High-molecular-weight polyquinoxaline-based helically chiral phosphine (PQXphos) as chirality-switchable, reusable, and highly enantioselective monodentate ligand in catalytic asymmetric hydrosilylation of styrenes

Article abstract of DOI:10.1021/ja102428q

A polyquinoxaline-based helical polymer ligand bearing both helical-sense-determining chiral side chains and coordinating diarylphosphino side chains exhibits solvent-dependent formation of P- or M-helical structures, with which either the S- or R-hydrosilylation product was obtained with high (>93% enantiomeric excess) enantioselectivities.

Full text of DOI:10.1021/ja102428q

Published on Web 05/20/2010
High-Molecular-Weight Polyquinoxaline-Based Helically Chiral Phosphine
(PQXphos) as Chirality-Switchable, Reusable, and Highly Enantioselective
Monodentate Ligand in Catalytic Asymmetric Hydrosilylation of Styrenes
Takeshi Yamamoto,† Tetsuya Yamada,† Yuuya Nagata,† and Michinori Suginome*,†,‡
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniVersity,
and CREST, Japan Science and Technology Agency (JST), Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
Received March 23, 2010; E-mail: suginome@sbchem.kyoto-u.ac.jp
Scheme 1. Synthesis of Oligomer-Based PQXphos
(P)-P(10*-1-10*) and (S,S)-(R)-P(10-1-10-20*)
Increasing attention has focused on polymer-based chiral catalysts
in catalytic asymmetric synthesis.1,2 They typically feature easy
separation from the reaction mixture and the possibility of reuse
of the catalyst. Most chiral polymer catalysts are designed to
immobilize small chiral units such as BINOL (1,1′-binaphthol) and
BINAP (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl), which are
chosen from the well-established chiral ligand library. In this
conventional molecular design, the polymer scaffolds must be
“transparent” to avoid any unfavorable perturbation to the chiral
reaction sites.
There is a highly contrasting molecular design for polymer-based
chiral catalysts, in which chiral induction relies solely on the chiral
main chain structure of the polymers.3 This class of chiral polymer
ligand system may be attractive in that the created chiral reaction
environment is unique for the polymer system, the catalysts are
easily separable and reusable, and fine-tuning or even a dramatic
change of the chiral reaction environment would be possible because
of the large conformational change of the polymer secondary
structures. However, lack of rigidity, homogeneity, and robustness
of the chiral polymer scaffold hampered realization of the effective
asymmetric catalyst system, although some attempts have already
been made using optically active helical polymers, such as the
poly(trityl methacrylate) system.4-8 DNA has been successfully
used as a chiral scaffold for highly enantioselective chiral catalysts,
in which a catalytically active group is incorporated via noncovalent
interactions.9 However, the restricted availability of enantiomeric,
i.e., unnatural, DNA may make application of this particular natural
scaffold to asymmetric synthesis difficult.
Quite recently, we have established that single-handed helical
poly(quinoxaline-2,3-diyl)10-12 can serve as a highly effective
scaffold to which a diarylphosphino pendant is attached covalently
as the metal-binding site.13 We prepared and used short polyqui-
noxaline-based phosphine (PQXphos) (ca. 20mers), which carried
just one phosphine-bearing unit in the middle of each polymer
molecule, whose chiral helical structure was induced solely by a
chiral group located at the terminus of the polymer. We achieved
87% ee in palladium-catalyzed asymmetric hydrosilylation of
styrenes. In this paper, we report that high-molecular-weight (ca.
1000mer) variants of PQXphos bearing chiral side chains exhibited
remarkable profiles for use as chiral polymer ligands in asymmetric
synthesis. They showed not only much higher enantioselectivity
in asymmetric hydrosilylation of styrenes and formation of insoluble
polymer complex but also a solvent-dependent switch of helical
chirality, which enables selective production of either enantiomer
from a single chiral catalyst at will.
We initiated our study from the synthesis of 20mer-based
PQXphos that carries chiral (R)-2-butoxymethyl groups instead of
achiral propoxymethyl groups in the original PQXphos (Scheme
1).14 The new PQXphos was prepared by living block copolym-
erization, in which enantiopure 1,2-diisocyanobenzene ((R)-1,
10 equiv), phosphorus monomer 3 (1 equiv), and (R)-1 (10 equiv)
were successively added to chiral organopalladium initiator
S,SAr*PdI(PMe2Ph).12 The obtained PQXphos showed remarkable
enantioselectivity in the hydrosilylation of styrenes (Table 1).15
In comparison with the previously reported PQXphos,13 which
bears achiral side chains and shows 85% ee for unsubstituted
styrene, the modified PQXphos exhibited much higher enanti-
oselectivity (entry 1). The high enantioselectivities hold generally
for the substituted styrene derivatives including 1-phenylpropene
(entry 8) as an internal alkene (entries 2-8).
To check the role of the chiral spacer unit in creating the chiral
reaction environment, a modified PQXphos whose phosphine-
bearing unit is separated from the chiral spacer block by 10 achiral
† Kyoto University.
‡ JST.
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10.1021/ja102428q  2010 American Chemical Society
J. AM. CHEM. SOC. 2010, 132, 7899–7901 7899

C O M M U N I C A T I O N S
Table 1. Palladium-Catalyzed Asymmetric Hydrosilylation of
Table 3. Pd-Catalyzed Hydrosilylation of Styrene with Reused
(S,S)-(R)-P(950*/0/50)a
Styrenes in the Presence of Oligomers-Based PQXphosa
entry
ligand
R
R′
% yieldb
% eec
1
2
3
4
5
6
7
8
9
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10*-1-10*)
(S,S)-(R)-P(10-1-10-20*)
H
H
H
H
H
H
H
H
Me
H
91
94
93
96
96
92
94
93
93
96 (S)
95 (S)
91 (S)
95 (S)
91 (S)
84 (S)
92 (S)
96 (S)
95 (S)
2-Me
3-Me
4-Me
4-MeO
4-t-Bu
4-F
run
time/h
%yieldb
%eec
run
time/h
%yieldb
%eec
init
1
2
3
4
12
24
24
24
32
94
95
96
97
97
96
97
98
97
97
5
6
7
8
9
37
50
64
70
12
98
97
99
97
98
97
98
98
98
96
H
H
a A styrene derivative (1.0 mmol) and trichlorosilane (2.0 mmol)
were stirred at 0 °C in the presence of [PdCl(π-allyl)]2 (0.50 µmol) with
a
polymer ligand (2.0 µmol P). b Isolated yield (bulb-to-bulb
a See footnote a in Table 2 for the reaction conditions. Product was
isolated by washing the reaction flask with acetonitrile three times
followed by bulb-to-bulb distillation. b Isolated yield. c Determined after
oxidation.
distillation). c Determined by chiral HPLC after conversion to the
corresponding R-phenylethyl alcohol by H2O2/KHCO3/KF oxidation.
spacer units was prepared by organonickel-initiated living polym-
erization (Scheme 1).16 The helical structure of the resultant
PQXphos (S,S)-(R)-P(10-1-10-20*) is induced by both the terminal
chiral group and a block of 20 chiral monomer units, which is
located at the other terminus of the polymer and separated from
the phosphine-bearing unit by the block of achiral spacer units.
Hydrosilylation of styrene with the modified PQXphos under the
optimized reaction conditions afforded 95% ee, indicating that the
chiral groups on the chiral spacer units do not take part in the local
chiral reaction sites directly but play a crucial role to induce a highly
pure single-handed helical structure (Table 1, entry 9). As mentioned
in the previous work,13 the helical structure of the polymer main
chain may induce axial chirality at the aryl-quinoxaline axis
effectively, resulting in creation of chiral reaction sites for highly
efficient enantio-discrimination.
monomer (R)-1 (x equiv to Ni), achiral monomer 2 (y equiv), and
phosphorus-containing monomer 4 (z equiv), in which the phos-
phorus atom is protected by a sulfur atom, were copolymerized
with various ratios in the presence of the chiral initiator. The use
of a sulfur-protected monomer 4 allowed use of HMPT reduction
(110 °C) instead of HSiCl3 reduction after polymerization, allowing
us to avoid the tedious and problematic filtration step. All of the
high-molecular-weight polymers (S,S)-(R)-P(x*/y/z) were found to
be soluble in common organic solvents such as toluene, THF, and
chloroform. Enantioselectivities of the hydrosilylation of styrene
nonlinearly increased with an increase in the ratio (x/(x + y)) of
the chiral monomer unit derived from (R)-1 (Table 2, entries 1-6).
For instance, (S,S)-(R)-P(0*/950/50), which has only the chiral
terminal group as a source of screw-sense induction, afforded only
24% ee in hydrosilylation of styrene (entry 1). In contrast, (S,S)-
(R)-P(950*/0/50), in which all the spacer units have chiral side
chains, showed remarkably high enantioselectivity (entry 6). The
content of the chiral spacer unit and enantioselectivity have a positive
nonlinear relationship, which may be rationalized by the screw-sense
excess (s.e.) of the polymer estimated from the g values (Kuhn
dissymmetry ratio).17,18 Higher PQXphos (S,S)-(R)-P(1900*/0/100)
(entry 7) and phosphine-rich (S,S)-(R)-P(900*/0/100) (entry 8) also
afforded comparable enantioselectivities.
Having achieved a significant improvement in enantioselectivity,
we moved to utilization of a high-molecular-weight random
copolymer (Table 2). We expected that a random copolymer would
be more easily accessible than a block copolymer and that a higher
polymer would allow us to recycle and reuse the polymer ligand
more conveniently than the lower polymers. Mixtures of chiral
Table 2. Palladium-catalyzed Hydrosilylation of Styrene with
High-Molecular-Weight PQXphos with Varied Unit Ratiosa
We found that (S,S)-(R)-P(950*/0/50) and [PdCl(π-allyl)]2
formed insoluble polymer complexes during the hydrosilylation
reaction (Table 3).19 The polymer complex was swollen by organic
materials, which could be extracted with an organic solvent, leaving
the insoluble polymer complex in the reaction vessel. The polymer
complex was not soluble in common organic solvents such as
toluene, THF, chloroform, DMSO, methanol, and acetonitrile. We
separately found that the insoluble polymer complex could be
obtained by mixing (S,S)-(R)-P(950*/0/50) with Pd2(dba)3. The
insoluble polymer complex was repeatedly reused as the chiral
catalyst for the hydrosilylation reaction (runs 1-8, Table 3). The
polymer complex constantly showed high enantioselectivities until
the eighth run, although the reaction gradually became sluggish,
probably because of a little leaching of the palladium metal in each
run.20 Even so, the eight-time reuse and the easy recovery of the
catalyst activity could be important practically.2 Addition of
[PdCl(π-allyl)]2 to the insoluble catalyst after the eighth run
successfully activated it to the level of the initial cycle, while
keeping the enantioselectivity high (run 9). It should be remarked
(S,S)-(R)-P(x*/y/z)
entry
x
y
z
% yieldb
% eec
1
2
3
4
5
6
7
8
0
950
900
850
750
500
0
50
50
50
50
50
50
100
100
98
98
96
96
98
94
98
97
24 (S)
70 (S)
84 (S)
91 (S)
94 (S)
97 (S)
97 (S)
94 (S)
50
100
200
450
950
1900
900
0
0
a A styrene derivative (2.0 mmol) and trichlorosilane (3.0 mmol)
were stirred at 0 °C in the presence of [PdCl(π-allyl)]2 (1.0 µmol) with
a
polymer ligand (4.0 µmol P). b Isolated yield (bulb-to-bulb
distillation). c Determined after oxidation.
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C O M M U N I C A T I O N S
Scheme 2. Asymmetric Hydrosilylation Using Chirality-Switchable
(R)-P(950*/0/50) Adopting (a) P-Helical Form or (b) M-Helical
Form
of the polymer backbone could be applied to switch the enantio-
induction in asymmetric catalysis. These new observations may
prompt exploration of new systems for polymer-based catalysts and
of new functions of helical polymers. Further optimization of the
catalyst system, extension to other catalyses including asymmetric
C-C bond formation, and mechanistic studies on the solvent-
dependent inversion of the helical sense are now being pursued in
this laboratory.
Figure 1. CD spectra of (R)-P(950*/0/50) in chloroform (blue line) and
in a 1,1,2-trichloroethane/toluene (2/1) mixture (red line).
that the insoluble polymer complex became soluble when 1,2-
bis(diphenylphosphino)ethane (dppe) was added with toluene. The
stronger coordination of dppe to palladium may cause dissociation
of the polymer ligand from palladium, leading to the recovery of
(S,S)-(R)-P(950*/0/50).
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research from MEXT.
We recently observed a solvent-dependent switch of the helical
sense in poly(quinoxaline-2,3-diyl)s prepared from chiral diisocya-
nide (R)-1.14 In comparison with some known macromolecular
systems for helix inversion,21-25 the helix inversion we observed
was unique in that both the P- and M-helices thus formed were
determined to have nearly 100% pure helical sense excesses. We
became interested in checking if the present PQXphos, which carries
a bulky phosphorus pendant group in addition to the aprotic chiral
side chains, also underwent reversible change of the helical
chirality. We prepared (R)-P(950*/0/50) through random copo-
lymerization of (R)-1 and 4 with use of achiral organonickel
initiator o-TolNiCl(PMe3)2 (Figure 1).16 Although lacking the
terminal chiral group, copolymer (R)-P(950*/0/50) showed exactly
the same circular dichroism (CD) spectrum as (S,S)-(R)-P(950*/
0/50) in CHCl3, indicating that an almost pure P-helical structure
was formed. The polymer obtained from its CHCl3 or toluene
solution showed excellent enantioinduction (97% ee) for the (S)-
product in asymmetric hydrosilylation of styrene (Scheme 2). When
the same polymer was dissolved in a mixture of 1,1,2-trichloroet-
hane/toluene (2/1), gradual inversion of the helical sense was
observed by CD measurement (Figure 1). The inversion of the
helical sense proceeded smoothly at 60 °C, completing after 6 h to
produce the almost pure M-helical polymer (Scheme 2). Using the
M-helical polymer, catalytic hydrosilylation of styrene was carried
out in 1,1,2-trichloroethane/toluene, affording 93% ee for the (R)-
enantiomer. To use the M-helical polymer in asymmetric hydrosi-
lylation, use of 1,1,2-trichloroethane with toluene as a solvent was
found essential for obtaining high enantioselectivity. Use of an
insoluble polymer complex obtained from the M-helical polymer
with Pd2(dba)3 without solvent resulted in a significant decrease in
ee to 70% (R) under otherwise the same reaction conditions.
In this paper, we have demonstrated the unique properties of
polymer-based chiral catalysts that cannot be achieved by small-
molecule-based, ordinary chiral catalysts. In addition to the easy
reuse of the chiral catalyst by virtue of the cross-linking by the
formation of a polymer complex, reversible conformational change
Supporting Information Available: Experimental procedures and
spectral data for the new compounds. This material is available free of
charge via the Internet at http://pubs.acs.org.
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