.
Angewandte
Communications
DOI: 10.1002/anie.201301830
Synthetic Methods
Asymmetric Ruthenium-Catalyzed Hydrogenation of 2- and
2,9-Substituted 1,10-Phenanthrolines**
Tianli Wang, Fei Chen, Jie Qin, Yan-Mei He, and Qing-Hua Fan*
Dedicated to Professor Zhi-Tang Huang on the occasion of his 85th birthday
Asymmetric hydrogenation of heteroaromatic compounds
has captured considerable attention because it offers straight-
forward and environmentally benign routes to optically active
compounds with chiral heterocyclic skeletons.[1] Recently,
various heteroarenes such as quinolines,[2] isoquinolines,[2b,3]
quinoxalines,[4] indoles,[5a–h] pyrroles,[5i,j] (benzo)furans,[6] pyr-
idines,[7] imidazoles,[8] and (benzo)thiophenes[9] have been
successfully hydrogenated with high enantiomeric excesses.
However, despite achievements made in this field, many
challenges still remain and polycyclic heteroarenes (contain-
ing more than one heterocycle) are particularly difficult
substrates.
OPhen (Scheme 1). To the best of our knowledge, only one
example of asymmetric transfer hydrogenation of 2- and 2,9-
substituted 1,10-phenanthrolines catalyzed by chiral Brønsted
acid has been reported.[13] However, several obvious limita-
tions remain, such as low reactivity or selectivity, and
1,10-Phenanthroline (Phen; 1) and its derivatives con-
taining two pyridyl rings are one of the most versatile
bidentate ligands for transition-metal catalysis.[10] Much less
attention has been directed toward the partially reduced
1,2,3,4-tetrahydro- and 1,2,3,4,7,8,9,10-octahydro-1,10-phe-
nanthroline [TPhen (2) and OPhen (3), respectively] deriv-
atives,[11–13] which are two kinds of heterocycle-containing
compounds with potential bioactivity[14] and can also be used
as new ligands such as vicinal diamines[15a,b] and benzimid-
azole-based N-heterocyclic carbenes.[15c,d] So far, few reports
have focused upon heterogeneous metal-catalyzed hydro-
genation[11] or reduction[12] with stoichiometric reducing
agents of 1,10-phenanthroline and its derivatives, and all
these methods suffered from low stereoselectivities and poor
reaction yields. Moreover, as far as we know, homogeneous
transition-metal catalyzed hydrogenation of such substrates
has never been reported, probably because of the aromaticity,
as well as the strong coordination and poisoning ability of the
substrate or the reduced product. For example, the cationic
half-sandwich ruthenium complex 4 containing a 1,10-phen-
anthroline ligand was found to be an effective catalyst for the
transfer hydrogenation of ketones.[16] Expectedly, it is more
challenging to realize the asymmetric reduction of substituted
1,10-phenanthrolines to selectively provide chiral TPhen and
Scheme 1. Reduction of 1,10-phenanthroline and its derivatives.
particularly low diastereoselectivity, as well as narrow sub-
strate scope. Therefore, the search for new catalytic systems
for the asymmetric hydrogenation of substituted 1,10-phe-
nanthrolines is highly desirable and of great significance.
During the course of our investigation into the asymmet-
ric hydrogenation of heteroaromatic compounds, we found
that cationic ruthenium complexes (such as (R,R)-5a[18a]; Tf =
trifluoromethanesulfonyl, Ts = 4-toluenesulfonyl) containing
chiral monotosylated diamine ligands[17] were very efficient
catalysts for the asymmetric hydrogenation[18,19] of a broad
range of quinolines[2f,g] and quinoxalines[4b] with excellent
reactivity and enantioselectivity. Encouraged by these results
and with our continued interest in the asymmetric hydro-
genation of heteroaromatic compounds and imines,[19] we
herein report the first example of the asymmetric hydro-
genation of substituted 1,10-phenanthrolines using a cationic
Ru-TsDPEN complex [(R,R)-5a]. It was found that a range of
readily available 2- and 2,9-substituted 1,10-phenanthroline
derivatives were successfully hydrogenated to selectively
provide optically active TPhen or OPhen derivatives with
unprecedented reactivity, enantioselectivity (up to > 99%
ee), and diastereoselectivity (up to > 20:1 d.r).
[*] T. L. Wang, F. Chen, J. Qin, Y.-M. He, Prof. Dr. Q.-H. Fan
Beijing National Laboratory for Molecular Sciences
CAS Key Laboratory of Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences (CAS)
Beijing 100190 (P. R. China)
E-mail: fanqh@iccas.ac.cn
[**] Financial support from the National Natural Science Foundation of
China (No 21232008), National Basic Research Program of China
(973 Program, 2010CB833300), and the Chinese Academy of
Sciences is greatly acknowledged.
In our initial study, we chose the hydrogenation of 2,9-
dimethyl-1,10-phenanthroline (1a) as the model reaction
using the cationic complex (R,R)-5a, which was an effective
catalyst in the asymmetric hydrogenation of quinolines. It was
Supporting information for this article is available on the WWW
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Angew. Chem. Int. Ed. 2013, 52, 1 – 6
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