Development of highly enantioselective polymeric catalysts using rigid and sterically regular chiral polybinaphthols

Full text of DOI:10.1021/ja964285k

J. Am. Chem. Soc. 1997, 119, 4313-4314
4313
the microenvironment of the catalytic sites in these polymers
to tune both of their catalytic activity and stereoselectivity.
Herein, we report the construction of a highly enantioselective
polymeric catalyst by using this systematic approach.
Development of Highly Enantioselective Polymeric
Catalysts Using Rigid and Sterically Regular Chiral
Polybinaphthols
Wei-Sheng Huang, Qiao-Sheng Hu, Xiao-Fan Zheng,
Julie Anderson, and Lin Pu*
The asymmetric reaction of aldehydes with alkylzinc com-
plexes in the presence of either chiral amino alcohols or chiral
titanium complexes has been demonstrated as a very useful
method to synthesize optically active alcohols.9-11 Attachment
of these chiral catalysts to polymer supports has also been
examined, and, in some cases, high enantioselectivity has been
observed.9-11 We have studied the use of the optically active
polybinaphthols to carry out the asymmetric reaction of alde-
hydes with diethylzinc as an example to explore the potential
of these new materials in asymmetric catalysis. When (R)-3
was used to catalyze the reaction of benzaldehyde with
diethylzinc at room temperature, a mixture of compounds
including the desired chiral alcohol, 1-phenylpropanol (4), and
the side product benzyl alcohol were obtained. The ratio of 4
versus benzyl alcohol was 53:47, and the ee of 4 was 13%. To
improve both the chemoselectivity and the stereoselectivity of
this reaction, we have studied another chiral polybinaphthol
(R)-5 [Mw ) 15 600 and Mn ) 8900 (PDI ) 1.75)].12 Unlike
(R)-3 which is insoluble in common organic solvents, (R)-5 can
be dissolved in methylene chloride, chloroform, and THF due
to the flexible hexyloxy groups on the phenylene spacers. When
(R)-5 was used to catalyze the reaction of benzaldehyde with
diethylzinc, only ca. 33% conversion of benzaldehyde was
observed in 20 h at room temperature. A mixture of 4 and
benzyl alcohol was generated in a 71:29 ratio. The ee of 4
was 40%.
Department of Chemistry, North Dakota State UniVersity
Fargo, North Dakota 58105
ReceiVed December 13, 1996
The application of polymeric chiral catalysts in asymmetric
catalysis has a number of advantages such as easy recovery of
the normally quite expensive chiral catalysts, simplified product
purification, and possibility to carry out flow reactor or flow
membrane reactor syntheses. The traditional approach to
prepare a polymeric chiral catalyst involves the development
of a monomeric chiral catalyst first which is then anchored to
an achiral and sterically irregular polymer backbone.1,2 How-
ever, this strategy often suffers from a significant drop of
enantioselectivity when a chiral metal complex is attached to a
polymer support. In these polymeric chiral catalysts, their
catalytic sites are randomly oriented, and the microenvironment
of the catalytic centers cannot be systematically modified to
achieve the desired stereoselectivity. As a result, the number
of polymeric catalysts with good enantioselectivity is far less
than the number of enantioselective monomeric catalysts.2
Recently, our laboratory has been working on the synthesis
of binaphthyl-based chiral conjugated polymers for materials
application as well as for catalysis.3-8 For example, we have
Both (R)-3 and (R)-5 are the major-groove polymers of 1,1′-
binaphthol where the polymerization occurs at the 6,6′-positions.
It has been shown that introduction of substituents to the 3,3′-
positions of binaphthyl catalysts can lead to better steric control
and better enantioselectivity.13 To further modify the microen-
vironment of the metal centers in the polymer, we have carried
out the Suzuki coupling of a binaphthyl monomer (R)-614 (MOM
) CH2OCH3) with a diboronic acid 715 (R ) OC6H13) followed
by hydrolysis to prepare a minor-groove binaphthol polymer
(R)-8 (Scheme 1). (R)-8 has two important features: 1. It is
produced by polymerization at the minor-groove of the binaph-
thyl monomer, i.e., at the 3,3′-positions, and thus both phenylene
spacers as well as the adjacent naphthyl units can provide steric
control around the binaphthyl units. 2. The two hexyloxy
groups in the p-pheneylene linkers not only make this polymer
soluble in organic solvent but also can act as ligands to bind
the metal centers. (R)-8a that has a molecular weight of Mw )
6700 and Mn ) 4600 (PDI ) 1.45) is used to catalyze the
(2) For polymer supported catalysts that have shown high enantioselec-
tivity, see: (a) Asymmetric dihydroxylation. Kim, B. M.; Sharpless, K. B.
Tetrahedron Lett. 1990, 31, 3003. Han, H.; Janda, K. D. J. Am. Chem. Soc.
1996, 118, 7632. (b) Asymmetric epoxidation. Itsuno, S.; Koizumi, T.;
Okumura, C.; Ito, K. Synthesis 1995, 50. (c) Asymmetric hydrogenation.
Baker, G. L.; Fritschel, S. J.; Stille, J. R. J. Org. Chem. 1981, 46, 2954.
Nagel, U. Angew. Chem., Int. Ed. Engl. 1984, 23, 435.
(3) Ma, L.; Hu, Q.-S.; Vitharana, D.; Wu, C.; Kwan, C. M. S.; Pu, L.
Macromolecules 1997, 30, 204.
(4) Cheng, H.; Ma, L.; Hu, Q.-S.; Zheng, X.-F.; Anderson, J.; Pu, L.
Tetrahedron: Asymmetry 1996, 7, 3083.
(5) (a) Hu, Q.-S.; Zheng, X.-F.; Pu, L. J. Org. Chem. 1996, 61, 5200.
(b) Hu, Q.-S.; Vitharana, D.; Zheng, X.-F.; Wu, C.; Kwan, C. M. S.; Pu, L.
J. Org. Chem. 1996, 61, 8370.
(6) (a) Hu, Q.-S.; Vitharana, D.; Liu, G.; Jain, V.; Wagaman, M. W.;
Zhang, L.; Lee, T.; Pu, L. Macromolecules 1996, 29, 1082. (b) Hu, Q.-S.;
Vitharana, D.; Liu, G.; Jain, V.; Pu, L. Macromolecules 1996, 29, 5075.
(7) Ma, L.; Hu, Q.-S.; Musick, K.; Vitharana, D.; Wu, C.; Kwan, C. M.
S.; Pu, L. Macromolecules 1996, 29, 5083.
discovered that the polymeric Lewis acid complex prepared from
the reaction of (R)-3 with diethyl aluminum chloride shows
greatly enhanced catalytic activity over the monomeric binaph-
thyl aluminum complex.5 This polymer-based metal complex
represents a new generation of polymeric chiral catalysts where
the catalytic sites are highly organized in a sterically regular
and inherently chiral polymer chain. Unlike the traditional
polymeric chiral catalysts, these binaphthyl-based rigid chiral
polymers will have a well-defined microenviroment around the
catalytic centers. It is therefore possible to systematically adjust
(1) (a) Itsuno, S. In Polymeric Materials Encyclopedia; Synthesis,
Properties and Applications; Salamone, J. C., Ed.; CRC Press: Boca Raton,
FL, 1996; Vol. 10, p 8078. (b) Blossey, E. C.; Ford, W. T. In ComprehensiVe
Polymer Science. The Synthesis, Characterization, Reactions and Applica-
tions of Polymers; Allen, G., Bevington, J. C., Eds.; Pergamon Press: New
York. 1989; Vol. 6, p 81.
(8) For a review of chiral conjugated polymers, see: Pu, L. Acta
Polymerica 1997, 48, 118.
(9) (a) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833. (b) Noyori, R.;
Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49.
S0002-7863(96)04285-0 CCC: $14.00 © 1997 American Chemical Society

4314 J. Am. Chem. Soc., Vol. 119, No. 18, 1997
Scheme 1. Preparation of the Chiral Polymer (R)-8
Communications to the Editor
aldehydes took 3-4 days. As shown in the table, excellent
enantioselectivity for the para substituted benzaldehydes as well
as the R,â-unsaturated aldehyde are achieved. Good enanti-
oselectivity is also observed for the addition to aliphatic
aldehydes. This is very remarkable since most of the polymer-
supported chiral amino alcohol catalysts can only give 8-65%
ee for the reaction of aliphatic aldehydes with diethyl zinc.9a,10
The best polymeric amino alcohol catalyst for aliphatic alde-
hydes was (1S,2R)-9 which gave 69% ee for the reaction of
diethylzinc with nonyl aldehyde.16,17 This polymer however
gave much lower ee for benzaldehyde than other polymer-
supported catalysts. The enantioselectivity of (1S,2R)-9 is also
significantly reduced from that of its monomer (1S,2R)-10.18
Table 1. The Asymmetric Reaction of Aldehydes with Diethylzinc
The general procedure for the reactions catalyzed by (R)-8a
is described in the following example. To a Schlenk flask
containing toluene (10 mL, dried with Na) was added the
polymer (R)-8a (28 mg, 0.05 mmol, based on the repeat unit)
and diethylzinc (0.14 mL, 1.3 mmol) under N2 at room
temperature. After ca. 15 min, the flask was cooled to 0 °C,
and benzaldehyde (0.1 mL, 1 mmol) was added dropwisely.
in the Presence of Chiral Catalysts
1
After the mixture was stirred for 12 h, the H NMR spectrum
of the crude mixture showed 100% conversion of benzaldehyde
with no side product. The reaction was then quenched with
the addition of 1 N HCl at 0 °C. After extraction with diethyl
ether, the polymer was precipitated out with methanol. The
product 4 was isolated in 89% yield by column chromatography
on silica gel. The ee was determined to be 92.2% on GC with
a chiral column. The recycled polymer showed the same ee
for the product. We have also used (R)-8b that was prepared
under different conditions with a much higher molecular weight
[(Mw ) 24 300 and Mn ) 9900 (PDI ) 2.45)] for this reaction.
The observed ee for the reaction of benzaldehyde is 92.7% and
for the reaction of p-chlorobenzaldehyde is 93.8%.
In summary, the first highly enantioselective polymeric
catalyst based on rigid and sterically regular chiral polymers
has been developed. We have shown that the high enantiose-
lectivity is reproducible even when the polymers prepared under
different conditions and having different molecular weights are
used. These polymers can be easily separated from the reaction
mixture by simple precipitation, and the recycled polymer gives
the same enantioselectivty as the original polymer. These
excellent properties of the new polymers and their easy
preparation demonstrate the great potentials of the rigid and
sterically regular chiral materials in asymmetric synthesis. This
study provides a new direction to design and synthesize
enantioselective polymeric catalysts.
a All of the reactions using (R)-8 were carried out in toluene solution
unless indicated otherwise. b THF was used as the solvent. c A mixed
solvent (2:1 mixture of hexane/toluene) was used. d All of the ee values
were determined by GC with a chiral column (â-Dex capillary column,
Supelco Company) unless indicated otherwise. e The recycled polymer
was used. f The ee was measured by HPLC-Chiracel OD column. g The
ee was measured by analyzing the acetate derivative of the product on
the GC-â-Dex capillary column. h The absolute configurations were
assigned by comparing the optical rotations with the reported data.9-11
reaction of diethylzinc with benzaldehyde. We found that in
toluene solution at 0 °C, (R)-8a catalyzed a 100% conversion
of benzaldehyde to 4 in 12 h without formation of the side
product. The ee of 4 was 92.2%. (R)-8a has been used for the
asymmetric reaction of different aldehydes with diethylzinc, and
the results are summarized in Table 1. All of these reactions
Acknowledgment. This work is supported by the Center for Main
Group Chemistry at North Dakota State University. Partial support
from the donors of the Petroleum Research Fund-ACS, the National
Science Foundation (DMR-9529805), and U.S. Air Force (F49620-
96-1-0360) is also gratefully acknowledged. We thank Professor Philip
Boudjouk at NDSU for his help.
o
were carried out at 0 C in the presence of 5 mol % (based on
Supporting Information Available: Detailed experimental pro-
cedures and characterizations involving (R)-5, (R)-8, and the use of
(R)-8 in the catalytic reaction (4 pages). See any current masthead
page for ordering and Internet access instructions.
the binaphthyl unit) of (R)-8a. This polymer was easily
recovered from the reaction mixture by simply adding methanol
to precipitate. The reactions of the aromatic aldehydes were
completed in 12-26 h, but the reactions of the aliphatic
JA964285K
(10) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.; Nakahama, S.;
Fre´chet. J. Org. Chem. 1990, 55, 304.
(11) Seebach, D.; Marti, R. E.; Hintermann, T. HelV. Chim. Acta 1996,
(16) Soai, K.; Watanabe, M. Tetrahedron: Asymmetry 1991, 2, 97.
(17) Seebach et al. recently reported that cross-linked polystyrenes
containing chiral R,R,R′,R′-tetraphenyl-1,3-dioxolane-4,5-dimethanol func-
tions can catalyze the reaction of diethylzinc with heptyl aldehyde in 92%
ee (75% yield) and with cyclohexanecarboxaldehyde in 86% ee (57%
yield).11 However, these reactions require 1.2 equiv of Ti(OCHMe2)4 Versus
the aldehydes.
79, 1710.
(12) The molecular weights of the polymers in this paper were determined
by gel permeation chromatography relative to polystyrene standards.
(13) Maruoka, K.; Itoh, T.; Shirasaka, T.; Yamamoto, H. J. Am. Chem.
Soc. 1988, 110, 310.
(14) Cox, P. J.; Wang, W.; Snieckus, V. Tetrahedron Lett. 1992, 17,
2253.
(18) Soai, K.; Yokoyama, S.; Hayasaka, T. J. Org. Chem. 1991, 56,
4264.
(15) Huber, J.; Scherf, U. Macromol. Rapid Commun. 1994, 15, 897.