Rh/Wudaphos-Catalyzed Asymmetric Hydrogenation of Sodium α-Arylethenylsulfonates: A Method to Access Chiral α-Arylethylsulfonic Acids

Article abstract of DOI:10.1021/acs.orglett.7b01021

A highly enantioselective hydrogenation of various sodium α-arylethenylsulfonates catalyzed by Rh/chiral ferrocenyl bisphosphorus ligand (Wudaphos) was successfully developed to construct a series of chiral α-arylethylsulfonic acids in the presence of CF₃SO₃H with full conversion and good to excellent enantioselectivity (>99% conversion, up to 96% ee) under mild reaction conditions for the first time. Moreover, the control experiment results showed that the non-covalent ion pair interaction between the α-arylethenylsulfonic acid and the Wudaphos ligand plays an important role in this asymmetric hydrogenation system.

Full text of DOI:10.1021/acs.orglett.7b01021

Letter
pubs.acs.org/OrgLett
Rh/Wudaphos-Catalyzed Asymmetric Hydrogenation of Sodium
α‑Arylethenylsulfonates: A Method To Access Chiral
α‑Arylethylsulfonic Acids
Xuguang Yin,† Caiyou Chen,† Xiu-Qin Dong,*,† and Xumu Zhang*,‡,†
†College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, P. R. China
‡Department of Chemistry, South University of Science and Technology of China, Shenzhen, Guangdong 518055, P. R. China
S
* Supporting Information
ABSTRACT: A highly enantioselective hydrogenation of
various sodium α-arylethenylsulfonates catalyzed by Rh/chiral
ferrocenyl bisphosphorus ligand (Wudaphos) was successfully
developed to construct a series of chiral α-arylethylsulfonic
acids in the presence of CF3SO3H with full conversion and
good to excellent enantioselectivity (>99% conversion, up to
96% ee) under mild reaction conditions for the first time.
Moreover, the control experiment results showed that the non-
covalent ion pair interaction between the α-arylethenylsulfonic acid and the Wudaphos ligand plays an important role in this
asymmetric hydrogenation system.
from the corresponding racemates by the resolution process
s one of the most important classes of acids, chiral sulfonic
Aacids have shown remarkable significance and owned wide with chiral amines.7 Only a few enantiomeric α-substituted
sulfonic acids can be obtained by “Dutch resolution”,8 and the
highest theoretical yield is just 50%. In 1992, Corey and co-
workers found that chiral (S)-(−)-1-phenylethanesulfonic acid
[(−)-PES] can be obtained from the transformation of (R)-1-
phenylethanol, which was obtained by the catalytic asymmetric
reduction of methyl phenyl ketone.9 In 2005, Enders and co-
workers reported the first auxiliary-controlled synthesis of
various α-substituted sulfonic acid derivatives, in which
enantiopure alcohols are used as chiral auxiliaries.10 In 2011,
Adamo and co-workers successfully developed catalytic
enantioselective addition of sodium bisulfite to α,β-unsaturated
alkenes using a bifunctional amine−thiourea catalyst.11
Subsequently, Zhao and co-workers reported a chiral Ir- and
Pd-complex-catalyzed asymmetric allylation reaction of allylic
carbonates with sodium sulfite to afford allylic sulfonic acids in
excellent yields and enantioselectivities.12 Despite the great
progress that has been achieved, it is still necessary to develop
efficient catalytic asymmetric methodologies for the preparation
of chiral sulfonic acids. Nowadays, catalytic asymmetric
hydrogenation of functionalized olefins is regarded as one of
the most powerful and environmentally friendly methods to
synthesize chiral compounds.13 To the best of our knowledge,
catalytic asymmetric hydrogenation of unsaturated sulfonic
acids has not been reported until now. Most recently, we
developed a new chiral ferrocenyl bisphosphorus ligand
(Wudaphos), which was successfully applied in Rh-catalyzed
asymmetric hydrogenation of α-substituted acrylic acids with
application in the areas of biochemistry and natural products.1
For example, 6-gingesulfonic acid, which was isolated from
Zingiberis rhizome, displays potent antiulcer activity;2 the
semisynthetic penicillin α-sulfobenzylpenicillin shows excellent
antibacterial activity against Pseudomonas aeruginosa;3 α-
phosphono sulfonates are squalene synthase inhibitors;4 and
echinosulfonic acids, which were isolated from southern
Australian marine sponges Echinodictyum, have good antibac-
tarial activity (Figure 1).5 In addition, chiral α-arylethylsulfonic
acids are excellent candidates as chiral resolving agents for
numerous amino acids.6
Because of their great importance, much effort has been
devoted to the development of efficient synthetic method-
ologies to approach chiral sulfonic acids. During the past
decades, chiral α-substituted sulfonic acids have been obtained
Figure 1. Several examples of pharmaceuticals and natural products
featuring a chiral sulfonic acid motif.
Received: April 4, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b01021
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
excellent results through the non-covalent ion pair interaction
between the unsaturated acid and Wudaphos.14 Since this
secondary interaction activation strategy played an important
role to obtain high reactivity and excellent enantioselectivity, we
believe that the asymmetric hydrogenation of α-arylethenylsul-
fonic acids should provide excellent results with our Wudaphos
ligand. In the present work, this novel synergistic activation
strategy was proved to be very efficient in Rh-catalyzed
asymmetric hydrogenation of various α-arylethenylsulfonic
acids formed in situ from sodium α-arylethylsulfonates using
CF3SO3H (>99% conversion, up to 96% ee).
Table 1. Optimization of the Reaction Conditions for the
Asymmetric Hydrogenation of Sodium α-
a
Phenylethenylsulfonate (1a)
equiv of
CF3SO3H
conv.
b
ee
(%)
c
entry
ligand
solvent
(%)
1
2
(S)-Binap
(S)-Segphos
Josiphos
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
iPrOH
TFE
0
52
>99
>99
54
13
0
0
The sodium α-arylethenylsulfonates were efficiently prepared
from the arylmethanesulfonyl chlorides as the starting materials
in three steps (Scheme 1).15 First, the methyl arylmethanesul-
3
0
15
0
4
Taniaphos
Wudaphos
Wudaphos
Wudaphos
Wudaphos
Wudaphos
Wudaphos
Wudaphos
Wudaphos
Wudaphos
0
5
0
>99
>99
>99
80
17
25
90
82
81
90
91
86
92
6
0.5
1.0
1.5
2.0
1.0
1.0
1.0
1.0
Scheme 1. Synthesis of Sodium α-Arylethenylsulfonates 1
7
8
9
20
10
11
12
13
>99
>99
7
THF
>99
a
All of the reactions were carried out with a substrate/catalyst ratio of
b
1
100:1 at 25 °C under 30 atm H2 for 12 h. Determined by H NMR
spectroscopy. Determined by HPLC on a chiral phase.
fonates were easily synthesized through a simple nucleophilic
substitution reaction of the arylmethanesulfonyl chlorides and
sodium methoxide. Then the methyl 1-arylethene-1-sulfonates
were obtained by the reaction between the methyl
arylmethanesulfonates and paraformaldehyde in the presence
of K2CO3 and tetrabutylammonium iodide (TBAI). Finally, the
sodium 1-arylethene-1-sulfonates 1 were prepared through the
replacement of the methyl 1-arylethene-1-sulfonates with NaI.
We began our study by using sodium 1-phenylethene-1-
sulfonate (1a) as a model substrate in Rh-catalyzed asymmetric
hydrogenation (substrate/catalyst (S/C) = 100, 30 atm H2, 25
°C). As shown in Table 1, several chiral phosphine ligands,
such as (S)-Binap, (S)-Segphos, Josiphos, Taniaphos, and
Wudaphos (Figure 2) displayed poor results (52−99%
conversion, 0−17% ee; Table 1, entries 1−5). Compared
with other chiral phosphine ligands, Wudaphos provided the
best result (>99% conversion, 17% ee; Table 1, entry 5). To
our delight, the enantioselectivity was gradually improved
substantially in the Rh/Wudaphos catalytic system when the
amount of CF3SO3H was increased from 0.5 to 1.0 equiv
(>99% conversion, 25−90% ee; Table 1, entries 6 and 7). In
addition, when the amount of CF3SO3H was increased to 1.5 or
2.0 equiv, both the conversion and the enantioselectivity
became worse (20−80% conversion, 81−82% ee; Table 1,
entries 8 and 9). It is possible that the extra CF3SO3H interacts
with the dimethylamine motif of Wudaphos, which may reduce
the reactivity and chiral induction ability in our catalytic system.
Then, we inspected the solvent effects of this transformation in
the presence of 1.0 equiv of CF3SO3H. Substrate 1a is soluble
c
Figure 2. Several phosphine ligands for asymmetric hydrogenation of
sodium 1-phenylethene-1-sulfonate (1a).
Encouraged by these excellent results, we turned our
attention to an investigation of the generality of our catalytic
system in the asymmetric hydrogenation of various sodium α-
arylethenylsulfonates under the optimized reaction conditions.
These results are summarized in Scheme 2. A series of sodium
α-arylethenylsulfonates bearing different substituent groups on
the phenyl ring were hydrogenated well to afford the
corresponding chiral α-arylethylsulfonic acids with full con-
version and good to excellent enantioselectivity (87−96% ee).
The electric property and position of the substituent groups on
the phenyl ring of the substrates had little influence on both the
reactivity and enantioselectivity. The substrates containing
electron-donating groups (1b−d) or electron-withdrawing
groups (1e−j) on the phenyl ring reacted efficiently with
good to excellent results (full conversion, 87−99% ee).
i
in a few kinds of solvents, such as MeOH, EtOH, PrOH,
trifluoroethanol (TFE), and tetrahydrofuran (THF). We found
that the asymmetric hydrogenation proceeded well in MeOH,
i
EtOH, PrOH, and THF with full conversion and excellent
enantioselectivity (>99% conversion, 90−92% ee; Table 1,
entries 7, 10, 11, and 13). TFE provided poor conversion, albeit
with good enantioselectivity (7% conversion, 86% ee; Table 1,
entry 12). THF was selected as the best solvent in terms of
both reactivity and enantioselectivity (>99% conversion, 92%
ee; Table 1, entry 13).
Moreover, our catalytic system is very efficient in this
asymmetric hydrogenation. Substrate 1a was hydrogenated well
on a gram scale under the optimized reaction conditions, and
B
DOI: 10.1021/acs.orglett.7b01021
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Letter
Scheme 2. Scope of the Asymmetric Hydrogenation of
Scheme 4. Control Experiments for the Investigation of the
Interaction between the Substrate and Ligand
Sodium α-Arylethenylsulfonates 1 Catalyzed by Rh/
a
Wudaphos
for the first time. A series of chiral α-arylethylsulfonic acids
were obtained with full conversion and good to excellent
enantioselectivity (87−96% ee). Additionally, this asymmetric
hydrogenation was performed well on gram-scale without loss
of enantioselectivity. Furthermore, control experiment results
demonstrated that the non-covalent ion pair interaction
between the α-arylethenylsulfonic acid and the Wudaphos
ligand plays a critical role in obtaining high reactivity and
excellent enantioselectivity in this asymmetric hydrogenation.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b01021.
a
■
All of the reactions were performed with 0.1 mmol of substrate and
S
substrate/[Rh(NBD)2]BF4/Wudaphos = 1/0.01/0.011 at 25 °C under
30 atm H2 with 1.0 equiv of CF3SO3H in 1.0 mL of THF for 12 h.
Conversion was determined by H NMR spectroscopy. The ee values
1
were determined by HPLC on a chiral column. The absolute
configuration was determined according to the literature.9
Experimental details and characterization data (PDF)
the desired product 2a was obtained with 99% conversion and
92% ee (Scheme 3).
AUTHOR INFORMATION
Corresponding Authors
■
Scheme 3. Gram-Scale Asymmetric Hydrogenation of 1a
*E-mail: xumu@whu.edu.cn.
*E-mail: xiuqindong@whu.edu.cn.
ORCID
Xumu Zhang: 0000-0001-5700-0608
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
In order to explore the importance of the secondary
interaction between the substrate and ligand, some control
experiments were conducted. The asymmetric hydrogenation
of 1a was carried out under the optimized conditions without
CF3SO3H, and the corresponding product 2a was obtained
with only 17% ee (Scheme 4a). Furthermore, no reaction was
observed when methyl 1-phenylethene-1-sulfonate (3a) was
used as the substrate (Scheme 4b). These results demonstrated
that the α-arylethenylsulfonic acids were formed in situ by
adding CF3SO3H of our catalytic system, providing the
corresponding hydrogenation products with high enantiose-
lectivities. In addition, a non-covalent ion pair interaction
between the α-arylethenylsulfonic acid and the Wudaphos
ligand also exists and plays a critical role in obtaining high
activity and excellent enantioselectivity in this asymmetric
hydrogenation.
We thank Wuhan University (203273463, 203410100064), the
“111” Project of the Ministry of Education of China, the
National Natural Science Foundation of China (21372179,
21432007, 21502145), and the Natural Science Foundation of
Hubei Province (2016CFB449) for financial support.
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