Highly Enantioselective Asymmetric Hydrogenation of Carboxy-Directed α,α-Disubstituted Terminal Olefins via the Ion Pair Noncovalent Interaction

Article abstract of DOI:10.1021/acs.orglett.7b02972

The t-Bu-Wudaphos was successfully applied into Rh-catalyzed asymmetric hydrogenation of α,α-disubstituted terminal olefins bearing a carboxy-directed group with excellent reactivities and enantioselectivities via the ion pair noncovalent interaction (up to >99% conversion, 98% yield, 98% ee) under mild reaction conditions without base. In addition, control experiments were conducted, and the results demonstrated that the ion pair noncovalent interaction between ligand and substrate played an important role in achieving an outstanding performance in this asymmetric hydrogenation.

Full text of DOI:10.1021/acs.orglett.7b02972

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
Highly Enantioselective Asymmetric Hydrogenation of Carboxy-
Directed α,α-Disubstituted Terminal Olefins via the Ion Pair
Noncovalent Interaction
Songwei Wen,†,§ Caiyou Chen,†,§ Shuaichen Du,† Zhefan Zhang,† Yi Huang,† Zhengyu Han,†
Xiu-Qin Dong,*,† and Xumu Zhang*,†,‡
†Key Laboratory of Biomedical Polymers, Ministry of Education, College of Chemistry and Molecular Sciences, Wuhan University,
Wuhan, Hubei 430072, P. R. China
‡Department of Chemistry, Southern University of Science and Technology, Shenzhen, Guangdong 518000, P. R. China
S
* Supporting Information
ABSTRACT: The t-Bu-Wudaphos was successfully applied
into Rh-catalyzed asymmetric hydrogenation of α,α-disubsti-
tuted terminal olefins bearing a carboxy-directed group with
excellent reactivities and enantioselectivities via the ion pair
noncovalent interaction (up to >99% conversion, 98% yield,
98% ee) under mild reaction conditions without base. In addition, control experiments were conducted, and the results
demonstrated that the ion pair noncovalent interaction between ligand and substrate played an important role in achieving an
outstanding performance in this asymmetric hydrogenation.
he chiral benzylmethyl center is an important motif in
biologically active compounds and natural products,1 such
diarylethenes with the aid of −OH,10 −OMe,11 −NH2,12 and −
COOH7,8a,13 as directing groups.
T
as H1-antihistamine,2 (+)-curcudiol,1b,3 (+)-curcumene,4 and
(+)-curcuphenol1b,3 (Figure 1). Owing to its great importance,
Most recently, we were devoted to developing a series of
privileged ferrocenyl chiral bisphosphorus ligands Wudapho-
s,14a,b SPO-Wudaphos,14c−e and t-Bu-Wudaphos.14f These
ligands performed excellently in Rh-catalyzed asymmetric
hydrogenation of various types of unsaturated carboxylic acids
through the ion pair noncovalent interaction between the amino
group of the ligands and the acid group of the substrates.14 Since
there is great importance of the ion pair noncovalent interaction
between the amino group of the ligands and the acid group of the
substrates,14,15 we believe that the asymmetric hydrogenation of
α,α-disubstituted terminal olefins bearing a carboxy-directed
group should provide excellent results with our ferrocenyl chiral
bisphosphorus ligands. Herein, the ion pair noncovalent
interaction between the amino group of the ligands and the
acid group of the substrates proved to be very efficient in this Rh-
catalyzed asymmetric hydrogenation of α,α-disubstituted termi-
nal olefins (Scheme 1, up to 98% ee, >99% conversion, TON up
to 1000).
Our initial investigation was carried out by evaluating the
solvent effects in this asymmetric hydrogenation of 2-(1-
phenylvinyl)-benzoic acid (1a) as the model substrate and with
the catalyst generated in situ by mixing Rh(NBD)2BF4 with t-Bu-
Wudaphos (S/C = 100) at room temperature. As shown in Table
1, except EtOH and CF3CH2OH, other solvents, such as MeOH,
THF, DCM, ClCH2CH2Cl, and CH3CN, showed poor results
(Table 1, entries 1−7). EtOH and CF3CH2OH can provide full
conversions and excellent enantioselectivities (>99% conversion,
Figure 1. Biologically active compounds and natural products.
much more attention has been paid to the development of
efficient catalytic methodologies to prepare the chiral benzyl-
methyl motif in the last decades.5 The transition-metal-catalyzed
asymmetric hydrogenation of prochiral unsaturated compounds
is one of the most efficient and powerful methods to access chiral
compounds.6 Recently, Zhou and co-workers successfully
developed carboxy-directed asymmetric hydrogenation of 1,1-
diarylethenes and 1,1-dialkylethenes catalyzed by chiral iridium
catalysts bearing spiro phosphine−oxazoline ligands.7 Subse-
quently, they realized Ir-catalyzed asymmetric hydrogenation of
other olefins bearing carboxylic acid group.8 It is well-known that
substituents of double bonds with different sizes in asymmetric
hydrogenation were favorable in achieving excellent chiral
induction.5b,9 Therefore, it is difficult to realize highly efficient
asymmetric hydrogenation of 1,1-disubstituted ethenes bearing a
similar substituent group with excellent enantioselectivity.
Several groups developed asymmetric hydrogenation of α,α-
Received: September 21, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02972
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Asymmetric Hydrogenation of α,α-Disubstituted
Terminal Olefins Bearing Carboxy-Directed Group Catalyzed
by Rh/t-Bu-Wudaphos with Ion Pair Noncovalent Interaction
Table 2. Screening Metal Precursor for the Asymmetric
a
Hydrogenation of 2-(1-Phenylvinyl)-benzoic Acid (1a)
b
c
entry
[Rh]
conv (%)
ee (%)
1
2
3
4
Rh(NBD)2BF4
Rh(COD)2BF4
Rh(COD)2SO3CF3
[Rh(COD)Cl]2
>99
>99
>99
>99
98
97
97
90
Table 1. Screening Solvents for the Asymmetric
Hydrogenation of 2-(1-Phenylvinyl)-benzoic Acid (1a)
a
a
Unless otherwise noted, all reactions were carried out with a [Rh]/t-
Bu-Wudaphos/1a (0.1 mmol) ratio of 1:1.1:100 in 1.0 mL of EtOH/
CF3CH2OH (V/V = 1:1) at room temperature under hydrogen (10
b
c
1
bar) for 12 h. Determined by H NMR analysis. Determined by
HPLC analysis using a chiral stationary phase. NBD = norbornadiene.
COD = 1, 5-cyclooctadiene.
b
c
entry
solvent
conv (%)
ee (%)
1
MeOH
EtOH
<5
55
93
95
25
NA
65
NA
94
94
98
95
94
Scheme 2. Substrate Scope of the Carboxy-Directed
2
>99
>99
<5
Asymmetric Hydrogenation of α,α-Disubstituted Terminal
3
CF3CH2OH
a
Olefins 2
4
THF
5
DCM
NR
<5
6
ClCH2CH2Cl
7
CH3CN
NR
>99
>99
>99
>99
>99
8
EtOH/CF3CH2OH = 1:10
EtOH/CF3CH2OH = 1:5
EtOH/CF3CH2OH = 1:1
EtOH/CF3CH2OH = 5:1
EtOH/CF3CH2OH = 10:1
9
10
11
12
a
Unless otherwise noted, all reactions were carried out with a
[Rh(NBD)2BF4]/t-Bu-Wudaphos/1a (0.1 mmol) ratio of 1:1.1:100 in
1.0 mL of solvent at room temperature under hydrogen (10 bar) for
b
1
12 h, EtOH/CF3CH2OH is volume ratio. Determined by H NMR
c
analysis. Determined by HPLC analysis using a chiral stationary
phase. NR = no reaction. NA = not available.
93%−95% ee, Table 1, entries 2−3). In order to improve the
enantioselectivity of this transformation, a series of ratios of
mixed solvents of EtOH and CF3CH2OH were investigated
(Table 1, entries 8−12). We found that the mixture solvents of
EtOH/CF3CH2OH (V/V = 1:1) displayed the best results
(>99% conversion, 98% ee, Table 1, entry 10). It is possible that
these alcohols were involved in the ion pair noncovalent
interaction, which may contribute to high efficiency of the
catalytic system.
Subsequently, we examined the catalytic effect of t-Bu-
Wudaphos with different rhodium sources in the mixture
solvents of EtOH/CF3CH2OH (V/V = 1:1) (Table 2, entries
1−4). To our delight, all of the rhodium sources can provide full
conversions and excellent enantioselectivities (90%−98% ee,
Table 2, entries 1−4). Rh(NBD)2BF4 afforded the best result
with >99% conversion and 98% ee (Table 1, entry 1).
With the optimized reaction conditions established (Rh-
(NBD)2BF4/t-Bu-Wudaphos/10 bar H2, S/C = 100/room
temperature), an array of various α,α-disubstituted terminal
olefins 1 bearing an ortho-carboxy group were employed as
substrates to inspect the generality of this asymmetric hydro-
genation. These results are summarized in Scheme 2. A series of
α,α-diaryl terminal olefins were hydrogenated smoothly to
provide various chiral 2-substituted benzoic acids with full
conversions, 97−98% yields and 92−98% ee. The 2-(1-
a
The reaction was conducted in 0.1 mmol scale in 1.0 mL of EtOH/
CF3CH2OH (V/V = 1:1) at room temperature, [Rh(NBD)2]BF4 was
used as metal precursor, t-Bu-Wudaphos as the ligand, H2 pressure =
10 bar, S/C = 100, and reaction time = 12 h.
aryllvinyl)-benzoic acid substrates bearing electron-donating
groups (1b−1f) and electron-withdrawing groups (1g−1i) on
the phenyl ring performed well with excellent results (>99%
conversion, 94−98% ee). It is worth noting that the hydro-
genation of heterocyclic aromatic 2-(1-thienylvinyl)-benzoic acid
(1j) can achieve 92% ee and >99% conversion. To our delight,
B
DOI: 10.1021/acs.orglett.7b02972
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
the aliphatic substrates 2-(but-1-en-2-yl)benzoic acid (1k) and 2-
(3-methylbut-1-en-2-yl)benzoic acid (1l) also performed
efficiently (>99% conversion, 94−97% ee).
control experiment results demonstrated that the noncovalent
ion pair interaction between ligand and acid substrate was critical
in affording excellent results in this asymmetric hydrogenation.
Encouraged by these excellent results, gram-scale reaction with
low catalyst loading was conducted to demonstrate the practical
application of this Rh/t-Bu-Wudaphos-catalyzed hydrogenation.
As shown in Scheme 3, when the catalyst loading was reduced to
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b02972.
Scheme 3. Gram-Scale Reaction with Lower Catalyst Loading
Experimental details and characterization data (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: xumu@whu.edu.cn.
*E-mail: xiuqindong@whu.edu.cn.
ORCID
0.1 mol % (S/C = 1 000), the asymmetric hydrogenation of 2-(1-
phenylvinyl)-benzoic acid (1a) with 1.12 g proceeded smoothly
with full conversion, 97% yield, and 98% ee at room temperature.
In order to reveal the critical role of the ion pair interaction
between the ligand and the substrate, primary control experi-
ments were conducted under the standard reaction conditions.
The asymmetric hydrogenation of methyl 2-(1-phenylvinyl)-
benzoate ester 3 was investigated and poor results were observed
(<5% conversion, 0% ee, Scheme 4a). In addition, the base was
Xumu Zhang: 0000-0001-5700-0608
Author Contributions
§S.W. and C.C. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Scheme 4. Control Experiments for the Investigation of the
Ion Pair Noncovalent Interaction Effect
We are grateful for the financial support of the Important Sci-
Tech Innovative Project of Hubei Province (2015ACA058), the
National Natural Science Foundation of China (Grant No.
21372179, 21432007, 21502145), Natural Science Foundation
of Hubei Province (Grant No. 2016CFB449), and Wuhan
Morning Light Plan of Youth Science and Technology (Grant
No. 2017050304010307). The Program of Introducing Talents
of Discipline to Universities of China (111 Project) is also
appreciated.
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