Functionalized major-groove and minor-groove chiral polybinaphthyls: Application in the asymmetric reaction of aldehydes with diethylzinc

Article abstract of DOI:10.1021/ja972623r

A series of functionalized and optically active major-groove polybinaphthyls and minor-groove polybinaphthyls have been synthesized by using the Suzuki coupling reaction and have been spectroscopically characterized. The application of these chiral polymers in the asymmetric addition of diethylzinc to aldehydes has been studied. A minor-groove polybinaphthyl is found to be an excellent catalyst for the asymmetric reaction of diethylzinc with a number of aldehydes. The molecular weight and the molecular weight distribution of the polymer have little effects on the catalytic process. The chiral polymer can be easily recovered and reused without loss of catalytic activity as well as enantioselectivity. These rigid and sterically regular chiral polybinaphthyls represent a new generation of enantioselective polymeric catalysts. The reaction of the polybinaphthyls as well as certain monomeric binaphthyl molecules with diethylzinc has been investigated which has provided further information on the novel polymeric catalysts.

Full text of DOI:10.1021/ja972623r

12454
J. Am. Chem. Soc. 1997, 119, 12454-12464
Functionalized Major-Groove and Minor-Groove Chiral
Polybinaphthyls: Application in the Asymmetric Reaction of
Aldehydes with Diethylzinc
Qiao-Sheng Hu, Wei-Sheng Huang, Dilrukshi Vitharana, Xiao-Fan Zheng, and
Lin Pu*
Contribution from the Department of Chemistry, UniVersity of Virginia,
CharlottesVille, Virginia 22901
ReceiVed July 31, 1997X
Abstract: A series of functionalized and optically active major-groove polybinaphthyls and minor-groove polybi-
naphthyls have been synthesized by using the Suzuki coupling reaction and have been spectroscopically characterized.
The application of these chiral polymers in the asymmetric addition of diethylzinc to aldehydes has been studied. A
minor-groove polybinaphthyl is found to be an excellent catalyst for the asymmetric reaction of diethylzinc with a
number of aldehydes. The molecular weight and the molecular weight distribution of the polymer have little effects
on the catalytic process. The chiral polymer can be easily recovered and reused without loss of catalytic activity as
well as enantioselectivity. These rigid and sterically regular chiral polybinaphthyls represent a new generation of
enantioselective polymeric catalysts. The reaction of the polybinaphthyls as well as certain monomeric binaphthyl
molecules with diethylzinc has been investigated which has provided further information on the novel polymeric
catalysts.
Introduction
of novel chiral conjugated materials.7-10 Figure 1 shows a few
chiral polybinaphthyls prepared in our laboratory. These rigid
and sterically regular chiral polymers not only are potentially
useful in electrical and optical applications but also can be used
to prepare a new generation of polymeric chiral catalysts when
appropriate functional groups are introduced. For example, we
have studied the direct polymerization of the chiral binaphthyl
monomers (R)-1a-c in the presence of either Ni(0)(cy-
clooctadiene) or NiCl2/Zn to generate polymers (R)-2a-c
(Scheme 1).11 These polymers are then converted to the
optically active poly(1,1′-bi-2-naphthol) (R)-3 by removal of
the protecting groups. In the helical structure of an 1,1′-
binaphthyl molecule, there exists a major groove and a minor
groove divided by the 1,1′-bond as indicated in Scheme 1. We
therefore designate the polymers obtained from the polymeri-
zation at the 6,6′-positions as “major-groove” polybinaphthyls
and the polymers obtained from the polymerization at the 3,3′-
positions as “minor-groove” polybinaphthyls. (R)-3 is a major-
groove polymer of 1,1′-bi-2-naphthol. When (R)-3 is reacted
with diethylaluminum chloride, a polymeric aluminum complex
(R)-4 is obtained. This polymer shows greatly enhanced
catalytic activity over the corresponding monomeric binaphthyl
aluminum complex in a Mukaiyama aldol condensation, al-
though no enantioselectivity is observed. In (R)-4, all of the
aluminum centers are expected to be highly organized in the
rigid and sterically regular chiral polymer chain, leading to a
well-defined microenvironment for the catalytic sites. It is
therefore possible to systematically adjust the steric and
electronic properties of the metal centers in the polymer to
The use of polymeric chiral catalysts in asymmetric synthesis
has important practical advantages. Due to the solubility
difference between macromolecules and small molecules,
polymeric reagents or catalysts can be easily separated from
the reaction mixture by simple filtration or by precipitation with
the addition of a nonsolvent. The recovery of chiral catalysts
is particularly important since it is often quite expensive to
obtain these optically pure materials. Using polymeric catalysts
also makes it possible to carry out reactions in flow reactors or
in flow membrane reactors for large-scale production. Tradi-
tionally, polymeric chiral catalysts are prepared by anchoring a
chiral metal complex to a flexible and sterically irregular achiral
polymer backbone.1-3 It is generally observed that the polymer-
supported chiral catalysts are usually less efficient than their
monomeric version. This indicates that the microenvironment
of the catalytic sites in the polymers is very important for
their effectiveness in steric control. The flexible and sterically
irregular polymer backbone of the traditional polymeric chiral
catalysts generates randomly oriented catalytic sites which
cannot be systematically modified to achieve the desired
catalytic activity and stereoselectivity.
Optically active binaphthyl compounds have been extensively
applied in asymmetric catalysis and in molecular recognition.4-6
We have used optically active binaphthyls to construct a family
X Abstract published in AdVance ACS Abstracts, December 15, 1997.
(1) Itsuno, S. In Polymeric Materials Encyclopedia; Synthesis, Properties
and Applications; Salamone, J. C., Ed.; CRC Press: Boca Raton, FL, 1996;
Vol. 10, p 8078.
(2) Blossey, E. C.; Ford, W. T. In ComprehensiVe Polymer Science. The
Synthesis, Characterization, Reactions and Applications of Polymers; Allen,
G., Bevington, J. C., Eds.; Pergamon Press: New York, 1989; Vol. 6, pp
81.
(3) Pittman, C. U. Jr. in ComprehensiVe Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon Press: Oxford,
1983; Vol. 8, pp 553.
(7) (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.
(8) Ma, L.; Hu, Q.-S.; Musick, K.; Vitharana, D.; Wu, C.; Kwan, C. M.
S.; Pu, L. Macromolecules 1996, 29, 5083.
(9) Ma, L.; Hu, Q.-S.; Vitharana, D.; Wu, C.; Kwan, C. M. S.; Pu, L.
Macromolecules 1997, 30, 204.
(4) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P. Synthesis 1992,
503.
(5) Whitesell, J. K. Chem. ReV. 1989, 89, 1581.
(6) Bringmann, G.; Walter, R.; Weirich, R. Angew. Chem., Int. Ed. Engl.
1990, 29, 977.
(10) For a review of chiral conjugated polymers, see: Pu, L. Acta
Polymerica 1997, 48, 116.
(11) (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.
S0002-7863(97)02623-1 CCC: $14.00 © 1997 American Chemical Society

Major-GrooVe and Minor-GrooVe Chiral Polybinaphthyls
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12455
Figure 1.
Scheme 1. Preparation of a Chiral Polybinaphthyl Aluminum Complex
optimize their catalytic activity and stereoselectivity. Herein,
we report the detailed synthesis and characterization of novel
functionalized major-groove and minor-groove chiral polybi-
naphthyls. Their application in the catalysis of diethylzinc
addition to aldehydes is found to be highly enantioselective.12
aqueous solution, but it is not soluble in common organic
solvents such as methylene chloride, toluene, and THF. In order
to prepare soluble polybinaphthyls, we have synthesized the
benzenediboronic acid monomers 6a,b that contain long-chain
alkyl groups (Scheme 2).13 Hydroquinone is alkylated and then
brominated to give 5 which is then reacted with n-butyllithium,
triethyl borate, and diluted hydrochloric acid to generate 6a,b.
Compound 6a contains two hexyloxy groups and 6b contains
two octadecyloxy groups.
Results and Discussion
1. Synthesis and Characterization of Functionalized
Major-Groove Chiral Polybinaphthyls. The major-groove
polybinaphthol (R)-3 can be dissolved in DMSO or basic
The Suzuki coupling14 of (R)-1a with 6a produces (R)-7,
which is converted to the major-groove polybinaphthol (R)-8
by hydrolysis (Scheme 3). The polymerization is carried out
(12) A portion of this work has been communicated: Huang, W.-S.; Hu,
Q.-S.; Zheng, X.-F.; Anderson, J.; Pu, L. J. Am. Chem. Soc. 1997, 119,
4313.
(13) Huber, J.; Scherf, U. Macromol. Rapid Commun. 1994, 15, 897.

12456 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Hu et al.
Scheme 2. Preparation of the Diboronic Acid Monomer 6a,b
Scheme 3. Preparation of the Major-Groove Polybinaphthyl (R)-8
by heating a 1:1 mixture of (R)-1a and 6a in THF in the presence
of 5 mol % Pd(PPh3)4 and aqueous K2CO3 at reflux under
nitrogen for 48 h. The resulting polymer (R)-7 is then dissolved
in THF and treated with 6 N HCl at 80 °C for 12 h to give
(R)-8 as a pale white solid in an overall yield of 85%. Since
the chiral configuration of 1,1′-binaphthyl molecules is known
to be stable at high temperature over extended periods of time,15a
there should not be racemization during the preparation of (R)-
8. We have also shown previously that the optical activity of
the binaphthyl polymers is quite stable at over 100 °C in
solution.7b Unlike (R)-3, (R)-8 is soluble in organic solvents
such as THF, chloroform, and methylene chloride. Gel
permeation chromatography (GPC) analysis shows its molecular
weight is Mw ) 18 500 and Mn ) 9000 (PDI ) 2.1). The
specific optical rotation of (R)-8 is [R]D ) -398.6 (c ) 1.00,
CH2Cl2). A well-resolved 1H NMR spectrum of (R)-8 is
obtained which is consistent with the polymer structure. Small
peaks corresponding to the end groups are also observed.
A chiral binaphthyl polymer containing pyridine ligands is
prepared. The reaction of (R)-6,6′-dibromo-1,1′-bi-2-naphthol,
(R)-9,15b with 2-picolyl chloride hydrochloride salt in the
presence of K2CO3 in refluxing acetone gives (R)-10 (Scheme
4). Direct polymerization of (R)-10 using NiCl2/Zn catalysts
produces a mostly insoluble polymer (R)-11. The Suzuki
coupling of (R)-10 with 6b generates polymer (R)-12. This
polymer is soluble in normal organic solvents. GPC analysis
shows its molecular weight is Mw ) 9900 and Mn ) 8100 (PDI
) 1.2). The specific optical rotation of (R)-12 is [R]D ) -73.1
(c ) 0.20, CH2Cl2). The polymer with shorter alkyl groups (R
) n-C6H13) has very poor solubility.
2. Synthesis and Characterization of Functionalized
Minor-Groove Chiral Polybinaphthyls. Polymers (R)-3, (R)-
8, and (R)-12 are the major-groove binaphthyl polymers. We
have also prepared minor-groove polybinaphthols by carrying
out the polymerization at the 3,3′-positions of a binaphthyl
monomer (R)-15. This compound is readily prepared following
the literature procedures (Scheme 5).16,17 Protection of the
phenolic groups of (R)-1,1′-bi-2-naphthol, (R)-13,16 as meth-
oxymethyl ether gives (R)-1417a {[R]D ) +97.75 (c ) 1.00,
THF)}. Reaction of (R)-14 with n-butyllithium followed by
treatment with iodine gives (R)-15.17b The optical purity of this
molecule is over 99.9% as determined by HPLC analysis on a
Chiracel OD column. The specific optical rotation of (R)-15
is [R]D ) -11.05 (c ) 1.01, THF).
The Suzuki coupling polymerization of (R)-15 with 6a is
conducted (Scheme 6). When Pd(OAc)2 is used as the
catalyst,18 a low molecular weight polymer (R)-16a is obtained.
This polymerization involves the reaction of a 1:1 mixture of
(R)-15 and 6a in the presence of Ba(OH)2‚8H2O, Pd(OAc)2,
and tri-o-tolylphosphine in DMF and H2O at reflux under
nitrogen. After 42 h, (R)-16a is obtained as a yellow solid in
93% yield. GPC analysis of (R)-16a shows that its molecular
weight is Mw ) 5900 and Mn ) 3900 (PDI ) 1.5). The specific
optical rotation of (R)-16a is [R]D ) -63.4 (c ) 0.50, THF).
(14) Selected references on the Suzuki coupling: (a) Miyaura, N.; Yanagi,
T.; Suzuki, A. Synth. Commun. 1981, 11, 513. (b) Wallow, T. I.; Novak,
B. M. J. Am. Chem. Soc. 1991, 113, 7411. (c) Suzuki, A. Acc. Chem. Res.
1982, 15, 178.
(15) (a) Kyba, E. P.; Gokel, G. W.; Jong, F. de.; Koga, K.; Sousa, L. R.;
Siegel, M. G.; Kaplan, L.; Sogah, G. D. Y.; Cram, D. J. J. Org. Chem.
1977, 42, 4173. (b) Sogah, G. D. Y.; Cram, D. J. J. Am. Chem. Soc. 1979,
101, 3035.
(16) Optically pure 1,1′-bi-2-naphthol can be conveniently obtained: Hu,
Q.-S.; Vitharana, D. R.; Pu, L. Tetrahedron: Asymmetry 1995, 6, 2123.
(17) (a) Kitajima, H.; Aoki, Y.; Ito, K.; Katsuki, T. Chem. Lett. 1995,
1113. (b) Cox, P. J.; Wang, W.; Snieckus, V. Tetrahedron Lett. 1992, 17,
2253.
(18) Watanabe, T.; Miyaura, N.; Suzuki, A. Synlett 1992, 207.

Major-GrooVe and Minor-GrooVe Chiral Polybinaphthyls
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12457
Scheme 4. Synthesis of a Pyridine Containing Chiral Polybinaphthyl (R)-12
Scheme 5. Preparation of the Monomer (R)-15
Scheme 6. Synthesis of the Minor-Groove Chiral Polybinaphthyls (R)-16 and (R)-17
Because of the low molecular weight of this polymer, significant
end group signals are observed in the 1H NMR spectrum.
Higher molecular weight polymer (R)-16b is obtained by using
Pd(PPh3)4 as the catalyst.14 This polymerization is carried out
by heating a 1:1 mixture of (R)-15 and 6a in THF in the presence
of 5 mol % Pd(PPh3)4 and aqueous K2CO3 at reflux under
nitrogen. After 36 h, polymer (R)-16b is isolated in 97% yield
also as a yellow solid. GPC analysis of this polymer shows
Mw ) 20 200 and Mn ) 7300 (PDI ) 2.8). The specific optical
rotation of (R)-16b is [R]D ) -90.1 (c ) 0.51, THF). The 1H
NMR spectrum of (R)-16b does not show the end group signals
as observed in (R)-16a.
The methoxymethyl protecting groups of these polymers are
easily hydrolyzed to generate (R)-17a and (R)-17b by refluxing

12458 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Hu et al.
Figure 2. 1H NMR spectrum of (R)-17b in CDCl3.
the THF solution of (R)-16a and (R)-16b in the presence of
aqueous HCl.19 GPC analysis of (R)-17a shows that its
molecular weight is Mw ) 6700 and Mn ) 4600 (PDI ) 1.5).
Its specific optical rotation is [R]D ) +11.8 (c ) 0.50, THF).
GPC analysis of (R)-17b shows that its molecular weight is Mw
) 24 300 and Mn ) 9900 (PDI ) 2.45). Its specific optical
rotation is [R]D ) -16.6 (c ) 0.5, THF). Both (R)-17a and
(R)-17b are soluble in common organic solvents such as THF,
methylene chloride, chloroform, and toluene. Figure 2 shows
0.51, THF)}. However, the circular dichroism (CD) spectrum
of this polymer exhibits very strong Cotton effects. This
indicates that the optical rotation of these polymers at λ ) 589
nm (the sodium D line) is not suitable to determine their optical
activity. Figure 3 shows the CD spectra of (S)-17 and (R)-
17b. The CD signals of these two polymers are exact mirror
images of each other.
Both of the methoxymethyl protecting groups and the hexyl
groups of (R)-16 can be hydrolyzed simultaneously when this
polymer is treated with excess BBr3. A new polymer (R)-18,
whose possible structure is shown in Scheme 7, is isolated. The
structure of this polymer is interesting since it closely resembles
the ligands of (R)-1920 and (R)-20.21 These chiral Lewis acid
complexes are discovered by Yamamoto et al. to catalyze the
highly enantioselective Diels-Alder reaction. However, (R)-
18 cannot be dissolved in organic solvents and basic aqueous
solution which prevents the structural characterization of this
polymer. We are working on the structural modification of this
polymer in order to make it soluble for characterization and
application purposes.
3. Comparison of the Spectroscopic Properties of the
Major-Groove Polybinaphthol (R)-8 with the Minor-Groove
Polybinaphthol (R)-17. The UV spectrum of (R)-8 in CH2Cl2
displays maximum absorptions at λmax ) 238, 270, 336 nm and
the UV spectrum of (R)-17 in CH2Cl2 displays maximum
absorptions at λmax ) 244, 260, 322 nm. There is ca. 14
nm blue-shift from the major-groove polymer to the minor-
groove polymer, indicating a reduced effective conjugation in
(R)-17. According to our earlier work on the binaphthyl-based
1
the H NMR spectrum of (R)-17b in CDCl3. This very well-
1
resolved H NMR spectrum suggests a well-defined structure.
The singlet at δ 6.34 is due to the phenolic groups of the
polymer as shown by a D2O exchange experiment. The singlet
at δ 8.01 is assigned to H-4 of the binaphthyl unit.
The minor-groove polymer (R)-17 has two important features
that are different from the major-groove polymer (R)-8. First
of all, since (R)-17 is produced by polymerization at the 3,3′-
positions of the binaphthyl monomer, both the phenylene spacers
as well as the adjacent naphthyl groups can provide steric control
around each binaphthyl unit where metal centers are introduced
when used as a catalyst. Secondly, the two hexyloxy groups
in the p-phenylene linkers of (R)-17 not only make this polymer
soluble in organic solvent but also act as ligands to bind the
metal center.
By using the same experimental procedure as the preparation
of (R)-17b, polymer (S)-17 is obtained from the polymerization
of (S)-15 with 6a. GPC shows its molecular weight is Mw )
10 000 and Mn ) 4600 (PDI ) 2.17). Its specific optical
rotation is [R]D ) -14.2 (c ) 1.01, CH2Cl2). In THF, the
optical rotation of (S)-17 is almost zero {[R]D ) +0.5 (c )
(20) Maruoka, K.; Murase, N.; Yamamoto, H. J. Org. Chem. 1993, 58,
2938
(21) Ishihara, K.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 1561.
(19) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis; John Wiley & Sons: New York, 1991; p 18.

Major-GrooVe and Minor-GrooVe Chiral Polybinaphthyls
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12459
Figure 3. CD spectrum of (S)-17 and (R)-17b in methylene chloride.
Scheme 7. Preparation of (R)-18
chiral conjugated polymers, the conjugation of these ma-
terials is determined by their repeat units and there is no
extended conjugation along the polymer chain.10 Therefore, the
reduced effective conjugation of (R)-17 is due to a steric
interaction between the alkoxy groups on the phenylene spacer
and the hydroxyl groups on the binaphthyl unit which dis-
rupts the planarity of the repeat unit. Such interaction is absent
in the repeat unit of (R)-8.
There is also a very large change in optical rotation from the
major-groove polymer to the minor-groove polymers. The
absolute value of the optical rotation of (R)-8 ([R]D ) -398.6)
is much larger than those of (R)-17a ([R]D ) +11.8) and (R)-
17b ([R]D ) -16.6), although they all have the same functional
groups. To gain more information on the structure of these
polymers, their CD spectra in CH2Cl2 are compared (Figure 4).
Although (R)-17a and (R)-17b have opposite signs for their
optical rotations, their CD signals are almost identical. This
indicates that these two polymers should have the same
macromolecular structure and their differences in optical rotation
and CD intensity are most likely due to the end groups. The
1H NMR spectrum of the low molecular weight material (R)-
17a shows a significant amount of unreacted binaphthyl iodide
end groups for this low molecular weight material. This
polymer may also have some boronic acid end groups. Both
the minor-groove polymer (R)-17 and the major-groove polymer
(R)-8 are made of optically pure (R)-binaphthyl monomer.
Figure 4. Comparison of the CD spectra of (R)-8, (R)-15, and (R)-
17a,b.
However, their CD effects are almost mirror image of each other
except that the long wavelength CD signal of (R)-8 is red-shifted
because of its better conjugation. Further investigation is needed
in order to understand this phenomena.

12460 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Hu et al.
Table 1. Reaction of Benzaldehyde with Diethylzinc in the Presence of Chiral Polybinaphthyls
polymer
solvent
toluene
toluene
CH2Cl2
CH2Cl2
toluene
toluene
CH2Cl2
toluene
tempa (°C)
time (h)
conv (%)
21:22
ee (%)b
(R)-2b
(R)-2c
(R)-3
rt
rt
rt
rt
rt
rt
rt
rt
0
24
48
112
20
48
24
70
10
10
16
12
trace
54
100
33
no reaction
85
100
100
79
19:35
53:47
71:29
8
13
40
(R)-8
(R)-12
(R)-16b
(R)-17a
(R)-17a
(R)-17a
(R)-17a
(R)-17a
97.6:2.3
94:6
99.6:0.4
100:0
100:0
100:0
19
67.0
89.4
84.7
91.7
92.2
THF
hexane:toluene (2:1)
toluene
0
0
100
100
a rt ) room temperature. b All the ees were determined by GC with a chiral column (â-Dex capillary column, Supelco Co.).
Table 2. Asymmetric Reaction of Aldehydes with Diethylzinc in
the Presence of the Polybinaphthols
4. Asymmetric Reaction of Aldehydes with Diethylzinc
Catalyzed by the Functionalized Chiral Polybinaphthyls. As
an example to study the applications of the chiral polybinaph-
thyls in asymmetric catalysis, we have used these polymers to
catalyze reaction of benzaldehyde with diethylzinc.22,23 The
results are summarized in Table 1. All of the reactions are
carried out under nitrogen in the presence of ca. 5 mol % (based
on the binaphthyl unit) of the polymer and 1-2 equiv of
diethylzinc. Formations of a chiral alcohol product 1-phenyl
propanol (21) and a side product benzyl alcohol (22) are
observed in many cases. As shown in the table, (R)-17a is an
excellent catalyst for this reaction with high enantioselectivity
and good catalytic activity. Polybinaphthyl (R)-12, which
contains pyridine functional groups, has no catalytic activity at
all. (R)-16b, the polymer in which the phenolic groups are
protected, is a more efficient catalyst than most of other
polymers, but it gives much lower enantiomeric excess (ee) for
21 compared to its unprotected version (R)-17a. From the
major-groove polybinaphthols (R)-3 and (R)-8 to the minor-
groove polybinaphthol (R)-17a, there is a dramatic increase of
both the catalytic activity and enantioselectivity. The best
condition for the use of (R)-17a is to carry out the reaction in
toluene solution at 0 °C which produces 21 in 92.2% ee without
formation of the side product 22. Further lowering of the
temperature to -40 °C shows no increase of the ee.
isolated
yield (%)
polymer
aldehyde
benzaldehyde
ee (%)a
89
91
90
94
84
63
86
90
86
67
89
70
65
90
95
94
92.2
92.0b
92.5b
93.4b
88.3b,c
74.3b,c
35.1b
59.0b
89.7b,d
82.8b,d,e
73.5d
83.3b,d
74.3b,d
92.7
(R)-17a
p-methylbenzaldehyde
p-cholorobenzaldehyde
p-methoxybenzaldehyde
p-tert-butylbenzaldehyde
o-fluorobenzaldehyde
o-methoxybenzaldehyde
cinnamaldehyde
3,3,7-trimethyl-6-octenal
nonyl aldehyde
cyclohexanecarbaldehdye
hexaldehyde
(R)-17b
(S)-17
benzaldehyde
p-cholorobenzaldehyde
benzaldehyde
93.8
93.0
a All of the ees were determined by GC with a chiral column (â-
Dex capillary column, Supelco Co.) except those specifically indicated.
b The recycled polymer was used. c The ee was measured by HPLC-
Chiracel OD column. d The ee was measured by GC analysis (â-Dex
capillary column) of the corresponding acetate derivative. e The absolute
configuration of the product was not determined. [R]D ) -13.25 (c )
1.95, THF).
Polymer (R)-17a has therefore been used to catalyze the
asymmetric reaction of different aldehydes with diethylzinc, and
the results are listed in Table 2. The ee’s are determined relative
to the racemic mixture of the alcohol products. These reactions
are carried out in toluene solution at 0 °C in the presence of 5
mol % (based on the binaphthyl units) of (R)-17a. All of the
alcohol products except the one from the reaction of 3,3,7-
trimethyl-6-octenal have the R configuration as determined by
comparing their specific optical rotations with the reported
data.22,23 The reactions are completed in 12-26 h for aromatic
aldehydes and trans-cinnamaldehyde. The addition to aliphatic
aldehydes are much slower and take 70-100 h to go to
completion. As shown in the table, excellent enantioselectivities
for the para-substituted benzaldehydes as well as for trans-
cinnamaldehyde are achieved. But much lower ee’s are
observed for the reaction of the o-substituted aromatic aldehydes.
The ee’s observed for the addition to the aliphatic aldehydes
are also very significant since few polymeric catalysts are good
for the reaction of aliphatic aldehydes.
In these reactions, (R)-17a can be easily recovered from the
reaction mixture by precipitation with methanol. The recycled
polymer shows a similar enantioselectivity. When the higher
molecular weight polymer (R)-17b is used, the ee for the
reaction of benzaldehyde is 92.7% and for the reaction of
p-chlorobenzaldehyde is 93.8%. Therefore, both the molecular
weight of the polymer and the method of polymer preparation
have little effect on the asymmetric process. This is an excellent
property for practical application.
(S)-17 is also used to catalyze the reaction of benzaldehyde
with diethylzinc. In the presence of (S)-17, 21 is obtained in
93.0% ee, similar to that obtained from (R)-17. As expected,
the configuration of the resulting chiral alcohol is opposite of
that obtained with (R)-17. Thus, the R polybinaphthyl produces
the R chiral alcohol and the S polymer generates the S chiral
alcohol.
A number of highly enantioselective monomeric amino
alcohol catalysts have been developed.22 Polymer-supported
chiral amino alcohols have also been studied, and in some cases,
high enantioselectivities have been observed.22 However, the
best polymeric chiral amino alcohol catalyst gives only 69%
ee for the reaction of aliphatic aldehydes, and at the same time
(22) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833.
(23) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30,
49.

Major-GrooVe and Minor-GrooVe Chiral Polybinaphthyls
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12461
it shows much lower enantioselectivity for aromatic aldehydes
compared to other polymeric chiral catalysts.24 Excellent
enantioselectivity for certain aliphatic aldehydes and benzalde-
hyde is recently observed by Seebach et al. when polymer-
supported chiral R,R,R′,R′-tetraphenyl-1,3-dioxolane-4,5-dimeth-
anol-Ti(IV) complexes are used to carry out the diethylzinc
addition, but more than 1 equiv of Ti(OiPr)4 versus the aldehydes
are required in the reaction.25
of (R)-25, a new compound (R)-27 is produced probably via
(R)-26. In the H NMR spectrum of (R)-27, a multiplet is
1
observed at δ -0.88 for the methylene protons adjacent to the
zinc atoms. Both the 1H and 13C NMR spectra of (R)-27 show
a C2 symmetric molecular structure. Cryoscopic molecular
weight determination of (R)-27′ in cyclohexane confirms a
bisbinaphthyl structure for this compound in solution. The
measured molecular weight of (R)-27′ is 964, and the calculated
molecular weight for the dimer is 926. The similar dinuclear
zinc complexes have been obtained and structurally character-
ized from the reaction of amino alcohols with diethylzinc by
Noyori et al.27 When more diethylzinc is added to (R)-27, the
aromatic NMR signals of this compound do not show observable
change but more peaks are observed at δ -0.3 to -1.15. This
may be due to the reversible coordination of diethylzinc with
the oxygen atoms in (R)-27 in the presence of excess diethylzinc.
The reaction of diethylzinc with (R)-1,1′-bi-2-naphthol [(R)-
13] is more complicated. When 1 equiv of diethylzinc is added
into the CDCl3 solution of (R)-13 at room temperature, a white
precipitate is formed with the release of ethane. The addition
of the second equiv of diethylzinc converts the suspension to a
clear solution. The precipitate is probably a polymeric binaph-
thyl zinc complex formed through Zn-O-Zn bridging bonds.
Excess diethylzinc breaks some of these bridging bonds to form
soluble complexes as observed in the reaction of (R)-17 with
excess diethylzinc. Earlier, Katsuki et al. have made a similar
observation in the reaction of a binaphthyl amide derivative with
5. Reaction of (R)-17 and Some Monomeric Binaphthols
with Diethylzinc. We have studied the reaction of (R)-17 with
diethylzinc in the absence of aldehydes. We find that when 1
equiv of diethylzinc is added to a toluene solution of (R)-17b
at room temperature, the solution becomes viscous. With the
addition of the second equiv of ZnEt2, the polymer solution is
changed to an unmovable gel, suggesting the formation of a
cross-linked polymer network. (R)-23 is one of the possible
structures proposed for the polymer generated from the reaction
of (R)-17 with 2 equiv of diethylzinc. The cross-linked polymer
gel is probably formed through the interchain coordination of
the oxygen atoms to the zinc atoms in (R)-23. After 6-16 equiv
of diethylzinc is added, a viscous but clear solution is obtained.
This indicates that the cross-linked polymer gel has collapsed
in the presence of excess diethylzinc, probably through multiple
zinc coordination to the oxygen atoms of the polymer as shown
by the structure of (R)-24. Such interaction breaks the interchain
coordination and destroys the cross-linked polymer gel. The
coordinated diethylzinc in (R)-24 should be in equilibrium with
free diethylzinc in solution since free diethylzinc is observable
1
diethylzinc.26 The H and 13C NMR spectra of the product
1
by H NMR spectroscopy when 3 equiv or more diethylzinc
solution obtained from the reaction of (R)-13 with 2 equiv of
diethylzinc suggest the formation of two compounds. They are
probably multibinaphthyl complexes with multiple zinc coor-
dination. Their actual structures are not determined at this time
due to the difficulty in their separation. Previously, Yamamoto
et al. have used the complex made from the reaction of (R)-
1,1′-bi-2-naphthol with dimethylzinc at low temperature to
catalyze asymmetric ene reactions, and up to 90% ee is
observed.28
1
are added to the polymer solution. However, the H NMR
spectrum of the polymer in the presence of diethylzinc is too
broad to give any structural information.
Both (R)-13 and (R)-25 are used to catalyze the reaction of
diethylzinc with benzaldehyde. (R)-13 is a poor catalyst for
this reaction. In toluene solution at room temperature, 37%
conversion of benzaldehyde is observed over 24 h in the
presence of 5 mol % of (R)-13. The formation of 21 and 22 is
observed in 95.9:4.1 ratio. The ee of 21 is 32.9%. When the
reaction is carried out in methylene chloride solution, after more
than 5 days, 84% conversion of benzaldehyde is observed in
the presence of 10 mol % of (R)-13. The ratio of 21 versus 22
is 61:39, and the ee of 21 is 15%.
(R)-25 shows higher catalytic activity than (R)-13. After 24
h in toluene solution, 72% conversion of benzaldehyde is
observed in the presence of 5 mol % of (R)-25. The ratio of
21 versus 22 is 90.6:9.4 and the ee of 21 is 57.0%.
Unlike (R)-27 whose bridging Zn-O-Zn bonds are stable
even in the presence of excess diethylzinc, the cross-linked
polymer gel of (R)-23 collapses when excess diethylzinc is
added and a structure of (R)-24 may be produced. In this
polymeric zinc complex, its central zinc atoms that are
responsible for the catalysis are coordinatively less saturated
than those in (R)-27. This may explain the enhanced catalytic
activity of (R)-17 over the monomeric compounds (R)-13 and
(R)-25. It is our general observation that higher catalytic activity
is associated with higher asymmetric induction in the chiral
binaphthyl-catalyzed reaction of aldehydes with diethylzinc.
In order to learn more about the binaphthyl-zinc species in
the polymer, we have studied the reaction of a monomeric
binaphthyl compound (R)-25 with diethylzinc (Scheme 8).
When 1 equiv of diethylzinc is added to a chloroform-d solution
(24) Soai, K.; Watanabe, M. Tetrahedron: Asymmetry 1991, 2, 97.
(25) Seebach, D.; Marti, R. E.; Hintermann, T. HelV. Chim. Acta 1996,
79, 1710.
(26) The reaction of diethylzinc with a binaphthol molecule containing
3,3′-bis(amide) groups has been studied. Formation of a trimeric binaph-
thylzinc complex is observed and its crystal structure is obtained: Kitajima,
H.; Ito, K.; Aoki, Y.; Katsuki, T. Bull. Chem. Soc. Jpn. 1997, 70, 207.
(27) Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc.
1989, 111, 4028.
(28) Sakane, S.; Maruoka, K.; Yamamoto, H. Tetrahedron Lett. 1985,
26, 5535.

12462 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Hu et al.
Scheme 8. Formation of a Bisbinaphthyl Dinuclear Zinc Complex
2938 (s), 2872 (m), 2857 (m), 1495 (s), 1468 (s), 1418 (s), 1389 (s),
1300 (s), 1271 (m), 1202 (s), 1127 (m), 1084 (m), 1047 (s), 887 (w),
822 (m), 793 (m), 725 (m). Anal. Calcd for C18H32O6B2: C, 59.08;
H, 8.81. Found: C, 58.79; H, 8.74. 6b is prepared and characterized
similarly.
Summary
In summary, a series of soluble major-groove and minor-
groove chiral polybinaphthyls with hydroxyl or pyridine func-
tional groups have been synthesized and characterized. We find
that a minor-groove polybinaphthyl has less effective conjuga-
tion than its corresponding major-groove polymer due to the
steric hindrance in the repeat unit of the minor-groove polymer.
The application of these chiral polymers in the asymmetric
reaction of aldehydes with diethylzinc has been studied. We
have discovered that the minor-groove polybinaphthols (R)-17
and (S)-17 are excellent enantioselective catalysts for the
reaction of a number of aldehydes with diethylzinc. The
molecular weight and the molecular weight distribution of these
polymers have little effect on the catalytic process. They can
be easily recovered and reused without loss of both catalytic
activity and enantioselectivity. These rigid and sterically regular
chiral polymers represent a new generation of enantioselective
polymeric catalysts different from the traditionally prepared
polymer-supported catalysts. The reactions of the polybinaph-
thol (R)-17 and certain monomeric binaphthol compounds with
diethylzinc in the absence of the aldehyde substrates have been
studied in order to gain more understanding on the catalytically
active chiral zinc species. The use of the functionalized chiral
polybinaphthyls in other asymmetric organic reactions is also
under investigation in our laboratory.
Preparation and Characterization of (R)-8. Under N2, a mixture
of (R)-1a (1.06 g, 2.0 mmol), 6a (0.73 g, 2.0 mmol), and Pd(PPh3)4
(116 mg, 0.10 mmol, 5 mol %) in THF (10 mL) and 1 M K2CO3 (10
mL) was heated at reflux for 48 h. CH2Cl2 (200 mL) was then added
to the reaction mixture, and the organic layer was separated. The
solution was washed with brine and dried over Na2SO4. After the
solution was concentrated under vacuum, methanol was added to
precipitate out the polymer. This precipitation was repeated one more
time, and the resulting polymer (R)-7 was dissolved in THF (10 mL)
and 6 N HCl (10 mL). After the solution was degassed with nitrogen,
it was heated at 80 °C for 12 h. CH2Cl2 (200 mL) was then added to
extract the hydrolyzed polymer. The organic layer was washed with
brine and dried over Na2SO4. After removal of the solvent, the residue
was redissolved in a minimum amount of CH2Cl2 and precipitated with
MeOH. This process was repeated three times to give (R)-8 as a pale
white solid in 85% yield. GPC analysis shows its molecular weight is
Mw ) 18 500 and Mn ) 9000 (PDI ) 2.1). The specific optical rotation
of (R)-8 is [R]D ) -398.6 (c ) 1.00, CH2Cl2). Another batch of
reaction generated (R)-8 with Mw ) 15 600 and Mn ) 8900 (PDI )
1.8). The UV spectrum of this polymer in CH2Cl2 shows maximum
absorptions at λmax ) 238, 270, 336 nm: 1H NMR (CDCl3, 400 MHz)
δ 8.16 (s, 2H), 8.01 (d, J ) 8.3 Hz, 2H), 7.64 (d, J ) 8.6 Hz, 2H),
7.42 (d, J ) 8.3 Hz, 2H), 7.27 (d, J ) 8.6 Hz, 2H), 7.10 (s, 2H), 3.96
(m, 4H), 1.68 (m, 4H), 1.36 (m, 4H), 1.22 (m, 8H), 0.78 (s, 6H), very
small peaks for the end groups were observed at δ 8.09, 7.57, 7.36,
7.01, 6.93, 3.90, 3.72, 3.57, 1.84, 1.76, 0.90; 13C NMR (CDCl3, 100
MHz) δ 152.93, 150.51, 134.28, 132.44, 131.75 (br), 130.37, 129.66
(br), 129.50, 128.89 (br), 123.82, 117.96, 116.29, 110.87, 69.64, 31.52,
29.36, 25.87, 22.63, 14.03, very weak signals were observed at δ
132.25, 132.15, 131.53. Anal. Calcd for C38H40O4: C, 81.40; H, 7.19.
Found: C, 80.23; H, 7.26.
Experimental Sections
General Data. NMR spectra were recorded on JEOL-270 MHz
and JEOL-400 MHz spectrometers. Infrared spectra were recorded on
a 2020/Galaxy Series FT-IR spectrometer by preparing KBr pellets of
the materials. Elemental analyses were carried out using a Perkin-
Elmer 2400 Series II CHN S/O analyzer. Mass spectra were obtained
using Hewlett-Packard 5890 Series II GC/DIP MS. Gel permeation
chromatography (GPC) utilized a Waters 510 HPLC pump, a Waters
410 differential refractometer, and Ultrastyragel linear GPC columns.
THF was used as the solvent for the GPC analysis and polystyrene
standard was used. UV-vis spectra were recorded on a Hewlett-
Packard 8451A diode array spectrophotometer. Circular dichroism
spectra were recorded using a JASCO J-710 spectropolarimeter. Optical
rotations were measured on a JASCO polarimeter at λ ) 589 nm. THF
and ether were dried with sodium/benzophenone. Tetrakis(triphen-
ylphosphine)palladium(0) and palladium(II) acetate were purchased
from Strem and used directly. All of the aldehydes were purchased
from Aldrich.
Preparation and Characterization of 6a. To a THF (80 mL)
solution of 1,4-bis(hexyloxy)-2,5-dibromobenzene (6.4 g, 14.7 mmol)
at -78 °C was added n-BuLi (20 mL, 2.5 M in hexanes, 50 mmol).
After 2 h of stirring at this temperature, the resulting solution was
cannulated into a solution of B(OEt)3 (15 mL) in THF (40 mL) over
30 min. The mixture was warmed to room temperature and stirred for
12 h. Excess 2 N HCl was then added. After filtration, the solid was
washed with water and CH2Cl2 and dried under vacuum to give pure
6a (4.05 g, 75.4% yield) as a white solid: 1H NMR (DMSO-d6, 400
MHz) δ 7.81 (s, 4H, B-OH), 7.17 (s, 2H), 3.98 (t, J ) 6.4 Hz, 4 H),
1.72 (m, 4H), 1.41 (m, 4H), 1.31 (m, 8H), 0.87 (t, J ) 7.0 Hz, 6H,
2CH3); 13C NMR (DMSO-d6, 100 MHz) δ 157.40, 125.08, 118.45,
68.90, 31.50, 29.29, 25.69, 22.60, 14.43; FT-IR (KBr, cm-1) 3353 (s),
Preparation and Characterization of (R)-10. Under nitrogen, to
a 50 mL Schlenk flask were added (R)-6,6′-dibromo-1,1′-bi-2-naph-
thol, (R)-9 (1.0 g, 2.25 mmol), 2-picolyl chloride (1.05 g, 6.4 mmol),
K2CO3 (4.0 g, 2.8 mmol), and acetone (30 mL). After the mixture
was heated at reflux for 24 h, it was cooled to room temperature, and
water (20 mL) was added. The solution was extracted with EtOAc (2
× 100 mL), and the organic layer was dried over Na2SO4. After
filtration, the organic solution was concentrated under reduced pressure.
Column chromatography (silica gel, hexane:EtOAc ) 1:1) of the residue
gave (R)-10 as a yellow solid in 72% yield (1.01 g): 1H NMR (CDCl3,
270 MHz) δ 5.20 (s, 4H), 6.70 (d, J ) 6.9 Hz, 2H), 7.04 (tm, Jt ) 7.5
Hz, 2H), 7.03 (dm, Jd ) 8.9 Hz, 2H), 7.28 (dd, J ) 2.0, 9.1 Hz, 2H),
7.26 (dd, J ) 2.2, 7.4 Hz, 2H), 7.45 (d, J ) 9.1 Hz, 2H), 7.85 (d, J )
8.9 Hz, 2H), 8.03 (d, J ) 2.0 Hz, 2H), 8.44 (ddd, J ) 4.9, 1.8, 1.8 Hz,
2H); 13C NMR (CDCl3, 100 MHz) δ 71.50, 115.97, 117.82, 119.71,
120.72, 122.43, 127.14, 129.00, 130.03, 130.04, 130.46, 132.57, 136.65,
148.89, 154.00, 157.31; MS(DIP) for C32H22Br2N2O2 (m/z) M+ (626),
M+ - C6H6N (534).
Preparation and Characterization of the Pyridine-Containing
Polymer (R)-12. Under nitrogen, to a 50 mL Schlenk flask were added
(R)-10 (316 mg, 0.5 mmol), 6b (315 mg, 0.5 mmol), K2CO3 (1 M
aqueous solution, 7.2 mmol, degassed with N2), Pd(PPh3)4 (30 mg, 0.026
mmol in 5 mL THF), and THF (15 mL). After the mixture was heated
at reflux for 28 h, it was cooled to room temperature, and water (25

Major-GrooVe and Minor-GrooVe Chiral Polybinaphthyls
J. Am. Chem. Soc., Vol. 119, No. 51, 1997 12463
mL) was added. CH2Cl2 (20 mL) was used to extract, and the organic
solution was washed five times with H2O. The polymer was then
precipitated out of the methylene chloride solution with MeOH. It was
redissolved and reprecipitated for two more times. After centrifuge
separation and drying under vacuum, (R)-12 was isolated as a dark
yellow solid in 65% yield: GPC Mw ) 9900 and Mn ) 8100 (PDI )
The general procedure to carry out the reaction of aldehydes with
diethylzinc in the presence of (R)-17 is described in the following
examples.
(a) Reaction of Benzaldehyde with Diethylzinc Catalyzed by (R)-
17a. To a Schlenk flask containing toluene (10 mL, dried with Na
and degassed with N2) were added the polymer (R)-17a (28 mg, 0.05
mmol) 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 dropwise. After 12 h of
1
1.2); [R]D ) -73.1 (c ) 0.20, CH2Cl2); H NMR (CDCl3, 270 MHz)
δ 0.86 (m, 6H), 1.16-1.25 (m, 60H), 1.64 (m, 4H), 3.90 (m, 4H),
5.22 (m, 4H), 6.78 (m, 2H), 7.04 (m, 2H), 7.08 (m, 2H), 7.25 (m, 4
H), 7.39 (m, 2H), 7.45 (dm, Jd ) 9.2 Hz, 2H), 7.56 (d, J ) 9.2 Hz,
2H), 8.01 (d, J ) 9.4 Hz, 2H), 8.15 (br s, 2H), 8.44 (m, 2H), small
peaks were observed at δ 3.09, 5.22, 6.70, 6.82, 7.16, 7.18, 7.20, 7.44,
7.47, 7.55, 7.86, 7.88, 8.05, and 8.13 due to the end groups; 13C NMR
(CDCl3, 100 MHz) δ 14.24, 22.08, 26.21, 29.39, 29.48, 29.70, 29.78,
29.83, 32.03, 69.64, 71.57, 115.02, 115.45, 116.44, 120.11, 120.97,
122.20, 122.32, 125.11, 128.41, 128.71, 128.74, 129.46, 129.84, 129.92,
130.57, 133.06, 133.28, 134.03, 136.58, 148.67, 148.84, 150.60, 153.86,
157.85, small peaks were observed at δ 68.73, 116.05, 117.74, 119.30,
120.55, 120.75, 124.68, 127.55, 128.00, 128.94, 129.63, 130.18, 130.51,
130.65, 132.78, 134.17, 154.06, 157.55, and 157.63 due to the end
groups.
Preparation and Characterization of (R)-17a. A mixture of (R)-
15 (7.32 g, 11.7 mmol), 6a (4.3 g, 11.7 mmol), Ba(OH)2‚8H2O (6.17
g, 36.0 mmol), Pd(OAc)2 (0.134 g, 0.6 mmol), tri-o-tolylphosphine
(0.365 g, 1.2 mmol) in DMF (60 mL), and H2O (10 mL) was heated
at reflux under nitrogen for 42 h. EtOAc was then added, and the
organic layer was washed with H2O and filtered. After removal of
EtOAc with rotary evaporation, the residue polymer was redissolved
in CH2Cl2 and precipitated with MeOH. This procedure was repeated
three times. The precipitate was collected and dried under vacuum to
give a yellow solid polymer (R)-16a (7.0 g, 93%). (R)-16a (3.0 g)
was then dissolved in THF (30 mL) to which 6 N HCl (20 mL) was
added subsequently. After the mixture was heated at reflux for 16 h,
CH2Cl2 was added. The organic layer was separated and washed with
H2O. Removal of the solvent with rotary evaporation gave a polymer
residue which was redissolved in CH2Cl2 and precipitated with MeOH.
This procedure was repeated three times. After being dried under
vacuum, (R)-17a was obtained as a yellow solid in 89% yield (2.3 g).
GPC analysis of (R)-17a showed its molecular weight to be Mw ) 6700
and Mn ) 4600 (PDI ) 1.5): [R]D ) +11.8 (c ) 0.50, THF); 1H NMR
(CDCl3, 400 MHz) δ 8.49 (s, low intensity), 8.00 (s, 2H), 7.92 (d, J )
8.0 Hz, 2H), 7.77 (d, low intensity), 7.34 (m, 6H), 7.24 (m, 2H), 6.32
(s, 2H), 6.15-7.4 (low intensity) 4.01 (m, 4H), 1.66 (m, 4H), 1.26 (m,
4H), 1.13 (m, 8H), 0.73 (m, 6H). The observed lower intensity peaks
are due to the end groups.
1
stirring, 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, and the aqueous
layer was extracted with diethyl ether. The combined organic layer
was washed with brine until pH ) 7 and then dried over anhydrous
Na2SO4. Concentration of the solution in vacuum gave a pale yellow
oil, which upon treatment with MeOH (20 mL) precipitated the polymer.
The filtrate was concentrated and purified by column chromatography
on silica gel with EtOAc/hexanes (1:4) to afford the product, (R)-1-
phenylpropanol, as a colorless liquid (122 mg, 89%). (R)-1-phenyl-
propanol, 21: 1H NMR (270 MHz, CDCl3) δ 0.90 (t, J ) 7.5 Hz, 3H),
1.74 (m, 2H), 2.73 (s, 1H), 4.52 (t, J ) 6.5 Hz, 1H), 7.23-7.38 (m,
5H); [R]D ) 42.91 (c ) 2.44, CHCl3). The ee was determined to be
92.2% on GC with a chiral column (â-Dex capillary column, Supelco
Co.). GC conditions: injection temperature, 200 °C; detector temper-
ature, 280 °C; flow rate, 1.05 cm3/min; increasing the oven temperature
from 105 to 220 °C at the speed of 1.0 °C/min. The retention time is
22.31 min for the R enantiomer and 23.09 min for the S enantiomer.
The recovery of the polymer: After the precipitation with methanol,
the polymer was collected and dissolved in acetone. A very small
amount of insoluble inorganic impurity was filtered off, and the solvent
of the filtrate was removed under reduced pressure. The solid residue
was washed with methanol and dried under vacuum prior to use.
(b) The Reaction of 3,3,7-Trimethyl-6-octenal with Diethylzinc
Catalyzed by (R)-17a. To a Schlenk flask containing toluene (10 mL,
dried with Na and degassed with N2) were added (R)-17a (28 mg, 0.05
mmol) and diethylzinc (0.21 mL, 2 mmol) under N2 at room
temperature. After ca. 15 min, the flask was cooled to 0 °C, and 3,3,7-
trimethyl-6-octenal (0.19 mL, 1 mmol) was added dropwise. After
1
the reaction solution was stirred at this temperature for 63 h, the H
NMR spectrum of the crude mixture showed 79% conversion of the
aldehyde. The reaction was quenched with 1 N HCl, and the aqueous
layer was extracted with ether. The combined organic layer was washed
with brine until pH ) 7 and then dried over anhydrous Na2SO4.
Removal of the solvent under reduced pressure gave a pale yellow oil,
which upon treatment with MeOH precipitated the polymer. The filtrate
was concentrated, and the residue was purified by column chromatog-
raphy on silica gel with EtOAc/hexanes (1:15) to afford the product as
a colorless liquid (132 mg, 67%): 1H NMR (270 MHz, CDCl3) δ 0.90
(t, J ) 7.4 Hz, 3H), 0.91 (s, 3H), 0.92 (s, 3H), 1.21-1.47 (m, 3CH2
and OH, 7H), 1.57 (s, 3H), 1.65 (s, 3H), 1.90 (m, 2H), 3.65 (m, 1H),
5.07 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 10.03, 17.63, 22.85,
25.78, 27.74, 32.46, 32.73, 42.89, 48.86, 70.66, 125.25, 130.98. GC
showed two peaks for the two enantiomers of the product but the
resolution is not good. The carbinol product was therefore converted
to its acetate derivative for the determination of ee. The carbinol was
dissolved in acetic anhydride (20 equiv) and triethylamine (10 equiv)
was added. The resulting mixture was stirred at room temperature.
The reaction was monitored by TLC. After 80 h, the reaction was
complete. The volatile component was removed under reduced
pressure, and the residue was subjected to column chromatography on
silica gel to give the pure acetate derivative: 1H NMR (270 MHz,
CDCl3) δ 0.86 (s, 6H), 0.88 (t, J ) 7.2 Hz, 3H), 1.15-1.56 (m, 6H),
1.58 (s, 3H), 1.66 (s, 3H), 1.89 (m, 2H), 1.99 (s, 3H), 4.94 (m, 1H),
5.07 (m, 1H). GC: increasing the oven temperature from 100 to 150
°C. The retention time for the two enantiomers was 34.16 and 34.74
min, respectively.
Preparation and Characterization of (R)-17b. To a flask contain-
ing (R)-15 (13.70 g, 22 mmol), 6a (8.0 g, 22.0 mmol), THF (75 mL),
and 1 M K2CO3 (100 mL) was added Pd(PPh3)4 (0.5 g in 25 mL THF),
and the reaction mixture was heated at reflux under nitrogen for 36 h.
EtOAc was then added, and the organic layer was washed with H2O
and filtered. After removal of EtOAc with rotary evaporation, the
residue polymer was redissolved in CH2Cl2 and precipitated with
MeOH. This procedure was repeated three times. After being dried
under vacuum, (R)-16b was obtained as a yellow solid polymer in 97%
yield (13.90 g). (R)-16b was hydrolyzed to (R)-17b in a procedure
similar to the hydrolysis of (R)-16a. GPC analysis of the resulting
(R)-17b showed its molecular weight to be Mw ) 24 300 and Mn )
1
9900 (PDI ) 2.5): [R]D ) -16.6 (c ) 0.5, THF); H NMR (CDCl3,
400 MHz) δ 8.01 (s, 2H), 7.92 (d, J ) 8.0 Hz, 2H), 7.32 (m, 6H), 7.24
(br s, 2H), 6.34 (s, 2H), 4.02 (m, 4H), 1.66 (m, 4H), 1.26 (m, 4H),
1.13 (m, 8H), 0.73 (t, J ) 7.0 Hz, 6H); 13C NMR (CDCl3, 100 MHz)
δ 150.74, 150.47, 133.83, 131.32, 129.35, 128.82, 128.76, 128.37,
126.82, 125.04, 123.96, 117.89, 116.58, 70.75, 31.55, 29.40, 25.63,
22.58, 14.10; UV-vis λmax (CH2Cl2, nm) 244, 260, 322. FT-IR (KBr,
cm-1) 3530 (s), 3393 (s), 2926 (s), 2865 (s), 1622 (m), 1599 (w), 1501
(s), 1431 (s), 1383 (s), 1256 (s), 1198 (s), 1148 (s), 1128 (s), 1011 (s),
938 (m), 891 (m), 785 (w), 747 (s). Anal. Calcd for C38H40O4: C,
81.40; H, 7.19. Found: C, 80.16; H, 7.21.
Preparation and Characterization of (R)-25. Under N2, K2CO3
(2.0 g, 14.5 mmol) was added to a solution of (R)-13 (1.41 g, 5 mmol)
and iodoethane (0.4 mL, 5 mmol) in acetone (30 mL), and the resulting
mixture was heated at reflux for 5 h. After the mixture was cooled to
room temperature, H2O was added and EtOAc (2 × 50 mL) was used
to extract. The combined organic layer was washed with brine and
Preparation and Characterization of (S)-17. (S)-17 was prepared
and characterized in a similar way as (R)-17b. GPC Mw ) 10 000 and
Mn ) 4600 (PDI ) 2.2). [R]D ) -14.2 (c ) 1.01, CH2Cl2). 1H NMR
and 13C NMR spectra of (S)-17 are similar to those of (R)-17b.

12464 J. Am. Chem. Soc., Vol. 119, No. 51, 1997
Hu et al.
dried over Na2SO4. After removal of the solvent by rotary evaporation,
the residue was purified with flash chromatography to give (R)-25 as
a white solid in 91% yield (1.43 g): mp 81.0-83.0 °C, [R]D ) -26.9
(c ) 1.01, CH2Cl2); FT-IR (KBr, cm-1) 3455 (s), 3057 (w), 3000 (w),
2928 (w), 1620 (s), 1593 (s), 1508 (s), 1460 (m), 1431 (w), 1381 (s),
1329 (m), 1262 (s), 1238 (s), 1204 (s), 1175 (s), 1146 (s), 1076 (s),
1051 (s), 810 (s), 750 (s); 1H NMR (CDCl3, 400 MHz) δ 1.11 (t, J )
6.9 Hz, 3H), 4.08 (m, 2H, OCH2), 4.99 (s, 1H, OH), 7.08 (d, J ) 8.2
Hz, 1H), 7.19-7.40 (m, 6H), 7.45 (d, J ) 8.7 Hz, 1H), 7.90 (m, 3H),
8.02 (d, J ) 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ 14.96, 65.29,
115.34, 115.66, 116.41, 117.58, 123.23, 124.30, 125.06, 125.13, 126.36,
127.29, 128.16, 128.22, 129.19, 129.62, 129.77, 130.96, 133.91, 134.20,
151.34, 155.37; MS (EI) m/z 314 (M+, 100), 286 (M+ + 1 - Et, 38).
Anal. Calcd for C22H18O2: C, 84.05; H, 5.77. Found: C, 83.67; H,
5.66.
was prepared similarly as the preparation of (R)-25; 1H NMR (CDCl3,
270 MHz) δ 0.73 (t, J ) 7.0 Hz, 3H), 0.99 (m, 6H), 1.43 (m, 2H),
3.98 (m, 2H), 4.95 (s, 1H), 7.04 (d, J ) 8.3 Hz, 1H), 7.16-7.39 (m,
6H), 7.45 (d, J ) 9.0 Hz, 1H), 7.86 (m, 3H), 8.01 (d, J ) 9.0 Hz, 1H);
13C NMR (CDCl3, 100 MHz) δ 14.10, 25.58, 29.31, 31.40, 69.86,-
115.38, 115.75, 116.49, 117.62, 123.24, 124.32, 125.10, 125.20, 126.39,
127.35, 128.18, 128.29, 129.26, 129.63, 129.79, 130.97,134.02, 134.26,
151.43, 155.70. (b) Molecular weight measurement of (R)-27′:
Diethylzinc (100 µL, 1.0 mmol) was added to a solution of (R)-25′
(370 mg, 1.0 mmol) in cyclohexane (7.4 mL). After 10 min at room
temperature, the produced ethane was removed by bubbling N2 through
for 5 min. The resulting solution was used for the melting point
depression measurement.29 This solution was loaded in a test tube that
is equipped with a thermometer under N2. The test tube was inserted
into a saturated NaCl aqueous solution in a beaker. The beaker was
then placed into an 2-propanol-dry ice bath at -15 °C. The change
of temperature was recorded every 30 s. The measured frozen point
is 5.0 °C. According to ∆Tf ) kfm, the measured molecular weight of
(R)-27′ is 964 (Tf° ) 6.7, kf ) 20.4). The calculated molecular weight
is 926.
Preparation and Characterization of (R)-27. Diethylzinc (3.5 µL,
0.035 mmol) was added to a CDCl3 solution (0.60 mL) of (R)-25 (11.0
1
mg, 0.035 mmol). After the solution was shaken for 5 min, the H
NMR spectrum showed the quantitative formation of (R)-27: 1H NMR
(CDCl3, 400 MHz) δ -0.88 (m, 2H, ZnCH2), 0.44 (t, J ) 8.2 Hz,
3H), 0.88 (s, ethane), 0.92 (t, J ) 6.9 Hz, 3H), 3.94 (m, 1H), 4.02 (m,
1H), 7.02 (d, J ) 8.7 Hz, 1H), 7.12 (d, J ) 8.7 Hz, 1H), 7.18 (m, 3H),
7.24 (t, J ) 7.2 Hz, 1H), 7.35 (t, J ) 7.4 Hz, 1H), 7.39 (d, J ) 8.7 Hz,
1H), 7.79 (d, J ) 8.7 Hz, 1H), 7.81 (d, J ) 7.7 Hz, 1H), 7.88 (d, J )
8.2 Hz, 1H), 7.98 (d, J ) 9.2 Hz, 1H); 13C NMR (CDCl3, 100 MHz)
δ -2.17, 6.97, 11.79, 15.00, 67.89, 118.59, 119.10, 122.53, 122.62,
123.00, 123.86, 124.86, 125.43, 125.94, 126.49, 127.12, 128.13, 128.33,
128.70, 129.58, 130.36, 134.12, 134.28, 153.33, 157.33.
Acknowledgment. The support for this work was provided
by the Department of Chemistry at North Dakota State
University and then by the Department of Chemistry at
University of Virginia. Partial support from the donors of the
Petroleum Research Fund-ACS, the National Science Founda-
tion (DMR-9529805), and U.S. Air Force (F49620-96-1-0360)
is also gratefully acknowledged.
Cryoscopic Molecular Weight Determination of (R)-27′. (R)-25′
and (R)-27′ were prepared because of their better solubility in
cyclohexane than (R)-25 and (R)-27, which is important for the
molecular weight measurement. (a) Preparation of (R)-25′: (R)-25′
JA972623R
(29) Shoemaker, D. P.; Garland, C. W.; Nibler, J. W. Experiments in
Physical Chemistry, 3rd ed.; McGraw-Hill: New York, 1996; p 179.