Ketone Unsaturated, epoxidation

The opening of epoxides with neighboring keto groups, accompanied by vinylogous jS-elimination, has already been mentioned (section V). This is an extension of the jS-elimination reactions which occur when a,p- or jS,y-epoxy ketones are opened with acid or base. a,jS-Epoxy ketones give a-substituted a,jS-unsaturated ketones [(162), for example], and j5,y-epoxy ketones give y-substituted a,jS-unsaturated ketones [(163), for example] ... 

Many selective epoxidations are possible with polyunsaturated steroids. In general, oc, -unsaturated ketones are not attacked by peracid, although linear dienones react slowly at the y,5-double bond. Aw-Chloroperbenzoic acid is the reagent of choice for this reaction.When two isolated double bonds are present in the steroid nucleus, e.g. (27) and (30), the most highly substituted double bond reacts preferentially with the peracid. Selective epoxidation of the nuclear double bond of stigmasterol can likewise be achieved.However, one exception to this general rule has been reported [See (33) (34)]. ... 

The lack of strong ultraviolet absorption by oxiranes is particularly useful for monitoring the epoxidation of a, -unsaturated ketones. 

Epoxidation of a, -Unsaturated Ketones with Alkaline Hydrogen Peroxide ... 

Due to the high reactivity of sulfonium ylide 2 for a,P-unsaturated ketone substrates, it normally undergoes methylene transfer to the carbonyl to give the corresponding epoxides. However, cyclopropanation did take place when 1,1-diphenylethylene and ethyl cinnamate were treated with 2 to furnish cyclopropanes 53 and 54, respectively. 

Treatment of Na2pe(CO)4 with an acyl halide produces 143 that, when treated with an alkyl halide, gives a ketone or, when treated with an epoxide, gives an ot,P-unsaturated ketone. 

Sulfonic peracids (66) have also been applied recently to the preparation of acid sensitive oxiranes and for the epoxidation of allylic and homoallylic alcohols, as well as relatively unreactive a, p - unsaturated ketones. These reagents, prepared in situ from the corresponding sulfonyl imidazolides 65, promote the same sense of diastereoselectivity as the conventional peracids, but often to a higher degree. In particular, the epoxidation of certain A -3-ketosteroids (e.g., 67) with sulfonic peracids 66 resulted in the formation of oxirane products (e.g., 68) in remarkably high diastereomeric excess. This increased selectivity is most likely the result of the considerable steric requirements about the sulfur atom, which enhances non-bonded interactions believed to be operative in the diastereoselection mechanism <96TET2957>. 

Although hydrogenation of A-benzylideneaniline in the presence of 11 afforded the corresponding product (eq. 1 in Scheme 11), the a,(3-unsaturated ketone was converted into a mixture of unsaturated and saturated alcohols in the 42 56 ratio (eq. 2 in Scheme 11). Several substrates (nitrile derivatives, epoxides, esters, internal alkynes, and terminal alkenes), which are shown in Fig. 4, are not hydrogenated in this catalytic system. 

C. Reactions not involving P=0 or P=S Groups.—Enamine phosphine oxides (45) have been prepared by the addition of amines to 1-alkynyl-phosphine oxides, and the reactions of their anions with various electrophiles have been reported. - With ketones a Wittig-type reaction leads to the formation of a/3-unsaturated ketones, in 53—70% yield, while with epoxides cyclopropyl ketimines are formed. A Diels-Alder reaction of l-phenyl-A -phospholen-l-oxide (46) with 1,4-diacetoxybutadiene has been used in the preparation of l-phenyl-benzo[/>]phosphole (47), as... 

The introduction of various metal-catalyzed reactions, however, remarkably expanded the scope of the epoxidation of Q,.3-unsaturatcd ketones. Enders et al. have reported that a combination of diethylzinc and A-methyl-pseudoephedrine epoxidizes various o,. j-unsaturatcd ketones, under an oxygen atmosphere, with good to high enantioselectivity (Scheme 23).126 In this reaction, diethylzinc first reacts with the chiral alcohol, and the resulting ethylzinc alkoxide is converted by oxygen to an ethylperoxo-zinc species that epoxidizes the a,/3-unsaturated ketones enantioselectively. Although a stoichiometric chiral auxiliary is needed for this reaction, it can be recovered in almost quantitative yield. 

The epoxidation of electon-defident olefins using a nucleophilic oxidant such as an alkyl hydroperoxide is generally nonstereospecific epoxidation of both cis- and /nmv- ,/3-unsatii rated ketones gives the trans-epoxide preferentially. However, the epoxidation of cis-ofi-unsaturated ketones catalyzed by Yb-(40) gives civ-epoxides preferentially, with high enantioselectivity, because the oxidation occurs in the coordination sphere of the ytterbium ion (Scheme 26).132... 

In contrast to the epoxidation of a,/3-unsaturated ketones, the metal-catalyzed asymmetric epoxidations of o,/3-unsaturated esters are much more limited in number. Epoxidation of ethyl m-cinnamatc with Mn(salen) (26) has been reported to give a mixture of the corresponding cis-(93% ee) and trans-epoxides in a ratio of 4 1.133... 

Addition of benzotriazole to l-phenyl-2-aroylacetylenes gives a,/3-unsaturated ketones 221 in high yields. By treatment with dimethylsulfonium ylide, ketones 221 are converted to epoxides 222, Opening of the oxirane ring and electrophilic attack of the obtained tertiary carbocation on N-2 of the benzotriazole system leads to betaines 223 that consecutively eliminate formaldehyde to give triazapentalenes 224 (Scheme 28) <2004ARK(iii)109>. 

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

Biomimetic reactions should also be considered for the preparation of optically active cyanohydrins (using a cyclic dipeptide as catalyst) and also for the epoxidation of a, (3-unsaturated ketones (using polyleucine or congener as a catalyst). 

Chapters 4-6 present an overview and a comparison between the various existing strategies for asymmetric epoxidation of unfunctionalized alkenes, a, (3-unsaturated ketones and allylic alcohols. 

As a, (3-unsaturated ketones are electron-poor alkenes, they do not generally give epoxides when treated with peracids. They can be epoxidized with hydrogen peroxide which involves nucleophilic attack by HOO- to give the epoxy ketone (Figure 4.1). 

Bentley et al.m recently improved upon Julia s epoxidation reaction. By using urea-hydrogen peroxide complex as the oxidant, l,8-diazabicyclo[5,4,0]undec-7-ene (DBU) as the base and the Itsuno s immobilized poly-D-leucine (Figure 4.2) as the catalyst, the epoxidation of a, (3-unsaturated ketones was carried out in tetrahydrofuran solution. This process greatly reduces the time required when compared to the original reaction using the triphasic conditions. 

The asymmetric epoxidation reaction with polyleucine as catalyst may be applied to a wide range of a, 3-unsaturated ketones. Table 4.1 shows different chalcone derivatives that can be epoxidized with poly-L-leucine. The substrate range included dienes and tctracncs151. Some other examples were reported in a previous edition161 and by M. Lastcrra-Sanchcz171. 

Abstract In the first part of this mini review a variety of efficient asymmetric catalysis using heterobime-tallic complexes is discussed. Since these complexes function at the same time as both a Lewis acid and a Bronsted base, similar to enzymes, they make possible many catalytic asymmetric reactions such as nitroal-dol, aldol, Michael, Michael-aldol, hydrophosphonyla-tion, hydrophosphination, protonation, epoxide opening, Diels-Alder and epoxi-dation reaction of a, 3-unsaturated ketones. In the second part catalytic asymmetric reactions such as cya-nosilylations of aldehydes... 

The N-anthracenylmethyl ammonium catalysts 11 and 12 also proved to be very effective in the asymmetric epoxidation of a,p-unsaturated ketones utilizing aqueous sodium165,661 or potassium1671 hypochlorite solution as an oxidant. Protection of the hydroxyl group in the N-anthracenylmethyl ammonium salts may be essential to attain high enanti-oselectivities in the epoxidation165"671, and use 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... 

S. Arai, H. Tsuge, T. Shioiri, Asymmetric Epoxidation of a,p-Unsaturated Ketones under Phase-Transfer Catalyzed Conditions , Tetrahedron Lett. 1998,39,7563-7566. 

---