Helical poly(quinoxaline-2,3-diyl)s bearing metal-binding sites as polymer-based chiral ligands for asymmetric catalysis

Article abstract of DOI:10.1002/anie.200803719

Living it up: Helical polyquinoxalines with single and multiple metal-binding sites, prepared by living polymerization of o-diisocyanobenzenes, are used in the asymmetric hydrosilylation of styrenes, resulting in comparable enantioselectivities to those obtained by low-molecular-weight catalyst systems (up to 87% ee, stereochemistry was determined by a chiral initiator) and a turnover number of almost 1000. (Chemical Equation Presented).

Full text of DOI:10.1002/anie.200803719

Angewandte
Chemie
DOI: 10.1002/anie.200803719
Chiral Catalysts
Helical Poly(quinoxaline-2,3-diyl)s Bearing Metal-Binding Sites as
Polymer-Based Chiral Ligands for Asymmetric Catalysis**
Takeshi Yamamoto and Michinori Suginome*
In memory of Yoshihiko Ito
A helix is one of the simplest and best-organized chiral
structural motifs, being widely found not only in molecules,
but in natural and artificial materials. Naturally occurring
helical macromolecules, such as DNA, RNA, and polypep-
tides, adopt one of the two helical senses (right or left) and
play vital biological roles, which depend on their three-
dimensional chiral structure. Helical synthetic polymers have
also gained increasing interest on the basis of recent progress
in asymmetric polymer synthesis, which has enabled the
selective construction of unnatural macromolecular architec-
Figure 1. A system for catalytic asymmetric synthesis using optically
tures with nonracemic helical structures.[1] Efficient induction
active, single-handed helical polymers as a chiral catalyst.
of the main chain helical sense to polymers, such as
poly(methacrylate)s,[2]
poly(isocyanate)s,[3]
poly(isocya-
nide)s,[4] poly(acetylene)s,[5] and polyguanidines,[6], has been
achieved. In the unnatural macromolecular world, even
achiral monomers, which have no stereogenic centers, can
form helical structures in which either a left- or right-handed
helical sense is prevalent.
systems that enable higher selectivity and catalyst efficiency
for the development of practical chiral polymer catalysts.
The conditions for synthetic helical polymers to serve as
practical chiral catalysts in asymmetric synthesis include:
a) very high purity for a one-handed screw sense; b) a highly
stable helical structure, even in solution, with no racemization
or denaturation; c) modifiable side chains onto which cata-
lytically active sites can be introduced without affecting the
helical structure. Most nonracemic helical polymers are
unable to fulfill all of these requirements, leading to the
paucity of highly effective polymer catalysts for asymmetric
synthesis.
Poly(quinoxaline-2,3-diyl)s are a unique class of helical
polymers prepared by living polymerization of o-diisocyano-
benzenes.[12] They feature an exceptionally robust helical
structure, which shows no change even at 808C in solution for
several days.[13] The most striking feature of these polymers is
the high screw-sense excess, which relies on the chiral
terminal group derived from the chiral initiator for the
asymmetric living polymerization.[14] With these unique
characteristics, we have studied the application of the
polyquinoxaline scaffold to new chiral polymer catalysts.
Herein, we report the asymmetric synthesis of new quinoxa-
line polymers with a coordinating group on a side chain, and
their use as chiral ligands for transition-metal catalysts. The
new monodentate polymer-based ligands are used in palla-
dium-catalyzed asymmetric hydrosilylation of styrenes,
affording a remarkable level of asymmetric induction.
For the synthesis of phosphine-substituted polymers, we
prepared the o-diisocyanobenzene 1, bearing a diphenylphos-
phine oxide group, as the monomer for the living polymer-
ization (Scheme 1). To obtain good solubility and to simplify
the structural analysis of the polymer, we copolymerized 1
with “spacer monomer” 2, which has no coordinating group
and thus served as the framework of the helical structure. The
One of the important functions of chiral biopolymers is to
undertake biocatalyses, in which highly enantioselective
reactions take place on the chiral architecture. It seems
likely that unnatural polymer scaffolds can be tailored exhibit
the same properties by virtue of the freedom of molecular
design, which allows the possibility of using either a left- or
right-handed helix and the introduction of metallic elements
that usually are not contained in natural biosystems
(Figure 1).[7] The use of chiral helical polymers as scaffolds
for chiral reaction environments was first realized with
poly(methylmethacrylate)-based chiral polymers,[8,9] followed
by the use of other helical polymers as chiral catalysts.[10]
However, the degree of asymmetric induction and catalyst
efficiency in these systems were still moderate in comparison
with existing low-molecular-weight chiral catalysts and poly-
mer catalysts into which low-molecular-weight chiral catalysts
are embedded.[11] It is highly desirable to find new polymer
[*] T. Yamamoto, Prof. Dr. M. Suginome
Department of Synthetic Chemistry and Biological Chemistry
Graduate School of Engineering, Kyoto University
Katsura, Nishikyo-ku, Kyoto 615-8510 (Japan)
Fax: (+81)75-383-2722
E-mail: suginome@sbchem.kyoto-u.ac.jp
Homepage: http://www.sbchem.kyoto-u.ac.jp/suginome-lab/
[**] This work was supported by Grants-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science, and
Technology (Japan) and the Ogasawara Foundation for the Promo-
tion of Science and Engineering.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200803719.
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539

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polymer ligand we employed was prepared as follows: Using a
Using this copolymer as a chiral ligand, asymmetric
hydrosilylation of styrene was examined.[17] The catalyst was
prepared by mixing P(10-1-10) with [{Pd(m-Cl)(h3-C3H5)}2] in
toluene at room temperature. The palladium catalyst pre-
pared from the homopolymer of 2, which had no phosphine
group, had no catalytic activity at all (Table 1, entry 1). In
contrast, the catalyst prepared with phosphine polymers (P)-
and (M)-P(10-1-10) exhibited remarkable catalytic activity,
giving a-trichlorosilylethylbenzene in high yields (Table 1,
entries 2 and 3). The hydrosilylation was complete within 24 h
with 0.1 mol% palladium loading. Remarkably, the enantio-
meric excess of the resultant hydrosilylation products reached
85% ee (enantiomeric ratio of 8:92) for both of the enantio-
meric helical polymer ligands. The right-handed polymer
ligand, (P)-P(10-1-10), gave an enantioenriched hydrosilyla-
tion product with the S configuration and the left-handed
ligand, (M)-P(10-1-10), gave the R product selectively.
chiral organopalladium initiator (S,S)-in* or (R,R)-in*
(Scheme 1) with 0.5 equivalents of dimethylphenylphos-
phine,[15] 10 equivalents of the spacer monomer 2 was
Other styrene derivatives were also subjected to the
enantioselective hydrosilylation using (P)-P(10-1-10). Both o-
Table 1: Palladium-catalyzed asymmetric hydrosilylation of styrenes in
the presence of optically active helical polymers.[a]
Scheme 1. Synthesis and structure model (right) of optically active P
and S isomers of helical poly(quinoxaline-2,3-diyl) P(10-1-10), bearing a
phosphine unit.
Entry
R
Ligand
Yield [%][b]
ee [%][c]
polymerized at room temperature. To this living oligomer,
which possesses an active palladium site at the terminus,
1.0 equivalents of 1 was added, and the mixture was allowed
to react for several hours, until complete consumption of 1
had occurred. The resulting living co-oligomer was treated
once more with 10 equivalents of 2, and then quenched with
NaBH4, giving copolymer PO(10-1-10). The phosphine oxide
moiety was converted into the diphenylphosphino group by
reduction with trichlorosilane.[16] No drop in the screw-sense
excess of the polymer backbone was appreciable during the
reduction step, which required 24 h at 808C. The resultant
polymer P(10-1-10) was highly soluble in organic solvents,
such as THF, toluene, and CH2Cl2, and clearly identified by
1H, 13C, and 31P NMR spectroscopy, gel-permeation chroma-
tography (GPC) analysis, and circular dichroism (CD)
spectroscopy, which revealed a screw-sense excess of > 90%
on the basis of our previous reports.[14d] Right- and left-
handed helical polymers (P)-P(10-1-10) and (M)-P(10-1-10)
were produced selectively using initiators (S,S)-in* and (R,R)-
in*, respectively.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
H
H
H
2-Me
3-Me
4-Me
4-tBu
4-MeO
4-F
H
(P)-poly-2
0
97
98
95
94
98
98
96
97
88
89
94
86
92
91
–
(P)-P(10-1-10)
(M)-P(10-1-10)
(P)-P(10-1-10)
(P)-P(10-1-10)
(P)-P(10-1-10)
(P)-P(10-1-10)
(P)-P(10-1-10)
(P)-P(10-1-10)
(P)-P(30-1-10)
(P)-P(10-1-30)
(P)-P(10-1-0)
(P)-P(10-2-10)
(P)-P(10-3-10)
(P)-P(10-5-10)
85 (S)
85 (R)
86 (S)
79 (S)
87 (S)
74 (S)
84 (S)
84 (S)
84 (S)
84 (S)
5 (S)
H
H
H
H
80 (S)
76 (S)
70 (S)
H
[a] A styrene derivative (1.0 mmol) and trichlorosilane (2.0 mmol) were
stirred at 08C in the presence of [{Pd(m-Cl)(h3-C3H5)}2] (0.50 mmol,
0.05 mol%) with a polymer ligand (2.0 mmol, 0.2 mol%). [b] Yield of
product isolated by bulb-to-bulb distillation. [c] Determined by chiral
HPLC after conversion into the corresponding a-phenylethyl alcohol by
H2O2/KHCO3/KF oxidation.
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Chemie
and p-methylstyrenes afforded the corresponding hydrosily-
lation products with high enantioselectivity, whereas m-
methylstyrene resulted in a small drop in enantiomeric
excess (Table 1, entries 4–6). Interestingly, substitution by a
bulky group at the p-position also lowered the enantioselec-
tivity (Table 1, entry 7). Substitution by heteroatomic func-
tional groups at the para position did not affect the
enantioselectivity (Table 1, entries 8 and 9).
To gain insight into the polymer structure for optimization
of enantioselectivity, copolymers (P)-P(l-m-n) with different
monomer composition were prepared under identical reac-
tion conditions to the synthesis of P(10-1-10). Use of the
polymer (P)-P(30-1-10), in which the phosphine moiety and
the terminal chiral group were separated by more spacer units
than in (P)-P(10-1-10), also led to high enantioselectivity,
suggesting that the terminal chiral group has no direct effect
on the chiral reaction environment around the palladium
atom (Table 1, entry 10). An increase in the number of spacer
units on the other side of the phosphorus unit ((P)-P(10-1-
30)) led to the same high enantioselectivity (Table 1,
entry 11). However, a polymer with no spacer units on one
of the two sides of the phosphine-containing unit,(P)-P(10-1-
0), failed to give enantioenriched products (Table 1, entry 12).
Further examination was undertaken of the influence of the
phosphine units in the polymer chain through the synthesis of
polymers (P)-P(10-m-10) (m = 2, 3, and 5). An increase in the
number of contiguous phosphine units resulted in a decrease
in the enantioselectivity (Table 1, entries 13–15).
Taking into account the structural requirements for the
polymer ligands, we attempted the synthesis of higher
polymers with multiple phosphino groups in the polymer
chain. The synthesis was achieved by block polymerization, in
which batches of 2 (10 equivalents) followed by 1 (1.0 equiv-
alents) were added repeatedly to the reaction mixture and
given time (7–25 h) to react prior to subsequent monomer
addition (Scheme 2). A heptablock copolymer (P)-P(10-1-10-
1-10-1-10), in which three phosphine units in the polymer
chain were separated by blocks of approximately 10 spacer
units, was isolated and used in the catalytic hydrosilylation
reaction.
Scheme 2. Synthesis of heptablock copolymer (P)-P(10-1-10-1-10-1-10)
by living asymmetric copolymerization of 1 and 2 using chiral initiator
(S,S)-in*.
tion of the polymer structure is currently being undertaken in
this laboratory.
Received: July 30, 2008
Revised: October 21, 2008
Published online: December 15, 2008
Keywords: asymmetric catalysis · block copolymers ·
.
chiral ligands · helical structures · hydrosilylation
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