| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | March 28, 2000 |
| PATENT TITLE |
Preparation of optically active phospholanes, their metal complexes and use in asymmetric synthesis |
| PATENT ABSTRACT |
Phospholanes and diphospholanes of the formula I ##STR1## where: R.sup.1 and R.sup.2 are, independently of one another, C.sub.1 -C.sub.6 -alkyl, aryl, alkylaryl, R.sup.1 is also hydrogen, A is either R.sup.1 or ##STR2## B is a linker having 1-5 carbon atoms between the two phosphorus atoms, and their use as catalyst in asymmetric synthesis. |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | June 8, 1998 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT REFERENCES CITED |
Carmichael et al., "Hybrid P-chiral diphosphines for asymmetric hydrogenation", Chem. Commun., pp. 261-262, 1999. Holz et al., "Synthesis of a New Class of Functionalized Chiral Bisphospholane Ligands and the Application in Enantioselective Hydrogenations", J. Org. Chem., vol. 63: 8031-8034, 1998. Genet et al., "New Developments in Chiral Ruthenium (II) Catalysts for Aymmetric Hydrogenation and Synthetic Applications", ACS Sympos. Ser. 641 (Reductions in Organic Synthesis), pp. 31-51, 1996. Burk et al., "Asymmetric catalytic routes to chiral building blocks of medicinal interest", Pure & Appl. Chem., vol. 68(1): 37-44, 1996. Brunner et al., "Enantioselektive Katalysen. LIX. Addition von optisch aktiven P-H Verbindungen an P-substutierte Olefine", Journal of Organometallic Chemistry, vol. 413: 55-63, 1991. Brunner et al., "Optisch aktive Ubergangsmetallkomplexe.", Journal of Organometallic Chemistry, vol. 393: 401-409 & 411-422, 1990. Brunner et al., "Asymmetric Catalyses. XXXIII. New Optically Active Phospholanes Derived From Tartaric Acid.", Journal of Organometallic Chemistry, vol. 328: 71-80, 1987. J. Am. Chem. Soc., 1996, 118, 5142-5143, Burk et al. Inorganica Chim. Acta, 73 (1983) 275-279, Uson et al. J. Am. Chem. Soc., 1995, 117, 9375-9376, Burk et al. J. Am. Chem. Soc., 1993, 115, 10125-10138, Burk et al. J. Am. Chem. soc. 1991, 113, 8519-8521, Burk. Tetrahedron: Asymmetry vol. 2, No. 7, pp 569-592, 1991, Burk et al. Asymmetric Synthesis, vol. 5 chiral Catalyst, 1985, pp. 12-23. Acc. Chem. Res. 1990, 23, 345-350, Noyori et al. J. Am. Chem. Soc. 1984, 5208-5217, Tani et al. Asymmetric catalyses, Jrl. Org. Chem. 328 (1987) 71-80, Brunner et al. |
| PATENT CLAIMS |
We claim: 1. A phospholane or diphospholane of the formula I ##STR22## where R.sup.1 is H, C.sub.1 -C.sub.6 -alkyl, aryl, or alkylaryl, R.sup.2 is C.sub.1 -C.sub.6 -Alkyl, aryl, or alkylaryl, A is either R.sup.1 or ##STR23## B is a linker having 1-5 carbon atoms between the two phosphorous atoms. 2. A phospholane as claimed in claim 1, wherein the substituents have the following meaning: R.sup.1 benzyl, methyl, tert-butyl, or together with the other substituent R.sup.1, isopropylidene or benzylidene. 3. A diphospholane as claimed in claim 1, wherein the substituents have the following meaning: ##STR24## 4. A diphospholane as claimed in claim 3, wherein the substituents have the following meaning: m=0, n=1. 5. A metal complex of a phospholane as claimed in claim 1 and a central atom selected from the group of Rh, Ru, Ir, Pd, Pt, Ni. 6. A metal complex as claimed in claim 5, wherein Rh or Ru is selected as central atom. 7. A metal complex as claimed in claim 6, wherein the phospholane or diphospholane is selected from those claimed in claims 2-4. 8. A process for hydrogenation, hydroformylation, hydrocyanation, allylic substitution, or isomerization of allylamines to enamines by using as a catalyst the metal complex of claim 5. 9. A process for the asymmetric hydrogenation of compounds by reacting the starting compounds which are to be hydrogenated with hydrogen in the presence of a metal complex as claimed in claim 5. 10. A process as claimed in claim 9, wherein the hydrogenation is carried out under a hydrogen pressure of from 1 to 2 bar. -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
The invention describes novel optically active phospholanes and bisphospholanes, their preparation and use 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 of great importance for synthesizing optically active compounds (eg. Tani et al. J. Am. Chem. Soc. 106 (1984) 5211; R. Noyori, Acc. Chem. Res. 23 (1990) 345). The stoichiometric starting material hydrogen is not costly, but the catalysts used, which are mostly prepared from an optically active diphosphine ligand and a rhodium or ruthenium compound, are very costly and obtainable only in a complicated way. The known methods for preparing optically active phosphines and diphosphines are uniformly complicated and mostly include a technically elaborate and costly racemate resolution (eg. EP-A 0614901; EP-A 0271311; H. B. Kagan, "Chiral Ligands for Asymmetric Catalysis" in Asymmetric Synthesis 5 (1985) 13-23, EP-A 0151282; EP-A 0185882; R. Noyori, Acc. Chem. Res. 23 (1990) 345; EP-269395; M. J. Burk, Tetrahedron Asymmetry (1991) 569-592; J. Am. Chem. Soc. 113 (1991) 8518-9, ibid. 115 (1993) 10125-138, ibid. 117 (1995) 9375-76, ibid 118 (1996) 5142. 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, namely phospholanes obtainable from the chiral pool (2). The starting material in this case is mannitol and other carbohydrates, which are available at low cost and in large quantity. 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 (1991) 569-592; J. Am. Chem. Soc. 113 (1991) 8518-9, ibid. 115 (1993) 10125-138, ibid. 117 (1995) 9375-76, ibid. 118 (1996) 5142) are, in contrast to the present invention, much more complicated to synthesize. Synthesis of the DUPHOS ligands requires, inter alia, an impracticable electrolytic Kolbe synthesis plus an asymmetric hydrogenation. The present invention avoids these difficulties by using the sugar mannitol which is available enantiomerically pure from natural sources. In addition, this starting material opens up a route to structural analogs substituted in the 3 and 4 positions of the phospholane ring, ie. to analogs which cannot be prepared by the known DUPHOS synthesis. The invention relates to phospholanes and diphospholanes of the formula I ##STR3## where R.sup.1 and R.sup.2 are, independently of one another, C.sub.1 -C.sub.6 -alkyl, aryl, alkylaryl, R.sup.1 is also hydrogen, A is either R.sup.1 or ##STR4## B is a linker having 1-5 carbon atoms between the two phosphorus atoms. Preferred substituents R.sup.1 and R.sup.2 are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, benzyl. Furthermore, also those radicals R.sup.1 where the two R.sub.1 radicals together mean isopropylidene or benzylidene. Preferred diphospholanes are those where ##STR5## Particularly preferred linkers B are those where n is 1 or 2 or m is 0. The invention furthermore relates to metal complexes comprising the abovementioned phospholanes. Particularly preferred metal complexes are those which contain ruthenium or rhodium as central atom. These complexes can be prepared by synthesizing in a known manner (eg. Uson, Inorg. Chim. Acta 73 (1983) 275, EP-A 0158875, EP-A 437690) catalytically active complexes by reaction with rhodium, iridium, ruthenium, palladium, platinum or nickel complexes which contain labile ligands (eg. [RuCl.sub.2 (COD)]n, Rh(COD).sub.2 BF.sub.4, Rh(COD).sub.2 ClO.sub.4, [Ir(COD)Cl].sub.2, p-cymene-ruthenium chloride dimer). The invention furthermore relates to the use of these metal complexes in asymmetric synthesis, in particular as catalyst for hydrogenations, hydroformylations, hydrocyanations, allylic substitutions and isomerizations of allylamines to enamines. These reactions can be carried out with the novel metal complexes under conditions familiar to the skilled worker. Hydrogenation with the novel metal complexes is, as a rule, carried out at from -20 to 150.degree. C., preferably at 0 to 100.degree. C., and particularly preferably at 15-40.degree. C. The hydrogen pressure can vary within a wide range from 0.1 bar to 300 bar for the novel hydrogenation process. Very good results are obtained in a pressure range of 1-10, preferably 1-2, bar. It is a particular advantage with the novel ligands that the hydrogenations can be carried out very efficiently at the low hydrogen pressure of 1-2 bar |
| PATENT EXAMPLES | Available on request |
| PATENT PHOTOCOPY | Available on request |
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