Epoxidation with alkaline hydrogen peroxide

Further progress in the use of ler -butyl hydroperoxide was made recently by Payne.1SlB -who conducted the reaction under carefully controlled pH conditions. Qimemaldhbyde, which had previously failed to yield the desired epoxide with alkaline hydrogen peroxide, gave this substance in good yield (Eq 81) when the reaction was tarried out at pll 8.C in methanol. 

The rules that apply to acyclic systems are also applicable to cyclic compounds with an exo-double bond. Thus 3-arylideneflavanones 1 were stereo selectively epoxidized with alkaline hydrogen peroxide and stereospecifically with 3-chloroperoxybenzoic acid20 and potassium hypochlorite21 and, similarly, 6-methoxyaurones 6 were stereoselectively epoxidized with alkaline hydrogen peroxide and stereospecifically with 2-chloroperoxybenzoic acid22. 

The selectivity of the epoxidation, in conjunction with the availability of optically active terpenes from natural sources, has resulted in the application of terpene epoxides as starting materials for the synthesis of several natural products. Both enantiomers of carvone, (10) and (ent-l0), have been used for the synthesis of methyl trans- and c/.v-chrysanthemates 15 and ent-15. i+Hsy Carvone (10) was converted into hydrochlorinated compound 13 and the methylated derivative 11, which were selectively epoxidized with alkaline hydrogen peroxide, and further converted into methyl trum-chrysanthcmate 15. The same route led from (— )-(/ )-carvone ent-10) to m-chrysanthemate ent-1543 ent-13 was converted to ( + )-a-3,4-epoxycaran-2-one 1644. 

In the final step of the total synthesis of ( + )-hirsutic acid C, enone 11 was epoxidized with alkaline hydrogen peroxide to give selectively epoxide 12, which was converted in situ to the final product72. 

The tricyclic enone 15 was epoxidized with alkaline hydrogen peroxide to give an inseparable mixture of a and / epoxides 16 and 17 in a ratio of 2 181. Ketone 18 was selectively epoxidized under similar conditions yielding epoxide 1982. 

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. 

The most dependable reagent for the epoxidation of unsaturated ketones is hydrogen peroxide, especially in alkaline media [142, 143, 149, 151]. Because the Baeyer-Villiger reaction is acid-catalyzed, it does not take place during epoxidations with alkaline hydrogen peroxide or its neutral derivatives, such as fe/ t-butyl hydroperoxide [220]. Most examples of epoxidation involve unsaturated ketones with conjugated double bonds. 

Alkaline Hydrogen Peroxide. ajS-Unsaturated ketones (123) were epoxidized with alkaline hydrogen peroxide to form 4/5,5/ -epoxyandrostane-6,17-diones (124). The presence of a 3j -hydroxy-group was found to be advantageous during epoxidation. Initial attempts to epoxidize zerumbone (125)... 

The reaction of perfluoroalkenes with alkaline hydrogen peroxide is a good general method for the preparation of the corresponding epoxides with the exception of the most reactive of the series, TFEO (eq. 6). 

Double bonds in a,/3-unsaturated keto steroids can be selectively oxidized with alkaline hydrogen peroxide to yield epoxy ketones. In contrast to the electrophilic addition mechanism of peracids, the mechanism of alkaline epoxidation involves nucleophilic attack of hydroperoxide ion on the con-... 

Thus, reaction of 3 -acetoxypregna-5,16-dien-20-one (48) with alkaline hydrogen peroxide produces the 16a,17a-epoxide in 95 % yield, and only a 2% yield of the 16, 17 -epoxide. ... 

Nonconjugated double bonds fail to react with alkaline hydrogen peroxide, e.g., see ref. 53, 54 and 56a. The 1,2-double bond of A " -3-ketones e.g., 61, reacts with alkaline peroxide to give the la,2a-epoxide in over 70% yield.""... 

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

Isophorone oxide has been prepared by the epoxidation of isophorone with alkaline hydrogen peroxide.2 3... 

Reports have appeared claiming that triperoxo vanadates behave as nucleophilic oxidants. In particular, triperoxo vanadium complexes, A[V(02)3]3H20 (A=Na or K), are proposed as efficient oxidants of a,-unsaturated ketones to the corresponding epoxide, benzonitrile to benzamide and benzil to benzoic acid, reactions which are usually carried out with alkaline hydrogen peroxide. Subsequent studies concerning the oxidation of cyclobutanone to 4-hydroxybutanoic acid, carried out with the above-cited triperoxo vanadium compound, in alcohol/water mixtures, clearly indicated that such a complex does not act as nucleophilic oxidant, but only as a source of HOO anion. 

Hori et have recently reported aza crown ether chiral quaternary ammonium salts for the epoxidation of ( )-chalcone with alkaline hydrogen peroxide as the terminal oxidant. The oxidation proceeded in high yield and good enantio-selectivity the success of the reaction depended on the length of the carbon chain on the nitrogen atom. These PTC catalysts are shown in Figure 1.50. 

Epoxides of a-methylene ketones f poxidulion of a-methylene ketones is generally unsatisfactory. The desired epoxides have usually been prepared by epoxidation of allylic alcohols followed by oxidation. Another route involves oxidation of salts of Munnich bases with alkaline hydrogen peroxide (equation 1). 

Diaryl-2-hydroxypropiophenones (607) are obtained from 4-hydroxychalcone and a reactive phenol on treatment with alkaline hydrogen peroxide in an epoxide-mediated coupling reaction. The ketones undergo a base-catalyzed a-ketol rearrangement to the isomeric l-hydroxypropan-2-ones (608) and acid-catalyzed ring closure provides a route to 4-arylflavan-3-ones (Scheme 231) (80JCS(Pl)1025). 

A large number of epoxid tions has been carried out with alkaline hydrogen peroxide and a variety of [Pg.356]

A novel process for the construction of benzodihydrofurans via a procedure involving a heteroatom-directed photoarylation provided the basis for another total synthesis of ( )-lycoramine (299) (Scheme 32) (167). Thus, 339, which was obtained from 1,3-cyclohexanedione in two straightforward steps, was converted to 340 by sequential treatment with LiAlH4, methyl chloroformate, and aqueous acid. Epoxidation of 340 with alkaline hydrogen peroxide followed by... 

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

Epoxidation of enones, enals, a,unsaturated esters.1 Epoxidation of these substrates is generally effected with alkaline hydrogen peroxide, but can also be effected with this new reagent with high stereoselectivity. 

Chemical reactions on - and Z-isomers usually give the same type of product, though often with different stereochemistry. The two geometrical isomers may also react at very different rates. For example, the reaction of these conjugated - and Z-enones with alkaline hydrogen peroxide gives in each case an epoxide, but with different stereochemistry and at very different rates. 

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