Enantioselective allylic alkylation using polymer-supported palladium catalysts

Article abstract of DOI:10.1016/S0957-4166(99)00416-4

Chiral 2'-(4'',5''-dihydro-2''-oxazolyl)-6'-(1-hydroxyalkyl)pyridines were grafted via ester-linkages directly to cross-linked polystyrene and to polyethyleneglycol-containing resins TentaGel and ArgoGel functionalized with carboxylic acid groups or via s

Full text of DOI:10.1016/S0957-4166(99)00416-4

Pergamon
Tetrahedron: Asymmetry 10 (1999) 4037–4046
Enantioselective allylic alkylation using polymer-supported
palladium catalysts
Kristina Hallman, Emmanuel Macedo, Kerstin Nordström and Christina Moberg ∗
Department of Chemistry, Organic Chemistry, Royal Institute of Technology, SE 100 44 Stockholm, Sweden
Received 9 September 1999; accepted 16 September 1999
Abstract
Chiral 20-(400,500-dihydro-200-oxazolyl)-60-(1-hydroxyalkyl)pyridines were grafted via ester-linkages directly
to cross-linked polystyrene and to polyethyleneglycol-containing resins TentaGel and ArgoGel functionalized
with carboxylic acid groups or via spacers containing a carboxylic acid group. The polymeric ligands were
used in the palladium-catalyzed substitution of rac-1,3-diphenyl-2-propenyl acetate with dimethyl malonate. The
enantioselectivities (up to 80% ee) were similar to those observed employing an analogous monomeric catalyst.
© 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
In recent years the interest in using functionalized polymers has been constantly growing. The
development of solid-supported reagents and catalysts1 has been stimulated by the preparation of new
types of polymeric supports, such as graft-copolymers of gel-type polystyrene and polyoxyethylene,2
which have complemented the traditionally used polystyrene–divinylbenzene resins.3 Reagents bound
to the new types of resins can be used in solvents with a wider range of polarity and are more easily
analyzed by spectroscopic methods in the solvent-swollen state.
Solid phase asymmetric metal catalysts have attractive properties as they can be easily separated
from the reaction mixture after the catalytic reaction, thereby facilitating the purification of the product.
Occasionally such catalysts may also be recovered and reused in the catalytic process.4 The palladium-
catalyzed allylic alkylation is a synthetically important process in that new carbon–carbon bonds are
formed.5 With chiral catalysts, high enantioselectivities have often been observed.5a Pyridinooxazolines
1 are highly useful ligands in the reaction.6 The selectivity is highly dependent on the structure of the
substituent in the 6-position of the pyridine ring; ees ranging from 15 to >99% have been observed.6a In
addition, pyridinooxazolines are known to induce chirality in various metal-mediated processes such as
∗
Corresponding author. Fax: 46-8-791 2333; e-mail: kimo@orgchem.kth.se
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00416-4

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Rh7- and Co-catalyzed8 hydrosilylations, Diels–Alder reactions,9 Cu-catalyzed allylic acyloxylations,10
Meerwein arylation of activated olefins,11 1,4-additions,12 epoxidations,13 additions of diethylzinc14 and
of allylsilanes15 to aldehydes, monophenylation of meso-diols16 and in π-complexation.17
A polymeric pyridinooxazoline has previously been prepared and employed in Rh-catalyzed
hydrosilylations.18 The polymeric ligand was prepared via reaction of the pyridinooxazoline with
lithiated 2% cross-linked polystyrene, resulting in substitution primarily at the 6-position of the pyridine
ring. Since we have found that pyridinooxazolines containing 1-alkoxymethyl or 1-hydroxymethyl
groups in the 6-position of the pyridine ring (1, R0=CH(OR1)R2) induce high selectivity in catalytic
reactions as a result of restricted rotation around the pyridine carbon–carbinol carbon bond,19 attachment
of 6-hydroxymethyl derivatives of 1 (R0=CH2OH) was preferred. In principle, immobilization of such
derivatives to a polymer can be achieved by substitution of the pyridine ring or via functionalization of
the substituent in the oxazoline ring (R) or of the substituent in the pyridine ring (R0). A route involving
functionalization at oxygen was expected to yield suitable polymeric derivatives and was therefore
chosen.
We present here the preparation of pyridinooxazolines supported on appropriately functionalized 1%
cross-linked polystyrene, TentaGel and ArgoGel. The new polymers have been assessed in the palladium-
catalyzed allylation of dimethyl malonate.20 The results are compared to those obtained employing
monomeric analogs as catalysts.
2. Results and discussion
2.1. Preparation of polymeric ligands
(400R)0-020-(400,500-Dihydro-400-phenyl-200-oxazolyl)-60-(hydroxymethyl)pyridine6 b 1a, (400R,2R)-
20-(400,5 -dihydro-400-phenyl-200-oxazolyl)-60 -(2,2-dimethyl-1-hydroxypropyl)pyridine
(R,R)-1b
and (400R,2S)-20-(400,500-dihydro-400-phenyl-200-oxazolyl)-60-(2,2-dimethyl-1-hydroxypropyl)pyridine
(R,S)-1b were selected as suitable ligands for attachment to polymeric supports, either via a spacer
containing a carboxylic acid group or directly to a polymer functionalized with carboxylic acid groups.
Since phenolic compounds react readily with chloromethylated polymers,21 reaction of 1a with
a spacer containing a protected phenolic residue was considered as an appropriate strategy for the
preparation of the polymer-supported ligand. Carbonate 2a was selected as a suitable compound for
this purpose,22 as the carbonate group can be deprotected under mild conditions after reaction with the
pyridinecarbinol, to yield the desired phenol. Chloromethylated polystyrene–1% divinylbenzene (5a,
1.6 mmol chloromethyl groups/g resin) and ArgoGel™–Wang–Cl (5b, 0.35–0.45 mmol chloromethyl
groups/g resin) were chosen as polymeric supports.

K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
4039
Since esterification of 2a with the model alcohol 2-(hydroxymethyl)pyridine using DCC/DMAP23
resulted in a low yield (20%) of product, Mitsunobu coupling24 of 1a and 2a was employed, affording
the desired 3a (Scheme 1) as a crude product which was used in the next step without further purification.
Deprotection with aqueous ammonia yielded phenol 4a (56% over two steps), which was treated
with chloromethylated polystyrene–1% divinylbenzene 5a and ArgoGel™–Wang–Cl 5b in DMF in the
presence of K2CO3 to afford polymers 6a and 6b, respectively. The increase in weight of the polystyrene
resin 6a indicated a conversion of about 57%, which was in agreement with the elemental analysis (1.78%
N, corresponding to 51% conversion). The signal at δ 46.29 (CH2Cl) in the 13C NMR spectrum of
the ArgoGel resin 6b disappeared completely, but the resin was shown to contain merely 0.56% N by
elemental analysis (corresponding to ca 55% conversion).
Scheme 1.
Ligands (R,R)-1b and (R,S)-1b (Scheme 2) were also grafted on an ArgoGel resin. Attempts to react a
model compound containing a secondary alcohol group, rac-2-(2,2-dimethyl-1-hydroxypropyl)pyridine,
with 2a under Mitsunobu conditions were unsuccessful. The sterically less hindered carbonate 2b,
containing two carbon atoms between the carboxylic acid function and the aromatic ring, was also
unreactive under the same conditions, but reacted with (R,R)-1b and (R,S)-1b in the presence of DCC and
DMAP to yield (R,R)-3b (65%) and (R,S)-3b (58%), respectively. Subsequent deprotection (to give (R,R)-
4b, 93%, and (R,S)-4b, 95%) and reaction with ArgoGel™–Wang–Cl (5b) gave the desired polymers
(R,R)-6c and (R,S)-6c (0.42% and 0.43% N, respectively, corresponding to ca 40% conversion).
Scheme 2.

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K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
A TentaGel resin containing carboxylic acid group 5c was also used as a solid support in order to
allow direct attachment of the ligand to the polymer. Ligand 1a was thus reacted with 5c in the presence
of DCC/DMAP to yield, according to 13C NMR spectroscopy, the desired polymer 6d (Scheme 3). From
ligands (R,R)-1b and (R,S)-1b polymers (R,R)-6e and (R,S)-6e, respectively, were prepared using the
same procedure. According to elemental analysis, essentially complete conversion to the products 6d
and (R,R)-6e took place. Polymer (R,S)-6e was formed in about 80% yield.
Scheme 3.
Finally, in order to allow comparison of the reactivity and selectivity of the polymeric catalysts with a
monomeric analog, ester 7 was prepared from 1a and benzoic acid.
2.2. Catalytic reaction
Polymer-supported ligands 6d, (R,R)-6e and (R,S)-6e, which were conveniently obtained in high
yields, and monomer 7, were assessed in the palladium-catalyzed allylic substitution of rac-1,3-diphenyl-
2-propenyl acetate 8. The reactions were performed in CH2Cl2 at room temperature in the presence of a
(π-allyl)palladium–ligand complex generated in situ from 2.0 mol% of bis[(π-allyl)palladium chloride]
and ca 6 mol% of the appropriate ligand. The nucleophile was generated from dimethyl malonate in the
presence of N,O-bis(trimethylsilyl)acetamide (BSA) and a catalytic amount of KOAc (Scheme 4).25
Scheme 4.
The reactions were slow, requiring about seven days reaction time. All ligands (i.e. polymers 6d, 6e
and monomer 7) gave the product 9 of R absolute configuration with similar enantioselectivities (Table 1).
Very low yields of 9 were observed when the sterically bulky ligands 6e were employed. The yields of 9
using 6d and 7 varied considerably (60–100%) but the enantioselectivity was always reproducible.
In contrast to previous investigations,6a only minor differences in the enantioselectivity exhibited by
diastereomeric ligands were observed in the present study. However, the low yields of products obtained
using ligands (R,R)-6e and (R,S)-6e do not allow definite conclusions regarding the selectivity, which has
previously been shown to depend on the conformational preferences of the ligands.26

K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
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Table 1
Alkylation of rac-1,3-diphenyl-2-propenyl acetate with dimethyl malonatea
3. Conclusion
Chiral polymer-supported pyridinooxazolines have been prepared and assessed in the palladium-
catalyzed substitution of rac-1,3-diphenyl-2-propenyl acetate. The use of a polymer obtained in high
yield from (400R)-20-(400,500-dihydro-400-phenyl-200oxazolyl)-60-(hydroxymethyl)pyridine 1a and Tenta-
Gel HL-COOH® resulted in high yield and good enantioselectivity (80% ee).
4. Experimental
4.1. General
1H and 13C NMR spectra were recorded in CDCl3 at 400 and 100.6 MHz, respectively, unless
otherwise stated. Enantiomeric excesses were determined by HPLC using a chiral column (Chiralcel OD-
H). Merck Kieselgel 60H was used for flash chromatography. Three different polymeric supports were
used: chloromethylated27 SX1, which is a polystyrene resin cross-linked with 1% divinylbenzene from
Bio-Rad, 5a, ArgoGel™–Wang–Cl 5b from Aldrich, bead size ca 170 µm and TentaGel HL-COOH® 5c
from Fluka, bead size ca 110 µm, which are graft-copolymers of a gel-type polystyrene (cross-linked
with 1% divinylbenzene) and polyoxyethylene. The palladium-catalyzed allylations were performed as
described previously.6a
4.2. Compound 1a. Imidate
To a solution of 2-cyano-6-(hydroxymethyl)pyridine (0.25 g, 1.83 mmol) in methanol (6 mL) was
added sodium methoxide (10 mg, 0.19 mmol). The mixture was stirred for 1 day at room temperature
and the solvent removed under pressure to give the expected product as a yellow solid, which was used
1
without further purification: H NMR δ 9.31 (1H, NH, s), 7.77–7.83 (2H, aromatic, m), 7.35–7.41 (1H,
aromatic, m), 4.83 (2H, CH2, s), 4.01 (3H, CH3O).
To the above imidate (0.29 g, 1.72 mmol) in CH2Cl2 (7 mL) was added a solution of (R)-2-
phenylglycinol (0.24 g, 1.72 mmol) in CH2Cl2 (2.5 mL). A few drops of conc. H2SO4 were added,
the mixture was stirred at reflux for 3 days, and then saturated aqueous Na2CO3 (8 mL) was added.
The phases were separated, the aqueous layer was extracted with CH2Cl2 (3×8 mL), and the combined

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K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
organic phases were dried over MgSO4. Evaporation of the solvent in vacuo gave 1a (0.43 g, 91%) as an
oil, according to 1H NMR identical to 1a prepared previously in lower yield using another method.6b
4.3. 4-(Methoxycarbonyloxy)benzoic acid 2a
4-Hydroxybenzoic acid (2.03 g, 14.6 mmol) was added to a slurry of sodium hydroxide (1.69 g, 42.3
mmol) in water (45 mL) at −10°C under vigorous stirring. The reaction mixture was allowed to warm to
−5°C and methyl chloroformate (2.22 g, 23.3 mmol) was added over a period of 10–15 min. The reaction
was allowed to warm to room temperature, then stirred overnight and quenched by adding a mixture of
HCl:H2O, 1:1, until a pH of 3 was reached, which resulted in the formation of a thick white precipitate.
The white solid was filtered off, washed with water and finally dried to yield 2a (2.83 g, 99%): mp
163–168°C; 1H NMR δ 8.16 (2H, aromatic, d, J=8.5 Hz), 7.31 (2H, aromatic, d, J=8.5 Hz), 3.94 (3H,
CH3O, s); the acidic proton was not observed.
4.4. Compound 3a
Spacer 2a (69.3 mg, 0.353 mmol) and DEAD (diethyl azodicarboxylate, 55 µL, 0.346 mmol) were
added to a solution of ligand 1a (88.1 mg, 0.347 mmol) in THF (2.5 mL). PPh3 (92.2 mg, 0.551 mmol)
was added to the resulting yellow solution, whereby the color of the solution faded with time. After 3.5
h of stirring at room temperature, the solvent was evaporated under reduced pressure. The product was
extracted from the oil with 4×5 mL of a mixture of hexane:EtOAc, 80:20. The combined organic layers
were filtered through glasswool and then concentrated to give 3a (190 mg) as a slightly yellow oil. The
crude product was used for the next step without further purification.
4.5. Compound 4a
An aqueous solution of NH3 (25%, 1.5 mL) was slowly added to a solution of 3a (179 mg of the
crude product described above) in absolute ethanol (4 mL). After stirring at room temperature for 4
h, the solvent was removed under reduced pressure to give a yellow oil, which was purified by flash
chromatography on silica gel (3.5×2 cm column, hexane:EtOAc, 60:40, and hexane:EtOAc, 30:70) to
yield 4a (24 mg, 56% yield based on 1a) as a colorless oil: [α]D +26.9 (c 0.48, CH2Cl2); 1H NMR δ
20
8.10 (1H, aromatic, d, J=7.6 Hz), 7.94 (2H, aromatic, d, J=8.6 Hz), 7.83 (1H, aromatic, app t, J=7.9 Hz),
7.58 (1H, aromatic, d, J=7.6 Hz), 7.27–7.40 (5H, aromatic, m), 6.83 (2H, aromatic, d, J=8.6 Hz), 5.49
(2H, CH2, s), 5.47 (1H, oxazoline, dd, J=10.1, 8.6 Hz), 4.92 (1H, oxazoline, dd, J=10.1, 8.6 Hz), 4.42
(1H, oxazoline, t, J=8.6 Hz); the acidic proton was not observed. 13C NMR δ 163.91, 160.65, 156.91,
146.14, 141.57, 137.68, 132.11, 128.89, 127.91, 126.86, 124.12, 123.54, 121.81, 115.44, 76.29, 76.06,
75.59, 70.22, 66.81.
4.6. Polymer-supported ligand 6a
K2CO3 (21 mg, 0.153 mmol) was added in one portion to a suspension of chloromethylated polysty-
rene 5a (1.6 mmol of chloromethyl groups/g of polymer, 53.5 mg, 0.085 mmol) and 4a (35 mg, 0.094
mmol) in dry DMF (1.2 mL) in a dry round-bottomed flask. The reaction mixture was stirred overnight
under a nitrogen atmosphere at 60°C. The polymer was filtered off and washed in succession with MeOH
(2 mL), THF:H2O, 1:1 (2 mL), H2O (2 mL), acetone (2 mL), CH2Cl2 (2 mL) and MeOH (2 mL). The
polymer was dried at room temperature in vacuo overnight, resulting in 70.4 mg of 6a containing 1.78%

K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
4043
N, corresponding to 0.64 mmol of ligand/g of polymer (51% conversion). Due to poor resolution we were
not able to assign the signals in the 13C NMR spectrum.
4.7. Polymer-supported ligand 6b
This polymer was prepared according to the procedure described for 6a starting from
ArgoGel™–Wang–Cl 5b (0.35–0.45 mmol of chloromethyl groups/g of polymer, 0.179 g, 0.072
mmol), 4a (29.6 mg, 0.079 mmol), K2CO3 (17.9 mg, 0.130 mmol) and dry DMF (1 mL). The polymer
was dried at room temperature in vacuo overnight, resulting in 170 mg of 6b containing 0.56% N,
corresponding to 0.20 mmol of ligand/g of polymer (ca 54% conversion, assuming 0.40 mmol/g of
functional groups in 5b): 13C NMR δ 163.70, 158.91, 156.92, 141.83, 137.63, 131.93, 131.64, 129.28,
128.86, 128.50, 127.83, 126.91, 123.50, 114.87, 114.70, 114.53, 75.54, 69.75–71.41 (several signals),
67.56, 66.85.
4.8. 3-(4-Methoxycarbonyloxyphenyl)propionic acid 2b
This compound was prepared according to the procedure described for 2a starting from 3-(4-
hydroxyphenyl)propionic acid (0.395 g, 2.38 mmol), a solution of sodium hydroxide (0.276 g, 6.9 mmol)
in water (7 mL) and methyl chloroformate (0.364 g, 3.85 mmol). The thick white precipitate obtained
after lowering the pH to 3 was filtered off and washed with water, and then dissolved in CH2Cl2. The
resulting solution was dried over MgSO4. Evaporation followed by drying in vacuo afforded 2b (0.322
g, 60%): mp 66°C; 1H NMR δ 7.22 (2H, aromatic, d, J=8.3 Hz), 7.09 (2H, aromatic, d, J=8.3 Hz), 3.90
(3H, CH3O, s), 2.97 (2H, CH2, t, J=7.6 Hz), 2.68 (2H, CH2, t, J=7.6 Hz); the acidic proton was not
observed.
4.9. Compound (R,R)-3b
DCC (1,3-dicyclohexylcarbodiimide, 35 mg, 0.17 mmol) was added to a solution of (R,R)-1b (47 mg,
0.15 mmol), 2b (34 mg, 0.15 mmol) and DMAP (4-dimethylaminopyridine, 1.8 mg, 0.015 mmol) in
CH2Cl2 (0.1 mL). The resulting mixture, which became thick and white, was stirred for 4.5 h at room
temperature, then diluted with Et2O (5 mL) and filtered through a glass filter. Evaporation of the filtrate
in vacuo afforded a yellow oil which was purified by flash chromatography on silica gel (3.5×2 cm
20
column, hexane:EtOAc, 60:40) to give (R,R)-3b (50 mg, 65%) as a colorless oil: [α]D +17.9 (c 0.69,
CH2Cl2); 1H NMR δ 8.06 (1H, aromatic, d, J=7.7 Hz), 7.68 (1H, aromatic, t, J=7.7 Hz), 7.28–7.40 (5H,
aromatic, m), 7.06–7.21 (3H, aromatic, m), 7.07 (2H, aromatic, d, J=8.6 Hz), 5.71 (1H, CHO, s), 5.42
(1H, oxazoline, app t, J=9.5 Hz), 4.88 (1H, oxazoline, dd, J=10.1, 8.6 Hz), 4.36 (1H, oxazoline, app t,
J=8.6 Hz), 3.90 (3H, OCH3), s), 2.98 (2H, CH2, app t, J=7.6 Hz), 2.74 (2H, CH2, td, J=7.6, 2.5 Hz),
0.95 (9H, C(CH3)3, s).
4.10. Compound (R,R)-4b
An aqueous solution of NH3 (25%, 370 µL) was slowly added to a suspension of (R,R)-3b (30.5 mg,
0.059 mmol) in absolute ethanol (1 mL). After stirring at room temperature for 4 h, the solvent was
removed under reduced pressure to give (R,R)-4b (25 mg, 93%) as a colorless oil: [α]D20+30.8 (c 0.83,
CH2Cl2); 1H NMR δ 8.05 (1H, aromatic, d, J=7.9 Hz), 7.65 (1H, aromatic, t, J=7.9 Hz), 7.25–7.38 (5H,
aromatic, m), 7.16 (1H, aromatic, d, J=7.9 Hz), 7.02 (2H, aromatic, d, J=8.4 Hz), 6.69 (2H, aromatic,

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K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
d, J=8.4 Hz), 5.70 (1H, CHO, s), 5.43 (1H, oxazoline, app t, J=9.5 Hz), 5.15 (1H, OH, s), 4.88 (1H,
oxazoline, dd, J=10.1, 8.5 Hz), 4.37 (1H, oxazoline, t, J=8.5 Hz), 2.89 (2H, CH2, app t, J=7.4 Hz), 2.69
(2H, CH2, app t, J=6.9 Hz), 0.95 (9H, C(CH3)3, s).
4.11. Polymer-supported ligand (R,R)-6c
The same procedure as that used for the preparation of 6a was followed, starting from 5b (0.35–0.45
mmol of chloromethyl groups/g of polymer, 0.120 g, 0.048 mmol), (R,R)-4b (24.2 mg, 0.053 mmol),
K2CO3 (11.9 mg, 0.086 mmol) and dry DMF (800 µL). Polymer (R,R)-6c was obtained as yellow beads
(116 mg) containing 0.42% N, corresponding to 0.15 mmol ligand/g of polymer (ca 40% conversion,
asumming 0.40 mmol/g of functional groups in 5b): 13C NMR δ 171.98, 164.20, 158.87, 158.27, 142.06,
136.46, 133.88, 132.64, 130.09, 129.18, 128.83, 128.50, 127.76, 126.88, 123.53, 123.16, 114.96, 114.78,
114.62, 83.41, 75.56, 70.5–70.9 (several signals), 69.8, 67.55, 64.59, 46.30, 42.81, 36.14, 35.10, 30.14,
26.13.
4.12. Compound (R,S)-3b
This compound was prepared according to the procedure described for (R,R)-3b, starting from DCC
(35 mg, 0.17 mmol), (R,S)-1b (48 mg, 0.15 mmol), 2b (35 mg, 0.15 mmol), DMAP (1.9 mg, 0.015 mmol)
and CH2Cl2 (0.1 mL). The colorless oil obtained after chromatography was dried at room temperature in
vacuo overnight, resulting in 46.7 mg of (R,S)-3b (58%): [α]D20 +47.3 (c 0.60, CH2Cl2); 1H NMR δ 8.07
(1H, aromatic, d, J=7.8 Hz), 7.69 (1H, aromatic, t, J=7.8 Hz), 7.26–7.38 (5H, aromatic, m), 7.17–7.20
(3H, aromatic, m), 7.07 (2H, aromatic, d, J=8.6 Hz), 5.71 (1H, CHO, s), 5.43 (1H, oxazoline, dd, J=4.7,
4.7 Hz), 4.89 (1H, oxazoline, dd, J=10.1, 8.6 Hz), 4.36 (1H, oxazoline, app t, J=8.6 Hz), 3.90 (3H, OCH3,
s), 2.98 (2H, CH2, app t, J=7.6 Hz), 2.74 (2H, CH2, td, J=7.6, 2.5 Hz), 0.95 (9H, C(CH3)3, s).
4.13. Compound (R,S)-4b
The same procedure as that used for the preparation of (R,R)-4b was followed, starting from (R,S)-
3b (41.9 mg, 0.081 mmol), NH3 (aq, 25%, 505 µL) and absolute ethanol (1.4 mL). A white solid was
obtained, which was dried in vacuo overnight, resulting in 35.7 mg of (R,S)-4b (95%): mp 208–210°C;
[α]D +44 (c 0.63, CH2Cl2); 1H NMR δ 8.06 (1H, aromatic, d, J=7.8 Hz), 7.67 (1H, aromatic, t, J=7.8
20
Hz), 7.21–7.38 (5H, aromatic, m), 7.20 (1H, aromatic, d, J=9.5 Hz), 7.04 (2H, aromatic, d, J=8.5 Hz),
6.70 (2H, aromatic, d, J=8.5 Hz), 5.71 (1H, CHO, s), 5.43 (1H, oxazoline, app t, J=9.3 Hz), 4.90 (1H,
oxazoline, app t, J=7.9 Hz), 4.64 (1H, OH, s), 4.37 (1H, oxazoline, t, J=8.5 Hz), 2.91 (2H, CH2, app t,
J=7.6 Hz), 2.69 (2H, CH2, td, J=7.6, 2.8 Hz), 0.95 (9H, C(CH3)3, s).
4.14. Polymer-supported ligand (R,S)-6c
The same procedure as that used for the preparation of 6a was followed, starting from 5b (0.35–0.45
mmol of chloromethylated groups/g of polymer, 0.178g, 0.071 mmol), (R,S)-4b (35.7 mg, 0.078 mmol),
K2CO3 (17.9 mg, 0.127 mmol) and dry DMF (1.1 mL). Polymer (R,S)-6c was obtained as yellow beads
(185 mg) containing 0.43% N, corresponding to 0.15 mmol ligand/g of polymer (41%, assuming 0.40
mmol/g of functional groups in 5b): 13C NMR (125.7 MHz) δ 172.3, 164.6, 159.3, 159.2, 136.8, 136.5,
135.7, 134.3, 130.5, 129.6, 129.2, 128.9, 128.1, 127.3, 127.0, 123.6, 121.4, 115.2, 115.1, 115.0, 83.7,
83.2, 78.0, 70.2–71.8 (several signals), 67.9, 65.0, 53.9, 46.7, 43.2, 40.8, 36.5, 35.5, 30.5, 26.5.

K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
4045
4.15. Polymer-supported ligand 6d
DCC (22.8 mg, 0.111 mmol) was added to a suspension of TentaGel HL-COOH® 5c (0.40–0.60 mmol
of acid groups/g of polymer, 0.225 g, 0.090 mmol), 1a (25.3 mg, 0.099 mmol) and DMAP (2.0 mg,
0.016 mmol) in dry CH2Cl2 (1.5 mL). The reaction mixture was stirred for 22 h at room temperature.
The polymer was filtered off and washed in succession with MeOH (2 mL), EtOH (2 mL), THF:H2O,
1:1 (2 mL), H2O (2 mL), acetone (2 mL), CH2Cl2 (2 mL) and MeOH (2 mL), and then dried at room
temperature in vacuo overnight, resulting in 238.4 mg of 6d containing 1.29% N, corresponding to 0.46
mmol ligand/g of polymer (100%, assuming 0.50 mmol/g of functional groups in 5c): 13C NMR δ 172.3,
171.31, 163.64, 156.50, 146.24, 141.82, 137.63, 133.76, 131.90, 128.85, 127.80, 126.88, 123.44, 75.48,
70.6–75.5 (several signals), 69.78, 66.67, 39.40, 30.73, 29.50.
4.16. Polymer-supported ligand (R,R)-6e
The same procedure as that used for the preparation of 6d was followed, starting from 5c (0.40–0.60
mmol of acid groups/g of polymer, 0.231g, ca 0.092 mmol), (R,R)-1b (31.4 mg, 0.101 mmol), DMAP
(1.1 mg, 0.009 mmol), dry CH2Cl2 (1.5 mL) and DCC (21.1 mg, 0.101 mmol). Polymer 6e was obtained
as beads (244 mg) containing 1.15% N, corresponding to 0.41 mmol ligand/g polymer (93%, assuming
0.50 mmol/g of functional groups in 5c): 13C NMR (125.7 Hz) δ 172.20, 171.61, 164.22, 158.92,
154.55, 145.57, 142.13, 136.68, 128.95, 127.90, 126.98, 124.14, 123.33, 83.47, 75.61, 70.8–69.9 (several
signals), 54.78, 39.48, 35.25, 32.52, 31.27, 30.77, 29.95, 29.72, 26.31, 25.70, 24.92.
4.17. Polymer-supported ligand (R,S)-6e
This polymer was prepared in the same manner as 6d starting from 5c (0.278 g, ca 0.111 mmol),
(R,S)-1b (38.0 mg, 0.122 mmol), DMAP (1.4 mg, 0.011 mmol), dry CH2Cl2 (1.8 mL) and DCC (25.4
mg, 0.122 mmol). Polymer (R,S)-6e was obtained as beads (292 mg) containing 1.02% N, corresponding
to 0.36 mmol ligand/g polymer (82% assuming 0.50 mmol/g of functional groups in 5c): 13C NMR (125.7
Hz) δ 172.18, 171.67, 164.31, 158.95, 154.57, 145.58, 142.19, 136.71, 128.98, 127.93, 127.01, 124.15,
123.40, 83.48, 75.62, 70.8–69.9 (several signals), 54.75, 39.46, 35.29, 32.50, 31.19, 30.75, 29.92, 29.68,
28.30, 26.30, 24.91.
4.18. Compound 7
The procedure used for the preparation of (R,R)-3b was followed. Starting from 1a (33.2 mg, 0.131
mmol), benzoic acid (16.5 mg, 0.135 mmol), DMAP (1.8 mg, 0.015 mmol) and DCC (27.5 mg, 0.152
mmol) in 200 µL CH2Cl2 afforded 35 mg of 7 (75%) as a white solid after purification by flash
chromatography on silica gel (4×1.5 cm column, hexane:EtOAc, 40:60): [α]D20 +57.3 (c 0.59, CH2Cl2);
mp 98–102°C; 1H NMR δ 8.13 (2H, aromatic, app d, J=7.3 Hz), 7.84 (1H, aromatic, app t, J=7.9 Hz),
7.59 (1H, aromatic, app t, J=7.3 Hz), 7.47 (1H, aromatic, app t, J=7.5 Hz), 7.3–7.4 (8H, aromatic, m),
5.61 (2H, CH2, s), 5.46 (1H, oxazoline ring, app t, J=9.3 Hz), 4.92 (1H, oxazoline ring, app t, J=9.5
Hz), 4.42 (1H, oxazoline ring, app t, J=8.7 Hz); 13C NMR δ 166.14, 163.68, 156.65, 146.45, 141.78,
137.60, 133.34, 129.87, 129.79, 128.86, 128.53, 127.83, 126.89, 123.62, 123.56, 75.54, 70.40, 67.12.
Anal. calcd for C22H18N2O3: C, 73.73; H, 5.06; N, 7.82. Found C, 73.06; H, 4.92; N, 7.55. The product
probably contained approximately 0.1 equiv. of water which we were unable to get rid of: calcd for
C22H18N2O3·0.1H2O: C; 73.36; H, 5.09; N, 7.78.

4046
K. Hallman et al. / Tetrahedron: Asymmetry 10 (1999) 4037–4046
Acknowledgements
This work was supported by the Swedish Research Council for Engineering Sciences.
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