Enhanced catalyst activity and enantioselectivity with chirality-switchable polymer ligand PQXphos in Pd-catalyzed asymmetric silaborative cleavage of meso -methylenecyclopropanes

Article abstract of DOI:10.1021/ja303506k

The poly(quinoxaline-2,3-diyl)-based helically chiral phosphine ligands PQXphos exhibited high enantioselectivities up to 97% ee in palladium-catalyzed desymmetrization of meso-1,2-dialkylsubstituted-3-methylenecyclopropanes through silaborative cleavage

Full text of DOI:10.1021/ja303506k

Communication
pubs.acs.org/JACS
Enhanced Catalyst Activity and Enantioselectivity with
Chirality-Switchable Polymer Ligand PQXphos in Pd-Catalyzed
Asymmetric Silaborative Cleavage of meso-Methylenecyclopropanes
Yuto Akai, Takeshi Yamamoto, Yuuya Nagata, Toshimichi Ohmura, and Michinori Suginome*
Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Katsura,
Nishikyo-ku, Kyoto 615-8510, Japan
S
* Supporting Information
ABSTRACT: The poly(quinoxaline-2,3-diyl)-based heli-
cally chiral phosphine ligands PQXphos exhibited high
enantioselectivities up to 97% ee in palladium-catalyzed
desymmetrization of meso-1,2-dialkylsubstituted-3-methyl-
enecyclopropanes through silaborative cleavage of the
C−C bond. The observed enantioselectivities were higher
than those obtained with 2-diarylphosphino-1,1′-binaphth-
yl in our original report. Remarkable rate enhancement
was also observed with a series of PQXphos in comparison
with the corresponding low-molecular weight ligands.
uch attention has been focused on the development of
polymer-based chiral ligands in organic synthesis from the
M
viewpoint of practicality on the basis of their ease in recovery
from the reaction mixture and reusability.1 Efforts are now being
devoted to the exploration of next-generation chiral polymer
ligands, whose chiral reaction environment relies largely on the
polymer backbone.2 The establishment of new catalyst systems
that feature higher enantioselectivities, higher catalytic activities,
and reusability is eagerly desired on the basis of the polymer-
based approach. Furthermore, it is also expected for the next-
generation polymer catalysts that the polymer backbones play a
positive effect on the enhancement of catalyst activities through
their huge “long-range steric effect,” which is proposed as the
steric effect remote from the reaction center, around which
enough space for the reaction is still left.3 Such special steric
effect is established only for the finely synthesized large
molecules, including some bowl-shaped bulky phosphine
ligands.3
We have recently reported a new class of polymer-based chiral
ligand PQXphos (e.g., L1−L3), whose chirality relies on a single-
handed helical structure of the backbone of poly(quinoxaline-
2,3-diyl) (Figure 1).4−7 The new polymer-based ligand showed
remarkably high enantioselectivities in Pd-catalyzed hydro-
silylation of styrenes4a,b and Suzuki−Miyaura coupling of
phosphinyl-substituted 1-naphthylbromide with o-methylaryl-
boronic acids.4c In the latter case, enantioselectivities higher than
the original low-molecular weight system were attained,
demonstrating the advantage of using a polymer-based chiral
ligand system in obtaining higher enantioselectivities. Also
noteworthy is that the polymer ligand underwent reversible,
perfect switching of helical chirality by the solvent effect,8 leading
to production of either enantiomer from a single catalyst with
high enantioselectivities. However, the polymer system has so far
Figure 1.
shown almost the same or rather low catalytic activities in
comparison with the corresponding low-molecular weight ligand
systems.9 We wondered if our polyquinoxaline backbone could
Received: April 12, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/ja303506k | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX

Journal of the American Chemical Society
Communication
show significant rate enhancement in asymmetric catalysis on the
basis of the long-range steric effect. In this paper, we demon-
strate that, using PQXphos as a ligand, Pd-catalyzed reaction of
meso-methylenecyclopropanes with silylborane proceeds with
much higher enantioselectivities along with a much higher reac-
tion rate than the original silaboration system using 2-diarylphos-
phino-1,1′-binaphthyl (MOP) as ligands. In addition, remarkably
sharp dependence of the enantioselectivity upon the substituents
on the phosphorus atoms of PQXphos has been established.
In 2007, we reported asymmetric silaboration of meso-
methylenecyclopropanes (meso-MCPs) using a palladium
catalyst bearing a MOP-type, monodentate chiral phosphine
ligand L4 (eq 1 and Figure 1).10 Although up to 91% ee was
Table 1. Asymmetric Silaborative C−C Cleavage of meso-
a
MCPs Using PQXphos (P)-L1−3 as Chiral Ligands
attained for bicyclic MCPs whose three-membered ring is fused
to five- to eight-membered ring cycloalkanes, monocyclic MCPs
gave much lower enantioselectivity up to 81% ee. Furthermore,
MCPs having oxygen functionalities showed much lower
reactivities than the unfunctionalized, hydrocarbon derivatives.
We chose this reaction system for the test of our polymer-based
ligand as a more active and enantioselective chiral ligand.
In the reaction of bicyclic MCP 2a in the presence of PQXphos
L1−L3, enantioselectivities varied significantly, depending on
the aryl groups on the phosphorus atoms (Table 1, entries 1−3).11
Although the diphenylphosphino derivative L1 showed 67% ee,
2-naphthyl derivative L2 resulted in 7% ee. In contrast, 3,5-xylyl
derivative L3 showed remarkably high enantioselectivity (96% ee),
exceeding the enantioselectivity of 91% ee obtained with MOP-
type ligand L4 modified with 3,5-xylyl groups on the phosphorus
atom.10a,12 It should be noted that L2 and L3 showed similarly
high enantioselectivities in asymmetric Suzuki−Miyaura cou-
pling in our previous report, while such varied selectivities are
obtained in the present reaction system. The enantioselectivities
were generally higher than those with L4 for some additional
MCPs, including fused and nonfused MCPs. In particular, the
selectivity (95% ee) for the nonfused MCP 2e with L3 was
significantly higher than that with L4 (81% ee) (entry 7).10a
MCPs 2f and 2g bearing oxygen functionalities, which were
hardly reactive with L4 in the previous system, successfully
underwent the silaboration with high enantioselectivities (entries 8
and 9).
a
MCP 2 (0.30 mmol), Ph2MeSiB(pin) (0.20 mmol), Pd2(dba)3 (2.0 μmol),
and ligand (4.8 μmol) were heated with toluene (0.40 mL) at 50 °C.
Reaction time: 168 h (entry 1); 240 h (entry 2); 48 h (entries 3−5 and
7−9); 72 h (entry 6). Isolated yield. Determined after oxidation to
the corresponding β-silyl ketones.
b
c
Scheme 1. Use of Inverted PQXphos (M)-(R,R)-L3 as a
Ligand for Asymmetric Silaboration of meso-MCP 2a
The right-handed helical PQXphos L3 was dissolved in a 3/1
mixture of 1,1,2-trichloroethane (1,1,2-TCE) and toluene at
60 °C for 24 h, leading to the complete switch of the main chain
helical chirality to M (left-handed) (Scheme 1). Upon use of a
palladium complex of the inverted PQXphos (M)-(R,R)-L3
under the same reaction conditions as those for (P)-(R,R)-L3,
the reaction of 2a was found to be significantly slower. Although
we observed a reasonable reaction rate and the formation of an
enantiomeric product under the solvent-free reaction conditions,
enantioselectivity was moderate (75% ee), probably because of
M-to-P helix reinversion during the reaction at 50 °C. We could
improve the enantioselectivity to 91% ee by using a small amount
of 1,1,2-TCE as an additive, which is likely to maintain the left-
handed helical structure during the reaction.
(Pd/P = 1:1.2) (Table 2, entry 1). Under the same reaction
conditions, even the MOP ligand L4, which showed the best
enantioselectivity in the original report, just exhibited low
catalytic activity (entry 2). The quinoxaline-based triarylphos-
phine ligand L6, which was prepared as a model of PQXphos,
also failed to give reasonable conversion (entry 3). When we used
racemic PQXphos L10−L12 bearing achiral side chains,
significant enhancement of the reaction rate was observed
We observed interesting rate acceleration with the polymer-
based PQXphos ligands. The MCP 2f hardly underwent the
silaborative C−C cleavage in the presence of Pd2(dba)3/PPh3
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Table 2. Silaboration of meso-MCP 2f in the Presence of
Various Phosphine Ligands
Table 3. Dependence of Time Course of Silaboration of meso-
MCP 2a on Phosphine Ligands
a
a
b
c
entry
ligand
% yield
% ee
1
2
3
4
5
6
7
8
9
PPh3
L4
0
3
−
−
−
−
−
L6
5
L10
23
22
61
30
51
98
L11
L12
−
(P)-L1
(P)-L2
(P)-L3
75
49
95
a
MCP (0.15 mmol), Ph2MeSiB(pin) (0.10 mmol), Pd2(dba)3 (1.0 μmol),
and ligand (2.4 μmol) were heated with toluene (0.20 mL) at 50 °C
b
c
for 48 h. NMR yield. Determined after oxidation to the correspond-
ing β-silyl ketones.
(entries 4−6). Among racemic PQXphos L10−L12 bearing phenyl
(L10), 2-naphthyl (L11), and 3,5-xylyl (L12) groups on the
phosphorus atom of PQXphos, L12 showed remarkably higher
reactivity than the other PQXphos-based ligands (L10 and L11)
and low-molecular weight ligands L4 and L6. The remarkable effect
of the 3,5-xylyl group on the phosphorus ligand held for
single-handed PQXphos (P)-L1−L3 bearing chiral side chains
(entries 7−9). Only L3 bearing the di(3,5-xylyl)phosphino
group showed acceptable catalytic activity at 50 °C, giving the
silaboration product 3 in good yield and high enantioselectivity,
as shown above (Table 1, entry 8; Table 2, entry 9).
a
MCP (0.15 mmol), Ph2MeSiB(pin) (0.10 mmol), Pd2(dba)3 (1.0 μmol),
ligand (2.4 μmol), and n-tetradecane (internal standard, 30 μL) were
heated with toluene (0.2 mL) at 50 °C. Determined by GC. Isolated
yield unless otherwise noted. Determined after oxidation to the
corresponding β-silyl ketones. GC yield.
b
c
d
e
Scheme 2. Asymmetric Silaboration with Lower Catalyst
Loading or at Room Temperature
A higher catalyst efficiency was also observed in silaboration of
the rather reactive MCP 2a. Use of triphenylphosphine and low-
molecular weight ligands L4−L6 showed significantly slow
reaction rates (Table 3, entries 1−4). This sluggishness had been
overcome by applying higher concentration (0.4 mmol
silylborane with 0.2 mL toluene) in our previous report using
L4 as a chiral ligand. It is interesting to note that, during our
screening of bulky ligands, 2,3,4,5-tetraphenylphenyl-substituted
triarylphosphine L713 showed similar rate enhancement (entry
5). On the other hand, a bulky bowl-shaped triarylphosphine
(BSP5) L8,3 which showed a similar rate acceleration effect to L7
in Pd-catalyzed cross-coupling of aryl chlorides, gave no
remarkable rate enhancement in the present reaction (entry 6).
To look at the effect of the polymer backbone on the catalytic
activity, diphenylphosphino-polystyrene L914 was tested, result-
ing in almost no catalytic activity (entry 7). In contrast, PQXphos
L10−L12 and L1−L3 showed apparently higher reaction rates
(entries 8−13). Comparing the catalytic activities of a PPh2 series
(PPh3, L1, L5, L7, L9, and L10), we observed high catalytic
activity of L1 on the basis of the unique steric characteristics of
the polyquinoxaline backbone. The effect does not arise from a
local electronic effect or a simple polymer effect. The apparent
rate enhancement with the bulky o-G1P (L7) ligand supports
this hypothesis. It should be noted that use of highly active L3
allowed us to apply a lower catalyst loading (0.2 mol % Pd at 50 °C)
and room temperature reaction conditions (Scheme 2). The
latter reaction condition afforded us the highest enantioselectiv-
ity of 97% ee by virtue of the lower reaction temperature.
In summary, we have established the third reaction system in
which PQXphos serves as highly efficient chiral ligand/catalysts
with high enantioselectivities comparable with or better than the
known asymmetric catalyst systems. It is particularly interesting
that a clear rate enhancement was observed with the polymer-
based ligands, while it is widely accepted that the polymer
backbone should have an adverse effect in terms of catalytic
activity as well as on enantioselectivity. We assume that the rate
enhancement is due to a type of “long-range steric effect”
reported previously, which would make catalytically active
monomeric palladium species more favorable and more stable.3
It should be pointed out that this result clearly shows that fine
polymer synthesis can greatly contribute to the development of
highly stereoselective and catalytically active chiral catalysts.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and characterization data of the products.
This material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
suginome@sbchem.kyoto-u.ac.jp
■
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Journal of the American Chemical Society
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(12) Hayashi, T.; Hirate, S.; Kitayama, K.; Tsuji, H.; Torii, A.; Uozumi,
Y. Chem. Lett. 2000, 1272.
Notes
The authors declare no competing financial interest.
(13) Iwasawa, T.; Komano, T.; Tajima, A.; Tokunaga, M.; Obora, Y.;
Fujihara, T.; Tsuji, Y. Organometallics 2006, 25, 4465.
(14) PS-PPh3 was purchased from Biotage. Resin type, 1% cross-linked
poly(styrene-co-divinylbenzene); loading, 2.09 mmol/g (based on
uptake of benzylbromide); mean bead size, 123 μm, 100−200 mesh
(95% within).
ACKNOWLEDGMENTS
■
We thank Professors Yasushi Tsuji and Tetsuaki Fujihara (Kyoto
University) for providing phosphorus ligands L7 and L8. This
work was supported by CREST, Japan Science and Technology
Agency (JST).
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D
dx.doi.org/10.1021/ja303506k | J. Am. Chem. Soc. XXXX, XXX, XXX−XXX