Novel polymer-bound aminoalcohol ligands for the asymmetric addition of diethylzinc to aldehydes

Article abstract of DOI:10.1080/00397910701356553

The synthesis of several novel polymer-supported aziridine-containing aminoalcohol chiral ligands has been accomplished, and the polymers have been used as ligands for the catalytic asymmetric addition of diethylzinc to benzaldehyde, giving up to 89% ee. Incorporation onto a polymer support prevents the variation of ee with time that is observed in reactions of one unsupported ligand, perhaps as a result of site isolation of the ligand within the polymer, preventing cooperative effects. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910701356553

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Novel Polymer‐Bound Aminoalcohol Ligands
for the Asymmetric Addition of Diethylzinc to
Aldehydes
Philip C. Bulman Page a , Steven M. Allin a , Suzanne J. Dilly a & Benjamin R.
Buckley a
a Department of Chemistry, Loughborough University, Loughborough,
Leicestershire, England
Version of record first published: 22 Jun 2007.
To cite this article: Philip C. Bulman Page , Steven M. Allin , Suzanne J. Dilly & Benjamin R. Buckley (2007):
Novel Polymer‐Bound Aminoalcohol Ligands for the Asymmetric Addition of Diethylzinc to Aldehydes,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
37:12, 2019-2030
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Synthetic Communicationsw, 37: 2019–2030, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701356553
Novel Polymer-Bound Aminoalcohol
Ligands for the Asymmetric Addition
of Diethylzinc to Aldehydes
Philip C. Bulman Page, Steven M. Allin,
Suzanne J. Dilly, and Benjamin R. Buckley
Department of Chemistry, Loughborough University,
Loughborough, Leicestershire, England
Abstract: The synthesis of several novel polymer-supported aziridine-containing ami-
noalcohol chiral ligands has been accomplished, and the polymers have been used as
ligands for the catalytic asymmetric addition of diethylzinc to benzaldehyde, giving
up to 89% ee. Incorporation onto a polymer support prevents the variation of ee
with time that is observed in reactions of one unsupported ligand, perhaps as a result
of site isolation of the ligand within the polymer, preventing cooperative effects.
Keywords: addition, aldehyde, aminoalcohol, asymmetric dialkyl zinc, ligand
Chiral b-amino alcohols have been well documented as effective ligands for
the asymmetric addition of diethylzinc to aromatic aldehydes,[1] and the
mechanism has been thoroughly studied over the past few years. The postu-
lated mechanism involves a two-zinc species in the diastereofacially
selective step: one zinc atom, bearing one ethyl group, is chelated by the ami-
noalcohol ligand and is also associated with the aldehyde oxygen atom; a
second zinc atom, of a diethylzinc unit, is associated with both the ligand
and aldehyde oxygen atoms. Ethyl group transfer then takes place.[2] The
incorporation of an aziridine moiety into these ligands allows the reaction
to be carried out with up to 99% ee.[3] We have recently reported the
Received in the USA November 7, 2006
Address correspondence to Philip C. Bulman Page, Department of Chemistry,
Loughborough University, Loughborough, Leicestershire LE11 3TU, U.K. E-mail:
p.c.b.page@lboro.ac.uk
2019

2020
P. C. B. Page et al.
synthesis of a number of aziridine ligands and their use as ligands in the
enantioselective addition of diethylzinc to benzaldehyde.[4] We report here
the preparation and use of polymer-supported versions of three of these
ligands.
A polymer-supported aziridine ligand 1, derived from L-serine and
supported through the nitrogen substituent, has been shown by Holte et al. to
be effective as a ligand in the enantioselective addition of diethylzinc to ben-
zaldehyde, providing (S)-1-phenylpropanol in up to 96% ee.[5] In contrast, to
allow variation of N-substitution in the aziridine ligand framework, we have
attached the polymer to our ligands through the tertiary alcohol phenyl ring
substituents to give the polymer-supported motif 2.
The synthesis of the ligand monomers was carried out from aziridinyl
esters 3 and 4 and 4-bromobenzaldehyde dimethyl acetal 5 (Scheme 1). The
aziridinyl esters 3 and 4 were prepared by the method of Zwanenburg,
whereby N-protected L-serine methyl ester was treated with methanesulfonyl
chloride and subsequently ring-closed to form the aziridine with either trityl or
benzhydryl N-substitution.[6] The protected 4-bromobenzaldehyde 5 was
lithiated, and the anion underwent smooth double addition to give esters 3
and 4. Deprotection of the aldehyde units was effected with para-toluene
sulfonic acid and water, and the aldehydes converted into vinyl moieties
with methyl Wittig reagent, giving ligand monomers 8 and 9.
Suspension copolymerization was carried out with styrene and divinyl
benzene in the presence of poly(vinyl alcohol) (MW 14000) as an emulsifier,
by the method of Far et al.,[7] to produce functionalized copolymers 10 and 11,
each of which was found by elemental analysis to contain a loading of
aziridine ligand of 0.1 mmol/g (Scheme 2).
Scheme 1. i) n-BuLi, THF, 2788C (R ¼ CPh3, 75%; R ¼ CHPh2, 62%); ii) pTsOH,
DCM, H2O, rt (R ¼ CPh3, 69%; R ¼ CHPh2, 60%); iii) MePPh3Br, KHMDS, THF,
08C (R ¼ CPh3, 81%; R ¼ CHPh2, 80%).

Polymer-Bound Aminoalcohol Ligands
2021
Scheme 2. i) Styrene, divinyl benzene, PhCl, benzoyl peroxide, PVA, NaCl, H2O,
1008C.
The copolymer 10 containing the N-tritylated aziridine was treated with
trifluoroacetic acid to achieve detritylation, giving the corresponding NH-
functionalized copolymer 11 (Scheme 3).
The three styrene copolymers generated were then tested as ligands in the
addition of diethylzinc to benzaldehyde. The copolymers were allowed to
swell in toluene at room temperature before being cooled to 08C prior to
the addition of benzaldehyde followed by diethylzinc. The reactions were
allowed to reach room temperature over a further 24 h. After quenching
with aqueous ammonium chloride, the dried crude products were analyzed
by GC (Chrompak, Chirasil CB, 1408C, 10 psi) and 250-MHz 1H NMR spec-
troscopy to obtain the ee and conversions respectively. The results are shown
in Table 1. For comparison, our previously reported results for the unsup-
ported ligand analogues are also shown.[4]
In each case, the major product enantiomer was found to have the (S)-
configuration. We observed the same sense of asymmetric induction with
the solution-phase analogues of these ligands, as did Holte et al. with ligand
1.[5] Compared to the unsupported analogues, however, polymer-supported
ligands 10 and 11 both induce slightly reduced enantioselectivities and con-
versions for the same addition reaction. We were disappointed to note that
Scheme 3. TFA, DCM, MeOH.

2022
P. C. B. Page et al.
Table 1. Addition of diethylzinc to benzaldehyde in the presence of polymeric
aziridine ligandsa
Unsupported
ligand analogue[4]
conversion (%)
Unsupported
ligand analogue[4]
ee (%)
Ligand
Conversion (%)b
Ee (%)c
10
11
11d
12
.95
62
3
89
88
0
.99
.99
—
95
96
—
62
52
84
85
aReaction conditions: benzaldehyde (2.0 mmol), ligand (5 mol%), diethyl zinc
(4.0 mmol), toluene, 08C, 24 h.
1
bConversion after 24 h determined by 250-MHz H NMR spectroscopy.
cEe values determined by GC, Chrompak, Chirasil CB.
dRecycled polymer.
the reuse of ligand 11 demonstrated the complete loss of enantioselectivity and
catalytic ability of the recycled polymer-supported ligand.
It is particularly interesting, therefore, that polymer-supported ligand 12
induces a substantially higher level of enantioselectivity in the addition of
diethylzinc to benzaldehyde than does its unsupported analogue in the
solution phase after reaction for 24 h at room temperature. Further, we have
reported a reduction of ee with time throughout this reaction using the corre-
sponding unsupported ligand from 85% ee after 15 min to 62% ee after 24 h.[4]
It is fascinating to note that the reaction using the polymer-supported ligand 12
displays no such variation of ee with reaction time and that the enantioselec-
tivity of the reaction with the polymer-supported ligand is equivalent to that
displayed after 15 min of reaction time when using the unsupported
analogue. The variation in ee with time during the reaction using the unsup-
ported ligand may be caused by cooperative effects involving more than
one ligand molecule in the reaction. We therefore suggest that the use of
these polymer-supported ligands restricts this effect, possibly due to site
isolation of the ligand within the polymer.
EXPERIMENTAL
General Experimental Detail
All infrared spectra were obtained using a Perkin-Elmer Paragon 1000 FT-IR
spectrophotometer; thin-film spectra were acquired using sodium chloride

Polymer-Bound Aminoalcohol Ligands
2023
plates. All 1H and 13C NMR spectra were measured at 250.13 and 62.86 MHz
with a Bruker AC 250-MHz spectrometer or at 400.13 and 100.62 MHz with a
Bruker DPX 400, in deuteriochloroform solution unless otherwise stated,
using TMS (tetramethylsilane) as the internal reference. Mass spectra were
recorded using a Jeol-SX102 instrument utilizing electron-impact (EI), fast
atom bombardment (FAB), and the EPSRC national mass spectrometry
service at the University of Wales, Swansea, utilizing electrospray (ES).
Analysis by gas chromatography-mass spectrometry (GCMS) utilized a
Fisons GC 8000 series (AS 800), using a 15 m ꢀ 0.25 mm DB-5 column
and an electron-impact low-resolution mass spectrometer. Melting points
were recorded using an Electrothermal-IA 9100 melting-point instrument
and are uncorrected. Optical rotation values were measured with an optical
activity polAAar 2001 instrument operating at l ¼ 589 nm, corresponding
to the sodium D line, at the temperatures indicated. Microanalyses were
performed on a Perkin-Elmer elemental analyser 2400 CHN. All chromato-
graphic manipulations used silica gel as the adsorbent. Reactions were
monitored using thin-layer chromatography (TLC) on aluminium-backed
plates coated with Merck Kieselgel 60 F254 silica gel. TLC plates were visu-
alized by UV radiation at a wavelength of 254 nm or stained by exposure to an
ethanolic solution of phosphomolybdic acid (acidified with concentrated
sulfuric acid), followed by charring where appropriate. Reactions requiring
anhydrous conditions were carried out using flame-dried glassware under a
nitrogen atmosphere unless otherwise stated. Reaction solvents were used as
obtained commercially unless otherwise stated. Light petroleum (bp
40–608C) was distilled from calcium chloride prior to use. Ethyl acetate
was distilled over calcium sulfate or chloride. Dichloromethane was
distilled over calcium hydride. Tetrahydrofuran was distilled under a
nitrogen atmosphere from the sodium/benzophenone ketyl radical.
(–)-(S)-Methyl N-Tritylaziridine-2-carboxylate 3
A suspension of L-serine methyl ester (74.0 g, 476.0 mmol) in chloroform
(600 mL) was treated with triethylamine (115.5 g, 1140.0 mmol), and
the solution was cooled to 08C. Triphenylmethyl chloride (132.5 g,
476.0 mmol) was added in portions. The reaction mixture was maintained at
08C for 3 h, allowed to reach room temperature, and washed with water
(600 mL) and brine (400 mL). The organic layer was dried over magnesium
sulfate. The solution was concentrated to 300 mL and treated with triethyl-
amine (115.5 g, 1140.0 mmol) and 4-dimethylaminopyridine (10 mol%,
5.83 g, 48.0 mmol). Methanesulfonyl chloride (75.8 g, 660.0 mmol) was
added dropwise over 90 min. The reaction mixture was heated to reflux for
20 h, allowed to cool to room temperature, and washed with water
(600 mL) and brine (500 mL). The organic layer was dried over sodium
sulfate and evaporated to dryness. The residue was recrystallized from

2024
P. C. B. Page et al.
ethanol (300 mL) to give the product as pale beige crystals (97.0 g, 59%); mp
122–1268C; [a]2D0 ¼ 2 85.9 (c 0.40, CH2Cl2) (Found: C, 79.9; H, 6.3; N, 3.8;
C23H21NO2 requires C, 80.4; H, 6.2; N, 4.1%); nmax/cm21 2950, 1749, 1448,
1199, 708; dH (400 MHz, CDCl3) 1.41 (dd, J ¼ 1.6, 6, 1H), 1.89 (dd, J ¼2.4,
6, 1H), 2.25 (dd, J ¼ 1.6, 2.4, 1H), 3.75 (s, 3H), 7.15–7.32 (9H, m), 7.50
(d, J ¼ 8, 6H); dC (100 MHz, CDCl3) 28.7, 31.7, 52.1, 74.4, 126.9, 127.8,
128.0, 128.7, 129.3, 143.6, 171.9; m/z 343.1565 (C23H21NO2 requires
343.1572) 105 (90%), 165 (95%), 244 (100%), 343 (.1%).
(–)-(S)-Methyl N-Benzhydryl-2-amino-3-hydroxypropanoate
A solution of L-serine methyl ester (5.0 g, 32.0 mmol) in chloroform (50 mL)
was treated with triethylamine (7.7 g, 77.0 mmol), and the solution was cooled
to 08C. Benzhydryl chloride (4.4 g, 22.0 mmol) was added dropwise, and the
mixture was heated to reflux for 20 h. The mixture was allowed to cool to
room temperature, and saturated aqueous ammonium chloride (20 mL) was
added. The mixture was extracted into dichloromethane (50 mL), and the
organic was later dried over magnesium sulfate and evaporated to dryness.
The residue was purified by chromatography on silica gel (eluent 8:1
petroleum ether–ethyl acetate) to give the product as a yellow oil (3.1 g,
49%); [a]D ¼ 2 31.1 (c 0.28, CH2Cl2); nmax/cm21 3447, 1741, 1452,
1204, 1056, 753; dH (400 MHz, CDCl3) 3.40–3.43 (m, 1H), 3.64–3.68
(m, 2H), 3.74 (s, 3H), 4.92 (s, 1H), 7.22–7.40 (m, 10H); dC (100 MHz,
CDCl3) 52.2, 60.4, 63.1, 65.3, 127.3, 127.4, 127.6, 128.6, 128.7, 142.3,
143.5, 173.7; m/z 284.1281 found (C17H19NO3 requires 284.1288) 77
(50%), 105 (70%), 167 (100%), 182 (90%), 284 (,1%).
(–)-(S)-Methyl N-Benzhydrylaziridine-2-carboxylate 4
(–)-(S)-Methyl N-benzhydryl-2-amino-3-hydroxypropanoate (3.0 g, 10.5 mmol)
and 4-dimethylamino pyridine (10 mol%, 0.12 g, 1.1 mmol) were dissolved in
chloroform (200 mL), triethylamine (2.54 g, 25.2 mmol) was added, and the
solution was cooled to 08C. A solution of methanesulfonic anhydride (2.4 g,
15 mmol) in chloroform (20 mL) was added dropwise. The mixture was main-
tained at 08C for 1 h, allowed to reach room temperature, heated to reflux for
24 h, and allowed to cool to room temperature. Water (50 mL) was added,
the mixture was extracted into dichloromethane (100 mL), and the organic
layer was dried over magnesium sulfate and evaporated to dryness. The residue
was purified by chromatography on silica gel (eluent: 3:1 petroleum ether–
ethyl acetate with 1% triethylamine added) to give the product as pale yellow
crystals (2.04 g, 73%), mp 84–878C; [a]D ¼ 293.3 (c 0.45, CH2Cl2);
nmax/cm21 1744, 1453, 1440, 1120; dH (400 MHz, CDCl3) 1.82 (d, J ¼ 6,
1H), 2.26 (dd, J ¼ 3, 6, 1H), 2.30 (d, J ¼ 3, 1H), 3.60 (s, 1H), 3.69 (s, 3H),

Polymer-Bound Aminoalcohol Ligands
2025
7.18–7.42 (m, 10H); dC (100 MHz, CDCl3) 34.9, 38.1, 52.1, 77.9, 126.6, 127.1,
127.3, 127.4, 127.5, 127.6, 128.2, 128.4, 128.5, 128.6, 142.4, 171.0; m/z
266.1183 (C17H17NO2 requires 266.1181) 105 (23%), 165 (35%), 167 (100%),
266 (12%), 267 (3%).
(–)-(S)-N-Tritylaziridin-2-ylDi(4-(dimethoxymethyl)phenyl)
methanol 6
A solution of 4-bromobenzaldehyde dimethylacetal 5 (2.8 g, 5.0 mmol) in
tetrahydrofuran (12 mL) was cooled to 2788C. A solution of n-butyllithium
in hexanes (2.5 M, 5.8 mL, 15.0 mmol) was added dropwise to the solution.
The reaction mixture was maintained at 2788C for 2 h, and (–)-(S)-methyl
N-tritylaziridine-2-carboxylate 3 (1.0 g, 2.9 mmol) was added. The green sus-
pension was allowed to reach room temperature, stirred for a further 19 h at
room temperature, and heated to reflux for 5 h. The resulting orange suspen-
sion was quenched with saturated aqueous ammonium chloride (20 mL) and
extracted into diethyl ether (50 mL). The organic layer was dried over
magnesium sulfate and evaporated to dryness. The residue was purified by
column chromatography on silica gel (eluent: 4:1 hexanes–ethyl acetate) to
give the product as a yellow oil (1.2 g, 67%); nmax/cm21 3422, 2935, 447,
1530, 1100, 1053; dH (250 MHz, CDCl3) 1.34 (d, J ¼ 6, 1H), 2.09
(d, J ¼ 3, 1H), 2.35 (dd, J ¼ 3, 6, 1H), 3.24 (s, 6H), 3.26 (s, 6H), 4.51
(s, 1H), 5.26 (s, 1H), 5.33 (s, 1H), 7.13–7.48 (m, 23H).
(–)-(S)-N-Benzhydrylaziridin-2-yl Di(4-(dimethoxymethyl)
phenyl)methanol 7
A solution of 4-bromobenzaldehyde dimethylacetal 5 (1.2 g, 5.0 mmol) in
tetrahydrofuran (6 mL) was cooled to 2788C. A solution of n-butyllithium
in hexanes (2.5 M, 3.0 mL, 7.5 mmol) was added dropwise, and the mixture
was maintained at 2788C for 2 h. A solution of (–)-(S)-methyl N-benzhydry-
laziridine-2-carboxylate (0.3 g, 1.2 mmol) in tetrahydrofuran (6 mL) was
added. The green suspension was allowed to reach room temperature and
stirred at room temperature for 19 h. The resulting orange suspension was
quenched with saturated aqueous ammonium chloride (10 mL) and
extracted into diethyl ether (50 mL), and the organic layer was dried over
magnesium sulfate and evaporated to dryness. The residue was purified by
column chromatography on silica gel (eluent: 4:1 hexanes–ethyl acetate) to
give the product as a yellow oil (0.4 g, 62%); nmax/cm21 3424, 2937, 1352,
1101, 1053; dH (250 MHz, CDCl3) 1.60 (d, J ¼ 6, 1H), 2.10 (d, J ¼ 4, 1H),
2.72 (dd, J ¼ 4, 6, 1H), 3.27 (s, 6H), 3.31 (s, 6H), 3.85 (s, 1H), 3.99
(s, 1H), 5.25 (s, 1H), 5.33 (s, 1H), 6.93–7.41 (m, 18H).

2026
P. C. B. Page et al.
(–)-(S)-N-Tritylaziridin-2-yl Di(4-formylphenyl)methanol
(–)-(S)-N-Tritylaziridin-2-yl di(4-(dimethoxymethyl)phenyl)methanol 6 (0.5 g,
0.8 mmol) and para-toluenesulfonic acid (50 mg) were dissolved in dichloro-
methane (20 mL) and water (5 mL). The mixture was stirred vigorously for 4
days. Saturated aqueous sodium hydrogen carbonate (10 mL) was added, the
mixture was extracted into dichloromethane (20 mL), and the organic layer
was dried over sodium sulfate and evaporated to dryness. The residue was
purified by column chromatography on silica gel (eluent: 5:1 petroleum
ether–ethyl acetate) to give the product as a colorless oil (0.25 g, 69%);
nmax/cm21 3443, 1699, 1604, 1212, 706; dH (250 MHz, CDCl3) 1.37
(d, J ¼ 6, 1H), 2.09 (d, J ¼ 3, 1H), 2.45 (dd, J ¼ 3, 6, 1H), 4.74 (s, 1H),
7.13–7.75 (m, 23H), 9.91 (s, 1H), 9.95 (s, 1H).
(–)-(S)-N-Tritylaziridin-2-yl Di(4-vinylphenyl)methanol 8
A solution of methyltriphenylphosphonium bromide (0.56 g, 1.6 mmol) in
tetrahydrofuran (10 mL) was cooled to 08C. A solution of potassium bis(tri-
methylsilyl)amide in toluene (0.5 M, 2.8 mL, 1.4 mmol) was added
dropwise, and the resulting bright yellow suspension was maintained at 08C
for 1 h. The suspension was transferred into a solution of (–)-(S)-N-tritylazir-
idin-2-yl di(4-formylphenyl)methanol (0.2 g, 0.4 mmol) in tetrahydrofuran
(10 mL). The mixture was allowed to reach room temperature over 3 h,
quenched with saturated aqueous ammonium chloride (10 mL), and
extracted into ethyl acetate (50 mL). The organic layer was dried over
sodium sulfate and evaporated to dryness. The residue was purified by
column chromatography on silica gel (eluent: 6:1 hexanes–ethyl acetate) to
give the product as a colorless oil (0.16 g, 81%); [a]D¼ þ13.1 (c 0.09,
CH2Cl2); nmax/cm21 3423, 1437, 1191, 1120, 722, 695; dH (250 MHz,
CDCl3) 1.28 (d, J ¼ 6, 1H), 2.08 (d, J ¼ 3, 1H), 2.35 (dd, J ¼ 3, 6, 1H),
4.34 (s, 1H), 5.10–5.16 (m, 2H), 5.61–5.65 (m, 2H), 6.61–6.65 (m, 2H),
7.14–7.36 (m, 23H); dC (100 MHz, CDCl3) 32.1, 47.5, 74.1, 114.2, 114.5,
125.7, 126.1, 126.3, 126.4, 126.9, 127.3, 128.5, 128.8, 135.7, 136.3, 136.7,
137.2, 143.2, 143.4, 146.0, 146.9.
(–)-(S)-N-Benzhydrylaziridin-2-yl Di(4-formylphenyl)methanol
(–)-(S)-N-Benzhydrylaziridin-2-yl di(4-(dimethoxymethyl)phenyl)methanol
7 (0.3 g, 0.6 mmol) was dissolved in dichloromethane (20 mL), and para-
toluenesulfonic acid (50 mg) and water (5 mL) were added. The suspension
was stirred at room temperature for 4 days. Saturated aqueous sodium
hydrogen carbonate (10 mL) was added, the mixture was extracted into
dichloromethane (20 mL), and the organic layer was dried over magnesium
sulfate and evaporated to dryness. The residue was purified by column

Polymer-Bound Aminoalcohol Ligands
2027
chromatography on silica gel (eluent: 5:1 petroleum ether–ethyl acetate) to
give the product as pale yellow crystals (0.15 g, 60%); nmax/cm21 3432,
2835, 1698, 1604, 1306, 1212, 1171; dH (250 MHz, CDCl3) 1.70 (d, J ¼ 6,
1H), 2.15 (d, J ¼ 3, 1H), 2.74–2.81 (m, 1H), 3.85 (s, 1H), 4.17 (s, 1H),
6.98–7.31 (m, 10H), 7.22 (d, J ¼ 8, 2H), 7.47 (d, J ¼ 8, 2H), 7.58
(d, J ¼ 8, 2H), 7.81 (d, J ¼ 8, 2H), 9.88 (s, 1H), 9.96 (s, 1H).
(–)-(S)-N-Benzhydryl aziridin-2-yl Di(4-vinylphenyl)methanol 9
A solution of methyltriphenylphosphonium bromide (0.42 g, 1.2 mmol) in
tetrahydrofuran (10 mL) was cooled to 08C. A solution of potassium bis(tri-
methylsilyl)amide in toluene (0.5 M, 1.4 mL, 0.7 mmol) was added
dropwise, and the suspension was maintained at 08C for 1 h. The suspension
was transferred into a solution of (–)-(S)-N-benzhydryl aziridin-2-yl di(4-for-
mylphenyl)methanol (0.1 g, 0.2 mmol) in tetrahydrofuran (10 mL). The
mixture was allowed to reach room temperature over 3 h, quenched with
saturated aqueous ammonium chloride (10 mL), and extracted into ethyl
acetate (50 mL). The organic layer was dried over sodium sulfate and evapor-
ated to dryness. The residue was purified by column chromatography on silica
gel (eluent: 6:1 petroleum ether–ethyl acetate) to give the product as pale
yellow crystals (0.05 g, 51%), mp 167–1708C; [a]2D0 ¼ þ10.4 (c 0.06,
CH2Cl2); nmax/cm21 3424, 2924, 1490, 1447, 706; dH (400 MHz, CDCl3)
1.60 (d, J ¼ 6, 1H), 2.14 (d, J ¼ 4, 1H), 2.70 (dd, J ¼ 4, 6, 1H), 3.82
(s, 1H), 3.88 (s, 1H), 5.14–5.20 (m, 2H), 5.59–5.71 (m, 2H), 6.67–6.70
(m, 2H), 6.95–7.44 (m, 18H); dC (100 MHz, CDCl3) 31.6, 46.7, 74.3, 77.5,
113.6, 114.1, 125.9, 126.2, 126.3, 126.4, 126.8, 127.4, 128.0, 128.7, 136.0,
135.7, 136.8, 137.0, 142.8, 143.1, 145.0, 146.7.
Polystyrene-Supported (–)-(S)-N-Tritylaziridin-2-yl
Diphenylmethanol 10
(–)-(S)-N-Tritylaziridin-2-yl di(4-vinylphenyl)methanol 8 (0.12 g, 0.23 mmol),
styrene (2.0 g, 19.2 mmol), and divinylbenzene (0.11 g, 0.68 mmol) were
dissolved in chlorobenzene (4 mL), and benzoyl peroxide (60 mg) was added.
A solution of sodium chloride (0.25 g) and poly(vinyl alcohol) (MW 14000,
80 mg in water (10 mL) was added as an emulsifying agent, and the mixture
was stirred to form an emulsion. The emulsion was degassed with dry
nitrogen and heated to 858C for 20 h. The resulting polymer beads were
removed by filtration and washed successively with methanol, acetone, water,
and tetrahydrofuran (2 ꢀ 50 mL each). The polymer was allowed to swell in
tetrahydrofuran (50 mL), and the mixture was heated to reflux for 1 h to
remove monomeric materials. The solvent was decanted, and methanol
(50 mL) was added to induce the polymer to contract. The beads were

2028
P. C. B. Page et al.
collected by filtration and dried under vacuum for 5 days to give the product
(2.2 g, 100%) (found: C, 90.4; H, 7.5, N, 0.1%); dmax/cm21 3446, 3059,
2922, 1718, 1601, 1492, 1451, 1436, 1270, 756, 695, 632. A loading of
0.1 mmol/g was calculated from the percentage of nitrogen present.
Polystyrene-Supported (–)-(S)-N-benzhydrylaziridin-2-yl
Diphenylmethanol 11
(–)-(S)-N-Benzhydrylaziridin-2-yl di(4-vinylphenyl)methanol 9 (0.1 g, 0.23
mmol), styrene (2.0 g, 19.2 mmol), and divinylbenzene (0.11 g, 0.68 mmol)
were dissolved in chlorobenzene (4 mL), and benzoyl peroxide (60 mg) was
added. A solution of sodium chloride (0.25 g) and poly(vinyl alcohol) (MW
14000, 80 mg) in water (10 mL) was added as an emulsifying agent, and the
mixture was stirred to form an emulsion. The emulsion was degassed with dry
nitrogen and heated to 858C for 20 h. The resulting polymer beads were
removed by filtration and washed successively with methanol, acetone, water,
and tetrahydrofuran (2 ꢀ 50 mL each). The polymer was allowed to swell in
tetrahydrofuran (50 mL), and the mixture was heated to reflux for 2 h to
remove monomeric materials. The solvent was decanted, and methanol
(50 mL) was added to induce the polymer to contract. The beads were
collected by filtration and dried under vacuum for 5 days to give the product
(2.2 g, 100%) (found: C, 89.9; H, 7.5; N, 0.1%); nmax/cm21 3448, 3025,
2923, 1719, 1602, 1492, 1451, 1420, 1271, 757, 696, 670. A loading of
0.1 mmol/g was calculated from the percentage of nitrogen present.
Polystyrene-Supported (–)-(S)-aziridin-2-yl Diphenylmethanol 12
Polystyrene-supported (–)-(S)-N-tritylaziridin-2-yl diphenylmethanol 10 (1.2 g,
0.12 mmol) was allowed to swell in dichloromethane (20 mL) for 30 min. Tri-
fluoroacetic acid (0.14 g, 1.2 mmol) was added dropwise. The mixture was
stirred at room temperature for 3 h. Triethylamine (0.12 g, 1.2 mmol) was
added, and the reaction was stirred at room temperature for a further 1 h. The
polymer beads were collected by filtration, and methanol (20 mL) was added
to cause the polymer to contract. The polymer beads were washed with
acetone (20 mL), water (50 mL), and methanol (50 mL) and dried under
vacuum for 5 days to give the product (1.1 g, 100%) (found: C, 90.1; H, 7.6;
N, 0.3%); nmax/cm21 3436, 3024, 2920, 1721, 1682, 1600, 1492, 1451, 1372,
1270, 756, 696.
General Procedure for the Addition of Diethylzinc to Benzaldehyde
To a suspension of polymer-supported ligand (5 mol%) in toluene (8 mL),
benzaldehyde (2 mmol) was added. The solution was cooled to 08C prior to

Polymer-Bound Aminoalcohol Ligands
2029
the addition of diethylzinc (1.1 M solution in toluene, 4 mmol), allowed to
reach room temperature, and stirred for a further 24 h. Saturated aqueous
ammonium chloride was added, and the mixture was extracted into diethyl
ether. The organic layer was dried over sodium sulfate to yield the crude
1-phenyl propanol, which was analyzed by GC (Chrompak, Chirasil CB, 10
psi, 1408C) without further purification.
ACKNOWLEDGMENTS
This investigation has enjoyed the support of Charnwood Molecular Ltd. and
the EPSRC. We are also indebted to the EPSRC Mass Spectrometry Service,
Swansea, U.K., and to the Royal Society for an industry fellowship.
REFERENCES
1. For recent reviews, see (a) Pu, L. Asymmetric alkynylzinc additions to aldehydes
and ketones. Tetrahedron 2003, 59, 9873–9886; (b) Pu, L. Catalytic asymmetric
organozinc additions to carbonyl compounds. Chem. Rev. 2001, 101, 757–824;
For recent papers, see (c) Scarpi, D.; Lo Galbo, F.; Occhiato, E. G.;
Guarno, A. Enantioselective addition of diethylzinc to aldehydes using 1,4-
aminoalcohols as chiral ligands. Tetrahedron: Asymmetry 2004, 15, 1319–1324;
(d) Barros, M. T.; Maycock, C. D.; Phillips, A. M. F. Novel cyclic 1,2-diacetals
derived from (2R,3R)-(þ)-tartaric acid: Synthesis and application as N,O
ligands for the enantioselective alkylation of benzaldehyde by diethylzinc. Eur.
J. Org. Chem. 2004, 1820–1829.
2. (a) Rosner, T.; Sears, P. J.; Nugent, W. A.; Blackmond, D. G. Kinetic investi-
gations of product inhibition in the amino alcohol-catalyzed asymmetric alkyla-
tion of benzaldehyde with diethylzinc. Org. Lett. 2000, 2, 2511–2513;
(b) Yamakawa, M.; Noyori, R. Asymmetric addition of dimethylzinc to benzal-
dehyde catalyzed by (2S)-3-exo-(dimethylamino)isobornenol: A theoretical
study on the origin of enantioselection. Organometallics 1999, 18, 128–133;
(c) Yamakawa, M.; Noyori, R. An AB-initio molecular-orbital study on the
amino alcohol–promoted reaction of dialkylzincs and aldehydes. J. Am. Chem.
Soc. 1995, 117, 6327–6335; (d) Noyori, R.; Kawai, S. K.; Okada, S.;
Kitamura, M. Enantioselective alkylation of carbonyl compounds—From stoiceo-
metric to catalytic asymmetric induction. Pure Appl. Chem. 1988, 60, 1597–1606;
(e) Kitamura, M.; Suga, S.; Niwa, M.; Noyori, R. Self and nonself recognition of
asymmetric catalysts—Nonlinear effects in the amino-alcohol-promoted anantio-
selective addition of dialkylzincs to aldehydes. J. Am. Chem. Soc. 1995, 117,
´
4832–4842; (f) Itsuno, S.; Frechet, J. M. J. Enantioselective addition of diethyl-
zinc to aldehydes catalysed by polymer-supported chiral amino-alcohols—
Evidence for a 2 zinc species mechanism. J. Org. Chem. 1987, 52, 4140–4142.
3. (a) Tanner, D.; Korno, H. T.; Guijarro, D.; Anderson, P. G. Aziridino alcohols as
catalysts for the enantioselective addition of diethylzinc to aldehydes. Tetrahedron
1998, 54, 14213–14232; (b) Tanner, D. Chiral aziridines—Their synthesis and use
in stereoselective transformations. Angew. Chem. Int. Ed. 1983, 33, 599–619;

2030
P. C. B. Page et al.
(c) Hermsen, P. J.; Cremers, J. G. O.; Thijis, L.; Zwanenburg, B. Enantioselective
diethylzinc addition to aldehydes using azetidine-derived chiral catalysts. Tetrahe-
dron Lett. 2001, 42, 4243–4245.
4. Page, P. C. B.; Allin, S. M.; Maddocks, S. J.; Elsegood, M. R. New ligands for
asymmetric diethylzinc additions to aromatic aldehydes, demonstrating substrate-
dependent nonlinear effects. J. Chem. Soc., Perkin Trans. 1 2002, 2827–2832.
5. Holte, P.; Wijgergangs, J. P.; Thijs, L.; Zwanenburg, B. Polymer-supported
N-tritylaziridinyl(diphenyl)methanol as an effective catalyst in the enantioselec-
tive addition of diethylzinc to aldehydes. Org. Lett. 1999, 1, 1095–1097.
6. Willems, J. G. H.; Hersmis, M. C.; Gelder, R.; Smits, J. M. M.; Hammink, J. B.;
Dommerholt, F. J.; Thijs, L.; Zwanenburg, B. Synthesis and crystal structure of
enantiopure N-tritylaziridin-2-yl-methanols from L-serine and L-threonine.
J. Chem. Soc., Perkin Trans. 1, 1997, 963–967.
7. Far, A. R.; Cho, Y. L.; Rang, A.; Rudkevich, D. M.; Rebek, J. Polymer-bound self-
folding cavitands. Tetrahedron 2002, 58, 741–755.