Ion-paired chiral ligands for asymmetric palladium catalysis

Article abstract of DOI:10.1038/nchem.1311

Conventional chiral ligands rely on the use of a covalently constructed, single chiral molecule embedded with coordinative functional groups. Here, we report a new strategy for the design of a chiral ligand for asymmetric transition-metal catalysis; our approach is based on the development of an achiral cationic ammonium-phosphine hybrid ligand paired with a chiral binaphtholate anion. This ion-paired chiral ligand imparts a remarkable stereocontrolling ability to its palladium complex, which catalyses a highly enantioselective allylic alkylation of α-nitrocarboxylates. By exploiting the possible combinations of the achiral onium entities with suitable coordinative functionalities and readily available chiral acids, this approach should contribute to the development of a broad range of metal-catalysed, stereoselective chemical transformations.

Full text of DOI:10.1038/nchem.1311

ARTICLES
PUBLISHED ONLINE: 1 APRIL 2012 | DOI: 10.1038/NCHEM.1311
Ion-paired chiral ligands for asymmetric
palladium catalysis
Kohsuke Ohmatsu, Mitsunori Ito, Tomoatsu Kunieda and Takashi Ooi
*
Conventional chiral ligands rely on the use of a covalently constructed, single chiral molecule embedded with coordinative
functional groups. Here, we report a new strategy for the design of a chiral ligand for asymmetric transition-metal catalysis;
our approach is based on the development of an achiral cationic ammonium–phosphine hybrid ligand paired with a chiral
binaphtholate anion. This ion-paired chiral ligand imparts a remarkable stereocontrolling ability to its palladium complex,
which catalyses a highly enantioselective allylic alkylation of a-nitrocarboxylates. By exploiting the possible combinations of
the achiral onium entities with suitable coordinative functionalities and readily available chiral acids, this approach should
contribute to the development of a broad range of metal-catalysed, stereoselective chemical transformations.
iomolecules exist almost exclusively as single enantiomers, and interaction (Fig. 1a, bottom). If this type of structurally flexible,
different enantiomers can exhibit markedly different biological ion-paired chiral ligand could impart notable activity and selectivity
B
activities. Thus, stereochemistry is of great importance in to the corresponding metal complex, it would provide unprece-
chemical interactions, such as in the natural molecular recognition dented possibilities in designing and preparing structurally diverse
events that occur within living organisms, and in interactions chiral ligands for asymmetric transition-metal catalysis. Here, we
between drugs and their targets. Accordingly, there is enormous report the successful implementation of this strategy through the
demand for methods that allow the preparation of chiral com- development of achiral ammonium–phosphine hybrid ligands
pounds in enantiomerically pure forms. Over the last few decades, paired with chiral binaphtholate anions for asymmetric palladium
enantioselective transformations mediated by chiral transition- catalysis. In particular, we developed a catalyst for the highly
metal catalysts have served as a powerful means to access chiral enantioselective allylic alkylation of a-nitrocarboxylates, thereby
non-racemic compounds1. A chiral transition-metal catalyst typi- offering a reliable catalytic process for the asymmetric synthesis of
cally comprises a central metal and a chiral ligand. The structural a,a-disubstituted a-amino-acid derivatives.
and electronic properties of the chiral ligand have a pivotal influence
on catalytic activity and its ability to impart stereocontrol. Results and discussion
The design and preparation of chiral ligands that can be used for As the achiral component of an ion-paired ligand, we chose ortho-
a given transformation, with efficiency in both reactivity and diphenylphosphinobenzyl-ammonium cation 1, because the coor-
stereoselectivity, is therefore a subject of central importance in the dinative group (triarylphosphine) and the quaternary onium
development of catalytic asymmetric reactions2.
cation (tetraalkylammonium) are arranged in close proximity to
There remains, however, a formidable challenge associated with one another13–15. The requisite triflate salt 1 OTf was readily syn-
this endeavour. The synthesis of effective ligands built from single thesized from commercially available N,N-dimethylbenzylamine
chiral molecules (Fig. 1a, top) can be complex, and this can hinder in a two-step sequence and transformed into the corresponding
.
.
the iterative process of design, testing and optimization. This intrinsic ammonium hydroxide 1 OH through an anion-exchange process
problem has been addressed by the introduction of supramolecular using amberlyst A-26 (OH2) in methanol (Fig. 1b, left). This inter-
coordination complexes, particularly the self-assembled, supra- mediate was neutralized by treatment with (R)-3,3′-disubstituted
molecular bidentate ligands and their transition-metal complexes BINOL (1,1′-bi-2-naphthol) derivatives 2a and 2b (1.0 equiv.).
for combinatorial asymmetric catalysis3–5. Several seminal studies in The resultant mixtures were co-evaporated with acetonitrile to
this emerging field have demonstrated the advantages and potential afford yellow solids, which were washed with distilled water
of non-covalent bidentate ligand construction. With the exception and dried under reduced pressure to give ion-paired chiral ligands
of the recent independent contributions by the groups of Reek6 and 3a and 3b (Fig. 1b, right), respectively (see Supplementary
van Leeuwen7, however, it has remained essential to use covalently Information for details). The three-dimensional molecular structure
constructed monodentate chiral ligands. On the other hand, the of 3b was unambiguously determined by X-ray diffraction analysis
chiral anion strategy has opened up chiral ligand-free asymmetric of its racemic single crystal (Fig. 2). The chiral binaphtholate anion
catalysis, enabling enantioselective transformations via chiral metal is located close to the ammonium cation, and an internal hydrogen-
salts (that is, cationic transition metals with chiral anions)8–12. This bonding interaction is observed between the remaining phenolic
system, however, is applicable only to the reactions of metal-activated proton and the naphthoxide anion. In addition, the diphenyl substi-
cationic intermediates with non-ionic nucleophiles.
tuents on the phosphorus centre and the trimethylammonium
We envisaged an essentially new strategy for the design of chiral moiety are spaced apart from one another to minimize possible
ligands. Our approach is based on the use of readily modifiable steric repulsion and thus the phosphine lone pair is oriented
achiral molecules bearing a coordinative functional group and qua- toward the ion-pairing site.
ternary onium moiety within appropriate proximity, which are
Our investigations then focused on the performance of 3a and 3b
linked with simple chiral molecules by means of electrostatic as chiral ligands. We chose palladium catalysis for the enantioselective
Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Nagoya 464-8603, Japan. e-mail: tooi@apchem.nagoya-u.ac.jp
*
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.1311
ARTICLES
a
Conventional chiral ligand
Chiral
scaffold
L
b
Ar1
Ar1
Single chiral molecule
constructed by covalent bond
OH
TfO
Amberlyst A-26 (OH–)
MeOH
OH
OH
O
Me3N
Me3N
+
Me3N
Ion-paired chiral ligand
OH
Ph2P
Ph2P
Ph2P
1·OTf
Q
Simple chiral
Ar1
Ar1
molecule
L
Ion-paired ligand 3a: Ar1 = Ph
3b: Ar1 = β-Naph
1·OH
2a: Ar1 = Ph
2b: Ar1 = β-Naph
Simple chiral molecule and achiral ligand
associated with electrostatic interaction
Q = quaternary onium cation
L = coordinating group
Figure 1 | Strategies for construction of a chiral environment around a metal catalyst. a, Conventional chiral ligand (top) and ion-paired chiral ligand
(bottom). b, Preparation of ion-paired ligand 3.
allylic alkylation of a-nitrocarboxylates16 for the following reasons. achieving stereocontrol. Moreover, no asymmetric induction was
(i) The advantage of using transition-metal catalysis is obvious due detected in similar alkylations with catalysts prepared from
to the inherent difficulty of obtaining the C-alkylation product from ion-paired ligand 8 consisting of a meta-diphenylphosphinobenzyl-
the nitronate anions over O-alkylation17. (ii) Stereochemical control ammonium cation13 and ligand 9 having one carbon-elongated
in the attack of a prochiral nucleophile (nitronate) on a p-allyl metal 2-(ortho-phosphinophenyl)ethylammonium cation, respectively
complex by a chiral ligand on the metal centre constitutes a general (entries 5 and 6). These observations indicate the critical impor-
challenge18–22
. (iii) Asymmetric reactions involving anionic tance of the orientational precision and spatial arrangement of
nucleophiles are not controllable by the chiral anion strategy. (iv) the coordinative phosphine functionality and the quaternary
This transformation, if successful, could provide a straightforward ammonium cation moiety pairing with an anion for inducing
catalytic process for the asymmetric synthesis of non-coded
a,a-disubstituted a-amino acids.23
Initial trials were carried out through the reaction of tert-butyl
2-nitropropionate (4a) with cinnamyl methyl carbonate (5a) in
Table 1 | Enantioselective allylation of a-nitrocarboxylate 4a
with cinnamyl carbonate 5a.
Pd2(dba)3
toluene at room temperature under the influence of the catalysts
(Pd 2.5 mol%)
Ligand (5 mol%)
CO2t-Bu
Me NO2
6a
O2N
CO2t-Bu
Ph
prepared in situ from tris(dibenzylideneacetone)dipalladium
[Pd2(dba)3] and chiral ligand 3a or 3b. After 5 h of stirring, the
desired alkylation product 6a was obtained in good yields with
moderate enantioselectivities. The palladium catalyst bearing 3b
as a ligand exerted higher catalytic and chiral efficiencies, demon-
strating that the ion-paired chiral ligand 3 is indeed able to
induce an appreciable enantiomeric excess (e.e.) on the prochiral
nitronate generated from 4a (Table 1, entries 1 and 2). In sharp
contrast, however, the attempted use of either triphenylphosphine
(PPh3) as a ligand in the presence of benzyltrimethylammonium
binaphthoxide 7 or achiral phosphinobenzylammonium bromide
Ph
OCO2Me
+
Toluene
Me
4a
5a
Z
Me3N
Z
Ph
Me3N
Z
Me3N
7
Ar22P
R
3b: Ar2 = Ph, R = H
Z
Ph2P
Me3N
3c: Ar2 = p-Cl-C6H4, R = H
9
3d: Ar2 = p-Cl-C6H4, R = t-Bu
3e: Ar2 = p-Cl-C6H4, R = Ph
PPh2
8
For 3, 7, 8, 9,
β-Naph
β-Naph
.
1 Br as a ligand in combination with the BINOL derivative 2b
O
Me3N
under otherwise identical conditions led to the formation of
racemic 6a (entries 3 and 4). These results strongly suggest that
ion-pairing between the ammonium–phosphine hybrid achiral
ligand and the chiral binaphtholate anion is a prerequisite for
O
OMe
Ph2P
Z
=
OH
β-Naph
β-Naph
10
Entry
Ligand
Conditions
Yield
(%)*
e.e.
(%)†
1
2
3
4
5
3a
3b
PPh3
r.t., 5 h
r.t., 5 h
With 7 (5 mol%), r.t., 5 h
With 2b (5 mol%), r.t., 5 h
r.t., 5 h
r.t., 5 h
r.t., 5 h
r.t., 5 h
r.t., 5 h
56
78
99
85
99
83
92
99
99
99
78
97
38
68
,1
,1
,1
,1
23
73
75
83
88
94
.
1 Br
P
8
9
N
6
7
O
10
3c
3d
3e
3e
3e
8
9
10
11
12
O
r.t., 5 h
0 8C, 24 h
To lu ene/H2O (20:1. v/v),
0 8C, 12 h
Reactions were performed with 0.2 mmol 4a and 0.24 mmol 5a in the presence of Pd2(dba)3 (Pd
2.5 mol%) and ligand (5 mol%) under the given reaction conditions. *Isolated yields. †Determined
by chiral high-performance liquid chromatography (HPLC). ‡The absolute configuration of product
6a was determined, after conversion to the known compound (see Supplementary Information for
details). r.t., room temperature.
Figure 2 | ORTEP diagram of 3b. Calculated hydrogen atoms are omitted
for clarity.
474
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.1311
ARTICLES
substituent (Ar2) by the electron-withdrawing para-chlorophenyl
group (3c) was beneficial in terms of reactivity and selectivity
(entry 8). Interestingly, the introduction of additional substituents
(R) such as tert-butyl (3d) and phenyl (3e) groups to the benzene
linkage increased the enantioselectivity to 75% e.e. and 83%
e.e., respectively (entries 9 and 10). Although the considerable rate
retardation was inevitable when the reaction was performed at
0 8C, despite the expected selectivity enhancement (entry 11), the
use of water as a co-solvent (toluene/H2O ¼ 20:1. v/v) improved
both catalytic activity and enantioselectivity, and 6a was isolated
quantitatively with 94% e.e. (entry 12). To gain insight into the
origin of the observed enhancement of reactivity and selectivity
in the presence of water, we carried out 31P NMR spectroscopic
analysis of the catalysts. The 31P NMR measurement of a mixture
of Pd2(dba)3 and 3e with a [Pd]/phosphine ratio of 1:2 in dry
toluene at 0 8C showed two sharp peaks at d ¼ 30.6 and
216.4 ppm, respectively. The signal at d ¼ 216.4 ppm was assigned
to the free ligand 3e, and the other peak presumably corresponded
to the palladium(0)–3e complex. However, only a single peak was
detected at d ¼ 30.7 ppm in the spectrum of the catalyst prepared
in toluene/H2O (20:1), suggesting that water would facilitate the
ligand exchange process, and the resulting palladium(0) complex
would probably be Pd(0)(3e)2(dba).
a
β-Naph
N
O
O
O
Me3N
Ar22P
H
P
OH
Ph
β-Naph
3e: Ar2 = p-Cl-C6H4
b
P
P
N
N
R2
OCO2Me
CO2
R2
Nu
Pd
L
H
H
O
5
6
O
O
O
Pd(0)(3e)2
P
P
P
P
N
N
N
N
Pd
Pd
H
O
H
O
H
H
R2
R2
O
O
O
O
MeO
O
O
Nu
B
A
O2N
R1
CO2t-Bu
To gain information about the structure of the palladium(II)
complex, we initially monitored the reaction of 4a with 5a under
H
MeOH
=
H
Nu
1
optimized conditions using H and 31P NMR spectroscopy. The
complete consumption of 4a and the formation of 6a were verified
by the 1H NMR analysis, but the signal appearing at d ¼ 30.7 ppm
in the 31P NMR measurement after catalyst preparation was virtually
unchanged throughout the reaction, and a signal from the
Figure 3 | Proposed catalytic cycle for enantioselective alkylation catalysed
by an ion-paired chiral catalyst. The Pd(II)–3e (1:2) complex exists in the
reaction mixture and functions as an active species.
enantiocontrol. This also provides compelling evidence that allows palladium(II) complex could not be detected. This observation
the possibility that the observed stereoselectivity can be delivered raised the possibility that the palladium(0) complex might be the
by the mere presence of the chiral binaphtholate anion as a counter- resting state and oxidative addition would be a rate-determining
ion of the cationic p-allyl palladium intermediate to be ruled out. It step. We therefore performed kinetic experiments to elucidate the
is worth noting that an additional control experiment with the ion- detailed reaction profiles, which revealed that the present palla-
paired chiral ligand 10 bearing a hydroxyl-protected binaphtholate dium-catalysed allylic alkylation using 3e as a chiral ligand had
anion under similar conditions furnished nearly racemic 6a (entry first-order dependence on 4a and zero-order dependence on 5a.
7), implying the crucial role of the free hydroxyl moiety of the These findings clearly indicate that the rate-determining step is
anionic component of 3 in the present asymmetric catalysis.
carbon–carbon bond formation, and the in situ prepared palla-
Based on the experimental validation of the stereocontrolling dium(0) complex is a non-reactive species from which reactive
ability of the ion-paired chiral ligand 3, we further examined Pd(0)(3e)2 would be generated in low concentration24. We then
the relationship between the structure of 3 and its consequent focused again on obtaining structural information about the
reaction efficiency, with the electronic and steric manipulations of palladium(II) complex. Because the continuous kinetic experiments
the readily modifiable achiral component emerging as key factors. showed first-order dependence of the reaction on the catalyst, a
As shown in Table 1, replacement of the phosphorus phenyl monomeric palladium complex is involved in the catalysis.
Table 2 | Substrate scope.
Pd2(dba)3 (Pd 2.5 mol%)
O2N
CO2t-Bu
3e (5 mol%)
CO2t-Bu
NO2
R2
R2
OCO2Me
+
R1
R1
6
Toluene/H2O (20:1. v/v)
0 ºC
4
5
Entry
4
R1
5
R2
Product
Time (h)
Yield (%)*
e.e. (%)†
1
2
3
4
4b
4c
4d
4e
4f
4a
4a
4a
4a
4a
4a
Et
5a
5a
5a
5a
5a
5b
5c
5d
5e
5f
Ph
Ph
Ph
Ph
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
24
36
30
30
24
18
24
30
24
48
12
97
96
97
94
98
90
99
99
98
94
91
93
97
95
97
93
90
90
93
91
CH2CHMe2
n-Hex
CH2Ph
5
(CH2)2CO2Me
Ph
p-Cl-C6H4
p-Br-C6H4
p-MeO-C6H4
2-naphthyl
2-thienyl
H
6
Me
Me
Me
Me
Me
Me
7‡
8
9‡
10
11
91
,1
5g
The reactions were performed with 0.2 mmol of 4 and 0.24 mmol of 5 in the presence of Pd2(dba)3 (Pd 2.5 mol%) and 3e (5 mol%) under the given reaction conditions. *Isolated yields. †Determined by chiral
HPLC. ‡Performed at 25 8C
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NATURE CHEMISTRY DOI: 10.1038/NCHEM.1311
ARTICLES
enantiomeric purity was detected. In addition, olefin cross metath-
esis of 6a with ethylene under the influence of Grubbs catalyst
afforded the same product of simple allylation 6l, without loss of
e.e. (Fig. 4c). These illustrations clearly demonstrate the utility of
the enantioselective nitroester alkylations as an expedient means
to synthesize various optically active, non-proteinogenic a-amino
acids and their derivatives.
a
CO2t-Bu
CO2t-Bu
Me NH2
11
H2 (1 atm)
Pd/C
Ph
Ph
Me NO2
6a
(94% e.e.)
MeOH
35 ºC, 12 h
80% yield, 94% e.e.
b
c
CO2t-Bu
In
CO2t-Bu
Ph
Ph
1 M HCl
Me NO2
Me NH2
12
95% yield, 94% e.e.
EtOH
r.t., 5 h
6a
Conclusion
(94% e.e.)
We have introduced a chiral ligand assembled from an achiral
quaternary ammonium–phosphine and a chiral binaphtholate
anion through electrostatic interaction. We successfully demon-
strated the remarkable ability of this ion-paired chiral ligand in
inducing stereocontrol over a prochiral anionic nucleophile in the
palladium catalysis by achieving a highly enantioselective allylic
alkylation of a-nitrocarboxylates. This study provides a concep-
tually new approach to the design of chiral ligands for asymmetric
transition-metal catalysis. On considering the multitude of
combinations created by achiral onium cations with suitable coordi-
native functionalities at requisite positions and readily available
chiral acids, we believe that this approach shows vast potential
CO2t-Bu
CO2t-Bu
Ph
Grubbs II (30 mol%)
ethylene (1 atm)
Me NO2
Me NO2
6l
6a
Toluene, reflux, 12 h
50% yield, 94% e.e.
(94% e.e.)
Figure 4 | Derivatization of alkylation product 6a. a, Usual hydrogenation
reaction affords the saturated a-amino ester. b, Selective reduction of the
nitro group using indium metal gives the unsaturated a-amino ester.
c, Olefin metathesis with ethylene provides the same product of simple
allylation 6l.
In addition, we confirmed second-order dependence on the in the development of transition-metal-catalysed stereoselective
ligand 3e, which was measured at constant concentration of bond-forming reactions, particularly those involving anionic
Pd2(dba)3, and also observed modest yet positive nonlinear species as a nucleophilic intermediate.
effects25, strongly suggesting that a palladium(II) complex bearing
Received 20 October 2011; accepted 21 February 2012;
published online 1 April 2012
two ion-paired ligands 3e on the palladium metal acts as a reactive
species in the bond-forming event (Supplementary Figs S6–S10).
These results allowed us to postulate a plausible catalytic cycle
(Fig. 3). The Pd(0)(3e)2 adds to allylic carbonate 5 to give a cationic
p-allyl palladium(II) complex A. This structure would be main-
References
1. Jacobsen, E. N., Pfaltz, A. & Yamamoto, H. (eds) Comprehensive Asymmetric
Catalysis, and Supplements 1 and 2 (Springer, 1999, 2004).
tained after it reacts with nitroester 4 (Nu–H) to form B, incorpor-
ating a nucleophilic nitronate anion (Nu2) that would probably
have a hydrogen-bonding interaction with the phenolic proton of
the binaphtholate anion. The organization of this intermediate
through non-bonded interactions in the transition state would be
essential in realizing the enantiofacial discrimination of the pro-
2. Yoon, T. P. & Jacobsen, E. N. Privileged chiral catalysts. Science 299,
1691–1693 (2003).
3. Wiester, M. J., Ulmann, P. A. & Mirkin, C. A. Enzyme mimics based upon
supramolecular coordination chemistry. Angew. Chem. Int. Ed. 50,
114–137 (2011).
4. Breit, B. Catalysts through self-assembly for combinatorial homogeneous
catalysis. Pure Appl. Chem. 80, 855–860 (2008).
chiral anionic nucleophile in its addition to the p-allyl palladium 5. Meeuwissen, J. & Reek, J. N. H. Supramolecular catalysis beyond enzyme
mimics. Nature Chem. 2, 615–621 (2010).
6. Dydio, P., Rubay, C., Gadzikwa, T., Lutz, M. & Reek, J. N. H. ‘Cofactor’-controlled
enantioselective catalysis. J. Am. Chem. Soc. 133, 17176–17179 (2011).
7. van Leeuwen, P. W. N. M., Rivillo, D., Raynal, M. & Freixa, Z. Enantioselective
moiety, liberating product 6 and the parent palladium(0) complex.
It should be emphasized that the results of a series of control experi-
ments, particularly those supporting the importance of the mutual
position of the ammonium cation and arylphosphine moieties of the
achiral component of 3 (Table 1, entries 5 and 6) as well as the free
hydroxyl moiety of the binaphtholate anion (entry 7), are consistent
with the proposed reaction pathway.
supramolecular catalysis induced by remote chiral diols. J. Am. Chem. Soc. 133,
18562–18565 (2011).
8. Hamilton, G. L., Kang, E. J., Mba, M. & Toste, F. D. A powerful chiral
counterion strategy for asymmetric transition metal catalysis. Science 317,
496–499 (2007).
Further experiments were conducted to explore the generality
of the present enantioselective allylic alkylation protocol, and
representative results are summarized in Table 2. A wide range of
a-nitrocarboxylates 4 with different a-substituents, including a
functionalized one, could be used as pronucleophiles, and excellent
chemical yields and enantioselectivities were uniformly observed
(entries 1–5). With respect to the electrophile component, variation
in the electronic nature of the g-substituents appears to have little
influence on the asymmetric induction (entries 6–8), and the
incorporation of fused aromatic and heteroaryl ring systems was
also well tolerated (entries 9 and 10). In the reaction with simple
allyl methyl carbonate, however, the product was obtained in an
almost racemic form (entry 11).
Alkylation product 6 can be selectively derivatized into the cor-
responding saturated and unsaturated a,a-disubstituted a-amino
esters in a facile manner through simple reduction processes
(Fig. 4a,b). For example, exposure of 6a to usual hydrogenation
conditions (H2, palladium on carbon in methanol) at 35 8C gave
rise to the corresponding saturated a-amino ester 11 in 80%
yield, while treatment of 6a with indium metal and 1 M HCl in
ethanol at room temperature left the double bond intact, affording
12 in 95% yield. In both transformations, no erosion of the
9. Mukherjee, S. & List, B. Chiral counteranions in asymmetric transition-metal
catalysis: highly enantioselective Pd/Brønsted acid-catalyzed direct a-allylation
of aldehydes. J. Am. Chem. Soc. 129, 11336–11337 (2007).
10. Liao, S. & List, B. Asymmetric counteranion-directed transition-metal catalysis:
enantioselective epoxidation of alkenes with manganese(III) salen phosphate
complexes. Angew. Chem. Int. Ed. 49, 628–631 (2010).
11. Jiang, G. & List, B. Direct asymmetric a-allylation of aldehydes with simple
allylic alcohols enabled by the concerted action of three different catalysts.
Angew. Chem. Int. Ed. 50, 9471–9474 (2011).
12. Jiang, G., Halder, R., Fang, Y. & List, B. A highly enantioselective Overman
rearrangement through asymmetric counteranion-directed palladium catalysis.
Angew. Chem. Int. Ed. 50, 9752–9755 (2011).
13. Okano, T., Harada, N. & Kiji, J. Transition metal phosphine complexes possessing
phase transfer function. Preparation and reactivities of palladium complexes
containing quaternary ammonium groups. Chem. Lett. 23, 1057–1060 (1994).
14. Chisholm, D. M. & McIndoe, J. S. Charged ligands for catalyst immobilisation
and analysis. Dalton Trans. 3933–3945 (2008).
15. Yuan, H., Zhou, Z., Xiao, J., Liang, L. & Dai, L. Preparation of quarternary
ammonium salt-tagged ferrocenylphosphine–imine ligands and their
application to palladium-catalyzed asymmetric allylic substitution.
Tetrahedron: Asymmetry 21, 1874–1884 (2010).
16. Sawamura, M., Nakayama, Y., Tang, W.-M. & Ito, Y. Enantioselective allylation
of nitro group-stabilized carbanions catalyzed by chiral crown ether phosphine–
palladium complexes. J. Org. Chem. 61, 9090–9096 (1996).
17. Shipchandler, M. T. The utility of nitroacetic acid and its esters in organic
synthesis. Synthesis 666–686 (1979).
476
NATURE CHEMISTRY | VOL 4 | JUNE 2012 | www.nature.com/naturechemistry
© 2012 Macmillan Publishers Limited. All rights reserved.

NATURE CHEMISTRY DOI: 10.1038/NCHEM.1311
ARTICLES
18. Trost, B. M. & Van Vranken, D. L. Asymmetric transition metal-catalyzed allylic
alkylations. Chem. Rev. 96, 395–422 (1996).
25. Guillaneux, D., Zhao, S.-H., Samuel, O., Rainford, D. & Kagan, H. B. Nonlinear
effects in asymmetric catalysis. J. Am. Chem. Soc. 116, 9430–9439 (1994).
19. Trost, B. M. & Crawley, M. L. Asymmetric transition-metal-catalyzed
allylic alkylations: applications in total synthesis. Chem. Rev. 103,
2921–2943 (2003).
20. Mohr, J. T. & Stoltz, B. M. Enantioselective Tsuji allylations. Chem. Asian J. 2,
1476–1491 (2007).
Acknowledgements
Financial support was provided by the Funding Program for Next Generation
World-Leading Researchers from JSPS (GR050) and the Global COE Program in
Chemistry of Nagoya University.
21. Lu, Z. & Ma, S. Metal-catalyzed enantioselective allylation in asymmetric
synthesis. Angew. Chem. Int. Ed. 47, 258–297 (2008).
22. Nakoji, M., Kanayama, T., Okino, T. & Takemoto, Y. Chiral phosphine-free
Pd-mediated asymmetric allylation of prochiral enolate with a chiral
phase-transfer catalyst. Org. Lett. 3, 3329–3331 (2001).
Author contributions
K.O. and T.O. conceived and designed the study, and co-wrote the paper. K.O., M.I. and
T.K. performed the experiments and analysed the data. All authors discussed the results and
commented on the manuscript.
´
23. Cativiela, C. & Dıaz-de-Villegas, M. D. Recent progress on the stereoselective
synthesis of acyclic quaternary a-amino acids. Tetrahedron: Asymmetry 18,
569–623 (2007).
24. Amatore, C. & Jutand, A. Role of dba in the reactivity of palladium(0) complexes
generated in situ from mixtures of Pd(dba)2 and phosphines. Coord. Chem. Rev.
178–180, 511–528 (1998).
Additional information
The authors declare no competing financial interests. Supplementary information and
chemical compound information accompany this paper at www.nature.com/
naturechemistry. Reprints and permission information is available online at http://www.
nature.com/reprints. Correspondence and requests for materials should be addressed to T.O.
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