Synthesis of optically active polymers with chiral units attached to rigid backbones and their application for asymmetric catalysis

Article abstract of DOI:10.1016/S0040-4039(01)01689-6

Optically active ephedrine-bearing poly(phenylene)s have been synthesized by using the Suzuki coupling polymerization. Their application as polymeric chiral catalysts for asymmetric addition of diethylzinc to aldehydes has been studied and good enantioselectivity was observed. The strategy to synthesize these optically active polymers is potentially useful in the design and synthesis of other polymeric chiral catalysts for asymmetric catalysis.

Full text of DOI:10.1016/S0040-4039(01)01689-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 7725–7728
Synthesis of optically active polymers with chiral units attached
to rigid backbones and their application for asymmetric catalysis
Qiao-Sheng Hu,* Chaode Sun and Colleen E. Monaghan
Department of Chemistry, The City University of New York-College of Staten Island, Staten Island, NY 10314, USA
Received 20 August 2001; revised 5 September 2001; accepted 10 September 2001
Abstract—Optically active ephedrine-bearing poly(phenylene)s have been synthesized by using the Suzuki coupling polymeriza-
tion. Their application as polymeric chiral catalysts for asymmetric addition of diethylzinc to aldehydes has been studied and good
enantioselectivity was observed. The strategy to synthesize these optically active polymers is potentially useful in the design and
synthesis of other polymeric chiral catalysts for asymmetric catalysis. © 2001 Elsevier Science Ltd. All rights reserved.
The development of polymeric chiral catalysts for
asymmetric catalysis has attracted extensive attention in
recent years.1 Due to the large size and solubility differ-
ences between the small organic molecules and poly-
mers, polymeric chiral catalysts could be easily
recovered from the reaction mixture by either filtration
or precipitation, and be reused. Using polymeric chiral
catalysts can also simplify the purification process and
make it possible to conduct reactions in a flow reactor
or flow membrane reactors for continuous production.
Traditionally, polymeric chiral catalysts were synthe-
sized by attaching a good monomeric chiral catalyst to
sterically irregular polymer backbones such as
polystyrenes.2 Although significant enantioselectivity
and reactivity drops are often observed due to the
microenvironment change after the monomeric catalyst
is attached to the irregular polymer backbone, this
side-chain attachment strategy has the advantage of
easy preparation. Recently, Pu and co-workers devel-
oped a new approach to optically active polymers with
main chain chirality by incorporating chiral units into
rigid polymer backbones.3 This strategy can mostly
preserve the high enantioselectivity of the monomeric
chiral catalysts. However, it is sometimes very difficult
or impossible to incorporate a monomeric chiral cata-
lyst into the main chain of a polymer.
In our laboratory, we are interested in the development
of new strategies, which will combine the advantages of
the side-chain attachment strategy and main-chain
OH
Ph
OH
Ph
N
N
OH
N
Ph
OR
(HO)2B
OR
OR
OR
OR
OR
OR
OR
OR
Pd(PPh3)4
+
K2CO3/THF
reflux, 24 hr
B(OH)2
OR
3
Br
Br
2
1
Ph
Ph
N
N
OH
OH
Scheme 1. Synthesis of optically active polymer 1.
* Corresponding author. Fax: 1-718-982-3910; e-mail: qiaohu@postbox.csi.cuny.edu
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01689-6

7726
Q.-S. Hu et al. / Tetrahedron Letters 42 (2001) 7725–7728
incorporation strategy, for the synthesis of novel opti-
cally active polymers. We have constructed optically
active polymers with chiral units attached to rigid back-
bones through the Suzuki coupling polymerization of
readily accessible chiral unit-bearing monomers with
rigid linkers. In this letter, we report the synthesis of
two optically active ephedrine-bearing poly(phenylene)s
and their application as polymeric chiral catalysts for
asymmetric diethylzinc addition to aldehydes.
Pd(0)-catalyzed Suzuki coupling polymerization of 2
and 3 yielded polymer 1 in 95% yield. 1 is soluble in
common organic solvents such as methylene chloride,
THF and chloroform. Gel permeation chromatography
(GPC) analysis (polystyrene standards) shows its
molecular weight is Mw=7,200, Mn=4,900 (PDI=
1.44). The specific optical rotation of 1 is [h]D=−28.2
(c=0.43, CH2Cl2). The well-resolved 1H NMR spec-
trum indicates a well-defined structure.
We have synthesized (1R,2S)-ephedrine-bearing poly-
(phenylene) 1 by reaction of dibromide 2 with a
diboronic acid 34 in the presence of a catalytic amount
of Pd(PPh3)4 (Scheme 1).4,5 (1R,2S)-Ephedrine was cho-
sen as the chiral unit because (1R,2S)-ephedrine-con-
taining monomers and polymers have been well
studied.6 The preparation of 2 is shown in Scheme 2. In
the presence of potassium carbonate, 4-bromobenzyl
bromide (4) reacted smoothly with (1R,2S)-ephedrine
(5) in acetonitrile to give 6. Pd(PPh3)4/CuI-catalyzed
cross-coupling of 6 with trimethylsilylacetylene fol-
lowed by deprotection with K2CO3/MeOH yielded 7.7,8
Reaction of 7 with 1,3,5-tribromobenzene (2 equiv.)
generated 2 in 80% yield. The excess 1,3,5-tribromoben-
zene can be easily removed by flash chromatography.
We have also carried out the synthesis of polymer 8
that has a longer linker between the adjacent chiral
units by polymerization of 2 with diboronic acid 9
(Scheme 3). Diboronic acid 9 was obtained by a two-
step procedure: the Suzuki coupling reaction of 3 with
1-bromo-4-iodobenzene generated 10 which was con-
verted to 9 by reaction with tert-butyllithium at −70°C
followed by treatment with triethyl borate and hydroly-
sis (Scheme 4). Polymer 8 was obtained in 95% yield
and is also soluble in CH2Cl2, THF and chloroform.
GPC analysis of 8 shows its molecular weight is Mw=
92 900, Mn=35 100 (PDI=2.65). The specific optical
rotation of 8 is [h]D=−76.6 (c 0.42, THF). 8 Also gives
1
well-resolved H NMR spectrum, which is consistent
with the polymer structures.9
OH
OH
Br
Br
N
Ph
Br
N
TMS
Pd(PPh3)4/CuI
Et3N/THF
1).
Ph
OH
Ph
Br
K2CO3
2
HN
+
Pd(PPh3)4/CuI
Et3N/THF
CH3CN, reflux
2). K2CO3, MeOH
Br
Br
4
6
5
7
Scheme 2. Synthesis of dibromide 2.
OH
Ph
OH
N
N
Ph
B(OH)2
OR
OR
OR
OR
OR
RO
Pd(PPh3)4
+
K2CO3/THF
reflux, 24 hr
2
OR
OR
B(OH)2
R = C6H13
9
8
Ph
Ph
N
N
OH
OH
Scheme 3. Synthesis of optically active polymer 8.
OR
OR
OR
1). tert-BuLi/THF, -70 oC
2). B(OEt)3/THF, -70 oC
3). H+
B(OH)2
Pd(PPh3)4
B(OH)2
(HO)2B
Br
Br
+
Br
I
(HO)2B
K2CO3/THF
reflux, 15 hr
RO
RO
OR
R = (CH2)5CH3
9
10
3
Scheme 4. Preparation of diboronic acid 9.

Q.-S. Hu et al. / Tetrahedron Letters 42 (2001) 7725–7728
7727
Table 1. Asymmetric addition of diethylzinc to aldehydes
catalyzed by polymers 1 and 8a
Congress—CUNY Research Award Program is grate-
fully acknowledged. This work also benefited from the
NSF-REU program at CUNY-College of Staten
Island. We also thank Professor Howard Haubenstock
for allowing us to use the polarimeter.
OH
O
5 mol% catalyst
Et2Zn
+
Toulene, r.t., 24 h
R
Et
R
H
Entry
Aldehydes
Polymer
Yield (%)
e.e. (%)b
References
1
2
3
Benzaldehyde
Anisoaldehyde
Benzaldehyde
Anisoaldehyde
Benzaldehyde
1
1
8
8
8
94
100
83
95
82
76
75
74
74
76
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) Pu, L. Chem. Rev. 1998, 98, 2405.
4
5c
2. For examples: (a) Bolm, C.; Dinter, C. L.; Seger, A.;
Ho¨cker, H.; Brozio, J. J. Org. Chem. 1999, 64, 5730;
(b) Dumont, W.; Poulin, J. C.; Dang, T. P.; Kagan, H.
B. J. Am. Chem. Soc. 1973, 95, 8295.
3. (a) Pu, L. Chem. Eur. J. 1999, 5, 2227; (b) Fan, Q.-H.;
Ren, C.-Y.; Yeung, C.-H.; Hu, W.-H.; Chan, A. S. C.
J. Am. Chem. Soc. 1999, 121, 7407; (c) Yu, H.-B.; Hu,
Q.-S.; Pu, L. J. Am. Chem. Soc. 2001, 122, 6500.
a The reactions were carried out in toluene by using a 5 mol%
polymeric catalyst (based on the polymer repeat unit) at rt for 24 h.
b The e.e.s were measured by using HPLC (Chiralcel OD column,
hexane/isopropanol =95:5; flow rate=1 ml/min). The configuration
of the product was assigned based on the specific optical rotation
and the retention time of HPLC.
c Recovered polymer was used.
4. Hu, Q.-S.; Huang, W.-S.; Vitharana, V.; Zheng, X.-F.;
Pu, L. J. Am. Chem. Soc. 1997, 119, 12454.
5. (a) Suzuki, A. Metal-Catalyzed Cross-Coupling Reac-
tions; Deiderich, F.; Stang, P. J., Eds.; Wiley-VCH,
1999; Chapter 2, p. 49; (b) Hu, Q.-S.; Huang, W.-S.;
Pu, L. J. Org. Chem. 1998, 63, 2798; (c) Giroux, A.;
Han, Y.; Prasit, P. Tetrahedron Lett. 1997, 38, 3841.
6. (a) Sato, I.; Kodaka, R.; Shibata, T.; Hirokawa, Y.;
Shirai, N.; Ohtake, K.; Soai, K. Tetrahedron: Asymme-
try 2000, 11, 2271; (b) Sato, I.; Shibata, T.; Ohtake,
K.; Kodaka, R.; Hirokawa, Y.; Shirai, N.; Soai, K.
Tetrahedron Lett. 2000, 41, 3123; (c) Yashima, E.;
Maeda, Y.; Okmamoto, Y. Polym. J. 1999, 31, 1033;
(d) Watanabe, M.; Soai, K. J. Chem. Soc., Perkin
Trans. 1 1994, 837; (e) Soai, K.; Niwa, S.; Watanabe,
M. J. Org. Chem. 1988, 53, 927; (f) Ituno, S.; Fre´chet,
J. M. J. J. Org. Chem. 1987, 52, 4142.
We have used 1 and 8 as polymeric chiral catalysts for
the asymmetric addition of Et2Zn to aldehydes (Table
1).10 When 1 was used to catalyze the reaction of
benzaldehyde with diethylzinc at room temperature,
chiral 1-phenylpropanol was obtained in 76% e.e. When
polymer 8 was used for the same reaction under same
conditions, 1-phenylpropanol was obtained in 74% e.e.
Similar enantioselectivity was also observed for the
diethylzinc addition to anisoaldehyde. The enantioselec-
tivity of these polymers is comparable to the results
reported by Soai6b and Fre´chet,6e but lower than that of
the monomeric ephedrine derivative 6 (83% e.e for
benzaldehyde). The fact that 1 and 8 exhibit the same
enantioselectivity indicates that the chiral environment
of the catalytically active sites of these two polymers
are the same. The polymer catalysts can be easily
recovered by precipitation from MeOH. The recovered
polymer catalyst showed the same reactivity and enan-
tioselectivity as the original polymer catalyst (entry 5).
7. For a different approach to 7, see Ref. 6b.
8. Sonogashira, K. Metal-Catalyzed Cross-Coupling Reac-
tions; Diederich, F.; Stang, P. J. Eds.; Wiley-VCH,
1999; Chapter 5, p. 203.
9. Synthesis and characterization of polymer 8: To a mix-
ture of dibromide 2 (540 mg, 1.05 mmol) and diboronic
acid 9 (571 mg, 1.10 mmol) in 2 M K2CO3/THF was
added Pd(PPh3)4 (30 mg) under N2. The mixture was
refluxed for 24 h and bromobenzene was added to cap
the end. After another 6 h refluxing, the reaction mix-
ture was cooled to room temperature and extracted
with CH2Cl2. After washing with brine, the solvent was
evaporated by using a rota-evaporator. The residue was
redissolved in CH2Cl2 and precipitated from MeOH.
The solid was collected by filtration. The dissolvation–
precipitation–filtration sequence was repeated twice
again. After drying under vacuum, polymer 8 was
obtained in 95% yield (778 mg). GPC (polystyrenes
standards): Mw=92 900, Mn=35 100 (PDI=2.65).
[h]D=−76.3 (c=0.42, THF). 1H NMR (CDCl3, 600
MHz) l 7.90 (s, 1H), 7.83 (s, 2H), 7.76 (br. s, 8H),
7.51 (d, J=8.4 Hz, 2H), 7.24–7.33 (m, 5H), 7.22 (d,
J=8.4 Hz, 2H), 7.09 (s, 2H), 8.70 (s, 1H), 3.99 (t,
In summary, optically active ephedrine-bearing
poly(phenylene)s based on polymerization of readily
accessible chiral unit-bearing monomers with rigid link-
ers have been synthesized and their application for
asymmetric diethylzinc addition to aldehydes has been
studied. The strategy to synthesize these optically active
ephedrine-bearing poly(phenylene)s are potentially use-
ful in the design and synthesis of other polymeric chiral
catalysts for asymmetric synthesis.
Acknowledgements
This work was supported by the Department of Chem-
istry, College of Staten Island-City University of New
York (CUNY). Partial support from Professional Staff

7728
Q.-S. Hu et al. / Tetrahedron Letters 42 (2001) 7725–7728
J=6.6 Hz, 4H), 3.62 (s, 2H), 3.21 (s, 1H), 2.93 (m, 1H),
29.32, 25.78, 22.61, 14.03, 9.85. UV–vis umax (CH2Cl2)
229, 293, 337 nm. Anal. calcd for C55H59NO3: C, 84.51;
H, 7.55; N, 1.79. Found: C, 83.36; H, 7.49; N 1.79.
10. Recent reviews: (a) Pu, L.; Yu, H.-B. Chem. Rev. 2001,
101, 757; (b) Soai, K.; Niwa, S. Chem. Rev. 1992, 92, 833;
(c) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed.
Engl. 1991, 30, 49.
2.21 (s, 3H), 1.72–1.77 (m, 4H), 1.42 (m, 4H), 1.29 (br, s,
8H), 1.01 (d, J=8.4 Hz, 3H), 0.87 (t, J=6.0 Hz, 6H). 13C
NMR (50 MHz, CDCl3) l 150.41, 142.53, 141.74, 140.16,
138.89, 137.89, 135.60, 131.63, 130.34, 130.04, 128.62,
128.04, 127.05, 126.76, 126.19, 124.30, 121.68, 116.15,
89.60, 89.23, 73.91, 69.67, 63.54, 58.85, 38.68, 31.47,