Polymer-supported N-tritylaziridinyl(diphenyl)methanol as an effective catalyst in the enantioselective addition of diethylzinc to aldehydes

Article abstract of DOI:10.1021/ol990892b

(matrix presented) Novel polymer-supported N-tritylaziridino alcohol 2 was utilized as chiral ligand in the asymmetric addition of diethylzinc to aldehydes. High enantioselectivities were obtained for both aromatic and aliphatic aldehydes. The catalyst wa

Full text of DOI:10.1021/ol990892b

ORGANIC
LETTERS
1
999
Vol. 1, No. 7
095-1097
Polymer-Supported
1
N-Tritylaziridinyl(diphenyl)methanol as
an Effective Catalyst in the
Enantioselective Addition of Diethylzinc
to Aldehydes
Peter ten Holte, Jan-Piet Wijgergangs, Lambertus Thijs, and Binne Zwanenburg*
Department of Organic Chemistry, NSR Institute for Molecular Structure, Design and
Synthesis, UniVersity of Nijmegen, ToernooiVeld, 6525 ED Nijmegen, The Netherlands
zwanenb@sci.kun.nl
Received July 30, 1999
ABSTRACT
Novel polymer-supported N-tritylaziridino alcohol 2 was utilized as chiral ligand in the asymmetric addition of diethylzinc to aldehydes. High
enantioselectivities were obtained for both aromatic and aliphatic aldehydes. The catalyst was successfully recycled and employed in subsequent
additions with retention of high enantioselectivity.
Chiral â-amino alcohols have been proven to be extremely
successful catalysts in the enantioselective addition of
diethylzinc to aldehydes (see Scheme 1).
facilitated workup procedures, easy recovery, and reuse of
the catalyst in successive additions. However, only few of
3
these immobilized amino alcohols display a high enantio-
selectivity for both aromatic and aliphatic aldehydes. Re-
cently, an exceptional class of amino alcohols, viz. the
aziridinylmethanols, has been successfully applied as catalyst
Scheme 1. Enantioselective Addition of Diethylzinc to
4
Aldehydes Catalyzed by a Chiral Amino Alcohol
in the asymmetric addition of diethylzinc to aldehydes. It
(2) (a) Reddy, K. S.; Sol a` , L.; Moyano, A.; Peric a` s, M. A.; Riera, A. J.
Org. Chem. 1999, 64, 3969. (b) Cho, B. T.; Chun, Y. S. Tetrahedron:
Asymmetry 1998, 9, 1489. (c) Shi, M.; Satoh, Y.; Makihara, T.; Masaki, Y.
Tetrahedron: Asymmetry 1995, 6, 2109. (d) Soai, K.; Ookawa, A.; Kaba,
T.; Ogawa, K. J. Am. Chem. Soc. 1987, 109, 7111.
(
3) (a) Vidal-Ferran, A.; Bampos, N.; Moyano, A.; Peric a` s, M. A.; Riera,
These ligands allow an efficient addition reaction and give
rise to high ee’s, as has been demonstrated for several
examples.1 Attachment of such â-amino alcohol ligands to
a polymeric support offers important advantages such as
A.; Sanders, J. K. M. J. Org. Chem. 1998, 63, 6309. (b) Liu, G.; Ellman,
J. A. J. Org. Chem. 1995, 60, 7712. (c) Watanabe, M.; Soai, K. J. Chem.
Soc., Perkin Trans. 1 1994, 837. (d) Soai, K.; Watanabe, M.; Yamamoto,
A. J. Org. Chem. 1990, 55, 4832. (e) Itsuno, S.; Fr e´ chet, J. M. J. J. Org.
Chem. 1987, 52, 4140.
,2
(
4) (a) Tanner, D.; Kornø, H. T.; Guijarro, D.; Andersson, P. G.
(
1) For reviews, see: (a) Soai, K.; Niwa, S. Chem. ReV. 1992, 92, 833.
Tetrahedron 1998, 54, 14232. (b) Lawrence, C. F.; Nayak, S. K.; Thijs, L.;
Zwanenburg, B. Synlett 1999, in press.
(
b) Noyori, R.; Kitamura, M. Angew. Chem., Int. Ed. Engl. 1991, 30, 49.
1
0.1021/ol990892b CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/09/1999

is worth noting that the aziridinylmethanols belong to the
class of â- as well as γ-amino alcohols. We showed that
especially N-tritylaziridinyl(diphenyl)methanol 1 (see Chart
The addition of diethylzinc to benzaldehyde in the presence
of 10 mol % of polymer-supported catalyst 2 gave the
corresponding (S)-alcohol in a high yield (92%) and an
enantiomeric excess of 96%. It is noteworthy that the solvent
system does not only affect the yield of the reaction to a
great extent but also has a considerable impact on the
enantioselectivity. The best result was obtained in a 1/1 (v/
v) mixture of toluene and dichloromethane (see Table 1).
1) is an excellent chiral catalyst in the solution-phase
Chart 1. N-Tritylaziridinyl(diphenyl)methanol 1 and Its
Polymer-Supported Analog 2, Tr ) Trityl
Table 1. Enantioselective Addition of Diethylzinc to Aromatic
and Aliphatic Aldehydes Employing Polymer-Supported Catalyst
2
solvent
yield eea
aldehyde
(toluene/CH2Cl2)
(%)
(%) confignd
benzaldehyde
benzaldehyde
benzaldehyde
benzaldehyde
p-chlorobenz-
aldehyde
anisaidehyde
cyclohexane-
carboxaldehyde
isovaleraldehyde
undecylic aldehyde
100/0
75/25
50/50
0/100
50/50
88
91
92
72
88
93b
96b
S
S
S
S
S
96b
enantioselective addition of diethylzinc to both aromatic and
91b
96b
4b
aliphatic aldehydes. These recent findings, and taking into
account the advantages of immobilized catalysts over
homogeneous ones, have prompted us to develop polymer-
supported N-tritylaziridinyl(diphenyl)methanol 2 (see Chart
50/50
50/50
88
90
95b
97c
S
S
1) as the chiral catalyst in diethylzinc additions to aldehydes.
50/50
50/50
77
80
81
77c
S
S
These investigations are part of our continuing studies on
functionalized small-ring heterocycles.5
a
Determined by chiral GC (Beta-DEX). b Determined by optical rotation.
In this paper, we describe the immobilized aziridino
alcohol 2, which is a highly potent catalyst in the asymmetric
addition of diethylzinc to both aliphatic and aromatic
aldehydes. Polymer-supported ligand 2 was obtained by
attachment of aziridino alcohol 3 to polymer-bound tri-
c
19
8 d
Determined by F NMR of Mosher’s ester. Determined by comparison
with absolute optical rotation given in the literature.
The presence of dichloromethane is essential for swelling
of the polymer and making the aziridino alcohol ligands
accessible for the substrates.
6
phenylchloromethane 4 (1.1 mequiv/g) as is depicted in
Scheme 2. The coupling of 3 to the trityl chloride resin took
In this toluene/dichloromethane (1/1, v/v) mixture, other
aromatic aldehydes such as p-chlorobenzaldehyde and anis-
aldehyde also underwent highly enantioselective addition of
diethylzinc (96 and 95% ee, respectively) in the presence of
ligand 2 (Table 1). An enantiomeric excess of 97% was
observed for the addition of diethylzinc to cyclohexanecar-
boxaldehyde (cy 90%) using polymer-bound ligand 2. This
is a remarkably high enantioselectivity for a heterogeneously
catalyzed asymmetric addition of diethylzinc to an aliphatic
aldehyde. Likewise, addition of diethylzinc to other aliphatic
aldehydes, such as isovaleraldehyde, took place with good
enantioselectivity in the presence of catalyst 2 (see Table
1).
The catalytic capability of our polymer-supported ligand
(2) was retained in successive addition cycles (see Table 2).
Addition of diethylzinc to benzaldehyde in the presence of
chiral ligand 2 occurred in the second reaction cycle with
an ee of 95% and in the third cycle with an ee of 94%. These
results demonstrate that in addition to highly facilitated
workup procedures, polymer-supported catalyst 2 shows the
advantage of easy recovery and utilization in consecutive
asymmetric diethylzinc additions.
Scheme 2. Synthesis of Polymer-Supported N-Tritylaziridino
Alcohol 2 from L-Serine
place in a yield of 70% as was determined by gravimetrical
analysis. Optically pure (S)-aziridinylmethanol 3 was readily
obtained from L-serine.5b The polymeric chloride moieties
that remained unreacted in the attaching step were capped
with methoxy groups.7
(5) (a) Starmans, W. A. J.; Thijs, L.; Zwanenburg, B. Tetrahedron 1998,
5
4, 629. (b) Willems, J. G. H.; Hersmis, M. C.; de Gelder, R.; Smits, J. M.
M.; Hammink, J. B.; Dommerholt, F. J.; Thijs, L.; Zwanenburg, B. J. Chem.
Soc., Perkin Trans. 1 1997, 963 and references therein. (c) Zwanenburg,
B.; Thijs, L. Pure Appl. Chem. 1996, 735 and references therein.
(
6) Triphenylchloromethane polymer bound, cross-linked with 1% DVB;
00-200 mesh, Fluka Chemika.
7) The resin was stirred for 15 min in a mixture of DCM/MeOH (1/1)
1
In summary, we have demonstrated that catalyst 1 is
suitable for immobilization and that polymer-supported
(
containing an excess of base, according to a procedure by Barlos et al.:
Barlos, K., Chatzi, O.; Gatos, D.; Stavropoulos, G. Int. J. Peptide Protein
Res. 1991, 37, 513.
(8) Dale, J. A.; Dull, D. L.; Mosher, H. S. J. Org. Chem. 1969, 34, 2543.
Org. Lett., Vol. 1, No. 7, 1999
1
096

aqueous solution of ammonium chloride (25 mL) was added,
and the mixture was stirred for 15 min. The resin was
removed by filtration and washed with dichloromethane (5
Table 2. Enantioselective Addition of Diethylzinc to
Benzaldehyde Using Recycled Polymer Supported Catalyst 2
×
4
5 mL) the organic layer was dried (MgSO ) and
aldehyde
run (no.)
yield (%)
eea,b (%)
concentrated under reduced pressure, and the product was
purified by column chromatography to give 0.25 g (92%)
of (1S)-1-phenyl-1-propanol.
benzaldehyde
benzaldehyde
benzaldehyde
1
2
3
92
92
92
96
95
94
a
Determined by chiral GC (Beta-DEX). b Determined by optical rotation.
Acknowledgment. The authors thank Miss Corrine F.
Lawrence for helpful discussions.
aziridino alcohol 2 is a highly efficient chiral ligand for
asymmetric addition of diethylzinc to aromatic as well as
aliphatic aldehydes.
Supporting Information Available: Experimental pro-
cedures for polymer bound catalyst 2. FT-IR spectrum of 2.
General procedure for the enantioselective addition of
diethylzinc to aldehydes catalyzed by 2. Chiral GC spectrum
of racemic and enantiomeric 1-(4-chlorophenyl)-1-propanol.
Typical procedure for the addition of diethylzinc to
benzaldehyde, catalyzed by polymer-bound ligand 2: Ben-
zaldehyde (0.21 g, 2.0 mmol) was added to a cooled (0 °C)
suspension of polymer-bound ligand 2 (0.28 g, 0.2 mmol)
in a mixture of dichloromethane and toluene (1/1, v/v, 16
mL), followed by gradual addition of diethylzinc (4.1 mL
of a 1 M solution of diethylzinc in n-hexane), and the mixture
was stirred at ambient temperature overnight. A saturated,
1
9
F NMR spectrum of Mosher’s ester of racemic and
enantiomeric 1-cyclohexyl-1-propanol. This material is avail-
able free of charge via the Internet at http://pubs.acs.org.
OL990892B
Org. Lett., Vol. 1, No. 7, 1999
1097