Novel ligands derived from S-tyrosine for the enantioselective addition of diethylzine to aldehydes

Article abstract of DOI:10.1016/S0957-4166(97)00150-X

(S)-2-N,N-dibutylamino-3-butyl-1-[4-(4-phenylmethoxy)-phenyl]heptan-3-ol 3 based on (S)-tyrosine has been synthesised. For the diethylzinc addition to both aliphatic and aromatic aldehydes, high enantiomeric excesses up to 95% were obtained.

Full text of DOI:10.1016/S0957-4166(97)00150-X

Tetrahedron" As)mmetry, Vol 8. No. 10, pp 1529-1530, I997
(~ 1997 Elsevier Science Ltd. All rights reserved.
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Novel ligands derived from S-tyrosine for the enantioselective
addition of diethylzinc to aldehydes
Juliane Beliczey, Guido Giffels, Udo Kragl * and Christian Wandrey
Forschungszentrum Jtilich GmbH, lnstitut for Biotechnologie, 52425 Jtilich, Germany
Abstract:
(S)-2-N,N-dibutylamino-3-butyl-l-[4-(4-phenylmethoxy)-phenyl]heptan-3-ol
3
based on (S)-tyrosine has been synthesised. For the diethylzinc addition to both aliphatic
and aromatic aldehydes, high enantiomeric excesses up to 95% were obtained. (~) 1997
Elsevier Science Ltd
Reactions for asymmetric carbon-carbon bond formation have been of interest for many years.
One important reaction that leads to optical active secondary alcohols is the addition of diethylzinc
to aldehydes1-4. The asymmetric induction can be achieved with among other compounds, chiral
[
3-amino alcohols. While enantiomeric excesses (ee's) up to >99% can be achieved with aromatic
aldehydes, in the reaction with aliphatic aldehydes ee's >90% are seldom obtained3. Therefore the
aim of our work has been to synthesise chiral amino alcohols which lead to high ee's particularly with
aliphatic aldehydes. Within the scope of our activities including research on polymer enlarged ligands
in enantioselective homogeneous catalysis5'6 ligands being based on tyrosine have been investigated.
The hydroxy group remote from the asymmetric center involved in the catalysis offers the opportunity
to bind the ligand to soluble polymers in an easy way7, which allows its utilisation in a membrane
reactor5.
For inductors derived from (L)-valine it has been shown8'9 that an increasing number of aliphatic
substituents in the ligand procures high ee's with aliphatic aldehydes. Also it is known4 that for N,N-
dialkylnorephedrine the n-butyl group is most suitable. The transfer of this observation to the tyrosinol
system led to the ligands 1, 2 and 3 l°.
C>o
H2N OH
f N H 2OH
l was prepared by Grignard addition of butylmagnesiumbromide to tyrosinethylester and benzylation
of the phenolic hydroxy function. Alkylation with iodobutane in the presence of potassium carbonate
procured 2 and 3.
All three inductors have been used in the addition of diethylzinc to benzaldehyde (Table 1).
H
OH
. . b
0:==(,
!. ZnEt2 + inductor, toluene
_
.
R
2. H+/I-I20
~
H R / V
In the case of the complete alkylation of the amino function the stereoselectivity of the reaction is
reversed. The special merits of ligand 3 are high activity and enantioselectivity. The utilisation of 3
in the reaction with various aldehydes gave the following results (Table 2):
*
Corresponding author. Tel: +49-2461-616772: Fax: +49-2461-613870; Email: u.kragl@kfa-juelich.de
520
1

1530
J. BELICZEY et al.
Table 1. Enantioselective addition of ZnEt2 (2 eq) to PhCHO in presence of 10 tool% inductor in toluene
Inductor Temp.[°CJ ee [%]a Con_fig. Conversion [%]~ Time [h] Selectivity[%]b
1
2
3
3
0
0
0
81.8
7
93
92
S
S
R
R
93
66
100
100
31
31
10
5
99
97
100
100
a.
•
determined by GC on a chira113-cyclodextrine phase;
bas side reaction the reduction ofthe aldehyde to the primary alcohol can take place.
Table 2. Enantioselective addition of ZnEt2 (2 eq) to aldehydes in presence of 10 tool% 3 in tolttt,qc
Aldehyde
ee [%]a Conversion [%]a Time [hi Selectivity [%]b
Hexanal
Heptanal
p-Chlorobenzaldehyde
Benzaldehyde
bsee Table I.
86
86
95
93
100
100
98
48
48
5
not det.
not det.
100
98
8
100
Especially the enantiomeric excesses achieved with the aliphatic aldehydes are remarkable. For the
addition of diethylzinc to hexanal with 3 as ligand an ee of 86% was reached which is similar to the
highest value reported so far4.* for this aldehyde.
3
was also bound to a soluble polystyrene derivative enabling retention by a membrane, and utilised
in the reaction with benzaldehyde under same conditions. The reaction proceeded with the same
selectivity and stereoselectivity as found for the free ligand. The conversion reached 70% after 10 h.
Acknowledgements
This work was supported by the Deutsche Forschungsgemeinschafl-SFB 380: "Asymmetrische
Synthesen mit chemischen und biologischen Methoden"
References
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4
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2
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(
Received in UK 10 March 1997)