Resolution method for a racemic mixture of aldehydes

Details Resolution method for a racemic mixture of aldehydes Resolution method for a racemic mixture of aldehydes

2001-08-07

2003-09-02

Vollano, Jean F. (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Phosphorus containing

C568S013000, C568S014000, C549S005000, C549S006000, C548S113000, C544S084000

Reexamination Certificate

active

06613945

ABSTRACT:

The application is a 371 of PCT FR/99/02700 filed Nov. 4, 1999, now WO 00/27778.
The present invention relates to a process for resolving a racemic mixture of aldehydes which can be used in their optically pure forms in the preparation of catalysts which may be used in olefin hydroformylation reactions.
A number of suitable catalysts which may be used in olefin hydroformylation are known in the art: these catalysts are complexes of a chiral phosphine with a transition metal such as rhodium or platinum. Of the chiral phosphines developed hitherto and acting as ligands for the rhodium or platinum, a distinction is made between the so-called class 1 phosphines in which the chiral centre is carried by the phosphorus (such as (2-methoxyphenyl)(methyl)(phenyl)phosphine), the so-called class 2 phosphines in which the chiral centre is carried by a carbon chain (such as (diphenyl)(2-isopropyl-5-methylphenyl)phosphine), and the class 3 phosphines carrying a chiral centre on the phosphorus and on a carbon chain, such as for example the following phosphine:
where Men denotes
The process according to the invention can be used in particular to resolve the aldehydes of formula A as follows, which carry at least two centres of asymmetry, the first on the phosphorus and the second on the carbon in position 4:
wherein
R
1
, R
4
, R
5
and R
6
, which may be identical or different, denote a hydrogen atom; a saturated or unsaturated, optionally substituted aliphatic hydrocarbon radical having 1 to 40 carbon atoms, wherein the hydrocarbon chain is optionally interrupted by a heteroatom; an optionally substituted carbocyclic or heterocyclic, saturated, unsaturated or aromatic, monocyclic or polycyclic radical; or a saturated or unsaturated aliphatic hydrocarbon radical wherein the hydrocarbon chain is optionally interrupted by a heteroatom and carries a carbocyclic or heterocyclic radical as hereinbefore defined, said radical optionally being substituted;
or R
4
and R
5
together with the carbon atoms which carry them form an optionally substituted saturated or unsaturated carbocyclic monocycle preferably having 5 to 7 carbon atoms;
R
2
denotes a hydrogen atom or the radical X;
R
3
denotes the radical X or the radical Y;
with the proviso that one and only one of the substituents R
2
and R
3
denotes the radical X;
X being selected from among a monocyclic or bicyclic aromatic carbocyclic or heterocyclic radical having 2 to 20 carbon atoms; a 1-alkenyl radical optionally having one or more additional unsaturated bonds in the hydrocarbon chain and having 2 to 12 carbon atoms; a 1-alkynyl radical optionally having one or more additional unsaturated bonds in the hydrocarbon chain and having 2 to 12 carbon atoms; a —CN; [(C
1
-C
12
)alkoxy]carbonyl; and [(C
6
-C
18
)aryloxy]carbonyl radical;
Y having any of the meanings for R
1
with the exception of a hydrogen atom.
These phosphines belong to class 3.
More generally, the process of the invention can be used to resolve aldehydes of formula I:
wherein
R
1
to R
6
are as hereinbefore defined for formula A;
n denotes 0 or 1; and
Z denotes an oxygen or sulphur atom.
The aldehydes of formula A correspond to the compounds of formula I wherein n denotes 0.
The aldehydes of formula A have a rigid 1-phosphanorbornadiene structure which fixes the relative configuration of the two stereogenic centres consequently, these compounds are present in the form of a racemic mixture of only two stereoisomers (in spite of the presence of two asymmetric centres).
The aldehydes of formula I are more particularly useful, in their optically pure forms, as ligands of transition metals for preparing catalytic complexes in olefin hydroformylation reactions, hence the interest in a suitable resolution process.
After the failure of several attempts at resolution by chromatography on a chiral column, the inventors were led to perfect the resolution process according to the invention.
This process comprises the following steps:
a) reacting said compound of formula I with an optically active compound of formula II:
 wherein
the group >C(A
1
)(A
2
) is distinct from the group >C(A
3
)(A
4
);
A
1
, A
2
, A
3
, A
4
being independently selected from among a hydrogen atom; a (C
1
-C
10
)alkyl group; a (C
6
-C
10
)aryl group optionally mono- or polysubstituted by (C
1
-C
10
)alkyl, (C
1
-C
10
)alkoxy, amino, (C
1
-C
10
)alkylamino, di(C
1
-C
10
)alkylamino or a halogen atom; a (C
3
-C
8
)cycloalkyl group optionally mono- or polysubstituted by (C
1
-C
10
)alkyl, (C
1
-C
10
)alkoxy, amino, (C
1
-C
10
)alkylamino, di(C
1
-C
10
)alkylamino or a halogen atom; a saturated, unsaturated or aromatic 5- to 7-membered heterocyclic group having 1 to 3 heteroatoms selected from among O, N and S and optionally mono- or polysubstituted by (C
1
-C
10
)alkyl, (C
1
-C
10
)alkoxy, amino, (C
1
-C
10
)alkylamino, di(C
1
-C
10
)alkylamino or a halogen atom; or
A
1
and A
3
together form a (C
2
-C
6
)alkylene chain optionally mono- or polysubstituted by (C
1
-C
10
)alkyl, (C
1
-C
10
)alkoxy, amino, (C
1
-C
10
)alkylamino, di(C
1
-C
10
)alkylamino or a halogen atom; or
A
1
and A
3
together with the carbon atoms which carry them form a saturated 5- to 7-membered oxygenated heterocycle optionally comprising one to two additional heteroatoms selected from among O, N and S, said heterocycle optionally being mono- or polysubstituted by (C
1
-C
10
)alkyl, (C
1
-C
10
)alkoxy, amino, (C
1
-C
10
)alkylamino, di(C
1
-C
10
)alkylamino, hydroxy or a halogen atom; and
E and G:
either both denote an oxygen atom,
or independently denote a divalent —NR
o
— radical wherein the R
0
groups independently denote a hydrogen atom, a (C
1
-C
10
)alkyl radical, a (C
6
-C
10
)aryl radical optionally substituted by (C
1
-C
10
)alkyl; or a (C
6
-C
10
)aryl-(C
1
-C
10
)alkyl radical wherein the aryl moiety is optionally substituted by a (C
1
-C
10
) alkyl radical; so as to form a compound of formula III
 wherein R
1
to R
6
, A
1
to A
4
, E, G, Z and n are as hereinbefore defined, which is a mixture of diastereoisomers;
b) separating the diastereoisomers of formula III by a suitable method; and
c) regenerating the aldehyde function of each of the diastereoisomers of formula III, by hydrolysing the acetal function in an acid medium.
According to a first particularly preferred embodiment, the invention can be used to resolve compounds of formula I wherein:
R
1
, R
4
, R
5
, R
6
independently denote a hydrogen atom or a T radical selected from among:
a saturated or unsaturated aliphatic hydrocarbon radical having 1 to 12 carbon atoms, wherein the hydrocarbon chain is optionally interrupted by a heteroatom selected from among O, N and S;
a monocyclic carbocyclic radical which is saturated or has 1 or 2 unsaturated bonds in the ring, having 3 to 8 carbon atoms;
a saturated or unsaturated bicyclic carbocyclic radical made up of 2 monocycles fused to each other, each monocycle optionally comprising 1 to 2 unsaturated bonds and having 3 to 8 carbon atoms;
an aromatic C
6
-C
10
mono- or bicyclic carbocyclic radical.
a saturated, unsaturated or aromatic 5- to 6-membered heterocyclic monocyclic radical having 1 to 3 heteroatoms selected independently from among N, O and S;
a saturated, unsaturated or aromatic bicyclic heterocyclic radical made up of two 5- to 6-membered monocycles fused to each other, each monocycle having 1 to 3 heteroatoms selected independently from among O, N and S; and
a saturated or unsaturated aliphatic hydrocarbon radical, having 1 to 12 carbon atoms, wherein the hydrocarbon chain carries a monocyclic carbocyclic or heterocyclic radical as hereinbefore defined,
said radical T optionally being substituted;
R
2
and R
3
are as hereinbefore defined for formula I, with the proviso that:
Y may assume any of the meanings given hereinbefore for R
1
with the exception of a hydrogen atom; and
X is selected from among a (C
2
-C
6
) alkenyl group, a (C
2
-C
6
) alkynyl, phenyl, naphthyl, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, pyridyl, pyrazinyl, pyridazinyl, isoth

Affiliated with

Also associated with

Rating

Resolution method for a racemic mixture of aldehydes does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Resolution method for a racemic mixture of aldehydes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Resolution method for a racemic mixture of aldehydes will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3024124