fan, Org. Lett. 2011, 13, 6568;
d) J. Qin, F. Chen, Y.-M. He, Q.-H. Fan, Org. Chem. Front. 2014,
1, 952.
Jerphagnon, A. J. Minnaard, B. L. Feringa, J. G. de Vries,
Tetrahedron: Asymmetry 2010, 21, 7; e) A. Baeza, A. Pfaltz,
Chem. Eur. J. 2010, 16, 2036.
[7] a) D.-S. Wang, Q.-A. Chen, W. Li, C.-B. Yu, Y.-G. Zhou, X.
Zhang, J. Am. Chem. Soc. 2010, 132, 8909; b) D.-S. Wang, J. Tang,
Y.-G. Zhou, M.-W. Chen, C.-B. Yu, Y. Duan, G.-F. Jiang, Chem.
Sci. 2011, 2, 803; c) Y. Duan, L. Li, M.-W. Chen, C.-B. Yu, H.-J.
Fan, Y.-G. Zhou, J. Am. Chem. Soc. 2014, 136, 7688.
[8] For recent reviews on AH of heteroaromatic compounds, see:
a) F. Glorius, Org. Biomol. Chem. 2005, 3, 4171; b) Y.-G. Zhou,
Acc. Chem. Res. 2007, 40, 1357; c) R. Kuwano, Heterocycles
2008, 76, 909; d) D.-S. Wang, Q.-A. Chen, S.-M. Lu, Y.-G. Zhou,
Chem. Rev. 2012, 112, 2557; e) Y.-M. He, F.-T. Song, Q.-H. Fan,
Top. Curr. Chem. 2014, 343, 145.
[9] Selected examples, see: a) F. Spindler, B. Pugin, H.-U. Blaser,
Angew. Chem. Int. Ed. Engl. 1990, 29, 558; Angew. Chem. 1990,
102, 561; b) T. Morimoto, N. Nakajima, K. Achiwa, Synlett 1995,
748; c) G. Zhu, X. Zhang, Tetrahedron: Asymmetry 1998, 9,
2415; d) A. M. Kluwer, R. J. Detz, Z. Abiri, A. M. van der Burg,
J. N. H. Reek, Adv. Synth. Catal. 2012, 354, 89.
[15] J. M. Keith, J. F. Larrow, E. N. Jacobsen, Adv. Synth. Catal. 2001,
343, 5.
[16] Few examples of kinetic resolution of imines via asymmetric
hydrosilylation, ATH or asymmetric imine amidation, see: a) J.
Yun, S. L. Buchwald, J. Org. Chem. 2000, 65, 767; b) J. Yun, S. L.
Buchwald, Chirality 2000, 12, 476; c) A. Bongers, P. J. Moon,
A. M. Beauchemin, Angew. Chem. Int. Ed. 2015, 54, 15516;
Angew. Chem. 2015, 127, 15736; d) H. Hu, Y. Liu, L. Lin, Y.
Zhang, X. Liu, X. Feng, Angew. Chem. Int. Ed. 2016, 55, 10098;
Angew. Chem. 2016, 128, 10252.
[10] For seminal works on asymmetric transfer hydrogenation (ATH)
of ketones and imines with Ru(diamine) complexes, see: a) S.
Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1995, 117, 7562; b) N. Uematsu, A. Fujii, S.
Received: August 13, 2016
Published online: && &&, &&&&
4
www.angewandte.org
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
These are not the final page numbers!

Angewandte
Communications
Chemie
Communications
Heterocycles
Setting the ambiance: The title reaction
was achieved in the presence of chiral
cationic ruthenium diamine complexes at
ambient temperature and pressure. The
method provides a promising approach
for obtaining a broad range of enan-
tioenriched indolines and 3H-indoles
with excellent stereoselectivities. HFIP=
hexafluoroisopropanol, THF=tetra-
hydrofuran.
Z. Yang, F. Chen,* Y.-M. He, N. Yang,
Q.-H. Fan*
&&&& — &&&&
Highly Enantioselective Synthesis of
Indolines: Asymmetric Hydrogenation at
Ambient Temperature and Pressure with
Cationic Ruthenium Diamine Catalysts
Angew. Chem. Int. Ed. 2016, 55, 1 – 5
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!