Production of optically active phospholanes

Details Production of optically active phospholanes Production of optically active phospholanes

2000-11-15

2003-10-14

Vollano, Jean F. (Department: 1621)

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

Organic compounds

Heavy metal containing

C568S012000

Reexamination Certificate

active

06632953

ABSTRACT:

The invention describes novel optically active phospholanes and bisphospholanes, the preparation thereof and use thereof as ligands in metal complexes, and the use of the metal complexes for enantioselective synthesis.
Enantioselective hydrogenation and isomerization with rhodium and ruthenium complexes is very important in the synthesis of optically active compounds (e.g. Tani et al. J. Am. Chem Soc 106, 5211, 1984; R. Noyori, Acc. Chem. Res. 23, 345 (1990). The stoichiometric starting material hydrogen costs little, but the catalysts employed, which are mostly prepared from an optically active diphosphine ligand and a rhodium or ruthenium compound, are very costly and can be obtained only in a complicated manner.
The known methods for preparing optically active phosphines and diphosphines are all complicated and usually include a technically elaborate and costly racemate resolution (e.g. EP-A 0614901; EP-A 0271311; H. B. Kagan, “Chiral Ligands for Asymmetric Catalysis” in Asymmetric Synthesis, Vol. 5 (1985), pages 13-23, EP-A 0151282; EP-A 0185882; R. Noyori, Acc. Chem. Res. 23, 345 (1990); EP-269395; M. J. Burk, Tetrahedron, Asymmetry, pages 569-592 (1991); J. Am. Chem. Soc. 113, pages 8518-9 (1991), ibid. 115, pages 10125-138 (1993), ibid. 117, pages 9375-76 (1995), ibid 118, page 5142 (1996)). These disadvantages make industrial use difficult and uneconomic.
It is an object of the present invention to provide phosphine ligands which can be prepared easily and at low cost and which are good ligands for metal complex catalysts for enantioselective synthesis.
We have found that this object is achieved by a particularly efficient class of ligands, mainly phospholanes, which can be obtained from the “chiral pool”. The starting material is in this case mannitol and other carbohydrates which can be obtained in large quantities at low cost.
The resulting phospholanes and diphospholanes provide excellent enantiomeric excesses in asymmetric hydrogenations. The known DUPHOS ligands of Burk et al. (M. J. Burk, Tetrahedron, Asymmetry, pages 569-592 (1991); J. Am. Chem. Soc. 113, pages 8518-9 (1991), ibid. 115, pages 10125-138 (1993), ibid. 117, pages 9375-76 (1995), ibid 118, page 5142 (1996); U.S. Pat. No. 5,008,457; WO 92/19630; WO 93/19040) are very much more elaborate to synthesize, in contrast to the present invention. Synthesis of the DUPHOS ligands requires, inter alia, an impractical electrolytic Kolbe synthesis in addition to an asymmetric hydrogenation.
The present invention avoids these difficulties by using the sugar mannitol which can be obtained enantiomerically pure from natural sources. In addition, this precursor provides a route to compounds which have alkoxymethyl or hydroxymethyl groups in positions 2 and 5 in the phospholane ring. Compounds of this type cannot be prepared by the known DUPHOS synthesis.
The invention relates to phospholanes and diphospholanes of the general formula I
where:
R is H, C
1
-C
6
-alkyl, aryl, alkylaryl, SiR
3
2
,
R
2
is alkyl or aryl,
A is H, C
1
-C
6
-alkyl, aryl, Cl or
B is a linker with 1-5 C atoms between the two P atoms.
Preferred substituents R are hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, benzyl, trityl and trialkylsilyl or triarylsilyl (SiR
3
2
where R
2
=C
1
-C
6
-alkyl or aryl).
In the case of the diphospholanes, those which are preferred have
with n=0, 1, 2, 3, 4
Particularly preferred linkers B are those where n is 1 or 2 and m is 0.
The invention further relates to metal complexes comprising the abovementioned phospholanes with central atoms from the group of Rh, Ru, Ir, Pd, Pt, Ni.
Particularly preferred metal complexes are those which contain ruthenium or rhodium as central atom.
These complexes can be prepared by synthesizing the catalytically active complexes in a known manner (e.g. Uson, Inorg. Chim. Acta 73, 275 (1983), EP-A 0158875, EP-A 437690) by reacting with rhodium, iridium, ruthenium, palladium, platinum or nickel complexes which contain labile ligands (e.g. [RuCl
2
(COD)]
n
, Rh(COD)
2
BF
4
, Rh(COD)
2
ClO
4
, [Ir(COD)Cl]
2
, p-cymene-ruthenium chloride dimer).
The invention further relates to the use of these metal complexes in asymmetric synthesis, especially as catalyst for hydrogenations, hydroformylations, hydrocyanations, allylic substitutions and isomerizations of allylamines to enamines.
These reactions can be carried out with the metal complexes according to the invention under conditions familiar to the skilled worker.
The hydrogenation with the metal complexes according to the invention is usually carried out at a temperature from −20 to 150° C., preferably at 0 to 100° C. and particularly preferably at 15 to 40° C.
The pressure of hydrogen for the hydrogenation process according to the invention can be varied in a wide range between 0.1 bar and 300 bar. Very good results are obtained with a pressure in the range from 1 to 10, preferably 1 to 2 bar.
It is particularly advantageous with the ligands according to the invention that the hydrogenations can be carried out very efficiently at the low pressure of 1 to 2 bar of hydrogen.
Preferred solvents for the hydrogenations are C
1
-C
4
-alkanols, especially MeOH. In the case of substrates of low solubility, solvent mixtures, e.g. methanol and CH
2
Cl
2
or THF, toluene are also suitable.
The catalyst is normally employed in amounts of from 0.001 to 5 mol %, preferably 0.001 to 0.01 mol %, based on the substrate to be hydrogenated.


REFERENCES:
patent: 3803225 (1974-04-01), Smith et al.
patent: 5008457 (1991-04-01), Burk
patent: 6043396 (2000-03-01), Sturmer et al.
patent: 151 272 (1985-08-01), None
patent: 185 882 (1986-07-01), None
patent: 269 395 (1988-06-01), None
patent: 271 311 (1988-06-01), None
patent: 614 901 (1994-09-01), None
patent: 889 048 (1999-01-01), None
patent: 91/17998 (1991-12-01), None
patent: 92/19636 (1992-12-01), None
patent: 93/19040 (1993-09-01), None
Tetrahedron Letters by Holz et al 40 (39) pp 7059-7062 Sep. 1999.*
J.Am.Chem.Soc.1996, 118, 5142-5143, Burk et al.
J.Am.Chem.Soc.1993, 115, 10125-10138,Burk et al.
J.Am.Chem.Soc.1995, 117, 9375-9376,Burk et al. 74.
Asymmetry vol. 2, No. 7,569-592, 1991, Burk et al.
J.Org. Chem., 328(1987) 71-80, Brunner et al.
Chiral Ligands for Asymmetic Catalysis, pp. 13-23 Acc.Chem.Res. 1990,23,345-350,Takaya.
J.Am.Chem.Soc., Oct. 23, 1991,No. 22, vol. 113, 8518-8519.

Affiliated with

Also associated with

Rating

Production of optically active phospholanes does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Production of optically active phospholanes, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Production of optically active phospholanes will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-3151808