Highly enantioselective transfer hydrogenation of quinolines catalyzed by gold phosphates: Achiral ligand tuning and chiral-anion control of stereoselectivity

Article abstract of DOI:10.1002/anie.201204179

A little gold goes a long way: As little as 0.01 mol % of chiral gold phosphate is sufficient to afford the asymmetric transfer hydrogenation of quinolines with high stereoselectivity (up to 98 % ee). The achiral ligands on gold were found to have conside

Full text of DOI:10.1002/anie.201204179

Angewandte
Chemie
DOI: 10.1002/anie.201204179
Gold Catalysis
Highly Enantioselective Transfer Hydrogenation of Quinolines
Catalyzed by Gold Phosphates: Achiral Ligand Tuning and Chiral-
Anion Control of Stereoselectivity**
Xi-Feng Tu and Liu-Zhu Gong*
The prevalence of 1,2,3,4-tetrahydroquinoline as a key struc-
tural element in numerous natural alkaloids, bioactive
molecules, and clinical pharmaceuticals has led to a great
demand for the efficient construction of this skeleton.[1] As
a consequence, a great deal of effort has been devoted to the
development of stereoselective methods for the manufacture
of highly enantioenriched tetrahydroquinolines.[2] Among the
available enantioselective approaches, the asymmetric hydro-
genation of quinolines is one of the most important methods.
Zhou and co-workers have described the use of a chiral
iridium catalyst for the hydrogenation of quinolines.[3] The
combined chiral catalyst system, which consists of
[{Ir(cod)Cl}2] with MeO-Biphep and I2, enabled the catalytic
generation of tetrahydroquinolines with high enantioselec-
tivity. Subsequent investigation into the iridium-catalyzed
hydrogenation of quinolines led to a number of highly
enantioselective variants by tuning of the chiral ligands.[4]
Recently, Fan demonstrated that the chiral ruthenium catalyst
Ru/Ts-dpen is highly enantioselective for the hydrogenation
of quinolines (up to 99% ee).[5] Subsequently, Xiao and co-
workers showed that the rhodium catalyst Rh/Ts-dpen affords
the highly enantioselective hydrogenation of quinolines in
water.[6] Rueping and co-workers established the first organo-
catalytic asymmetric transfer hydrogenation of quinolines by
using chiral phosphoric acid catalysts.[2d] Although the
methods are elegant, the catalytic efficiency still needs to be
improved. Moreover, the transition-metal-catalyzed hydro-
genation of quinolines exclusively relies on the use of chiral
ligands to control the stereochemistry and the metals
generally used are group VIII elements. Herein, we report
the transfer-hydrogenation of quinolones, with enantioselec-
tivities of up to 98% ee and a TON of > 10000, catalyzed by
gold phosphates. Moreover, the stereoselectivity of the
reaction was solely controlled by the chiral anion, and the
tuning of achiral ligands was able to modulate catalytic
efficiency.
Gold complexes have proven to be suitable catalysts for
a large number of carbon–carbon and carbon–heteroatom
bond-forming reactions.[7] Furthermore, gold complexes using
either chiral ligands[8] or chiral anions[9] to control stereo-
chemistry have been increasingly applied in asymmetric
catalysis. However, the effectiveness of gold complexes as
catalysts for hydrogenation has been much less recognized.[10]
In particular, even fewer reports describe the hydrogenation
of imines.[10a,d,e] Recently, Liu and Che found that a gold
phosphate prepared in situ from [(1a)Au]Cl and 2 could
catalyze a cascade hydroamination and asymmetric transfer
hydrogenation in high yield [Eq. (1)].[11] Just a little earlier we
had also found that 2-(3-phenylprop-2-ynyl)aniline under-
went a consecutive hydroamination and asymmetric transfer
hydrogenation reaction under catalyzed by a gold phosphate
prepared from [Ph3PAu]Cl with 3, but the reaction was
incomplete [Eq. (2)].[12] A comparison of these reactions
[*] X.-F. Tu, Prof. L.-Z. Gong
indicated that the different catalytic activity of the gold
complexes may originate from the phosphine ligands. Thus,
we envisioned that tuning of the achiral ligands coordinated
to chiral gold phosphates might lead to the discovery of an
efficient chiral gold-phosphate catalyst for transfer hydro-
genation.
Hefei National Laboratory for Physical Sciences at the Microscale
and Department of Chemistry
University of Science and Technology of China
Hefei, 230026 (China)
E-mail: gonglz@ustc.edu.cn
Homepage: http://staff.ustc.edu.cn/~gonglz/index.htm
The initial investigation was focused on the evaluation of
achiral ligands coordinated to gold phosphates for the transfer
hydrogenation of 2-phenylquinoline (5a; Figure 1). Indeed,
the achiral ligands exerted considerable effect on the
[**] We are grateful for financial support from NSFC (21172207), MOST
(973 project 2010CB833300), BASF, and the Ministry of Education.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201204179.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Table 1: Evaluation of gold complexes and optimization of reaction
conditions.[a]
Entry
L/PA (mol%)[b]
t [h]
T [8C]
ee [%][c]
1
2
3
4
5
6
7
8
9
IMes/7a (5)
IMes/7b (5)
IMes/7c (5)
IMes/7c (5)
IMes/7c (5)
18
18
22
22
22
22
11
12
24
12
40
40
40
40
40
40
80
90
100
90
91
91
95
92[d]
92[e]
93[f]
96
IMes/7c (5)
IMes/7c (0.05)
IMes/7c (0.01)
IMes/7c (0.001)
IMes/7c (0.01)
96
20
10
96[g]
[a] Unless indicated otherwise, the reaction of 5a (0.1 mmol) and
Hantzsch ester 6 (0.24 mmol) was carried out in toluene (2.0 mL) under
argon; >99% yield. [b] Ligand/phosphoric acid (L/PA) used in a 1:1
ratio. [c] Determined by HPLC analysis on a chiral stationary phase
(Chiralcel OD-H). [d] In o-xylene. [e] In m-xylene. [f] In chlorobenzene.
[g] In toluene (1.0 mL).
Figure 1. Kinetic studies on the effect of achiral Ligand on the catalytic
activity of gold phosphate: The reduction was performed in the
presence of 7a (5 mol%) and [LAuMe] (5 mol%); without [LAuMe]
!
~
&
*
(
), L=IMes ( ), L=PPh3 ( ), and L=PCy3 ( ).
reaction. The use of a gold phosphate generated in situ from
[Ph3PAuMe] and chiral phosphoric acid 7a[12,13] led to an
incomplete reaction.[14] The replacement of triphenylphos-
phine (Ph3P) with the more electron-rich tricyclohexylphos-
phine (PCy3) resulted in an even slower reaction. Interest-
ingly, the use of ligand 1a,[15] which was a good ligand for the
cascade hydroamination/asymmetric transfer hydrogena-
tion,[11] gave almost no reaction. In contrast, the use of
5 mol% chiral phosphoric acid 7a provided a much faster
reaction than gold phosphates coordinated with phosphine
ligands, as reported previously.[16] The carbene IMes (1b; see
Table 1 for structure)[17] was identified as the best ligand for
the gold phosphate complex, which showed more catalytic
activity than with the corresponding phosphoric acid 7a.
However, [(IMes)AuMe] alone did not catalyze the transfer
hydrogenation under the same conditions, indicating that the
counteranion also plays a crucial role in the catalytic activity.
The chiral gold phosphate complex provided a high
enantioselectivity of 91% ee (Table 1, entry 1), indicating
that the chiral phosphate anion was able to efficiently control
the stereoselectivity in the transfer hydrogenation.[9,18] Thus,
we subsequently screened chiral gold phosphates generated
in situ from a variety of binol-based phosphoric acids 7 and
[(IMes)AuMe]. Among the chiral phosphoric acids screened
(entries 1–3), 7c improved the stereochemical outcome to
95% ee (entry 3). An examination of solvents found that
toluene was still a suitable reaction medium in terms of
stereoselectivity (entries 4–6 vs. entry 3). Elevating the tem-
perature from 40 to 908C not only dramatically facilitated the
reaction, but also turned out to be beneficial for stereochem-
ical control (entries 6–8). As a result, an excellent stereo-
selectivity of 96% ee was obtained in the presence of only
0.01 mol% of the optimized gold phosphate at 908C (TON =
10000; entry 8). Such a low catalyst loading is unusual, both in
gold-catalyzed organic transformations and in the asymmetric
hydrogenation of quinolines.[19] However, further decreasing
the catalyst loading to 0.001 mol% resulted in a significant
erosion of stereoselectivity (entry 9). However, when the
reaction was conducted at a higher concentration, the
enanatioselectivity was retained (entry 10).
Under the optimized reaction conditions, we investigated
the reaction scope for different quinoline derivatives in the
presence of 0.01 mol% of chiral gold phosphate formed from
[(IMes)AuMe] and 7c (Table 2). Gratifyingly, a range of
2-aryl quinolones, from electron-deficient to electron-rich,
could be efficiently reduced in high yields and excellent
enantioselectivities (up to > 99% yields, 98% ee). A loading
of 0.01 mol% of phosphoric acid 7c was found to be sufficient
to catalyze the reaction, but provided a slightly lower
enantioselectivity than the gold phosphate, as seen in
entries 1, 3, 6, 10, and 12 (data in parentheses). Quinolines
with a 2,3-disubstitution pattern also underwent the reaction,
but the stereoselectivity was unsatisfactory.[20]
The reaction could also be successfully scaled up. The
transfer hydrogenation of 2-phenyl quinoline 5a in 1.0 mmol
scale still proceeded cleanly in the presence of 0.01 mol% of
the chiral gold phosphate, to give the product in quantitative
yield and with the enantioselectivity maintained at 95% ee
[Eq. (3)].
A gold(I) complex is essentially a kind of Lewis acid, and
therefore able to coordinate to unsaturated carbon–carbon
bonds and heteroatoms. In particular, gold complexes have
been found to coordinate to pyridine-type compounds.[21]
Thus, chiral-phosphate-catalyzed transfer hydrogenation of
2
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Table 2: Reaction scope for quinoline derivatives.[a]
Entry
R
t [h]
Yield [%][b]
ee [%][c,d]
1
2
3
4
5
6
7
8
C6H5
12
48
18
36
12
12
22
12
12
18
18
6
>99
89
>99
93
97
89
99
>99
93
>99
>99
82
96 (95)
97[e]
4-PhC6H4
2-naphthyl
2-FC6H4
4-CF3C6H4
4-FC6H4
3-ClC6H4
3-FC6H4
3-BrC6H4
4-MeOC6H4
3-MeOC6H4
CH3CH2CH2
98 (90)[f]
96[e]
98
96 (93)
95
98
94
9
10
11
12
96 (88)[f]
93
Scheme 1. Proposed mechanism for gold-phosphate-catalyzed transfer
hydrogenation of quinolines. L=IMes (1b).
54[g] (12)[f]
[a] Unless otherwise noted, the reaction of 5 (0.1 mmol), catalyst
(0.01 mol%) and Hantzsch ester 6 (0.24 mmol) was carried out in
toluene (1.0 mL) at 908C under argon. [b] Yield of isolated product after
column chromatography. [c] Determined by HPLC analysis on a sta-
tionary chiral phase. [d] Numbers given in parentheses are for reactions
using 0.01 mol% 7c as catalyst. [e] 808C, toluene (1.5 mL). [f] Average of
two experiments. [g] 708C, toluene (1.5 mL).
Experimental Section
A mixture of [(IMes)AuMe] (0.002 mmol) and phosphoric acid 7c
(0.002 mmol) was flushed with argon and suspended in toluene
(0.8 mL) in a screw-capped vial. The resulting mixture was stirred at
258C for 5 h to form the catalyst solution, which was then added (1 ꢀ
10À5 mmol, 0.0025m, 4 mL) to a mixture of quinoline 5 (0.1 mmol) and
6 (0.24 mmol) in toluene (1.0 mL) in a dry vial under Ar. The reaction
was stirred at 908C until the quinoline was consumed, as indicated by
TLC. The crude product was purified by column chromatography on
silica gel (ethyl acetate/petroleum ether 1:20) to afford the pure
tetrahydroquinoline.
quinolines might commence with the coordination of the gold
phosphate to quinoline to form active complex A (Scheme 1),
which principally undergoes asymmetric transfer hydrogena-
tion with a Hantzsch ester to generate intermediate B and
a pyridine salt. Subsequently, the protonation of intermediate
B with the pyridine salt occurs to produce dihydroquinoline
C, which undergoes enantioselective transfer hydrogenation
with a Hantzsch ester to form intermediate D. Once again,
a metathesis reaction between intermediate D and a pyridine
salt proceeds to furnish the tetrahydroquinoline product and
to release the chiral gold phosphate catalyst. In light of this
proposed mechanism, the reaction could be considered to be
a gold-catalyzed asymmetric cascade reaction with the
stereoselectivity solely controlled by the chiral anion.
In conclusion, we have found that chiral gold phosphate
complexes are able to serve as highly efficient catalysts for the
asymmetric transfer hydrogenation of quinolines,[22] with the
stereoselectivity controlled by the chiral anion. Only
0.01 mol% of the gold phosphate is needed to effectively
afford the highly enantioselective transfer hydrogenation of
quinolines. Tuning of the achiral ligands had a great impact on
the catalytic activity, with the chiral gold phosphate exhibiting
high catalytic efficiency when the carbene IMes was used as
a ligand. Facile scale-up makes this method of practical
interest.
Received: May 29, 2012
Published online: && &&, &&&&
Keywords: asymmetric hydrogenation · carbenes ·
.
chiral anions · gold · tetrahydroquinoline
[1] a) J. G. Keay in Comprehensive Organic Synthesis, Vol. 8 (Eds.:
B. M. Trost, I. Fleming), Pergamon, Oxford, 1991, p. 579;
b) A. R. Katritzky, S. Rachwal, B. Rachwal, Tetrahedron 1996,
52, 15031 – 15070; c) D. H. Barton, K. Nakanishi, O. M. Cohn,
Comprehensive Natural Products Chemistry, Vol. 1 – 9, Elsevier,
Oxford, 1999; d) V. Sridharan, P. A. Suryavanshi, J. C. Menꢁn-
dez, Chem. Rev. 2011, 111, 7157 – 7259.
[2] a) H. Ishitani, S. Kobayashi, Tetrahedron Lett. 1996, 37, 7357 –
7360; b) G. Sundararajan, N. Prabagaran, B. Varghese, Org. Lett.
2001, 3, 1973 – 1976; c) T. Akiyama, H. Morita, K. Fuchibe, J.
Am. Chem. Soc. 2006, 128, 13070 – 13071; d) M. Rueping, A. P.
Antonchick, T. Theissmann, Angew. Chem. 2006, 118, 3765 –
3768; Angew. Chem. Int. Ed. 2006, 45, 3683 – 3686; e) Y.-G.
Zhou, Acc. Chem. Res. 2007, 40, 1357 – 1366; f) Q.-S. Guo, D.-M.
Du, J.-X. Xu, Angew. Chem. 2008, 120, 771 – 774; Angew. Chem.
ˇ ´
Int. Ed. 2008, 47, 759 – 762; g) N. Mrsic, L. Lefort, J. A. F.
Boogers, A. J. Minnaard, B. L. Feringa, J. G. de Vries, Adv.
Synth. Catal. 2008, 350, 1081 – 1089; h) X.-B. Wang, Y.-G. Zhou,
J. Org. Chem. 2008, 73, 5640 – 5642; i) V. V. Kouznetsov,
Tetrahedron 2009, 65, 2721 – 2750; j) H. Liu, G. Dagousset, G.
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
3
These are not the final page numbers!

.
Angewandte
Communications
Masson, P. Retailleau, J. Zhu, J. Am. Chem. Soc. 2009, 131,
4598 – 4599; k) S. Murarka, I. Deb, C. Zhang, D. Seidel, J. Am.
Chem. Soc. 2009, 131, 13226 – 13227; l) G. Bergonzini, L.
Gramigna, A. Mazzanti, M. Fochi, L. Bernardi, A. Ricci,
Chem. Commun. 2010, 46, 327 – 329; m) Y. K. Kang, S. M.
Kim, D. Y. Kim, J. Am. Chem. Soc. 2010, 132, 11847 – 11849;
n) K. Mori, K. Ehara, K. Kurihara, T. Akiyama, J. Am. Chem.
Soc. 2011, 133, 6166 – 6169; o) Z.-X. Jia, Y.-C. Luo, P.-F. Xu, Org.
Lett. 2011, 13, 832 – 835; p) M. Rueping, J. Dofour, F. R.
Schoepke, Green Chem. 2011, 13, 1084 – 1105; q) L. Ren, T.
Lei, J.-X. Ye, L.-Z. Gong, Angew. Chem. 2012, 124, 795 – 798;
Angew. Chem. Int. Ed. 2012, 51, 771 – 774.
Hu, Chem. Commun. 2011, 47, 6605 – 6607; e) X.-Y. Liu, Z. Guo,
S. S. Dong, X.-H. Li, C.-M. Che, Chem. Eur. J. 2011, 17, 12932 –
12945.
[11] X.-Y. Liu, C.-M. Che, Org. Lett. 2009, 11, 4204 – 4207.
[12] Z.-Y. Han, H. Xiao, X.-H. Chen, L.-Z. Gong, J. Am. Chem. Soc.
2009, 131, 9182 – 9183.
[13] The consumption of phosphoric acid can be confirmed by
31P NMR spectroscopy, see the Supporting Information and: C.
Wang, Z.-Y. Han, H.-W. Luo, L.-Z. Gong, Org. Lett. 2010, 12,
2266 – 2269.
[14] The reaction proceeded to completion in the presence of
10 mol% gold phosphate catalyst at 458C. The 31P NMR spectra
of the reaction mixture showed that no phosphoric acid (7c) was
regenerated (Supporting Information, Figure S1).
[3] W.-B. Wang, S.-M. Lu, P.-Y. Yang, X.-W. Han, Y.-G. Zhou, J. Am.
Chem. Soc. 2003, 125, 10536 – 10537.
[4] For selected examples, see: a) L. Xu, K. H. Lam, J. Ji, J. Wu, Q.-
H. Fan, W.-H. Lo, A. S. C. Chan, Chem. Commun. 2005, 1390 –
1392; b) K. H. Lam, L. Xu, L. Feng, Q.-H. Fan, F. L. Lam, W.-H.
Lo, A. S. C. Chan, Adv. Synth. Catal. 2005, 347, 1755 – 1758;
c) M. T. Reetz, X. Li, Chem. Commun. 2006, 2159 – 2160; d) Z.-J.
Wang, G.-J. Deng, Y. Li, Y.-M. He, W.-J. Tang, Q.-H. Fan, Org.
Lett. 2007, 9, 1243 – 1246; e) S.-M. Lu, C. Bolm, Adv. Synth.
Catal. 2008, 350, 1101 – 1105; f) F.-R. Gou, W. Li, X. M. Zhang,
Adv. Synth. Catal. 2010, 352, 2441 – 2444; g) W. Tang, Y. Sun, L.
Xu, T. Wang, Q. Fan, K.-H. Lam, A. S. C. Chan, Org. Biomol.
Chem. 2010, 8, 3464 – 3471; see also, Refs [2e] and [2h].
[15] C. Nieto-Oberhuber, S. Lꢄpez, A. M. Echavarren, J. Am. Chem.
Soc. 2005, 127, 6178 – 6179.
[16] Previously, we observed that phosphoric acid showed higher
catalytic activity than gold phosphate, see Ref [12].
[17] For recent reviews, see: a) N. Marion, S. P. Nolan, Chem. Soc.
Rev. 2008, 37, 1776 – 1782; b) S. P. Nolan, Acc. Chem. Res. 2011,
44, 91 – 100.
[18] For selected asymmetric reactions controlled by chiral anions,
see: a) X. Wang, B. List, Angew. Chem. 2008, 120, 1135 – 1138;
Angew. Chem. Int. Ed. 2008, 47, 1119 – 1122; b) S. Liao, B. List,
Angew. Chem. 2010, 122, 638 – 641; Angew. Chem. Int. Ed. 2010,
49, 628 – 631; c) L. Yang, Q. Zhu, S. Guo, B. Qian, C. Xia, H.
Huang, Chem. Eur. J. 2010, 16, 1638 – 1645; d) G. Jiang, B. List,
Chem. Commun. 2011, 47, 10022 – 10024; e) M. Barbazanges, M.
Augꢁ, J. Moussa, H. Amouri, C. Aubert, C. Desmarets, L.
Fensterbank, V. Gandon, M. Malacria, C. Ollivier, Chem. Eur. J.
2011, 17, 13789 – 13794; f) Y. Wang, K. Zheng, R. Hong, J. Am.
Chem. Soc. 2012, 134, 4096 – 4099; g) M. Hatano, K. Moriyama,
T. Maki, K. Ishihara, Angew. Chem. 2010, 122, 3911 – 3914;
Angew. Chem. Int. Ed. 2010, 49, 3823 – 3826; h) S. Mukherjee, B.
List, J. Am. Chem. Soc. 2007, 129, 11336 – 11337; see also
Ref [9b].
[19] To the best of our knowledge, very few gold-catalyzed organic
transformations or asymmetric hydrogenations of quinolines are
effective at below 0.01 mol% catalyst loading, especially for
asymmetric processes; see: a) M. Bouhrara, E. Jeanneau, L.
Veyre, C. Copꢁret, C. Thieuleux, Dalton Trans. 2011, 40, 2995 –
2999; b) W.-J. Tang, J. Tan, L.-J. Xu, K.-H. Lam, Q.-H. Fan,
A. S. C. Chan, Adv. Synth. Catal. 2010, 352, 1055 – 1062.
[20] The reduction of 1,2,3,4-tetrahydroacridine gave > 99% yield,
1:1 d.r., 66/18% ee (trans/cis).
[21] a) J. A. Flores, H. V. Rasika Dias, Inorg. Chem. 2008, 47, 4448 –
4450; b) H. V. Rasika Dias, J. Wu, Angew. Chem. 2007, 119,
7960 – 7962; Angew. Chem. Int. Ed. 2007, 46, 7814 – 7816;
c) M. A. Cinellu, G. Minghetti, S. Stoccoro, A. Zucca a, M.
Manassero, Chem. Commun. 2004, 1618 – 1619; d) M. A. Cin-
ellu, G. Minghetti, F. Cocco, S. Stoccoro, A. Zucca a, M.
Manassero, Angew. Chem. 2005, 117, 7052 – 7055; Angew. Chem.
Int. Ed. 2005, 44, 6892 – 6895; e) M. A. Cinellu, G. Minghetti, F.
Cocco, S. Stoccoro, A. Zucca, M. Manassero, Dalton Trans. 2006,
5703 – 5716; f) H. Schmidbaur, A. Schier, Organometallics 2010,
29, 2 – 23.
[22] For selected examples of other metal-catalyzed transfer hydro-
genations with Hantzsch esters as the hydrogen source, see: a) S.
Zehani, G. Gelbard, J. Chem. Soc. Chem. Commun. 1985, 1162 –
1163; b) J. W. Yang, B. List, Org. Lett. 2006, 8, 5653 – 5655; c) D.-
W. Wang, W. Zeng, Y.-G. Zhou, Tetrahedron: Asymmetry 2007,
18, 1103 – 1107.
[5] 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 – 9891.
[6] C. Wang, C. Li, X. Wu, A. Pettman, J. Xiao, Angew. Chem. 2009,
121, 6646 – 6650; Angew. Chem. Int. Ed. 2009, 48, 6524 – 6528.
[7] For selected reviews, see: a) A. S. K. Hashmi, Chem. Rev. 2007,
107, 3180 – 3211; b) Z. Li, C. Brouwer, C. He, Chem. Rev. 2008,
108, 3239 – 3265; c) A. Corma, A. Leyva-Pꢁrez, M. J. Sabater,
Chem. Rev. 2011, 111, 1657 – 1712; d) A. Arcadi, Chem. Rev.
2008, 108, 3266 – 3325; e) N. Krause, C. Winter, Chem. Rev. 2011,
111, 1994 – 2009; f) M. Rudolph, A. S. K. Hashmi, Chem. Soc.
Rev. 2012, 41, 2448 – 2462; g) T. C. Boorman, I. Larrosa, Chem.
Soc. Rev. 2011, 40, 1910 – 1925.
[8] For selected examples, see: a) Y. Ito, M. Sawamura, T. Hayashi,
J. Am. Chem. Soc. 1986, 108, 6405 – 6406; b) M. P. MuÇoz, J.
Adrio, J. C. Carretero, A. M. Echavarren, Organometallics 2005,
24, 1293 – 1300; c) M. J. Johansson, D. J. Gorin, S. T. Staben, F. D.
Toste, J. Am. Chem. Soc. 2005, 127, 18002 – 18003; d) H. Teller, S.
Flꢂgge, R. Goddard, A. Fꢂrstner, Angew. Chem. 2010, 122,
1993 – 1997; Angew. Chem. Int. Ed. 2010, 49, 1949 – 1953; e) Y.-
M. Wang, C. N. Kuzniewski, V. Rauniyar, C. Hoong, F. D. Toste,
J. Am. Chem. Soc. 2011, 133, 12972 – 12975; f) S. Handa, L. M.
Slaughter, Angew. Chem. 2012, 124, 2966 – 2969; Angew. Chem.
Int. Ed. 2012, 51, 2912 – 2915; g) R. A. Widenhoefer, Chem. Eur.
J. 2008, 14, 5382 – 5391; for reviews, see: h) D. J. Gorin, B. D.
Sherry, F. D. Toste, Chem. Rev. 2008, 108, 3351 – 3378; i) A.
Pradal, P. Y. Toullec, V. Michelet, Synthesis 2011, 1501 – 1514.
[9] a) G. L. Hamilton, E. J. Kang, M. Mba, F. D. Toste, Science 2007,
317, 496 – 499; b) K. Aikawa, M. Kojima, K. Mikami, Angew.
Chem. 2009, 121, 6189 – 6193; Angew. Chem. Int. Ed. 2009, 48,
6073 – 6077; c) K. Aikawa, M. Kojima, K. Mikami, Adv. Synth.
Catal. 2010, 352, 3131 – 3135.
[10] a) C. Gonzꢃlez-Arellano, A. Corma, M. Iglesias, F. Sꢃnchez,
Chem. Commun. 2005, 3451 – 3453; b) A. Corma, E. Gutiꢁrrez-
Puebla, M. Iglesias, A. Monge, S. Pꢁrez-Ferreras, F. Sꢃnchez,
Adv. Synth. Catal. 2006, 348, 1899 – 1907; c) N. Debono, M.
Iglesias, F. Sꢃnchez, Adv. Synth. Catal. 2007, 349, 2470 – 2476;
d) M. Zhang, H. Yang, Y. Zhang, C. Zhu, W. Li, Y. Cheng, H.
4
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ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
These are not the final page numbers!

Angewandte
Chemie
Communications
Gold Catalysis
A little gold goes a long way: As little as
0.01 mol% of chiral gold phosphate is
sufficient to afford the asymmetric trans-
fer hydrogenation of quinolines with high
stereoselectivity (up to 98% ee). The
achiral ligands on gold were found to
have considerable effect on the catalytic
efficiency.
X.-F. Tu, L.-Z. Gong*
&&&& — &&&&
Highly Enantioselective Transfer
Hydrogenation of Quinolines Catalyzed
by Gold Phosphates: Achiral Ligand
Tuning and Chiral-Anion Control of
Stereoselectivity
Angew. Chem. Int. Ed. 2012, 51, 1 – 5
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
5
These are not the final page numbers!