Asymmetric epoxides, their synthesis and use

Details Asymmetric epoxides, their synthesis and use Asymmetric epoxides, their synthesis and use

1997-10-20

2001-05-08

Dawson, Robert (Department: 1712)

Synthetic resins or natural rubbers -- part of the class 520 ser

Synthetic resins

Mixing of two or more solid polymers; mixing of solid...

C549S525000, C549S530000, C549S539000, C549S549000

Reexamination Certificate

active

06228955

ABSTRACT:

FIELD OF THE INVENTION
This invention relates to epoxides, their synthesis by the asymmetric epoxidation of enones, and their use.
BACKGROUND OF THE INVENTION
The enantioselective epoxidation of prochiral alkenes is a valuable methodology, which enables two stereogenic centres to be created in a single synthetic operation. Established methods tend to be limited to specific classes of substrate. The best known is the titanium tartrate-catalysed epoxidation of allylic alcohols, which was first reported by Sharpless as a stoichiometric method, in Katsuki et al, J. Am. Chem. Soc. (190) 102:5974, and later adapted into a catalytic variant; see Gao et al, J. Am. Chem. Soc (1987) 109:5765.
More recently, epoxidations employing chiral (salen)Mn(III) catalysts have been applied to a variety of alkene substrates, both unfunctionalised and functionalised; see Jacobsen, Chapter 4.2 in Catalytic Asymmetric synthesis, ed. I. Ojima (1993) VCH, New York.
Although both these known processes are proven as generic methodologies for laboratory-scale synthesis, reliance on metal-based catalysts and reagents means that operation on a large scale can be disadvantageous in terms of cost, work-up procedure and effluent disposal.
A third and potentially more economical methodology is the use of metal-free synthetic polypeptides such as poly-L-leucine as catalysts for the asymmetric epoxidation of prochiral &agr;,&bgr;-unsaturated ketones of the general formula
R
1
R
2
C═CR
3
—CO—X  (II)
to give the corresponding optically-enriched epoxides
This process was first reported by Julia et al, Angew. Chem. Int. Ed. Engl. (1980) 19:929. However, it is reported that high enantioselectivities are confined to trans-chalcone derivatives; see Juliá et al, J. Chem. Soc., Perkin Trans. 1 (1982) 1317; Colonna et al, Tetrahedron (1983) 39:1635; Banfi et al, Tetrahedron (1984) 40:5297; Baures et al, Tetrahedron Lett. (1990) 31;6501; and Itsuno et al, J. org. Chem. (1990) 55:5047, Thus, this reaction has been considered to be of restricted scope in organic synthesis.
Optically-enriched epoxides are especially suited to nucleophilic ring-opening reactions to give, in stereocontrolled fashion, products bearing heteroatom functionality on adjacent chiral centres. In this respect, (2R,3S)-syn-3-phenylisoserine synthons are reported by Boa et al, Contemporary Organic Synthesis (1994) 1:47, and references therein. Several methods proceed via trans- or cis-phenylglycidate intermediates, prepared by enantioselective oxidation (epoxidation and dihydroxylation) of styrene derivatives; see Greene, J. Org. Chem. (1990) 55:1957; Jacobsen, J. Org. Chem. (1992) 57:4320; and Sharpless, J. Org. Chem. (1994) 59:5105. Although this is an effective overall strategy, provision of enantiopure phenylglycidates relies on the metal-based epoxidation methodologies described above, and aspects of the downstream chemistry are not well suited to operation on a large scale.
Compounds of formula I are known in racemic form. For example, compounds wherein R
1
is phenyl, R
2
and R
3
are each H, and X is t-butyl or cyclopropyl, are disclosed in EP-A-0336841 and WO-A-0113066, and by Matano, J. Chem. Soc. Perkin Trans. I (1994) 2703, Meth-Cohn, ib. 1517, and Treves, JACS (1967) 89:6257. The nature of the functional groups makes such compounds difficult to separate into constituent enantiomers, by conventional resolution techniques.
An optically-enriched epoxide of formula I (R
1
=CF
3
, R
2
=R
3
=H, X=t-butyl) is reported by Lin et al, J. Fluorine Chem. (1989) 44:113-120. Its synthesis is from optically-enriched 1,1,1-trifluoro-2-hydroxy-5,5-dimathylhexan-4-one, using lithium diisopropylamide. This is not a commercial process.
Corey et al, Tetrahedron Lett. (1991) 32:2857, report the t-butyl glycidate 5 (see Scheme 1) as the product of a chiral Darzens reaction between t-butyl bromoacetate and benzaldehyde.
SUMMARY OF THE INVENTION
It has surprisingly been discovered that asymmetric epoxidation of the type reported by Juliá at al can tolerate a greater range of substituents than is indicated by the prior art. More particularly, the present invention enables the preparation of novel optically-enriched epoxides of formula I wherein R
1
, R
2
and R
3
are each independently selected from H, R, R—CO— and R—O—CO—, each R independently being substantially a hydrocarbon group of up to 20 carbon atoms, and X is an alkyl or cycloalkyl group of up to 10 carbon atoms, provided that —CO—X is not enolisable. Novel epoxides of formula I constitute a further aspect of the invention.


REFERENCES:
patent: 5110959 (1992-05-01), Flisher et al.
patent: 0336841 (1989-10-01), None
patent: 9113066 (1991-09-01), None
Banfi, S. et al. (1984) “Asymmetric Epoxidation of Electron-Poor Olefins—V1: Influence on Stereoselectivity of the Structure of Poly-&agr;-Aminoacids Used as Catalysts”Tetrahedronvol. 40, No. 24, pp. 5207-5211.
Baures, P. et al. (1990) “An Efficient Asymmetric Synthesis of Substituted Phenyl Glycidic Esters”Tetrahedron Lett. vol. 31, No. 45, pp. 6501-6504.
Boa, A.N., P.R. Jenkins, N.J. Lawrence (1994) “Recent Progress in the Synthesis of Taxanes”Contemporary Organic Synthesis1:47-75.
Colonna, S. et al. (1983) “Synthetic Enzymes—41: Highly Enantioselective Epoxidation by Means of Polyaminoacids in a Triphase System: Influence of Structural Variations Within the Catalysts”Tetrahedronvol. 39, No. 9, pp. 1635-1641.
Corey, E.J. and S. Choi (1991) “Highly Enantioselective Routes to Darzens and Acetate Aldol Products from Achiral Aldehydes and t-Butyl Bromoacetate”Tetrahedron Lett. vol. 32, No. 25, pp. 2857-2860.
Gao, Y. et al. (1987) “Catalytic Asymmetric Epoxidation and Kinetic Resolution: Modified Procedures Including in Situ Derivatization”J. Am. Chem. Soc. 109:5765-5780.
Itsuno, S., M. Sakakura, K. Ito (1990) “Polymer-Supported Poly(amino acids) as New Asymmetric Epoxidation Catalyst of &agr;, &bgr;-Unsaturated Ketones”J. Org. Chem. 55:6047-6049.
Jacobsen, E. (1993) “Chapter 4.2 in Catalytic Asymmetric Synthesis: Asymmetric Catalytic Epoxidation of Unfunctionalized Olefins” Ed. I. Ojima, VCH, New York, pp. 159-202.
Juliá, S., J. Masana, J. Vega (1980) “Synthetic Enzymes'. Highly Stereoselective Epoxidation of Chalcone in a Triphasic Toluene-Water-Poly[(S)-alanine] System”Angew. Chem. Int. Ed. Engl. 19:929-931.
Juliá, S. et al. (1982) “Synthetic Enzymes. Part 2. Catalytic Asymmetric Epoxidation by means of Polyamino-acids in a Triphase System”J. Chem. Soc. Perkin Trans. I, 1317-1324.
Katsuki, T. et al. (1980) “The First Practical Method for Asymmetric Epoxidation”J. Am. Chem. Soc. vol. 102, No. 18, 5974-5976.
Lin, J.T. et al. (1989) “Stereoselective Synthesis of Chiral 2,3-Epoxycompounds Possessing Fluorinated Methyl Groups”J. Flourine Chem. 44:113-120.
Matano, Yoshihiro (1994) “Triphenylbismuthonium 2-Oxoalkylide, A Moderately Stabilized Bismuthonium Ylide: Generation and Reactions with Some Electrophiles”J. Chem. Soc. Perkin Trans. I, 2703-2709.
Meth-Cohn, O., R.M. Horak, G. Fouch{acute over (e )} (1994) “Baker's Yeast-mediated Transformations of &agr;-Keto Epoxides”J. Chem. Soc. Perkin Trans. I, 1517-1527.
Wang, Z.-M. H.C. Kolb, K.B. Sharpless (1994) “Large-Scale and Highly Enantioselective Synthesis of the Taxol C-13 Side Chain through Asymmetric Dihydroxylation”J. Org. Chem. 59:5104-5105.
Denis, Jean-Noël, Arlene Correa, Andrew E. Greene (1990) “An Improved Synthesis of the Taxol Side Chain and of RP 56976” Journal of Organic Chemistry 55:1957-1959.
Treves, Gino R., Hugo Stange, R.A. Olofson (1967) (The Base-Induced Rearrangements of &agr;-Epoxy Ketones Journal of American Chemical Society 89(24):6257-6260.
Li, Deng, Eric N. Jacobsen (1992) “A Practical, Highly Enantioselective Synthesis of the Taxol Side Chain via Asymmetric Catalysis” Journal of Organic Chemistry 57:4320-4323.
**Abstract** EP 0 336 841 By Derwent Info., 1998.

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