Angewandte
Chemie
DOI: 10.1002/anie.201307903
Asymmetric Hydrogenation
Catalytic Asymmetric Hydrogenation of a-CF3- or b-CF3-Substituted
Acrylic Acids using Rhodium(I) Complexes with a Combination of
Chiral and Achiral Ligands**
Kaiwu Dong, Yang Li, Zheng Wang, and Kuiling Ding*
Dedicated to Professor Manfred T. Reetz on the occasion of his 70th birthday
The introduction of trifluoromethyl (CF3) groups into organic
molecules can substantially modify the lipophilicity, meta-
bolic stability, and bioavailability of the biologically interest-
ing molecules, and thus has attracted much attention from
synthetic chemists over recent years.[1,2] Optically active
carboxylic acids with CF3 substituents are versatile chiral
building blocks for the synthesis of pharmaceuticals, agro-
chemicals, natural products and fragrances.[3] Accordingly, the
development of methodologies for the enantioselective con-
struction of trifluoromethylated carboxylic acid derivatives is
highly desirable and has become an important research
area.[2] However, the catalytic asymmetric synthesis of
optically active a-CF3- or b-CF3-substituted propanoic acid
derivatives is less explored, with a-trifluoromethylation of
some specific carbonyl compounds[4] and conjugate addition
of b-trifluoromethylated acrylic acid derivatives being among
the few documented examples.[5] In this context, asymmetric
hydrogenation (AH) of a- or b-trifluoromethylated acrylic
acid derivatives, one of the most straightforward and environ-
mentally benign approaches, still remains a big challenge,[6,7]
probably because of the highly electron-withdrawing nature
of the CF3 group in the olefinic substrates, despite the fact that
numerous chiral catalysts have been successfully developed
for the AH of various nonfluoro-substituted acrylic acids.
Even though a few RuII or RhI complexes with chiral
bisphosphine ligands catalyze the hydrogenation of some
specific a-CF3- or b-CF3-substituted acrylic acids, the proce-
dures are usually associated with only a single substrate.[6,7]
Herein, we report a highly enantioselective AH of a broad
range of a-CF3- or b-CF3-substituted acrylic acids, using a RhI
complex generated in situ with a mixture of a chiral secondary
phosphine oxide (SPO) and an achiral triarylphosphine
ligand, as the catalyst.
catalyzed AHs of a variety of olefinic substrates.[8] The
feasibility of using RhI/SPO-type catalysts in AHs of CF3-
substituted acrylic acid derivatives was first investigated by
screening several SPO ligands (L1–L6) with a-CF3-substi-
tuted cinnamic acid ((Z)-1a) as a model substrate (Table 1).
Table 1: Effect of PPh3 on the RhI-catalyzed asymmetric hydrogenation of
(Z)-1a in the presence of SPO preligands L1–L6.[a]
Entry
L ([mol%])
Ph3P [mol%]
Conv. [%][b]
ee [%][c]
1
2
3
4
(S,S)-L1 (2)
(R)-L2 (2)
(R,R)-L3 (2)
(S)-L4 (2)
(S)-L5 (2)
(S)-L6 (2)
(S)-L6 (2)
1
1
1
1
1
1
1
30
44
95
74
80
37 (S)
58 (R)
23 (S)
11 (R)
84 (R)
92 (R)
98 (R)
5
6
82
>99
7[d]
[a] Reaction conditions: 1 mol% [Rh(cod)2]BF4, [1a]=0.1m. [b] Deter-
mined by 19F NMR spectroscopy. [c] Determined by HPLC on a chiral
stationary phase after 2a was transformed to its corresponding methyl
ester with CH2N2. The absolute configurations were assigned by
comparison of their optical rotations with reported values (see the
Supporting Information). [d] The solvent mixture CHCl3/H2O (4/1) and
[Rh(cod)2]PF6 were used in the reaction. cod=1,5-cyclooctadiene.
The research project was inspired by the excellent
performance of chiral SPO molecules as preligands in RhI-
As shown in Table S1 in the Supporting Information, only
very poor conversions (16 h, < 15%) were obtained under the
initially tested conditions, indicating that the complexes
generated with RhI and these SPO ligands are not adequately
active for catalysis. Gratifyingly, when we investigated the
reaction using RhI complexes with SPO/PPh3[9] monodentate
ligand mixtures,[10–16] the addition of achiral PPh3 had
a profound influence on the catalysis, as evidenced by the
substantial improvement in the catalytic performance (30–
95% conversions, 11–92% ee, Table 1, entries 1–6). Such
a dramatic change in catalytic behavior upon addition of
Ph3P can be attributed to an active RhI species, coordinated
[*] K. Dong, Y. Li, Dr. Z. Wang, Prof. Dr. K. Ding
State Key Laboratory of Organometallic Chemistry, Shanghai
Institute of Organic Chemistry, Chinese Academy of Sciences
345 Lingling Road, Shanghai 200032 (P. R. China)
E-mail: kding@mail.sioc.ac.cn
[**] We thank the financial support of this work from the Major Basic
Research Development Program of China (grant
no.2010CB833300), the NSFC (grant nos. 91127041, 21121062, and
21232009), the Chinese Academy of Sciences, and the Science and
Technology Commission of Shanghai Municipality.
Supporting information for this article is available on the WWW
Angew. Chem. Int. Ed. 2013, 52, 14191 –14195
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
14191