Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1992-11-13
1993-12-28
Cintins, Marianne M.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
549 6, 548412, C07D30734, C07D33304, C07F 928, C07F 9547
Patent
active
052741257
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with novel, racemic and optically active phosphorus compounds of the general formula ##STR2## wherein R signifies lower alkyl, lower alkoxy or a protected hydroxy group, R.sup.1 signifies a five-membered heteroaromatic ring, R.sup.2 stands for lower alkyl or lower alkoxy and n represents the number 0, 1 or 2.
The invention is also concerned with the manufacture of the phosphorus compounds of formula I as well as their use for enantioselective reactions such as e.g. asymmetric hydrogenations or enantioselective hydrogen displacements in prochiral allylic systems.
The term "lower alkyl" signifies in the scope of the present invention straight-chain or branched alkyl groups with 1 to 4 carbon atoms such as methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl and tert.butyl. The term "lower alkoxy" signifies groups in which the alkyl residue has the foregoing significance. As protecting groups for the hydroxy group there come into consideration in the scope of the present invention especially the usual ether-forming groups such as e.g. benzyl, allyl, benzyloxymethyl, lower alkoxymethyl, 2-methoxyethoxymethyl and the like. The term "five-membered heteroaromatic ring" stands in the scope of the present invention for a substituent of the formula ##STR3##
In the substituents of formulae (a) to (d) A signifies oxygen, sulphur or --NR.sup.4. The substituent R.sup.3 signifies hydrogen, lower alkyl, especially methyl, or lower alkoxy, especially methoxy, and R.sup.4 stands for lower alkyl, preferably methyl.
The phosphorus compounds of formula I can be present not only in racemic form, but also in optically active form. Preferred compounds of formula I are those in which n stands for the number 0 and R signifies methoxy, methoxymethyl or methyl. Further, those in which R.sup.1 represents 2- or 3-furyl or 2-thienyl are also preferred. Especially preferred compounds of formula I are: (S)-[6,6'-bis(methoxymethoxy)biphenyl-2,2'-diyl]bis(di-2-furylphosphine), (S)-[6,6'-bis(methoxymethoxy)biphenyl-2,2'-diyl]bis(di-2-thienylphosphine) (S)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(5-methylfuran-2-yl)phosphine . (S)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[di-(2-benzo[b]furanyl)phosphine] . ne, (S)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis-(dibenzo[b]thiophen-2-yl)phosphi ne, ne], (S)-(6,6'-dimethoxybiphenyl-2,2'-diyl)bis[bis(1-methylpyrrol-2-yl)phosphin e].
The compounds of formula I in accordance with the invention can be manufactured e.g. by reacting a racemic or optically active compound of the general formula ##STR4## wherein R, R.sup.2 and n have the above significance and R.sup.5 signifies lower alkoxy, phenoxy, benzyloxy, chlorine or bromine, with a compound of the formula bromine or iodine, to give a compound of the formula ##STR5## wherein R, R.sup.1, R.sup.2 and n have the above significance, and reducing this, if desired after resolution into the (R) form and (S) form using O,O'-dibenzoyltartaric acid or O,O'-di-p-toluyltartaric acid, to a compound of formula I.
The reaction of a compound of formula II with R.sup.1 MgX or R.sup.1 Li can be effected in a manner known per se. This is preferably effected e.g. under the usual conditions of a Grignard reaction.
The reduction of a racemic compound of formula III or of a compound of formula III which is present in the (R) or (S) form can be carried out in a manner known per se. This can be effected, for example, with silanes such as e.g. trichlorosilane in an aromatic hydrocarbon such as, for example, in boiling xylene or in acetonitrile etc., conveniently in the presence of an auxiliary base such as, for example, triethylamine or preferably tributyl- amine. If desired, this reduction can also be carried out in an autoclave under pressure.
The compounds of formula II which are used as starting materials can be prepared, for example, by subjecting a compound of the formula ##STR6## wherein R, R.sup.2 and n have the above significance and R.sup.5 also has the above significance with the exception of chlorine or bromine, to an Ullmann coupling and
REFERENCES:
patent: 4556740 (1985-12-01), Hansen et al.
patent: 4634775 (1987-01-01), Beck et al.
C. K. Mirabelli, et al., J. Med. Chem., 30:2181-90, (1987).
Broger Emil A.
Foricher Joseph
Heiser Bernd
Schmid Rudolf
Cintins Marianne M.
Epstein William H.
Gould George M.
Hoffmann-La Roche Inc.
Page Margaret J.
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