A,P-epoxy ketone

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good... 

In a separate report, the Darzens reaction was recently used by Barluenga, Concellon, and coworkers for the preparation of enantiopure a"-amino a,P-epoxy ketones. Accordingly, the Z enolate of a"-amino a-bromo ketone 41 was generated with KHMDS at -100°C. Benzaldehyde was added, and trans epoxyketone 42 was isolated in 87% yield and >95% de. ... 

For other methods of fragmentation of an a,p-epoxy ketone derivatives, see Mac Alpine, G.A. Warkentin, J. Can. J. Chem., 1978, 56, 308, and references cited therein. 

Epoxides can also be rearranged to aldehydes or ketones on treatment with certain metallic catalysts.A good way to prepare p-diketones consists of heating a,P-epoxy ketones at 80-140°C in toluene with small amounts of (Ph3P)4Pd and 1,2-bis(diphenylphosphino)ethane. ... 

Table 4.2 a,p-Epoxy ketones prepared by epoxidation of ( )-2-alkyliden-l-oxo-l,2,3,4-tetrahydronaphthalenes using diethylzinc and (lR,2R)-V-methylpseudoephedrine[8l... 

Table 4.3 a, P-Epoxy ketones prepared by epoxidation of a-enones using diethylzinc and (1R, 2R)-/V-methylpseudoephedrine (according to the relevant publication)181. 

The asymmetric Darzens condensation, which involves both carbon-carbon and carbon-oxygen bond constructions, was realized by use of the chiral azacrown ether 75als2,s ,ss and the quaternary ammonium salts derived from cinchona alka-loids159"621 under phase transfer catalyzed conditions. The a,p-epoxy ketone 80 (R=Ph) was obtained with reasonable enantioselectivity by the reaction of... 

Epoxidation is another important area which has been actively investigated on asymmetric phase transfer catalysis. Especially, the epoxidation of various (i.)-a,p-unsaturated ketones 68 has been investigated in detail utilizing the ammonium salts derived from cinchonine and cinchonidine, and highly enantioselective and diastereoselective epoxidation has now been attained. When 30 % aqueons H202 was utilized in the epoxidation of various a, 3-unsaturated ketones 68, use of the 4-iodobenzyl cin-choninium bromide 7 (R=I, X=Br) together with LiOH in Bu20 afforded the a,p-epoxy ketones 88 up to 92% ee,1641 as shown in Table 5. The O-substituted... 

Fuson and oo-woikersW hare published the remarkable ohsm-a tion that certain aryl-substituted a,p-epoxy ketones simply lose oxygen to give a -nnsaturated ketones on treatment with ethyimagnoaiuin bromide or other Grignard reagents (Eq. 849). Although a mechanism... 

Reduction of ot, -epoxy ketones chiral aldols.3 a,p-Epoxy ketones are reduced by Sml2 in THF/CH3OH at -90° to p-hydroxy ketones with retention of stereochemistry at the p-, but not at the a-position. 

The method is a modification of one used by Barton and McCombie.8 Reduction of ketones.9 Ketones can be reduced to alcohols by Bu3SnH in the presence of either AIBN or a Lewis acid, but this reaction is limited to unhindered ketones. However, even sterically hindered ketones, such as f-butyl methyl ketone, can be reduced under high pressure (10 kbar) in the absence of a catalyst. This method is particularly useful in the case of cyclopropyl and a,p-epoxy ketones, which are reduced to the corresponding alcohols. Reduction of these ketones with Bu3SnH under radical conditions results in ring-opened products. 

P,Y-Unsaturated ketones.1 The reaction of acyclic a,p-epoxy ketones with two equivalents of 1 results in the cyclopropanols 2, which are converted into p,Y-enones on treatment with BF3 etherate or HC1. 

Reduction of a, -epoxy ketones. a,P-Epoxy ketones are reduced by NaTeH rc-gioselectively to (3-hydroxy ketones. Unactivated epoxides, such as stilbene oxide and a,3-epoxy alcohols, are not reduced. 

The double bond of an unsaturated ketone is deactivated towards electrophilic attack by the electron-withdrawing carbonyl group but is susceptible to nucleophilic addition. Base-catalysed epoxidation with alkaline hydrogen peroxide provides a useful method for the synthesis of a,P-epoxy ketones. 

Zinc borohydride was effective for the reduction of a,P-epoxy ketones (49) to the corresponding anti-a,3-epoxy alcohols (50) in ether at 0 °C irrespective of the substituents on the epoxide (equation 14). The selectivity was rationalized by intramolecular hydride delivery from a five-membered zinc chelate avoiding the epoxide ring. In a limited study of the stereoselective reduction of y,8-epoxy ketones (51), LAH and di-2-(o-toluidinomethyl)pyrrolidine in ether at -78 C gave the desired c/j-epoxy alcohols (52) required for ionophore synthesis with good selectivity (>10 1) (equation 15). ... 

This transformation has found extensive use in converting cyclopentenone and cyclohexenone ring systems to the rearranged allylic alcohols during the course of the total syntheses of natural products. In the preparation of ( )-quadrone (Scheme 12), the tricyclic enone was epoxidized and the resulting a,P-epoxy ketone treated with hydrazine to afford the allylic alcohol. The cyclopropane-directed epoxidation shown in Scheme 13 gives an allylic alcohol that is taken on to (-)- and (+)-carenones. In the total syn-... 

The Wharton reaction has also been applied to the conversion of exocyclic a,p-epoxy ketones to the corresponding exocyclic hydroxy methylene products (Scheme 17). Similar conditions transform exocyclic methyl ketones into the exocyclic ethylidene derivative (Scheme 18). Not unexpectedly, the (Z)-alkene is isolated in only slightly higher yields than the ( )-isomer. 

A good way to prepare p-diketones consists of heating a,p-epoxy ketones at 80-140°C in toluene with small amounts of (Ph3P)4Pd and l,2-bis(diphenyl-phosphino)ethane. ° Epoxides are converted to 1,2-diketones with Bi, DMSO, O2, and a catalytic amounts of Cu(OTf)2 at 100°C. a,p-Epoxy ketones are also converted to 1,2-diketones with a ruthenium catalyst or an iron catalyst. Epoxides with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of a ZnBr2 " or Tb(OTf)3 catalyst to give a y-hydroxy ketone. 

The reaction has also been carried out on a-hydroxy ketones and on a,p-epoxy ketones, which give p-hydroxy acids.The fact that an epoxide gives a reaction analogous to a halide indicates that the oxygen and halogen are leaving groups in a nucleophihc substitution step. 

A special reaction type involves the a,p-epoxy ketone to alkynone fragmentation, often cited as the Eschenmoser fragmentation . First published by Eschenmoser, and a little later and independently by Tanabe, the utility of this fragmentation for the synthesis of open-chained or cyclic alkynones (Scheme 3) is obvious. 

Shibata, I., Yamasaki, H., Baba, A., Matsuda, H. Stereoselective synthesis of a,P-epoxy ketones by the Darzen s reaction with methyl N-ethyl-N-(tributylstannyl)carbamate. Syrr/etf 1990, 490-492. 

Schreiber, J., et al. Synthesis of acetylenic carbonyl compounds by fragmentation of a,P-epoxy ketones with p-tolylsulfonylhydrazine. Helv. Chim. Acta 1967, 50, 2101-2108. 

Eelix, D., Schreiber, J., Ohioff, G., Eschenmoser, A. Synthetic methods. 3. a,P-Epoxy ketone->alkynone fragmentation. I. Synthesis of exaltone and ( )-muscone from cyclododecanone. Helv. Chim. Acta 1971, 54, 2896-2912. 

Stork, G., Williard, P. G. Five- and six-membered-ring formation from olefinic a,P-epoxy ketones and hydrazine. J. Am. Chem. Soc. 1977, 99, 7067-7068. 

Epoxides. Allylstannanes react under the influence of Pbl -HMPA with carbonyl compounds such as a,P-epoxy ketones and a-bromoketones give epoxy products. On the other hand, the reaction of l-chloro-3-tributylstannyl-l-propene with aldehydes leads to vinyl-epoxides. 

Aryl ethyl ethers are deethylai exposure to microwaves in the pres of selectivity by the addition of eth Palladium halide complexed to haloarenes with powdered NaCN ii Olefiturtions. Vinylogation 1,3-dioxolan-2-ylmethyltriphen> Ipl feasible. Similarly, asymmetric Ej been induced by RbOH in the pte Oxidations and reductions. benzylamines to benzamides with aldehydes can be carried out in tolu Epoxidation of various alken phase-transfer conditions using so economical and environmentally I a,P-epoxy ketones are deoxj H,NC(=NH)SO,H under phase-tnu... 

Dihydroxy allenes are generated from ketoenes and ethynyl epoxides. a,P-Epoxy ketones undergo reductive cleavage but the P-hydroxy ketones thus obtained can react further, for example with an e, -double bond to give cyclic 1,3-diols. Note that the double bond does not have to be activated, and furthermore, a silylalkyne moiety and a tricarbonylchromium-complexed arene can play the same role, although in the latter case the net result is a cine-substitution. 

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