Application of well-defined chain-end-functionalized polystyrenes with dendritic chiral ephedrine moieties as reagents for highly catalytic enantioselective addition of dialkylzincs to aldehydes

Article abstract of DOI:10.1016/j.tetasy.2007.12.020

A series of well-defined chain-end-functionalized polystyrenes having a definite number of chiral ephedrine moieties dendritically distributed at the periphery of their hyperbranched chain-ends were evaluated as chiral catalysts for the enantioselective addition of dialkylzinc reagents to aldehydes. These dendritic macromolecules worked well as homogeneous chiral catalysts and exhibited high catalytic activity and enantioselectivity very similar to those observed for the corresponding monomeric chiral catalysts. The optimum amount of chiral catalyst was found to be 5 mol %. A profound number effect of the chiral ephedrine moieties was observed, and PS(Ephed)₈ having eight chiral ephedrine moieties at the periphery was found to be superior to other dendritic chiral catalysts. The enantioselectivity reached a value of 95% in the addition of diisopropylzinc to 3-phenylpropanal. The dendritic chiral catalysts could be easily recovered from the reaction solution by using a solvent precipitation method, and the recovered catalyst showed no significant loss of its catalytic activity or enantioselectivity.

Full text of DOI:10.1016/j.tetasy.2007.12.020

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 425–434
Application of well-defined chain-end-functionalized polystyrenes with
dendritic chiral ephedrine moieties as reagents for highly catalytic
enantioselective addition of dialkylzincs to aldehydes
Ashraf A. El-Shehawy,* Kenji Sugiyama and Akira Hirao
Organic and Polymeric Materials Department, Graduate School of Science and Engineering, Tokyo Institute of Technology,
2-12-1, Ohokayama, Meguro-ku, Tokyo 152-8552, Japan
Received 18 October 2007; accepted 22 December 2007
Abstract—A series of well-defined chain-end-functionalized polystyrenes having a definite number of chiral ephedrine moieties dendri-
tically distributed at the periphery of their hyperbranched chain-ends were evaluated as chiral catalysts for the enantioselective addition
of dialkylzinc reagents to aldehydes. These dendritic macromolecules worked well as homogeneous chiral catalysts and exhibited high
catalytic activity and enantioselectivity very similar to those observed for the corresponding monomeric chiral catalysts. The optimum
amount of chiral catalyst was found to be 5 mol %. A profound number effect of the chiral ephedrine moieties was observed, and
PS(Ephed)8 having eight chiral ephedrine moieties at the periphery was found to be superior to other dendritic chiral catalysts. The
enantioselectivity reached a value of 95% in the addition of diisopropylzinc to 3-phenylpropanal. The dendritic chiral catalysts could
be easily recovered from the reaction solution by using a solvent precipitation method, and the recovered catalyst showed no significant
loss of its catalytic activity or enantioselectivity.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
enantioselectivity parallel to that of the monomeric chiral
catalysts have been developed, their efficiency for asymmet-
ric catalysis has been limited due to the nature of one cat-
alytic site per repeating unit.6 Moreover, unfortunately,
most of the insoluble polymer-supported chiral catalysts
often suffered from low catalytic activity and enantioselec-
tivity.7 In recent years, the utility of using dendronized chi-
ral b-amino alcohols in the catalytic asymmetric dialkylzinc
addition to aldehydes has been surveyed.8
One of the major challenges in organic synthesis is the
asymmetric preparation of organic compounds by means
of forming carbon–carbon bonds through asymmetric
catalysis.1 Among the different strategies, the catalytic
enantioselective 1,2-addition of organometallics to car-
bonyl compounds is probably the most straightforward
and useful manner of achieving this goal.2 Since Soai
et al. have reported the chiral ephedrine-catalyzed dialkyl-
zinc addition to benzaldehyde,3 numerous elegant investi-
gations have established the broad utility of using several
chiral b-amino alcohols,4 and their polymer-supported
analogues5 as chiral catalysts. However, a major problem
associated with most homogeneous chiral catalyst systems
is the separation and recycling of the expensive chiral cat-
alyst. Although linear polymeric chiral catalysts with an
Meanwhile, dendrimers or dendronized polymers are
among the most exciting molecular architectures that have
been recently developed, and they have paved the way for a
new class of materials with promising applications.9 The
dendritic rods can thus be used as ideal scaffolds for the
immobilization of chiral catalysts, yielding structurally
well-defined recyclable catalysts.10 Unlike ordinary poly-
mers, chiral dendrimers are characterized by their elaborate
structure, which allows us to precisely control their mole-
cular size, shape, and the numbers and positions of
functional groups.11 Organometallic dendrimers offer an
attractive avenue for catalyst development because of their
ease of characterization and their solubility in most
*
Corresponding author. Address: Department of Chemistry, Faculty of
Education, Kafr El-Sheikh University, Kafr El-Sheikh, PO Box 33516,
Egypt. Tel./fax: +20 47 3223415; e-mail addresses: ashraf@polymer.
titech.ac.jp; elshehawy2@yahoo.com
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.12.020

426
A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
common organic solvents. Thus, the unique feature of this
strategy is that the catalytic reactions are carried out in a
homogeneous manner (one phase) under appropriate reac-
tion conditions and the immobilized catalysts can be sepa-
rated from the reaction mixture afterwards by using a
solvent precipitation method (two-phase). In general,
catalyst efficiency is expected to be superior with a den-
dritic complex, since they could also overcome the dense
packing problem that exists in the linear polymeric
catalysts without sacrificing the advantage of easy recovery
by either filtration or precipitation.10,11 Thus, dendronized
chiral polymers may bridge the gap between homogeneous
and heterogeneous catalysis. Due to their unique struc-
ture and size, potential applications are manifold and
include their use as catalyst supports for asymmetric
synthesis.8,10,12
addition to a series of N-diphenylphosphinoyl arylimines
has also been reported.17
As an extension of our research program aimed at develop-
ing practical immobilized chiral catalysts, we herein report
the first application of the above-mentioned chiral dendri-
mers PS(Ephed)n as chiral catalysts in the dialkylzinc addi-
tion reaction to aldehydes. Our design demonstrated that
the chiral dendrimers serve as highly active homogeneous
chiral catalysts and allow for significantly more facial cat-
alyst recovery when compared to the corresponding non-
polymeric catalysts.
2. Results and discussion
Over the course of our continuing study on asymmetric
synthesis using recyclable chiral ligands and catalysts,13,14
we became interested in the attractive characteristics of
dendrimers. As a part of our research, we are interested
in the precise synthesis of a novel special shaped macro-
molecules with different architectures including chain-end
and in-chain-functionalized polystyrenes with a definite
number of benzyl halide functionalities by means of living
anionic polymerization.15,16 Thus, we have recently suc-
cessfully synthesized a novel series of chain-end-functional-
ized polystyrenes with a definite number of chiral ephedrine
moieties dendritically distributed at their hyperbranched
chain-ends PS(Ephed)n (Fig. 1), by an attractive iterative
methodology based on a divergent approach, by which
well-defined chain-end-functionalized polystyrenes with a
definite number of benzyl bromide functionalities were pre-
pared, followed by the introduction of the ephedrine moi-
eties.17 The preliminary application of these dendritic
chiral polymers in the highly enantioselective diethylzinc
As has been mentioned in the preceding section, we have
recently described the synthesis and application of a new
kind of dendronized polymers with chiral ephedrine incor-
poration at the polystyrene hyperbranched chain-ends
PS(Ephed)n as highly effective chiral ligands for the enan-
tioselective diethylzinc addition to a series of N-diphenyl-
phosphinoyl imines17 (Fig. 1 and Scheme 1). According
to our previous study,17 all dendronized chiral polymers
used were found to be highly active chiral ligands and the
addition products were obtained with high enantioselectiv-
ities (up to 93% ee). It was noted that higher enantioselec-
tivities of the addition products were observed when the
generation of the pendant dendron that includes the chiral
moieties was increased from two to eight, while dendron-
ized polymers with a higher generation of sixteen ephedrine
moieties PS(Ephed)16 drove the asymmetric ethylation
reaction to a lower yield and enantioselectivity. In contin-
uation of this study, the catalytic efficiency of the dendron-
ized chiral polymers PS(Ephed)2–PS(Ephed)16 as chiral
OH
Ph
Me
Ph
Me
OH
Me
N
Ph
OH
Me
Ph
OH
Me
Me
Me
N
Ph
OH
N
N
Me
Me
Ph
OH
Me
Me
Ph
HO
Ph
N
N
N
Me
OH
Me
N
OH
Me
Me
Ph
Me
Ph
Me
OH
Me
Ph
OH
Me
N
Me
Me
Ph
OH
N
Me
Me
Ph
N
OH
Me
Me
Ph
N
Me
Ph
Me
Me
N
N
N
Me
OH
OH
N
Me
Me
n
n
n
n
Me
OH
Ph
N
N
OH
Ph
Me
Me
Me
N
Me
Me
Me
OH
OH
Ph
Me
Ph
Me
Ph
N
N
Me
Me
OH
OH
Me
N
N
Me
N
Me
OH
Ph
(1R,2S)-PS(Ephed)2
Me
OH
Me
Ph
Ph
Me
Me
Ph
N
N
HO
(1R,2S)-PS(Ephed)4
Me
OH
Ph
Me
OH
Me
Me
Me
Me
N
N
Ph
Me
Me
OH
N
Me
Me
(1R,2S)-PS(Ephed)8a
(1S,2R)-PS(Ephed)8b
OH
Ph
N
Me
OH
Ph
OH
Ph
Ph
Ephed = Ephedrine
(1R,2S)-PS(Ephed)16
Figure 1. Structures of chain-end functionalized polystyrenes having 2, 4, 8, and 16 chiral ephedrine moieties PS(Ephed)n.

A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
427
O
P
Chiral dendrimers
PS(Ephed)n
O
P
H
H
Ph
Ph
Ph
Ph
Et2Zn
+
Ar
N
*
N
Toluene, rt, 48h
Ar
(up to 93% ee)
Scheme 1. Diethylzinc addition to N-diphenylphosphinoyl imines using chiral dendrimers Ps(Ephed)n.
H
catalysts in the enantioselective addition of dialkylzincs to
aldehydes was further examined.
In order to optimize the reaction conditions, the enantio-
selective diethylzinc addition reaction to benzaldehyde 1a
using the above-mentioned macromolecular chiral catalysts
PS(Ephed)2–PS(Ephed)16 was chosen as the model reaction
(Scheme 2). The results are summarized in Table 1. Under
the same reaction conditions, the asymmetric diethylzinc
addition to benzaldehyde 1a in the presence of catalytic
amounts of chiral dendrimers PS(Ephed)2–PS(Ephed)16
(5 mol %; based on the total number of chiral ephedrine
moieties at the periphery, relative to benzaldehyde) in tol-
uene at 0 °C for 48 h was first examined (Table 1, entries
1, 4, 7, and 8, respectively). As can be seen, when chiral
dendrimer PS(Ephed)2, bearing two stereogenic sites at
the periphery, was used as a chiral catalyst, the correspond-
ing enantiomerically enriched (R)-1-phenyl-1-propanol 2a
was obtained with a chemical yield of 63% and an enanti-
oselectivity of 72% ee (Table 1, entry 1). The same reaction
using chiral dendrimer PS(Ephed)4 afforded the addition
product (R)-2a with a higher ee value of 78% ee and chem-
ical yield of 77% (Table 1, entry 4). Interestingly, the chem-
ical yield as well as the enantioselectivity of the addition
As pointed out in the literature, when chiral dendrimers
with heteroatoms in their polymeric backbones were used
as chiral ligands in the enantioselective dialkylzinc addition
to aldehydes, an excess amount of dialkylzinc reagents
should be used due to the unfavorable coordination that
may occur with the dialkylzinc, and may also result in
reducing the enantioselectivity of the addition prod-
ucts.8b,f,g Therefore, it is necessary to avoid any unfavor-
able coordination between the dialkylzinc reagents and
the framework of the dendrimer. Thus, we have devised
the above-mentioned chiral dendrimers PS(Ephed)2–
PS(Ephed)16 that are shown in Figure 1 with hydrocarbon
backbone chains (i.e., without any heteroatoms either in
the polystyrene main chain or in the dendritic chain-ends).
In this case, the polymer backbone hardly coordinates with
the dialkylzinc reagent and each chiral site of the dendritic
chiral catalyst is anticipated to work independent of other
chiral sites.
O
H
H
HO
HO
Chiral dendrimers
PS(Ephed)n
H
Et2Zn
+
+
Toluene, 0 oC
(S)-2a
(R)-2a
1a
Scheme 2. Catalytic asymmetric addition diethylzinc to benzaldehyde using chiral dendrimers PS(EPhed)n.
a
Table 1. Catalytic enantioselective diethylzinc addition to benzaldehyde 1a using chiral dendrimers PS(Ephed)2–PS(Ephed)16
Entry
Chiral dendrimer
Reaction time (h)
Alcohol
eec (%)
(mol %)
Yieldb (%)
Config.d
1
2
3
4
5
6
7
8
9
10
11
12f
13
PS(Ephed)2
5
7
10
5
7
10
5
5
5
5
10
5
48
48
48
48
48
48
48
48
96
72
48
48
48
63
79
88
77
89
90
94 (98)e
86
86
90
95
93
72
76
79
78
82
83
90 (92)e
84
75
79
91
89
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(S)
PS(Ephed)2
PS(Ephed)2
PS(Ephed)4
PS(Ephed)4
PS(Ephed)4
PS(Ephed)8a
PS(Ephed)16
PS(Ephed)2
PS(Ephed)4
PS(Ephed)8a
PS(Ephed)8a
PS(Ephed)8b
5
95
90
a All reactions were performed in toluene at 0 °C using 2.2 M equiv of diethylzinc.
b Yields after purification by column chromatography (hexane/ethyl acetate = 4:1).
c Determined by HPLC analysis on a chiral stationary phase (Chiralcel OD-H).
d The absolute configurations were assigned by comparing the sign of their specific rotations with those reported in the literature.4c,d,i,5b,c,18
e Data in parentheses are obtained from the same reaction using (1R,2S)-N-benzylephedrine.5e
f Recovered chiral catalyst was used.

428
A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
product 2a was increased markedly on using PS(Ephed)8a
that having eight ephedrine moieties (90% and 94% ee,
respectively, Table 1, entry 7). More interestingly, chiral
dendrimer PS(Ephed)16, with sixteen ephedrine moieties
at the periphery of the hyperbranched chain-ends, drove
the asymmetric ethylation reaction of 1a with an enantio-
selectivity of 84% ee and a chemical yield of 86% (Table
1, entry 8).
also the enantioselectivity of the addition product. It is
interesting to note that the same behavior was also ob-
served during our previous study on the enantioselective
diethylzinc addition to N-diphenylphosphinoyl imines
using the same chiral dendrimers.17
Although the origin of reasons behind the remarkable
number effect of the chiral moieties at the periphery of
the hyperbranched chain-ends on the chemical yields and
enantioselectivities of the addition product remains un-
clear, a tentative explanation can be discussed on the basis
of our previous finding on similar dendrimers.19 It has been
found that the conformation of the polystyrene main chain
within the polystyrene end-functionalized with hyper-
branched dendritic moieties in nonpolar solvents strongly
depends on the number of end-functional moieties and
consequently on the molecular weight of the dendritic
hyperbranched chain-ends. However, the molecular weight
of the hyperbranched dendritic chain-ends that include the
chiral moieties is increased six times going from
PS(Ephed)2 to PS(Ephed)8. Thus, the volume ratio of the
dendritically hyperbranched chain-ends in the case of
PS(Ephed)8 relative to the polystyrene main chain is seen
to be high and apparently was found to be comparable
with the block copolymer. Therefore, it is possible to state
that the dendritic hyperbranched chain-ends in the case of
chiral dendrimer PS(Ephed)8 can behave as a block copoly-
mer in solutions. Considering the above-mentioned factors,
it is supposed that the chain conformation for PS(Ephed)8
may be more preferable for segregating the end-functional
chiral moieties from the polystyrene main chains and can
behave similarly to immiscible block copolymers. Further
investigation to address the detailed mechanism of the en-
hanced stereoselectivity of the addition products by
increasing the number of chiral moieties at the hyper-
branched chain-ends, together with the size of the hyper-
branched dendritic moieties, is now the focus of our
interest.
As can be seen from the results that are shown in Table 1
(entries 1, 4, 7, and 8), under the same reaction conditions,
the enantioselectivity of the addition product 2a obtained
from using PS(Ephed)8a (entry 7) was higher than that ob-
served when using PS(Ephed)16 (entry 8) as chiral catalysts.
It can be speculated that the lower enantioselectivity of 2a
that was obtained from using PS(Ephed)16 (entry 8) as a
chiral catalyst resulted from the highly condensed packing
of the chiral moieties at the periphery of the dendrimer,
which might cause the interference of the active chiral sites
at the periphery of PS(Ephed)16 either with each other and/
or with the polymer backbone chains, while the environ-
ments of chiral sites at the polystyrene hyperbranched
chain-ends of PS(Ephed)8a might have enough space to
work more independently as chiral catalysts.
The influence of the molar ratios of the dendritic chiral cat-
alyst was also examined to establish whether there is any
relationship between its molar ratios with the enantiomeric
excess of the resulting secondary alcohol. The results ob-
tained are also included as shown in Table 1. On perform-
ing the diethylzinc addition reaction to benzaldehyde 1a in
the presence of higher molar ratios of PS(Ephed)2 (7 and
10 mol %; Table 1, entries 2 and 3, respectively), the addi-
tion reaction turned out to be faster while the chemical
yield as well as the enantioselectivity of the addition prod-
uct 2a was increased markedly, but still lower than those
values obtained from the same reaction using 5 mol % of
PS(Ephed)8a (entry 7). The same observation could also
be seen using higher molar ratios of PS(Ephed)4 (7 and
10 mol %; Table 1, entries 5 and 6, respectively); the chem-
ical yield was significantly increased with increasing the
molar ratio from 5 to 10 mol % of PS(Ephed)4, while no
considerable change in the enantioselectivity of the addi-
tion product with increasing the molar ratio of PS(Ephed)4
from 7 to 10 mol % of chiral dendrimer PS(Ephed)4 (entry
6) was observed. However, on performing the diethylzinc
addition reaction to benzaldehyde 1a using 5 mol % of chi-
ral dendrimers PS(Ephed)2 and PS(Ephed)4 as chiral cata-
lysts, but for longer reaction times (Table 1, entries 9 and
10, respectively), significant increases in the chemical yields
and slightly higher enantioselectivities of the addition
product 2a were observed. Interestingly, the diethylzinc
addition reaction to benzaldehyde 1a using a higher molar
ratio of chiral catalyst PS(Ephed)8a (10 mol %) afforded the
addition product 2a with almost the same enantioselectivi-
ty (91% ee, entry 11) similar to that observed in the same
reaction using 5 mol % of PS(Ephed)8a (90% ee, entry 7).
An important feature of the design of dendronized
polymeric catalysts is the easy and reliable separation of
the chiral catalyst based on its rather large molecular size
with a rigid cylinder structure and different solubilities in
various organic solvents. Unlike the corresponding cross-
linked polystyrene-supported chiral ligands and most com-
mon linear polymers, the dendritic chiral polymers
PS(Ephed)n used in this study are well soluble in most com-
mon organic solvents such as THF, toluene, and chloro-
form, but they are insoluble in methanol. This different
solubility provides a convenient and reliable method for
the isolation of the addition products, as well as the recov-
ery of the dendritic catalysts by a precipitation method.
Herein, chiral dendrimer PS(Ephed)8a was used for a recy-
cling experiment. Upon completion of the reaction, a THF
solution of the resulting residue thus obtained after the
workup of the reaction mixture was added into a mixture
of MeOH and HCl. The chiral catalyst PS(Ephed)8a was
precipitated quantitatively and recovered by filtration pro-
cess (see Section 4). Thus, the isolation of the addition
products as well as the recovery of dendritic chiral catalyst
was very easy. Interestingly, as shown in Table 1, the dieth-
ylzinc addition reaction to benzaldehyde 1a using the
The above-mentioned set of experiments clearly revealed
that increasing the number of chiral ephedrine moieties at
the periphery and consequently the size of the pendant den-
dritic chain-ends improved not only the chemical yield but

A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
429
recovered dendronized polymer PS(Ephed)8a afforded the
addition product 2a with a comparable result to that of en-
try 7 (Table 1, entry 12). It is more interesting to note that
the high enantioselectivity observed in the asymmetric
diethylzinc addition to benzaldehyde 1a using chiral den-
drimer PS(Ephed)8a (90% ee, Table 1, entry 7) was found
to be comparable to that reported for the same reaction
using the corresponding monomeric chiral catalyst
(1R,2S)-N-benzylephedrine (92% ee, Table 1, entry 7)5e
under otherwise identical reaction conditions.
2-naphthylaldehydes 1b,c (entries 5 and 6, respectively).
More interestingly, the enantioselectivity of the addition
reactions was found to be subjected to a remote electronic
effect; the enantioselectivity remarkably increases with
more reactive substrates. The catalytic enantioselective
diisopropylzinc addition to an aldehyde possessing an
electron-withdrawing group at the para position of the aro-
matic ring proceeded with slightly higher enantioselectivity
than the addition to an aldehyde with an electron-donating
group (compare entries 11 vs 7 and 9 and 12 vs 8 and 10,
respectively, Table 2); however, the difference in enantiose-
lectivities for the ortho- and para-isomers 1d,e, 1f,g, and
1h,i, was negligible (entries 7–12, respectively). For exam-
ple, an electron-donating group (MeO) turned out to
reduce the level of asymmetric induction rather more than
an electron-withdrawing substituent (Cl) both in the para
(compare entries 10 vs 12 in Table 2) and ortho series (com-
pare entries 9 vs 11 in Table 2). This phenomenon was
found to be in quite good accordance with the earlier re-
ports by some groups,18a,21 who observed the enhancement
of enantioselection for benzaldehyde bearing strongly elec-
tron-withdrawing groups. Most importantly, the diisopro-
pylzinc addition to 3-phenylpropanal 1j proceeded in a
highly enantioselective manner to give the corresponding
secondary alcohol, 2-methyl-5-phenyl-3-pentanol, 2m with
a high enantioselectivity of 95% ee (entry 13). Thus,
dendritic chiral catalyst PS(Ephed)8a proved to induce the
formation of the secondary alcohols 2a–m with high
enantioselectivities (87–95% ee).
Since in the asymmetric reactions it is important that both
enantiomers of a given compound can be prepared, the
dendritic chiral catalyst PS(Ephed)8b having eight (1S,2R)-
ephedrine moieties at the hyperbranched chain-ends
was examined in the catalytic enantioselective ethylation
of benzaldehyde 1a. Dendritic chiral catalyst PS(Ephed)8b
worked well as in the case of using PS(Ephed)8a and led
smoothly to the desired secondary alcohol 2a with almost
the same chemical yield and enantioselectivity, but with
reversed stereoselectivity (Table 1, entry 13).
Once the dendronized chiral catalyst PS(Ephed)8, bearing
eight chiral sites of ephedrine moieties, has been found to
be the best catalyst for the enantioselective diethylzinc
addition to benzaldehyde 1a, its catalytic efficiency was fur-
ther demonstrated in the dialkylzinc addition reaction to a
series of substituted aldehydes. The dialkylzinc addition
reactions were performed under the optimal reaction con-
ditions that were identified for the diethylzinc addition
reaction to 1a using dendritic chiral catalyst PS(Ephed)8a
as specified in Table 1 (entry 7). The collective results of
dialkylzinc addition reactions to a series of aldehydes 1a–
j that are displayed in Scheme 3 are summarized in Table
2. The obtained results revealed that the dendritic chiral
catalyst PS(Ephed)8a promotes the highly enantioselective
addition of dialkylzincs to all aromatic substituted alde-
hydes 1a–j.
It should be mentioned that the obtained high yields and
enantioselectivities of the addition products suggested that
nearly all chiral sites at the periphery of the dendritic
hyperbranched chain-ends of catalyst PS(Ephed)8a worked
effectively. Thus, the observed selectivity clearly demon-
strated that, similar to the reaction using almost the same
molar ratios of the corresponding monomeric chiral li-
gand,5e the eight parts in situ formed alkylzinc alkoxides
of the amino alcohols (active sites) can operate indepen-
dently, as in solution system, and can form an appropriate
reaction field for the highly enantioselective addition of
dialkylzinc to aldehydes.
In the presence of a catalytic amount of PS(Ephed)8a
(5 mol %), the enantioselective addition of diisopropylzinc
(i-Pr2Zn) to benzaldehyde 1a afforded the addition product
(R)-2-methyl-1-phenylpropan-1-ol 2b with slightly higher
enantioselectivity (92% ee, entry 2) than that observed in
the same reaction using diethylzinc (90% ee, entry 1). Inter-
estingly, the diethylzinc addition to 2-naphthylaldehyde 1c
afforded the addition product (R)-1-(20-naphthyl)-1-propa-
nol 2d with a slightly higher enantioselectivity of 91% ee
(entry 4) than that observed with its analogue 1-naphthyl-
aldehyde 1c (89% ee, Table 2, entry 3). The same tendency
was also observed in the diisopropylzinc addition to 1- and
To the best of our knowledge, the present method is the
first example for the application of such a type of well-de-
fined macromolecular dendritic chiral catalysts as unique
soluble chiral catalysts for the enantioselective dialkylzinc
addition to aldehydes. Interestingly, the chemical yields
obtained and enantioselectivities, in most cases, were found
to be not only higher than those obtained when using the
corresponding polymer-supported ephedrine5b,c,e,f,22 but
also higher than those obtained from using several dendr-
onized polymers having the same chiral ephedrine moiety
with either hydrocarbon8b,c,23 or silicon8e,f,24 backbone
structures.
O
OH
*
PS(Ephed)8a (5 mol%)
Toluene, 0 oC, 48 h
R2Zn
+
Ar
1a-j
H
Ar
R
(2.2 equiv)
3. Conclusion
2a-m
(R = Et, i-Pr)
We have described the first application of chain-end-func-
tionalized polystyrenes bearing dendritic chiral b-amino
alcohol moieties at the periphery of their hyperbranched
Scheme 3. Catalytic asymmetric dialkylzinc addition to aldehydes using
chiral dendrimer Ps(Ephed)8a
.

430
A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
a
Table 2. Catalytic enantioselective addition of dialkylzinc reagents to aldehydes using dendritic chiral catalyst PS(Ephed)8a
Entry
Aldehyde
(Ar)
R2Zn
Alcohol
Yieldb (%)
eec,d (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
1a
1a
1b
1c
1b
1c
1d
1e
1f
Ph
Ph
Et2Zn
i-Pr2Zn
Et2Zn
2a
2b
2c
2d
2e
2f
94
93
90
91
92
90
91
93
88
89
93
91
94
90
92
89
91
90
92
89
91
87
88
92
94
95
1-Naphthyl
2-Naphthyl
1-Naphthyl
2-Naphthyl
2-Me–C6H4
4-Me–C6H4
2-MeO–C6H4
4-MeO–C6H4
2-Cl–C6H4
4-Cl–C6H4
PhCH2CH2
Et2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
i-Pr2Zn
2g
2h
2i
1g
1h
1i
2j
2k
2l
1j
2m
a All reactions were performed in toluene at 0 °C for 48 h using 2.2 M equiv of dialkylzinc and 5 mol % of chiral dendrimer PS(Ephed)8a
.
b Isolated yields after flash chromatography.
c The ee values were determined by HPLC analysis using a chiral stationary phase (Chiralcel-OD, Chiralcel OB-H or Chiralpak-AD column).
d Absolute configurations were determined by comparing the sign of their specific rotations with those reported in the literature.4a,c,d,h,i,5b,c,e,f,18,20
chain-ends as a new type of hybrid catalysts, with the po-
tential of combining the advantages of linear polymer
and perfect dendrimer chiral catalyst, for the enantioselec-
tive dialkylzinc addition to aldehydes. They exhibited high
catalytic activity and enantioselectivity very similar to
those observed with the corresponding monomeric chiral
N-benzyl ephedrine in solution system. The number of chi-
ral moieties at the periphery of pendant dendrons has a
major impact on the catalytic properties. Chiral dendrimer
PS(Ephed)8 showed high catalytic activity and enantiose-
lectivity affording the addition products with enantioselec-
tivities up to 95% ee. The immobilized chiral catalysts
could be easily recovered from the reaction solution by
using solvent precipitation. We believe that this study pro-
vides a new direction for the future design and synthesis of
highly efficient macromolecular chiral catalysts for asym-
metric synthesis. The design, synthesis, and reactivity of
other dendronized chiral ligands and catalysts are now
the focus of our continuing efforts.
dure previously reported.16a The benzyl bromide- and
chiral ephedrine-end-functionalized polystyrenes have been
designated by PS(BnBr)n and PS(Ephed)n, and the sub-
script numbers are corresponding to the number of the ter-
minal benzyl bromide and ephedrine moieties, respectively.
1H and 13C NMR spectra were measured on a Bruker DPX
1
(300 MHz for H and 75 MHz for 13C) in CDCl3 at 25 °C
with TMS as the internal standard. Size-exclusion chro-
matograms (SEC) were measured with a TOSOH HLC-
8020 at 40 °C equipped with ultraviolet (254 nm) and
refractive index detections. THF was used as a carrier sol-
vent at a flow rate of 1.0 mL/min 40 °C. Calibration curves
were made with standard polystyrene samples to determine
Mn and Mw/Mn values. FT-IR spectra were recorded on a
JEOL JIR-AQS20M FT-IR spectrophotometer. Flash
chromatography was performed on deactivated silica gel
(Matrix 60A, 37–70 lm) and the spots were detected with
UV model UVGL-58. Optical rotations were measured
on materials isolated either by bulb-to-bulb distillation or
by column chromatography. Optical rotations were mea-
sured using a Perkin–Elmer 341 Polarimeter in a 10 cm cell
at 25 °C. HPLC analyses were carried out using a DIACEL
Chiralcel-OD, Chiralcel OB-H or Chiralpak-AD column
(0.46 ꢁ 25 cm2) with Shimadzu LC-6A with a 254 nm UV
detector.
4. Experimental
4.1. General
All reactions were performed under nitrogen atmosphere.
All reagents (>98% purities) were purchased from Aldrich
Co and used as received unless otherwise stated. Tetrahy-
drofuran (THF) was refluxed over sodium wire, distilled
over LiAlH4 under a nitrogen atmosphere and finally dis-
tilled from its sodium naphthalene under high vacuum
(10ꢀ6 torr). DMF and toluene were freshly distilled over
CaH2 under dry nitrogen. Styrene was washed with 5%
NaOH, dried over MgSO4, and distilled over CaH2 under
reduced pressure, and after adding Bu2Mg (3 mol %), sty-
rene was finally distilled under high vacuum (10ꢀ6 torr).
All polymerizations were carried out under high vacuum
conditions (10ꢀ6 torr) in sealed glass reactors equipped
with break seals. 1,1-Bis(3-tert-butyldimethylsilyloxymeth-
ylphenyl)- ethylene was prepared according to the proce-
4.2. Synthesis of chain-end-functionalized polystyrenes with
2, 4, 8, and 16 benzyl bromide moieties PS(BnBr)n
The title chain-end-functionalized polystyrenes were syn-
thesized following our previously reported procedures.16,17
Polystyrene end-functionalized with two benzyl bromide
moieties PS(BnBr)2 was first synthesized by the following
typical experimental procedure: A solution of styrene
(10.82 g, 104 mmol) in tert-butyl benzene (42.6 mL) was
polymerized with sec-BuLi (0.534 mmol, 5.71 mL of a hep-
tane solution) at 0 °C for 20 min and then at room temp for
4 h. The reaction mixture was then chilled to ꢀ78 °C, and
48.7 mL of THF was first added followed by a solution of

A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
431
1,1-bis(3-tert-butyldimethylsilyloxymethylphenyl)ethylene
(0.31 g, 0.649 mmol) in THF (7.82 mL). The reaction mix-
ture was left at ꢀ78 °C for additional 30 min and then ter-
minated with degassed methanol. The resulting polymer
was precipitated in methanol, purified by reprecipitation
from its THF solution with methanol three times, and
freeze-dried from its absolute benzene solution for 24 h.
4.2.2. PS(BnBr)4. 1H NMR (CDCl3): d 0.36–0.82 (br m,
18H, CH(CH3)CH2CH3), 1.05–2.38 (br m, 577H, CH2CH),
2.98–3.40 (br m, 5H, ArCHAr + (Ar)2CCH2Ar), 4.33–4.39
(br m, 8H, ArCH2Br), 6.09–7.33 (m, 951H, ArH); 13C
NMR (CDCl3): d 11.41, 20.27, 20.59, 30.97, 31.54, 31.67,
33.74, 34.18, 40.39, 41.72, 42.46, 42.69, 43.57, 43.91,
44.28, 44.88, 46.09, 46.49, 50.89, 76.66, 77.07, 77.37,
125.57, 125.72, 127.39, 127.51, 127.73, 127.86, 128.05,
128.13, 128.33, 128.97, 137.74, 145.17, 145.28, 145.39,
145.77, 145.87, 145.98, 146.14, 149.08; FT-IR (KBr,
cmꢀ1): 1208 (CH2Br). Anal. Calcd for C1543H1553Br4: C,
90.83; H, 7.62; Br, 1.55. Found: C, 91.02; H, 7.69; Br, 1.52.
The two 3-tert-butyldimethylsilyloxymethylphenyl (SMP)
functionalities thus introduced at the polystyrene chain-
ends were transformed into two benzyl bromide functional-
ities by the following typical experimental procedure: The
resulting SMP-end-functionalized polystyrene (4.2 g,
0.425 mmol per two SMP functionalities) reacted with a
mixture of LiBr (1.85 g, 21.25 mmol) and (CH3)3SiCl
(2.88 g, 26.56 mmol) in a mixed solvent of chloroform
(125 mL) and acetonitrile (47 mL) at 40 °C for 24 h. After
quenching and usual workup, the polymer was precipitated
in methanol and purified by reprecipitation from its THF
solution with methanol two times. After being freeze-dried
in vacuo from its absolute benzene solution for 24 h, chain-
end-functionalized polystyrene with two benzyl bromide
moieties PS(BnBr)2 at the chain-ends was obtained.
4.2.3. PS(BnBr)8. 1H NMR (CDCl3): d 0.28–0.81 (br m,
42H, CH(CH3)CH2CH3), 1.09–2.39 (br m, 583H, CH2CH),
2.71–3.47 (br m, 13H, ArCHAr + (Ar)2CCH2Ar), 4.32–
4.39 (br m, 16H, ArCH2Br), 6.11–7.26 (br m, 981H,
ArH); 13C NMR (CDCl3): d 11.36, 20.28, 20.43, 30.29,
31.16, 31.58, 34.03, 40.44, 41.78, 42.65, 43.58, 44.26,
46.01, 46.51, 51.18, 76.68, 77.10, 77.31, 125.56, 125.71,
126.72, 127.38, 127.50, 127.72, 128.03, 128.11, 128.34,
128.88, 129.66, 137.27, 145.28, 145.39, 145.74, 145.76,
145.88, 145.98, 146.15, 149.06; FT-IR (KBr, cmꢀ1): 1208
(CH2Br). Anal. Calcd for C1620H1642Br8: C, 89.53; H,
7.56; Br, 2.88. Found: C, 89.50; H, 7.66; Br, 2.79.
A polystyrene end-functionalized with four benzyl bromide
functionalities PS(BnBr)4, was synthesized by the following
typical procedure: The 1,1,-diphenylalkylanion was first
synthesized by reacting 1.20 mmol of 1,1-bis(3-tert-butyl-
dimethylsilyloxymethylphenyl)ethylene in THF (14.5 mL)
with sec-BuLi (1.13 mmol, 3.67 mL in heptane) at ꢀ78 °C
for 15 min. A solution of chain-end functionalized polysty-
rene with two benzyl bromide functionalities PS(BnBr)2
(4.01 g, 0.42 mmol per two BMP groups) in THF
(49.3 mL) was then added at ꢀ78 °C. The reaction mixture
was left at ꢀ78 °C for an additional 2 h and terminated
with degassed methanol. The polymer was then precipi-
tated and reprecipitated three times from its THF solution
to methanol and freeze-dried from its absolute benzene
solution for 24 h. By the same procedure described previ-
ously, the resulting polymer with four SMP functionalities
was reacted again with a mixture of LiBr and (CH3)3SiCl in
a mixed solvent of chloroform and acetonitrile (4:3, v/v) at
40 °C for 24 h to afford the corresponding chain-end-
functionalized polystyrene having four benzyl bromide
functionalities. Similarly, chain-end-functionalized polysty-
renes PS(BnBr)8 and PS(BnBr)16 were successfully and
quantitatively synthesized by repeating the reaction
sequence two times more.
4.2.4. PS(BnBr)16. 1H NMR (CDCl3): d 0.17–0.88 (br m,
90H, CH(CH3)CH2CH3), 1.14–2.43 (br m, 698H, CH2CH),
2.72–3.51 (br m, 29H, ArCHAr + (Ar)2CCH2Ar), 4.33–
4.39 (br s, 32H, ArCH2Br), 7.25–6.08 (br m, 1045H,
ArH); 13C NMR (CDCl3): d 11.36, 20.31, 20.44, 29.88,
30.27, 31.18, 34.02, 34.66, 40.43, 41.67, 42.60, 43.55,
43.93, 44.25, 45.93, 46.47, 50.14, 51.13, 76.67, 77.10,
77.30, 77.52, 125.56, 125.71, 126.73, 127.37, 127.49,
127.71, 128.02, 128.11, 128.33, 128.90, 129.67, 137.29,
145.16, 145.26, 145.37, 145.76, 145.86, 145.98, 146.12,
149.04; FT-IR (KBr, cmꢀ1): 1208 (CH2Br). Anal. Calcd
for C1778H1824Br16: C, 87.36; H, 7.47; Br, 5.17. Found: C,
87.51; H, 7.49; Br, 5.20.
4.3. Synthesis of chain-end-functionalized polystyrenes with
2, 4, 8, and 16 chiral ephedrine moieties PS(Ephed)n
Typical procedure for the synthesis of PS(Ephed)8 is as fol-
lows: Under nitrogen atmosphere, a solution of ephedrine
(0.3 g, 1.8 mmol) in DMF (5 mL) was added drop-wise
within 5 min at 0 °C to a mixture of a DMF (20 mL) solu-
tion of chain-end-functionalized polystyrene with eight
benzyl bromide moieties [PS(BnBr)8 (0.5 g, Mn =
21.71 ꢁ 103 g/mol, 0.18 mmol), based on eight BnBr moie-
ties] and K2CO3 (0.25 g, 1.8 mmol). The reaction mixture
was allowed to warm gradually to 50 °C and stirred further
for 24 h. The reaction mixture was then allowed to return
to room temperature and then poured into 1 N HCl meth-
anolic solution (50 mL) to precipitate the polymer. The
polymer was reprecipitated from its THF solution to meth-
anol two times more followed by freeze-drying from its
absolute benzene solution to afford the corresponding chi-
ral polymer PS(Ephed)8. The other dendritic chiral poly-
mers PS(Ephed)2, PS(Ephed)4, and PS(Ephed)16 were
synthesized by the same procedure and under the same
reaction conditions.
4.2.1. PS(BnBr)2. 1H NMR (CDCl3): d 0.49–0.83 (br m,
6H, CH(CH3)CH2CH3), 1.09–2.37 (m, 563H, CH2CH),
3.41–3.52 (br s, 1H, ArCHAr), 4.33–4.39 (br m, 4H,
ArCH2Br), 6.25–7.23 (m, 940H, ArH); 13C NMR (CDCl3):
d 11.37, 20.43, 20.89, 30.29, 31.16, 31.58, 33.73, 40.44,
41.78, 42.47, 42.63, 43.56, 43.91, 44.28, 44.88, 46.09,
46.49, 51.18, 76.49, 77.11, 77.31, 77.53, 125.57, 125.72,
126.72, 127.38, 127.50, 127.72, 128.03, 128.13, 128.34,
128.88, 129.66, 137.27, 145.17, 145.39, 145.77, 145.87,
145.98, 146.14, 149.07; FT-IR (KBr, cmꢀ1): 1208 (CH2Br).
Anal. Calcd for C1511H1515Br2: C, 91.55; H, 7.65; Br, 0.79.
Found: C, 91.48; H, 7.76; Br, 0.77.

432
A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
The degree of chiral ephedrine end-functionalization was
determined by comparing the relative intensities of the
1H NMR resonance peaks at 3.69–3.91 ppm assigned for
the methylene protons of the benzyl ephedrine moieties,
with those at 0.17–0.84 ppm attributed for the methyl pro-
tons of the sec-butyl groups (initiator fragment). The inte-
4.3.4. PS(Ephed)16. 1H NMR (CDCl3): d 0.17–0.84 (m,
90H, CH(CH3)CH2CH3), 1.09–2.35 (m, 745H, CH2CH +
CH3N + CH3CHN), 2.81–3.55 (br m, 45H, ArCHAr +
(Ar)2CCH2Ar + CH3CHN), 3.71–3.91 (br s, 32H,
ArCH2N), 4.72–4.89 (br m, 16H, CHOH), 6.18–7.25 (br
m, 1133H, ArH); 13C NMR (CDCl3): d 9.89, 11.33,
20.29, 20.44, 30.22, 31.28, 34.19, 38.78, 40.88, 42.54,
43.93, 45.49, 47.14, 50.66, 59.12, 63.59, 73.44, 125.61,
125.87, 126.91, 127.34, 127.71, 127.93, 128.19, 128.37,
128.56, 128.89, 129.51, 133.75, 137.22, 139.97, 142.55,
145.29, 145.49, 145.70, 145.83, 146.28, 149.07; FT-IR
1
gral values of the H NMR resonance peaks attributed for
the other protons of ephedrine moieties were also taken
into consideration. The functionalities of chiral ephedrine
moieties thus determined were found to be in quite agree-
ment to those predicted within analytical limits. The Mn
1
values could be determined by H NMR by using the res-
(KBr, cmꢀ1): 3345 (OH). Anal. Calcd for C1953H2063
-
onances at 6.2–7.3 ppm (aromatic protons) and 0.17–
0.84 ppm (methyl protons of the initiator fragment) and
they were also found in quite well agreement with those
calculated.
N16O16: C, 90.21; H, 7.94; N, 0.86. Found: C, 89.98; H,
7.77; N, 0.85.
4.4. Typical procedure for the enantioselective addition of
dialkylzinc reagents to aldehydes catalyzed by chiral
dendrimers PS(Ephed)n (Table 2, entry 7)
4.3.1. PS(Ephed)2. 1H NMR (CDCl3): d 0.49–0.83 (br m,
6H, CH(CH3)CH2CH3), 1.08–2.32 (br m, 578H,
CH2CH + CH3N + CH3CHN), 2.87–2.99 (br m, 2H,
CH3CHN), 3.46–3.56 (br s, 1H, ArCHAr), 3.72–3.83 (br
m, 4H, ArCH2N), 4.78–4.90 (br m, 2H, CHOH), 6.30–
7.25 (br m, 949H, ArH); 13C NMR (CDCl3): d 9.85,
11.34, 20.28, 20.46, 29.85, 31.18, 33.77, 38.73, 40.59,
41.92, 43.50, 45.86, 46.59, 50.37, 59.14, 63.66, 73.52,
125.68, 125.83, 126.80, 127.22, 127.56, 127.81, 128.01,
128.25, 128.67, 129.07, 129.63, 133.46, 137.18, 140.21,
142.46, 145.09, 145.28, 145.58, 146.19, 149.17; FT-IR
To a dry toluene (2 mL) solution of a dendritic catalyst
PS(Ephed)8a (Mol. Wt., 22.54 ꢁ 103 kg/mol; 0.14 g, 0.05
mmol, 5 mol %, based on the total number of ephedrine
moieties at the periphery) at 0 °C was added a toluene solu-
tion of diethylzinc (2.2 mL of a 1 M toluene solution,
2.2 mmol) under a nitrogen atmosphere. After the reaction
mixture was stirred for 20 min at 0 °C, a toluene solution of
benzaldehyde (1a, 116 mg, 1 mmol) was added and the
reaction mixture was stirred for a further 48 h at 0 °C.
After being quenched with aqueous saturated NH4Cl solu-
tion (5 mL), the reaction mixture was extracted with
CH2Cl2 (10 mL ꢁ 3), washed with water and brine, and
dried over anhydrous magnesium sulfate (MgSO4). The
solvent was evaporated to dryness under reduced pressure
and the residue thus obtained was dissolved in THF (5 mL)
and poured drop-wise into methanol (25 mL) to precipitate
the polymer. After filtration, the precipitated polymer was
washed thoroughly with methanol and the filtrate was
evaporated to dryness under reduced pressure. The oil res-
idue thus obtained was purified by flash column chroma-
tography [developing eluent; hexane/ethyl acetate = 4:1
(v/v), Rf = 0.45] to afford the corresponding enantiomeri-
cally enriched optically active alcohol (R)-1-phenyl-1-
propanol 2a as a colorless oil (130 mg, 95%). The enantio-
meric excess4d,i,j,20f,h was determined to be 90% by HPLC
analysis using a DIACEL Chiralcel OD-H column (hex-
ane/2-propanol 98:2, flow rate: 1 mL/min, 254 nm UV
(KBr, cmꢀ1): 3345 (OH). Anal. Calcd for C1533H1545
-
N2O2: C, 91.97; H, 7.73; N, 0.14. Found: C, 91.75; H,
7.61; N, 0.14.
4.3.2. PS(Ephed)4. 1H NMR (CDCl3): d 0.39–0.82 (br m,
18H, CH(CH3)CH2CH3), 1.09–2.35 (br m, 590H,
CH2CH + CH3N + CH3CHN), 2.95–3.34 (br m, 9H,
ArCHAr + (Ar)2CCH2Ar + CH3CHN), 3.71–3.86 (br m,
8H, ArCH2N), 4.76–4.89 (br m, 4H, CHOH), 6.16–7.27
(br m, 975H, ArH); 13C NMR (CDCl3): d 9.84, 11.36,
20.33, 20.44, 29.99, 31.37, 34.12, 38.70, 40.82, 42.06,
44.52, 45.61, 47.22, 51.12, 59.17, 63.74, 73.67, 125.66,
125.77, 126.72, 127.30, 127.63, 127.74, 128.13, 128.38,
128.45, 128.76, 129.09, 133.67, 137.39, 140.24, 142.37,
145.18, 145.39, 145.68, 145.80, 146.29, 149.09; FT-IR
(KBr, cmꢀ1): 3345 (OH). Anal. Calcd for C1590H1616
-
N4O4: C, 91.66; H, 7.76; N, 0.27. Found: C, 91.72; H,
7.73; N, 0.26.
detector, 25 °C) tR = 11.93 min for (R)-enantiomer and
25
tR = 14.85 min for (S)-enantiomer; ½aꢂD ¼ þ43:7 (c 5.5,
22
4.3.3. PS(Ephed)8. 1H NMR (CDCl3): d 0.18–0.79 (br m,
42H, CH(CH3)CH2CH3), 1.11–2.33 (br m, 607H,
CH2CH + CH3N + CH3CHN), 2.79–3.50 (br m, 21H,
ArCHAr + (Ar)2CCH2Ar + CH3CHN), 3.69–3.87 (br m,
16H, ArCH2N), 4.73–4.90 (br m, 8H, CHOH), 6.20–7.23
(br m, 1027H, ArH); 13C NMR (CDCl3): d 9.91, 11.35,
20.30, 20.48, 30.17, 31.14, 33.98, 38.75, 41.18, 42.63,
44.39, 46.22, 46.97, 50.38, 59.08, 63.44, 73.59, 125.58,
125.73, 126.81, 127.39, 127.61, 127.89, 128.26, 128.35,
128.49, 128.76, 129.34, 133.59, 137.41, 140.07, 142.45,
145.33, 145.66, 145.84, 145.99, 146.31, 149.19; FT-IR
CHCl3, 90% ee) {lit.4c,d,i,5b,c,18 ½aꢂD ¼ ꢀ47:6 (c 6.11,
1
CHCl3) for 98% ee (S)-enantiomer}; H NMR (300 MHz,
CDCl3)18a,20b,g,h,21d,f: d 0.90 (t, J = 7.5 Hz, 3H, CH3),
1.67–1.83 (m, 2H, CH2), 2.05 (br s, 1H, OH), 4.58 (t,
J = 6.6 Hz, 1H, PhCH(OH)Et), 7.25–7.39 (m, 5H, Ar-H).
13C NMR (75 MHz, CDCl3): d 10.14, 31.85, 76.05,
125.85, 127.43 (2C), 128.39 (2C), 144.57; m/z136 (M+,
23%), 107 (100), 79 (93), 78 (17), 77 (49), 51 (33).
The chemical yields and the enantiomeric excesses of the
addition products are indicated in Tables 1 and 2. The
enantiomeric excesses of the addition products were deter-
mined by HPLC analysis using a DIACEL Chiralcel OD-
H, Chiralcel OB-H, or Chiralpak AD column and by
(KBr, cmꢀ1): 3345 (OH). Anal. Calcd for C1711H1765
-
N8O8: C, 91.10; H, 7.83; N, 0.50. Found: C, 91.23; H,
7.87; N, 0.49.

A. A. El-Shehawy et al. / Tetrahedron: Asymmetry 19 (2008) 425–434
433
comparison with those reported in the literature.4d,i,j,18,20f
The addition products were established by comparison of
their physical and spectroscopic data with those reported
in the literature.4d,18,20a,b,d,e,g,h,21d,f,25 The absolute configu-
ration of the major enantiomer of the addition products
was assigned either by comparing the retention times on
HPLC4d,i,j,18,20f,h and/or by comparising the sign of their
specific rotations with those reported in the litera-
ture.4a,c,d,h,i,5b,c,e,f,18,20
133–138; (g) Wassmann, S.; Wilken, J.; Martens, J. Tetrahe-
dron: Asymmetry 1999, 10, 4437–4445; (h) Paleo, M. R.;
Cabeza, I.; Sardina, F. J. J. Org. Chem. 2000, 65, 2108–2113;
(i) Dai, W.-M.; Zhu, H.-J.; Hao, X.-J. Tetrahedron: Asym-
metry 2000, 11, 2315–2337; (j) Ohga, T.; Umeda, S.; Kawa-
nami, Y. Tetrahedron 2001, 57, 4825–4829; (k) Yus, M.;
´
Ramon, D. J.; Prieto, O. Tetrahedron: Asymmetry 2002, 13,
1573–1579; (l) Rasmussen, T.; Norrby, P.-O. J. Am. Chem.
Soc. 2003, 125, 5130–5138; (m) Wu, K.-H.; Gau, H.-M.
´
Organometallics 2004, 23, 580–588; (n) Blay, G.; Fernandez,
I.; Marco-Aleixandre, A.; Pedro, J. Tetrahedron: Asymmetry
2005, 16, 1207–1213.
4.5. Recovery of the polymer
´
5. For representative examples, see: (a) Itsuno, S.; Frechet, J. M.
J. J. Org. Chem. 1987, 52, 4140–4142; (b) Soai, K.; Niwa, S.;
Watanabe, M. J. Org. Chem. 1988, 53, 927–928; (c) Soai, K.;
Watanabe, M.; Yamamoto, A. J. Org. Chem. 1990, 55, 4832–
4835; (d) Itsuno, S.; Sakurai, Y.; Ito, K.; Maruyama, T.;
The recovered dendritic chiral polymer thus obtained from
the dialkylzinc addition reaction through the filtration was
precipitated from its THF solution in a 4:1 mixture of
MeOH–2 M HCl followed by stirring for 4 h. The precipi-
tated dendritic chiral polymer was filtered off followed by
washing thoroughly with methanol. After being freeze-
dried from its absolute benzene solution for 24 h, the
recycled dendritic chiral polymer could be used in the
enantioselective addition of dialkylzinc to aldehydes.
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