Poly(quinoxaline-2,3-diyl)s bearing (S)-3-octyloxymethyl side chains as an efficient amplifier of alkane solvent effect leading to switch of main-chain helical chirality

Article abstract of DOI:10.1021/ja509531t

Poly(quinoxaline-2,3-diyl) containing (S)-3-octyloxymethyl side chains was synthesized to investigate the induction of a single-handed helical sense to the main chain in various alkane solvents. The polymer showed an efficient solvent dependent helix inversion between n-octane (M-helix) and cyclooctane (P-helix). After a screening of alkane solvents, it was found that linear alkanes having large molecular aspect ratios induced M-helical structure, and branched or cyclic alkanes having small molecular aspect ratios induced P-helical structure. A polymer ligand containing (S)-3-octyloxymethyl side chains and diphenylphosphino pendants also exhibited solvent-dependent helical inversion between n-octane and cyclooctane, leading to the highly enantioselective production of the both enantiomeric product in a palladium-catalyzed asymmetric hydrosilylation reaction of styrene (R-product 94% ee in n-octane and S-product 90% ee in cyclooctane).

Full text of DOI:10.1021/ja509531t

Communication
pubs.acs.org/JACS
Poly(quinoxaline-2,3-diyl)s Bearing (S)‑3-Octyloxymethyl Side Chains
as an Efficient Amplifier of Alkane Solvent Effect Leading to Switch of
Main-Chain Helical Chirality
Yuuya Nagata,† Tsuyoshi Nishikawa,† and Michinori Suginome*,†,‡
†Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 606-8501,
Japan
‡CREST, Japan Science and Technology Agency (JST), Katsura, Nishikyo-ku, Kyoto 615-8510, Japan
S
* Supporting Information
have been recognized as effective amplifiers for small local
energy differences.2 Green and co-workers clearly demon-
ABSTRACT: Poly(quinoxaline-2,3-diyl) containing (S)-
3-octyloxymethyl side chains was synthesized to investigate
the induction of a single-handed helical sense to the main
chain in various alkane solvents. The polymer showed an
efficient solvent dependent helix inversion between n-
octane (M-helix) and cyclooctane (P-helix). After a
screening of alkane solvents, it was found that linear
alkanes having large molecular aspect ratios induced M-
helical structure, and branched or cyclic alkanes having
small molecular aspect ratios induced P-helical structure. A
polymer ligand containing (S)-3-octyloxymethyl side
chains and diphenylphosphino pendants also exhibited
solvent-dependent helical inversion between n-octane and
cyclooctane, leading to the highly enantioselective
production of the both enantiomeric product in a
palladium-catalyzed asymmetric hydrosilylation reaction
of styrene (R-product 94% ee in n-octane and S-product
90% ee in cyclooctane).
strated the induction of a single-handed screw-sense by the
sergeants-and-soldiers effect3 and the majority-rule effect.4 This
feature of helical polymer backbones can be extended to the
invertible induction of polymer helicity by means of external
stimuli such as solvent change.5 Even though the degree of
helical sense induction, i.e., the screw-sense excess (se),
remained moderate at low temperature (−10 °C), the inversion
of the helical sense of a polysilane containing chiral side chains
by changing the alkane solvent from n-octane (P-helix, 50% se)
to isooctane (M-helix, 40% se) was one of the first examples of
the aforementioned amplification effect.5e More recent
examples showed that the helical supramolecular assembly
can also be influenced by a change from n-heptane to
methylcyclohexane.6 These macromolecular and supramolecu-
lar helical scaffolds allow a clear observation of the solvent
effect of alkanes through an appreciable change of the helical
sense, which is unequivocally quantifiable by measuring the
resulting circular dichroism (CD). Accordingly, the establish-
ment of more sensitive helical scaffolds, in order to detect the
solvent effects between alkanes, and to effectively apply the
obtained knowledge in chemical processes seems to be highly
desirable.
We have recently reported that poly(quinoxaline-2,3-diyl)s
can serve as a new macromolecular scaffold, which undergoes a
solvent-induced switch of helical chirality.7 In our original
system with (R)-2-butoxymethyl side chains, common organic
solvents such as chloroform induce a P-helical sense, whereas
1,1,2-trichloroethane induces an inversion of the helical sense
(M-helix). We also established a chirality-switchable helical
polymer system of which main-chain helical chirality is inverted
in tert-butyl methyl ether in contrast to other ether solvents.8
These helical macromolecular scaffolds were subsequently used
as ligands in polymer-based chiral catalysts with switchable
chirality. In a variety of catalytic asymmetric reactions, both
enantiomeric products could be generated with high
enantioselectivities.9 These helical scaffolds were also used for
the fabrication of solid polymer films exhibiting switchable
handedness, and a selective reflection of circularly polarized
light, which could be tuned across the entire visible spectrum.10
y stabilizing or destabilizing chemical species in the
Bground, transition, and/or exited state through solvation,
solvent effects play an important role in a variety of
thermodynamic and kinetic chemical events. The interactions
between solvent and solute are governed by various solvent
properties, e.g. polarity, acidity, basicity, and the ability to form
hydrogen bonds. Alkanes are generally considered as highly
hydrophobic solvents, allowing an exclusion of most of the
possibly occurring major solvent−solute interactions. This is
also reflected in the family name of alkanes, which are
commonly referred to as “paraffins”, originating from the Latin
parum affinis, meaning “little affinity”.1 Due to the minimal
solvent−solute interactions, a change between alkane solvents
hardly results in appreciable differences regarding the outcome
of chemical events. Although alkane solvent effects have been
investigated in detail with respect to spectroscopic properties,
reaction selectivity, and equilibrium constants, no dramatic
alternation has been observed. As far as small solute molecules
are concerned, it seems to be difficult to pinpoint chemical
events that show sharp changes induced by solvent effects
between two alkane solvents.
However, one possibility to render the solvent effect between
Received: September 16, 2014
alkanes appreciable exists. Helical macromolecular scaffolds
© XXXX American Chemical Society
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We envisioned that, once the chiral side chains are
appropriately optimized, the use of new helical macromolecular
scaffolds may provide us with the chance to observe otherwise
unappreciable alkane solvent effects. Such scaffolds may also
allow us to acquire new insights into the origins of the
induction and inversion mechanisms of the helical sense.
Herein, we demonstrate the highly selective induction of P- and
M-helical structures in poly(quinoxaline-2,3-diyl)s with chiral
side chains purely through the choice of alkane solvents. We
also report the successful application of these helical macro-
molecules as chiral ligands with switchable chirality (P-/M-
helix) for the preparation of asymmetric transition metal
catalysts.
results, we considered 4(100) to be a promising polymeric
scaffold, in order to demonstrate the effective helix inversion
induced by a change of alkane solvents.
Subsequently, we carried out an exhaustive screening of
alkane solvents with respect to the solvent-dependent helix
inversion of polymer 4(100) (Figure 2a). For example, a series
First, we prepared different polymers 1(100)−4(100) with a
degree of polymerization (DP) of 100, containing various chiral
side chains. We then measured the CD spectra of 1(100) with
(S)-2-butoxymethyl side chains in n-hexane and cyclohexane
(Figure 1a). The rod-like macromolecular shape of 1(100),
Figure 2. (a) Screw-sense excess (%) of polymer 4(100) in various
alkane solvents. Individual screw-sense excess values were determined
on the basis of CD intensities. Values for the molecular aspect ratio
(L/D) of the alkane solvents are also shown. (b) Relationship between
the screw-sense excess of polymer 4(100) and the molecular aspect
ratios of various alkane solvents, which were classified according to the
number of carbon atoms.
of linear n-alkanes (pentane to decane) induced exclusively an
M-helical conformation. For branched or cyclic alkanes, trends
with respect to the handedness of the helical chirality of 4(100)
were more complicated to be established. Whereas methyl-,
ethyl-, propyl-, and butyl-substituted cyclohexanes induced an
M-helix, unsubstituted cyclohexane, as well as isopropylcyclo-
hexane induced a P-helix. On the basis of these results, it seems
feasible to assume that the handedness of the induced screw-
sense depends on the molecular shape of the alkane solvents.
We focused our attention in the following on the relationship
between the molecular shape of the alkane solvents and the
resulting screw-sense excess of polymer 4(100). In order to
evaluate the molecular shapes of various alkane solvents
quantitatively, we adopted the molecular aspect ratio value,6a,11
which is defined as the ratio between the length of the major
axis (L) and the minor axis (D) of a given molecule after
performing a geometry optimization by the CONFLEX
program.12 We found that the screw-sense excess of 4(100)
is clearly correlated with the molecular aspect ratios of the
alkane solvent (Figure 2b). When examining saturated
hydrocarbons with 8 carbon atoms for example, n-octane
exhibited a relatively large molecular aspect ratio (L/D = 2.47),
which selectively induced an M-helical structure (95% se). In
contrast to that, isooctane showed only a moderate molecular
Figure 1. CD spectra of polymers 1(100)−4(100) in n-hexane and
cyclohexane. CD intensities are expressed as Kuhn’s dissymmetry
factor gabs (Δε/ε).
with protruding chiral side chains, resulted in a good solubility
in a variety of alkane solvents. Although 1(100) exhibited, as
previously reported, solvent-dependent helix inversion behavior
between chloroform (M-helix) and 1,1,2-trichloroethane (P-
helix),7 1(100) retained an M-helical structure when being
dissolved in either n-hexane or cyclohexane. Polymer 2(100)
with (S)-2-methylbutoxy side chains adopted, on the other
hand, a P-helical structure in both n-hexane and cyclohexane.
Although the helix sense of 2(100) was found to be
diametrically opposed to that of 1(100), neither exhibited a
helix inversion between n-hexane and cyclohexane (Figure 1b).
Polymer 3(100), bearing chiral (S)-2-octyloxymethyl groups,
did not show a helix inversion either (Figure 1c). However,
polymer 4(100) with (S)-3-octyloxymethyl side chains clearly
exhibited a solvent-dependent helix inversion between n-hexane
and cyclohexane, even though the CD intensity was found to be
relatively weak in the latter (Figure 1d). On the basis of these
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aspect ratio (L/D = 1.35), which resulted in the formation of
nearly racemic mixtures of P- and M-helices (M-helix, 4% se).
Cyclooctane, on the other hand, with a relatively small
molecular aspect ratio (L/D = 1.02), was able to efficiently
induce a P-helical structure (86% se). It is important to
mention here that no other correlation between the induction
of screw sense and any other solvent properties of the alkanes
such as polarity, permittivity, molecular volume, or topological
indexes5e was observed (see SI).
metric hydrosilylation of styrenes. Therefore, we prepared the
random copolymer 4(990/10) bearing (S)-3-octyloxymethyl
side chains and 2-(diphenylphosphino)phenyl pendants as a
chiral polymer ligand for the asymmetric hydrosilylation of
styrene with trichlorosilane (Scheme 1). When the reaction was
Scheme 1. Palladium-Catalyzed Asymmetric Hydrosilylation
of Styrene in n-Octane or Cyclooctane Using Chiral
Copolymer 4(990/10) as a Ligand
We were then interested in achieving high screw-sense excess
values in the pair of the alkane solvents, in which an efficient
helix inversion could be ensured. Therefore, we prepared a
series of polymers 4(DP) with varying degrees of polymer-
ization (DP = 30−300), containing (S)-3-octyloxymethyl side
chains. These polymers should allow an exact determination of
the energy difference gained per monomer unit (ΔGh) in
cyclooctane or n-octane, respectively. In accordance with
Green’s theory,13 the observed screw-sense excess values
increased nonlinearly with the increase in DP (Figure 3a).
carried out in n-octane, which induced an M-helical polymer
backbone, the major reaction product had (R)-configuration
(94% ee), whereas when the same reaction was carried out in
cyclooctane, the (S)-product was obtained in high enantiose-
lectivity (90% ee). This result clearly demonstrates that highly
enriched P- and M-helical structures of 4(990/10) are induced
in n-octane or cyclooctane, which is in good agreement with
our estimations based on the CD measurements.
In summary, we have investigated the induction of a single-
handed helical sense in the main chain of poly(quinoxaline-2,3-
diyl)s containing chiral (S)-3-octyloxymethyl side chains in
various alkane solvents. We observed a clear correlation
between the handedness of the induced screw-sense and the
molecular aspect ratio of the alkane solvents. Linear alkanes
with larger molecular aspect ratios induced M-helical structures,
whereas branched or cyclic alkanes with smaller molecular
aspect ratios induced P-helical structures. Finally, we
demonstrated that a random poly(quinoxaline-2,3-diyl) copoly-
mer containing (S)-3-octyloxymethyl and 2-
(diphenylphosphino)phenyl side chains can serve as a highly
enantioselective chiral ligand in the palladium-catalyzed hydro-
silylation of styrene in alkane solvents. The copolymer was
observed to undergo a solvent-dependent helical inversion
between n-octane and cyclooctane, leading to a highly
enantioselective production of both enantiomeric products.
Further studies exploring potential applications of helical
poly(quinoxaline-2,3-diyl)s with switchable chirality as a new
class of chiral supporting materials are currently undertaken in
our laboratory, together with systematic investigations into the
origin and mechanism of this solvent-dependent helix inversion.
Figure 3. (a) Correlation between the degree of polymerization (DP)
and the screw-sense excess (se) of polymers 4(DP) (DP = 30−300).
(b) CD spectra of polymer 4(250) in cyclooctane and n-octane.
The ΔGh values were found to be 0.06 and 0.10 kJ/mol in
cyclooctane and n-octane, respectively, which is smaller
compared to our previously reported polymer systems.7 At 20
°C, a DP of 250 was found to be sufficient in order to induce
absolute P- or M-helices (>99% se) in n-octane or cyclooctane.
The CD spectra of polymer 2(250) in n-octane and
cyclooctane are almost perfect mirror images of each other,
indicative of an almost perfect solvent-dependent helix
inversion (Figure 3b).
Finally, we demonstrate a conceivable catalytic applications
of the obtained P- and M-helical structures of polymer 4 in
cyclooctane or n-octane, e.g., in an asymmetric hydrosilylation
reaction. In one of our previous papers,9b a polymer ligand
containing (R)-2-butoxy side chains and 2-
(diphenylphosphino)phenyl pendants was used in the asym-
C
dx.doi.org/10.1021/ja509531t | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

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ASSOCIATED CONTENT
* Supporting Information
Experimental procedures and spectral data for the new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
suginome@sbchem.kyoto-u.ac.jp
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this research was provided by the Japan
Science and Technology Agency (CREST, “Development of
High-performance Nanostructures for Process Integration”
Area).
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