Heteroaromatic diphosphines as chiral ligands

Details Heteroaromatic diphosphines as chiral ligands Heteroaromatic diphosphines as chiral ligands

1999-04-05

2001-10-02

Vollano, Jean F. (Department: 1621)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S414000

Reexamination Certificate

active

06297387

ABSTRACT:

Object of the present invention are chiral diphosphines, complexes between said diphosphines and transition metals, and their utilization as chiral catalysts in stereoselective (stereocontrolled) reactions, such as, for instance, diastereo- and enantioselective reduction reactions in general, or asymmetric isomerization in general.
Another object of the present invention is a process for the preparation of said chiral diphosphines, as well as a process for the preparation of said chiral complexes and their utilization as catalysts in diastereo- and enantioselective reactions.
Further another object of the present invention are stereoselective processes, in particular diastereo- and enantioselective reductions in general, which utilize said chiral catalysts.
PRIOR ART
As is known, stereoselective reactions, in particular the reactions of stereocontrolled reduction, such as, for instance, diastereo- and enatioselective hydrogenations, are of great importance and have been studied for a long time; in fact, such reactions lead directly to the formation of optically active compounds which would be obtainable otherwise only as racemates, with the ensuing need of a subsequent separation of the enantiomers and the related drawbacks which sometimes are found in performing such separation, with the associated high probability of failing to obtain the pure enantiomeric forms; besides, in these cases a further drawback may arise from the presence of an unwished enantiomer, which must be reconverted or disposed of.
In general, the stereocontrolled reduction reactions realized by means of chiral calalysts allow to obtain the optically active reaction products, often also with good enantiomeric excesses.
For instance, the first enantioselective hydrogenation reaction of unsaturated compounds was carried out through the utilization of metal catalysts deposited on chiral supports and goes back to the thirties. Afterwards, homogeneous asymmetric hydrogenation reactions have been studied and described that had been realized by means of special chiral catalysts, constituted by complexes between transition metals and chiral phosphines which act as ligands towards the metal.
The literature reports on different types of chiral phosphines which can act as ligands and form chiral complexes with transition metals, such as, for instance, Ruthenium (Ru), Rhodium (Rh), Palladium (Pd), Iridium (Ir) and Platinum (Pt). In particular, chiral phosphines are characterized by one or two stereogenic atoms of phosphorus, which will have, in this case, three different substituents, such as, for instance, DIPAMP which (R,R) enantiomer has the following formula:
[KNOWLES W. S. et al., J. Chem. Soc. Chem. Commun. 10 (1972); VINEYARD B. D. et al., J. Am. Chem. Soc. 99, 5946(1977)]; phosphines are also described whose chirality is due to the presence of carbon-based stereocentres, such as for instance the compound known as CHIRAPHOS, which (S,S) enantiomer has the following formula:
[FRYZUK M. D. et al. J. Am. Chem. Soc. 99, 6262 (1977)]; also phosphines are reported whose chirality is due to the presence of an atropisomeric biaryl system, i.e. a system in which the rotation around the simple bond connecting two aryl groups is prevented; diphosphines of this type are for instance BINAP, BIPHEMP or BICHEP, which (R) enantiomers have the following formulae:
[NOYORI R. et al., J. Am. Chem. Soc. 102, 7932 (1980); SCHMID R. et al. Helv. Chim. Acta 71, 897(1988); MIYASHITA A. et al., Chem. Lett. 1849(1989)].
At present, for instance, the catalysts for the stereocontrolled reduction, such as the diastereo- and enantioselective hydrogenation of carbonyl groups, which allow to obtain the best diastereomeric and enantiomeric excesses of secondary chiral alcohols, are those constituted by complexes between transition metals and chiral diphosphines by atropisomery, and in particular complexes between Ru and BINAP.
Of course, the main problem is that of the synthesis of the chiral diphosphine which acts as ligand. In the aforementioned cases, the process of synthesis of the chiral diphosphine is rather complicated, as it involves numerous steps; besides, the diphosphine which is obtained as a racemate needs a laborious resolution process, with low yields and very high costs. As a consequence, the chiral catalyst obtained by formation of a complex between the chiral diphosphine and a transition metal may be very expensive.
AIMS OF THE INVENTION
An aim of the present invention is to provide a chiral diphosphine suitable for acting as a ligand for transition metals through the formation of particularly stable coordination bonds.
Another aim of the invention is to provide a chiral diphosphine such as to be obtainable more easily from the synthetic point of view compared to the known art.
Still another aim of the invention is to provide a process for the preparation of a chiral diphosphine suitable to act as a ligand for transition metals, consisting of simple steps, having contained costs and being industrially applicable.
Still a further aim of the present invention is to provide a new chiral catalyst to be used in stereocontrolled synthesis reactions.
Another aim of the invention is to provide a chiral catalyst to be used in stereocontrolled synthesis reactions, such as to be highly reactive and provided with a high regio-, chemo-, diastereo-, enantio-selectivity.
Still a further aim of the present invention is to provide a chiral catalyst to be used in stereocontrolled synthesis reactions, such as to allow to operate in mild reaction conditions, obtaining anyway high reaction rates.
Another aim of the invention is to allow the realization of stereocontrolled reactions, in particular reduction reactions or isomerization reactions involving the utilization of a chiral catalyst and leading to the formation of optically active products with high diastereomeric or enantiomeric excesses.
DESCRIPTION OF THE INVENTION
These and still other aims and associated advantages which will be more clearly expounded in the following description, are reached by a chiral diphosphine constituted by an aromatic pentatomic biheterocyclic system.
More particularly, said chiral diphosphine constituted by an aromatic pentatomic biheterocyclic system has the following general formula:
where:
R
2
is chosen among hydrogen, phenyl, aryl, linear, branched, cyclic alkyl C
1
-C
10
, COOR
3
, where R
3
is linear, branched, cyclic alkyl C
1
-C
10
;
Y is chosen among phenyl, substituted phenyl, aryl, substituted aryl, linear, branched, cyclic alkyl C
3
-C
10
;
R
1
is chosen among phenyl, substituted phenyl, aryl, substituted aryl, linear, branched, cyclic alkyl C
1
-C
10
, OR
5
, where R
5
is linear, branched, cyclic alkyl C
1
-C
10
, or
each pentatomic heterocyclic aromatic ring of said system is condensated to a substituted or unsubstituted benzene or naphthalene ring, according to the following formula:
where a ranges from 0 to 6, R
2
may also be equal to zero, R
4
is chosen among hydrogen, linear, branched, cyclic substituted or unsubstituted alkyl C
1
-C
10
.
The aforementioned graphic representation is to be construed as being non limitative, meaning that, for instance, each of said pentatomic heterocyclic aromatic rings is condensed to said substituted or unsubstituted benzene or naphthalene ring also according to the following formula:
where R
4
, n, R
2
are defined as above.
The aromatic pentatomic biheterocyclic system is chosen among;
1,1′-bipyrrole, 2,2′-bipyrrole, 3,3′-bipyrrole
3,3′-bithiophenee
3,3′-bifuran
1,1′-biimidazole and the and the corresponding benzocondensed (IIA′) (IIB′), (VA′)(VB′),
4,4′-bipyrazole, 5,5′-bipyrazole
1,1′-bi-1,3,4-triazole
4,4′-biisoxazole
4,4′-biisothiazole
5,5′-biimidazole
3,3-bibenzothiophenes
3,3′-bibenzofurans,
2,2′-biindoles
1,1′-bibenzoimidazoles.
The chiral diphosphines having the following formulae:
proved to be particularly advantageous according to the present

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