Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-03-15
1997-12-30
Richter, Johann
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
548956, 548968, 548969, 549215, 549217, 549519, C07C20300
Patent
active
057032467
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/02280 filed Oct. 19, 1994.
The present invention relates to a process for the preparation of oxiranes from aldehydes or ketones, of aziridines from imines, or of cyclopropanes from alkenes.
It is known to generate ylides from diazo compounds in the presence of rhodium (II) acetate (M. P. Doyle et al J. Org. Chem. (1981) 46 5094-5102). The use of sulphur ylides to prepare oxiranes from carbonyl compounds is well known (see, for example, B. M. Trost and L. S. Melvin "Sulphur Ylides" Academic Press, 1975). Known methods require that the reaction is carried out under basic conditions. Thus, forming oxiranes of carbonyl substrates which also contain base sensitive groups is not straightforward. Also, known methods require stoichiometric amounts of sulphide and base.
According to the present invention there is provided a process for the preparation of an oxirane, aziridine or cyclopropane of formula (I), wherein, X is oxygen, NR.sup.4 or CHR.sup.5 ; R.sup.1 is hydrogen, alkyl, aryl, heteroaromatic, heterocyclic, NHR.sup.13 or cycloalkyl; R.sup.2 is hydrogen, alkyl, aryl, heteroaromatic, CO.sub.2 R.sup.8, CHR.sup.14 NHR.sup.13, heterocyclic or cycloalkyl; or R.sup.1 and R.sup.2 join together to form a cycloalkyl ring; R.sup.3 is hydrogen, alkyl, aryl, heteroaromatic, CO.sub.2 R.sup.8, R.sup.8.sub.3 Sn, CONR.sup.8 R.sup.9 or trimethylsilyl; R.sup.4 and R.sup.5 are, independently, alkyl, cycloalkyl, aryl, heteroaromatic, SO.sub.2 R.sup.8, SO.sub.3 R.sup.8, COR.sup.8, CO.sub.2 R.sup.8, CONR.sup.8 R.sup.9 or CN, or R.sup.4 can also be P(O)(aryl).sub.2 ; R.sup.8 and R.sup.9 are independently alkyl, aryl or arylalkyl; R.sup.13 and R.sup.14 are independently hydrogen, alkyl or aryl; the process comprising reacting a mixture of a compound of formula (II), wherein R.sup.1, R.sup.2 and X are as defined above, and a sulphide of formula SR.sup.6 R.sup.7 wherein R.sup.6 and R.sup.7 are independently alkyl, aryl or heteroaromatic, or R.sup.6 and R.sup.7 join together to form a cycloalkyl ring which optionally includes an additional heteroatom, with either (i) a metallocarbon obtainable by reacting an alkylmetal with a methane derivative of formula CHR.sup.3 X'X", wherein R.sup.3 is as defined above, and X' and X" are independently, a leaving group, or (ii) a metallocarbon obtainable by reacting a compound of formula (III) (wherein R.sup.3 may not be hydrogen) with a suitable organometallic or inorganic reagent.
When the compound of formula (II) is an alkene (that is when X in the compound of formula (II) is CHR.sup.5) it is an electron deficient alkene.
When a compound of formula (II) (wherein X is O and neither R.sup.1 nor R.sup.2 is hydrogen (ie it is a ketone)) is used in the process of the present invention to prepare a required oxirane of formula (I) (wherein X is O), the reactivity of the compound of formula (II) should be balanced against the nucleophilicity of the product obtained by reacting the metallocarbon of (i) or (ii) with a sulphide of formula SR.sup.6 R.sup.7.
It is preferred that the process of the present invention is carried out in a solvent. Suitable solvents include chlorinated solvents (such as CH.sub.2 Cl.sub.2 or CHCl.sub.3), aromatic solvents (such as benzene, toluene and o-, m- or p-xylene), aliphatic alcohols (such as methanol, ethanol or tert-butanol), chain or cyclic ethers (such as diethyl ether, tert-butyl methyl ether, di-iso-propyl ether, glymes (for example monoglyme, diglyme or triglyme) or tetrahydrofuran), aliphatic or alicyclic hydrocarbons (such as n-hexane or cyclohexane), N,N-dimethylformamide, acetonitrile or N-methylpyrrolidone. The process may be carried out in a mixture of these solvents, or different reagents may be added in different solvents.
It is preferred that the process of the present invention is carried out at a temperature in the range -30.degree.-100.degree. C., especially in the range 0.degree.-50.degree. C., such as at ambient or room temperature.
The compounds of formula (I) have one, two or three chiral ring-carbon atoms and the
REFERENCES:
Adams, J., et al. Tetrahedron, "Rhodium (II) Catalyzed Reactions of Diazocarbonyl Compounds", vol. 47 No. 10/11, 1991, pp. 1765-1808.
Aggarwal, V., et al., Phosphorus, Sulfur, and Silicon,"A Novel Catalytic Cycle for the Synthesis of Epoxides Using Sulfur Ylides, and Application to the Synthesis of Cyclopropanes and Azindines", 1994, vol. 95-96, pp. 283-292.
Doyle, M., Chem. Rev., "Catalytic Methods for Metal Carbene Transformations", 1986, vol. 86, pp. 919-939.
Furukawa, N. et al., J. Org. Chem., "Camphoryl Sulfide as a Chiral Auxiliary and a Mediator for One-Step Synthesis of Optically Active 1,2-Diaryloxiranes", 1989, vol. 54, pp. 4222-4224.
Hudlicky, T., et al., J. Org. Chem., "Terpenic Acids by Cyclopentane Annulation of Exocyclic Dienes. Synthesis of Triquinane Portion of Retigeranic Acid", vol. 47, pp. 1522-1527.
Jennings, W. et al., Tetrahedron, "The Titanium Tetrachloride Induced Synthesis of N-Phosphinoylimines and N-Sulphonylimines Directly from Aromatic Aldehydes", 1991, vol. 47, No. 29, pp. 5561-5568.
Jonczyk, A. et al., Synthetic Communications, "A Simple Method for Generation Diazo Compounds in an Aqueous Two-Phase System", 8(8), 1978, pp. 569-572.
Jonczyk, A., et al., Bull. Soc. Chim. Belg., "Reactions of Organic Anions. LXVII. Synthetic Utility Of Tosylhydrazones Reactions in Two-Phase Aqueous System", vol. 86, No. 9, 1977, pp. 739-740.
Chemistry & Industry, 15 Aug. 1994, p.642.
Derwent Abstracts, No. 33423A/19, 1978.
Abdel-Rahman Hesham Nimer Hasan
Aggarwal Varinder Kumar
Lee Hee Yoon
Richter Johann
Snyder Joseph R.
Zeneca Limited
LandOfFree
Process for the preparation of an oxirane, azirdine or cycloprop does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of an oxirane, azirdine or cycloprop, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of an oxirane, azirdine or cycloprop will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-203738