Best design of heterogenized b-aminoalcohols for improvement of
enantioselective addition of diethylzinc to benzaldehyde
Sébastien Abramson, Monique Laspéras,* Anne Galarneau, Delphine Desplantier-Giscard and Daniel Brunel
Laboratoire de Matériaux Catalytiques et Catalyse en Chimie Organique, UMR 5618 - CNRS - Ecole Nationale
Supérieure de Chimie de Montpellier, 8, rue de l’Ecole Normale, 34296 Montpellier Cedex 5, France.
E-mail: lasperas@cit.enscm.fr; Fax: +33 4 67 14 43 49
Received (in Cambridge, UK) 10th July 2000, Accepted 4th August 2000
First published as an Advance Article on the web 4th September 2000
Covalent immobilization of (1R,2S)-(2)-ephedrine, used as
a model molecule of b-aminoalcohols, on the surface of
MCM-41-type mesoporous aluminosilicates, performed by a
new sol–gel method, leads to chiral auxiliaries which show
greatly enhanced rates and ee’s compared to those reported
up to now in the enantioselective addition of diethylzinc to
benzaldehyde.
Cl 1b, Al-MTS-Cl 2b) and reaction with (2)-ephedrine leads to
new hybrid materials (Al-MTS-Cl-E 1b, Al-MTS-Cl-E 2b)
(Scheme 1).
Loadings of grafted chloroalkylsiloxanes (Al-MTS-Cl 1a,
1b, 2b) or ephedrine moieties (Al-MTS-Cl-E 1a, 1b, 2b) have
been calculated from elemental and thermogravimetric analy-
ses. They depend mainly on the grafting method used, the sol–
gel method b leading to notably higher amounts of organics on
the surface.
Increasing interest has been devoted to the design of heteroge-
neous asymmetric catalysts.1 One major method involves
heterogenization of homogeneous catalysts by their immobili-
Textural properties are recorded in Table 1. Method a leads to
conservation of the mesoporosity after modification by
2
7,9,10
zation on organic polymers or inorganic supports. However,
organics. As shown previously
textures are maintained
the efficiency of the catalysts of the heterogenized catalysts is
different compared with their homogeneous counterparts. This
is the case for chiral b-aminoalcohols used in the enantio-
after grafting of halogens and substitution by (2)-ephedrine.
However, a decrease in the residual mesoporous volume is
observed. In the case of method b, the porosity of hybrids Al-
MTS-Cl 1b and Al-MTS-Cl-E 1b becomes a microporosity.
Increasing the initial pore diameter allows high residual
mesoporous volumes to be obtained even after immobilization
of a high density of organic functions by method b (Al-MTS-Cl
2b, Al-MTS-Cl-E 2b, Table 1).
Enantioselective addition of diethylzinc to benzaldehyde
conducted in the presence of these solid chiral auxiliaries leads
to the formation of (R)- or (S)-1-phenylpropan-1-ol (Scheme 2).
All experiments were performed at 0 °C using the same weight
3
selective addition of dialkylzincs to aldehydes in C–C bond
forming reactions. The efficiency of such catalysts depends
mainly on the native of the support. Since the pioneering work
4
of Frechet who used polymer-bound chiral aminoalcohols,
various authors have described such immobilization on organic
polymers.5 Ee’s are high, and only slightly lower than those
obtained in homogeneous conditions but rates are notably
lower. On the other hand, immobilization on mineral surfaces
has attracted little attention. Our first results using (2)-ephed-
,6
7
rine supported on MCM-41-type mesoporous silicas were in
2
of solid chiral auxiliary (0.29 g) and 2.3 eq. of Et Zn to
8
9,10
good agreement with precedent results of Soai et al. using
benzaldehyde.
Results are shown in Table 2.
silica gel or alumina supported (2)-ephedrine. Lower rates,
selectivities and enantioselectivities were obtained compared
with homogeneous catalysis. Investigations involving changes
Such chiral auxiliaries are efficient in the enantioselective
transfer of an ethyl group to benzaldehyde. The best results are
obtained using (2)-ephedrine anchored on the Al-MTS 2
support (entry 11) and it is worth noting that ee and activity are
close to those obtained in homogeneous catalysis (entries 2 and
3). On the other hand, efficiency depends on the synthetic
method and on the initial pore diameter of the support. The
9
10
in the pore size, the composition of the support, end-capping
9
9,10
of the surface and the dilution of the catalytic sites
failed to
improve the ee’s significantly. These results indicate significant
activity of the naked surface towards the formation of racemic
alcohols.
The aim of this work was to decrease the negative effects of
the uncovered mineral surface by increasing the coverage by
11
organics on the inner surface of the pores. In this work, the
synthesis of high surface densities of chloropropyl groups
covalently grafted on mesoporous micelle templated aluminosi-
licates (Al-MTS) of various initial pore diameters is performed.
The hybrid inorganic–organic materials resulting from halogen
substitution by (2)-ephedrine are applied in the enantio-
selective addition of diethylzinc to benzaldehyde.
Two mesoporous aluminosilicates of the same composition
2
21
(
Si/Al = 27) and 3.6 (Al-MTS 1, S = 833 m g , V = 0.76
2
1 12
2
21
mL g
mL g
)
and 8.3 nm (Al-MTS 2, S = 822 m g , V = 1.71
2
1 13
)
mean initial pore diameter were used as supports,
respectively. In order to remove the template, the as-synthesized
solids were activated before surface modification at 550 °C for
1
2 h under a flow of synthetic air. Up to now, covalent
anchorages have been performed in anhydrous conditions, by
silylation (method a) with 3-chloropropyltrimethoxysilane
(
CPTMS) (Al-MTS-Cl 1a) followed by the nucleophilic
substitution of chlorine by the basic amino group of (2)-ephed-
Scheme 1 Reagents and conditions: a, CPTMS, toluene, anhydrous
conditions, 2130 °C, 4 h; b, CPTMS, toluene, H O, NH F–pTsOH,
rine (Al-MTS-Cl-E 1a). Alternatively, grafting of the coupling
2
4
11,14
CPTMS agent by the sol–gel method
(method b, Al-MTS-
260 °C, 6 h; c, (1R,2S)-(2)-ephedrine, Xylene, 2140 °C, 6 h.
DOI: 10.1039/b005518m
Chem. Commun., 2000, 1773–1774
1773
This journal is © The Royal Society of Chemistry 2000
Abramson
