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Amino-acids as chiral synthons : synthesis of enantiomerically pure α-hydroxy esters.
oo4o-4039/84 $3.00 + .oo 01984 Pergamon Press Ltd.
Tetrahedron Letters,Vo1.25,No.34,pp 3705-3706,1984 Printed in Great Britain
AMINO-ACIDS AS CHIRAL SYNTHESIS
OF
Marc
Laboratoire
de 24
Reaction
Abstract. :
of
aspartic acid affords In
E.R.
Lhomond,
Lithium
a-hydroxy
12
a-hydroxy
the synthesis
of these molecules
du
of
CNRS,
with
high
:
Cl-HYDROXY
Yves
Paris
homocuprates
the course of studies directed active
and
75231
esters
ded optically
PURE
LarchevGque
Chimie,
rue
SYNTHONS
ENANTIOMERICALLY
Petit
Ecole
Cedex
Normale
05.
a-hydroxy
Superieure
France.
bromo ester Ppurity.
enantiomerica2
towards the synthesis
esters of high enantiomerical involve asymmetric
ESTERS.
derivated
of chiral pheromones,
purity. Conventionnal
reduction
from
of acetylenic
we nee-
routes for
ketones or pyruvic
esters,
nucleophilic addition to chiral glyoxylate esters and asymmetric synthesis via acetal (1) templates . However these methods usually fail to give the high enantiomeric excess required for our synthesis. pling reaction
We therefore
between
felt that these compounds
an orqanocuprate
perhaps could be generated
",/O = ?&CO
?/OH "Q
2Et
c& 2
1
The reaction
of
a-halohydrines
but is is usually are few examples
restricted
to simple compounds (3)
with complex molecules
of serine
this compound
.
of glyceric
tosylation
optically
pure a-hydroxy
-2 obtained by nitrous dehydroxyl group is too high in
acid. Nitrous deamination
esters in good yields
It must be underlined is known to accelerate
pur bromo-ester
(cf. Table).
When the free hydroxy ester is reacted
up to -20°C. The reaction
at -80°C with three equivalents
of the alcoolate _4 which may be alkylated is complete in about one hour.
of a cuprate
if the mixture
that the reaction must be carried out in ether. Although
the reactions
on
This compounds (4) -3 . of this ester 3 with lithium organ0 cuprates affords to furnish the optically
ether, there is at first formation warmed
of aspartic
excess of the crude product measured
by one or two recristallisations).
degradation
We wish to report here that the reaction
and there
of the primary one even at very low tempera-
-3 from aspartic
the methyl ester is 94% and may be increased by Hunsdiecker
groups,
(2)
ester
of the secondary
acid (R or S) affords the malic acid (the enantiomeric
is then decarboxylated
is well documented
without other fonctionnal
the tosylation
then the bromo-ester
with homocuprates
.
However the reactivity
to allow the selective
ture. We synthesized
o&e
2
and related compounds
Initially we investigated amination
by a cou-
and a chiral synthon such as 1 (X = leaving group).
of cuprates 3705
with primary bromides,
in is
T.H.F.
it does not give satis-
3706
Table - Reaction
R
Solvent
of lithium homocuprateswith
temp. OC
'I7 ratio
(i~oE1~
ester 3
Eroducts)
[IaF
(C, MeOH)
nC3HJ
ether
- 20
100 / 0
65
- 3",70 (J,O)
nC4H9
ether
- 20
100 / 0
71
- 6”,13
nC4H9
ether
0
66 / 34
(6,O)
35
nC4H9
THF
- 20
21 / 79
-
nC4H9
THF
- 50
50 / 50
-
SC4H9
ether
- 20
100 / 0
51
- 11",5 (3,051
iC5H11
ether
- 20
100 / 0
50
- 2",42 (J,O)
factory
results
here. In this solvent the cuprate
is basic enough to abstract
the proton a
to the ester ; this reaction is followed by the
elimination of a bromide ion from -5 to afford P . . a pyruvic ester which in turn react with the excess of cuprate to provide the a-ketols -7.
“06,
H\..eNHz HNO
-3
,c\
CH,
“\/OH
"O,C,
C Ck' C02H
C&H
“,/OH
-w
-* 3
H\,..0’-’
Br\ck \ 2
/' 3
+ n
“,/O”
0,Et
R\(&C\ a co+t
-)
e
4_
~p~ti
1.
y
“%
Br\cfi;o Et a
2
The use of a protected gated. However we observed
amount of pyruvic derivatives. CL proton more efficiently on a chiral capillary
hydroxy ester
during the reaction
::
[
2
,CQEt OH
1
(with MOM or Si(CH3)3 with cuprate
groups) was also investi-
the formation
of an increased
It seems that the alcoolate may prevent the abstraction
thp;lusual
column
malic acid and we never observed
protective
groups.Enantiomeric
of the
excess were mesured
by G.C.
. In all cases they were identical to the excess of the initial racemisation
to any extent during the reaction.
References (1)
1:; (41 (51
J.W. APSIMON and R.P. SEGUIN, Tetrahedron 35, 2797 (1979) ; A. OHNO, M. IKEGUCHI, T. KIMURA and P.E. LEE, J. Org. Chem., 46, and S. OKA, Chem. Comm., 328 (1978) ; M.M.-MIOLAND Cornmy 989 3933 (1981) ; J.K. WHITESELL, A. BHATTACHARYA, D.A. AGUILARand K.M,Chem. (1982) ; T.R. KELLY and A. ARVANITIS, Tetrahedron Letters, 25, 39 (1984) ; J.D. ELLIOT V.M.F. CHOI and W.S. JOHNSON, J. Org. Chem., 48, 2295 (1983X J.F. NORMANT, Pure and Appl. Chem., 50, 709 (n78). A. BERNARDINI, A.EL HALLAOUI, R. JACQUIER, C. PIGIERE, J. VIALLEFONT and J. BAJGROWICZ, Tetrahedron Letters, 24, 3717 (1983). D. SEEBACH and E. HUNTRBUHLER, Modern Synthetic methods., Editor,R. SCHEFFOLD, Salle and Sauerlgnder, Z_, 130 (1980). W.A. KijNIG, I. BENECKE and S. SIEVERS, J. Chromatogr. -238, 427 (1982).
(Received in France 6 June 1984)
Tetrahedron Letters,Vo1.25,No.34,pp 3705-3706,1984 Printed in Great Britain
AMINO-ACIDS AS CHIRAL SYNTHESIS
OF
Marc
Laboratoire
de 24
Reaction
Abstract. :
of
aspartic acid affords In
E.R.
Lhomond,
Lithium
a-hydroxy
12
a-hydroxy
the synthesis
of these molecules
du
of
CNRS,
with
high
:
Cl-HYDROXY
Yves
Paris
homocuprates
the course of studies directed active
and
75231
esters
ded optically
PURE
LarchevGque
Chimie,
rue
SYNTHONS
ENANTIOMERICALLY
Petit
Ecole
Cedex
Normale
05.
a-hydroxy
Superieure
France.
bromo ester Ppurity.
enantiomerica2
towards the synthesis
esters of high enantiomerical involve asymmetric
ESTERS.
derivated
of chiral pheromones,
purity. Conventionnal
reduction
from
of acetylenic
we nee-
routes for
ketones or pyruvic
esters,
nucleophilic addition to chiral glyoxylate esters and asymmetric synthesis via acetal (1) templates . However these methods usually fail to give the high enantiomeric excess required for our synthesis. pling reaction
We therefore
between
felt that these compounds
an orqanocuprate
perhaps could be generated
",/O = ?&CO
?/OH "Q
2Et
c& 2
1
The reaction
of
a-halohydrines
but is is usually are few examples
restricted
to simple compounds (3)
with complex molecules
of serine
this compound
.
of glyceric
tosylation
optically
pure a-hydroxy
-2 obtained by nitrous dehydroxyl group is too high in
acid. Nitrous deamination
esters in good yields
It must be underlined is known to accelerate
pur bromo-ester
(cf. Table).
When the free hydroxy ester is reacted
up to -20°C. The reaction
at -80°C with three equivalents
of the alcoolate _4 which may be alkylated is complete in about one hour.
of a cuprate
if the mixture
that the reaction must be carried out in ether. Although
the reactions
on
This compounds (4) -3 . of this ester 3 with lithium organ0 cuprates affords to furnish the optically
ether, there is at first formation warmed
of aspartic
excess of the crude product measured
by one or two recristallisations).
degradation
We wish to report here that the reaction
and there
of the primary one even at very low tempera-
-3 from aspartic
the methyl ester is 94% and may be increased by Hunsdiecker
groups,
(2)
ester
of the secondary
acid (R or S) affords the malic acid (the enantiomeric
is then decarboxylated
is well documented
without other fonctionnal
the tosylation
then the bromo-ester
with homocuprates
.
However the reactivity
to allow the selective
ture. We synthesized
o&e
2
and related compounds
Initially we investigated amination
by a cou-
and a chiral synthon such as 1 (X = leaving group).
of cuprates 3705
with primary bromides,
in is
T.H.F.
it does not give satis-
3706
Table - Reaction
R
Solvent
of lithium homocuprateswith
temp. OC
'I7 ratio
(i~oE1~
ester 3
Eroducts)
[IaF
(C, MeOH)
nC3HJ
ether
- 20
100 / 0
65
- 3",70 (J,O)
nC4H9
ether
- 20
100 / 0
71
- 6”,13
nC4H9
ether
0
66 / 34
(6,O)
35
nC4H9
THF
- 20
21 / 79
-
nC4H9
THF
- 50
50 / 50
-
SC4H9
ether
- 20
100 / 0
51
- 11",5 (3,051
iC5H11
ether
- 20
100 / 0
50
- 2",42 (J,O)
factory
results
here. In this solvent the cuprate
is basic enough to abstract
the proton a
to the ester ; this reaction is followed by the
elimination of a bromide ion from -5 to afford P . . a pyruvic ester which in turn react with the excess of cuprate to provide the a-ketols -7.
“06,
H\..eNHz HNO
-3
,c\
CH,
“\/OH
"O,C,
C Ck' C02H
C&H
“,/OH
-w
-* 3
H\,..0’-’
Br\ck \ 2
/' 3
+ n
“,/O”
0,Et
R\(&C\ a co+t
-)
e
4_
~p~ti
1.
y
“%
Br\cfi;o Et a
2
The use of a protected gated. However we observed
amount of pyruvic derivatives. CL proton more efficiently on a chiral capillary
hydroxy ester
during the reaction
::
[
2
,CQEt OH
1
(with MOM or Si(CH3)3 with cuprate
groups) was also investi-
the formation
of an increased
It seems that the alcoolate may prevent the abstraction
thp;lusual
column
malic acid and we never observed
protective
groups.Enantiomeric
of the
excess were mesured
by G.C.
. In all cases they were identical to the excess of the initial racemisation
to any extent during the reaction.
References (1)
1:; (41 (51
J.W. APSIMON and R.P. SEGUIN, Tetrahedron 35, 2797 (1979) ; A. OHNO, M. IKEGUCHI, T. KIMURA and P.E. LEE, J. Org. Chem., 46, and S. OKA, Chem. Comm., 328 (1978) ; M.M.-MIOLAND Cornmy 989 3933 (1981) ; J.K. WHITESELL, A. BHATTACHARYA, D.A. AGUILARand K.M,Chem. (1982) ; T.R. KELLY and A. ARVANITIS, Tetrahedron Letters, 25, 39 (1984) ; J.D. ELLIOT V.M.F. CHOI and W.S. JOHNSON, J. Org. Chem., 48, 2295 (1983X J.F. NORMANT, Pure and Appl. Chem., 50, 709 (n78). A. BERNARDINI, A.EL HALLAOUI, R. JACQUIER, C. PIGIERE, J. VIALLEFONT and J. BAJGROWICZ, Tetrahedron Letters, 24, 3717 (1983). D. SEEBACH and E. HUNTRBUHLER, Modern Synthetic methods., Editor,R. SCHEFFOLD, Salle and Sauerlgnder, Z_, 130 (1980). W.A. KijNIG, I. BENECKE and S. SIEVERS, J. Chromatogr. -238, 427 (1982).
(Received in France 6 June 1984)