Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Patent
1993-09-23
1995-06-20
Reamer, James H.
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
568336, 568316, C07C 4564
Patent
active
054262330
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND
Chiral hydroxyketones are useful intermediates for preparing various pharmaceutical compounds, such as anti-fungal reagents. Franklin A. Davis and M. Serajul Haque, J. Org. Chem. 1986, 51, pp. 4083-4085 describe the asymmetric oxidation at -78.degree. C. of the sodium enolates of ketones using chiral (camphorylsulfonyl)oxaziridines to give .alpha.-hydroxy ketones. Franklin A. Davis and Michael C. Weismiller, J. Org. Chem., Vol. 55, No. 12, 1990 pp. 3715-3717, reported the preparation of (S)-2-hydroxy-1-phenyl-1-propanone in greater than 95% enantiomeric excess (ee) and 61% yield by oxidation of the sodium enolate of the propiophenone at -78.degree. C. by (+)-((8,8-dichlorocamphoryl)sulfonyl)oxaziridine. Franklin A. Davis et al. J. Org. Chem., 1991. Vol 56, pp 1143-1145 discloses asymmetric hydroxylation with (+)-{(8,8 dimethoxycamphoryl)sulfonyl}sulfonyloxaziridine. None of these references disclose the use of temperatures lower than -78.degree. C. It would be desirable to provide a process for preparing chiral hydroxyketones and salts thereof, in as high or even greater yields and chirality than processes previously taught. It would also be desirable to provide a process for preparing hydroxyketones in which the oxidant (i.e., hydroxylating agent) can be readily recycled in order to reduce operating expenses associated with disposal of the oxidizing agent.
SUMMARY OF THE INVENTION
The present invention is directed toward a process for preparing an hydroxyketone of the formula (X) where R.sup.1 and R2 are different: ##STR4## wherein Ar represents substituted aromatic, substituted aromatic, aromatic heterocyclic, or substituted aromatic heterocyclic; R.sup.1 and R.sup.2 independently represent hydrogen, C-1 to C-16 alkyl, or aromatic, aromatic heterocyclic or substituted aromatic heterocyclic or C-1 to C-5 alkyl bonded to the Ar. The process comprises contacting a compound of the formula (V): ##STR5## with a solvent, a base and a chiral hydroxylating agent at a temperature of about -85.degree. C. or less. More preferably, the reaction is carded out at a temperature ranging from about -85.degree. C. to about -120.degree. C., more preferably from about -90.degree. C. to about -110.degree. C., most preferably at about -95.degree. C. In a preferred embodiment, the hydroxyketone is reacted to form a protecting group with the hydroxy moiety.
The present invention is also directed to novel intermediates of the formulae: ##STR6## wherein R.sup.1 is alkyl, preferably ethyl.
The present invention has the advantage of providing an efficient process for preparing chiral hydroxyketones and salts thereof, in as high or even greater yields and chirality than by processes previously taught. The present invention also has the advantage of providing a process for preparing chiral hydroxyketones which permits selection of the desired stereochemistry (i.e., R or S stereoisomer) of the hydroxyketone by selection of the appropriate starting materials aforehand. The present invention has the further advantage of providing a process for preparing hydroxyketones in which the oxidant can be readily recycled in order to reduce operating expenses associated with disposal of the oxidizing agent.
DETAILED DESCRIPTION OF THE EMBODIMENTS
When utilized herein the terms listed hereinbelow, unless otherwise indicated are defined as follows:
alkyl--comprise straight or branched saturated hydrocarbon moieties (i.e., hydrocarbons having carbon-carbon single bonds) containing from 1 to 16 carbon atoms, preferably from 1 to 6 carbon atoms, such as for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tertbutyl, pentyl, hexyl and the like.
-aromatic--comprises 1 to 3 unsaturated fused ring moieties such as phenyl, naphthyl etc. having from 4 to 14 carbon atoms.
aromatic heterocyclic-cyclic groups having at least one O, S and/or N heteroatom interrupting the ring structure and having a sufficient number of unsaturated carbon to carbon bonds, nitrogen to carbon bonds, etc., to provide aromatic character, with the aromatic
REFERENCES:
patent: 4613611 (1986-09-01), Floyd et al.
patent: 4613611 (1986-09-01), Middleton et al.
Davis et al, J. Org. Chem., vol. 49, pp. 3241-3243 (1984).
Davis et al, J. Org. Chem., vol. 51, pp. 4083-4085 (1986).
Davis et al, J. Org. Chem., vol. 55, pp. 3715-3717 (1990).
Davis et al, J. Org. Chem, vol. 56, pp. 1143-1145 (1991).
Theodora W. Greene, Protective Groups in Organic Synthesis, John Wiley and Sons, New York, N.Y. (1981). Chapter 2: pp. 10-22.
Franklin A. Davis, et al. J. Org. Chem. vol. 54, pp. 2021-2024 (1989).
Franklin A. Davis, et al., J.A.C.S. vol. 112, pp. 6679-6690 (1990).
Franklin A. Davis et al., Tetrahedron Letter vol. 1989, pp. 779-782 (1982).
Majka Joseph T.
Mazer Edward H.
Reamer James H.
Schering Corporation
LandOfFree
Preparation of chiral hydroxyketones does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Preparation of chiral hydroxyketones, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Preparation of chiral hydroxyketones will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1845293