Ketones, unsaturated Baeyer-Villiger reaction

Reaction with a, (-unsaturated ketone. Attempted Baeyer-Villiger reaction of 1, readily available from methyl ricinoleate, with tn-chloroperbenzoic acid under usual conditions unexpectedly leads to the known furanoid fatty acid (3), although in only 25% yield. When the epoxidation is conducted under milder conditions, the expected epoxide (2) is obtained readily. When this epoxide is refluxed in chloroform containing trace amounts of hydrogen chloride, 3 is obtained in 80% yield. This reaction may be relevant to biosynthesis of natural furanoid fatty acids such as 3. ... 

Peracids may epoxidize alkenes faster than they take part in Baeyer-Villiger reactions, so unsaturated ketones are not often good substrates for Baeyer-Villiger reactions. The balance is rather delicate. The two factors that matter are how electrophilic is the ketone and how nucleophilic is the alkene You might like to consider why this reaction does work, and why the C=C double bond here is particularly unreactive. 

Baeyer- Villiger reaction the oxidation of a ketone to an ester or lactone, nsnally by means of a peroxy acid Enone an unsaturated ketone, usually a, f relative to the carbonyl group... 

Peroxyphthalic add, o-C,iH4(C02H)C03H, is obtained from phthalic anhydride and hydrogen peroxide [330] or sodium hydrogen peroxide [331] and is applied usually in ethereal solutions to epoxidations [330, 332], the Baeyer-Villiger reaction [333, 334], and oxidations of sulfides to sulfoxides [163, 335] and sulfones [336, 337]. The oxidation of sulfides to sulfones takes precedence over epoxidation, as evidenced by the fact that unsaturated ketone thioacetals are oxidized to unsaturated disulfones [337]. 

Most of the discussion of the Baeyer-Villiger reaction of unsaturated ketones is devoted to a,(3-unsaturated ketones, such as mesityl oxide [254], benzalacetophenone [307, and, especially, benzalacetone [25S], The oxidation of ionones does not involve the Baeyer-Villiger reaction and is, therefore, discussed elsewhere (see equations 440 and 441). 

The Baeyer-Villiger reaction of hydroxy ketones and unsaturated diketones is very common in steroids, where it occurs preferentially at the keto group on C-17 and leaves the carbonyls in position 3 intact. 

Oxidations of unsaturated ketones affecting solely the carbonyl group were discussed in the section Baeyer-Villiger Reaction of Functionalized Ketones (equations 379-399). In this section, only such oxidations that add oxygen to the double bond will be described. 

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. 

Peroxy adds may epoxidize unsaturated ketones [299, 332], but a concomitant Baeyer-Villiger reaction is possible [254] (equations 389 and 391). Other ways of forming epoxy ketones are reactions with salts of hypochloric acid [691, 704] and with V-bromosuccinimide [746]. Mesityl oxide is converted into its epoxide, as shown in equation 437 [142, 220, 254, 746]. 

Epoxidation of the electron-deficient double bond in a,[3-unsaturated ketones may be complicated by the Baeyer-Villiger reaction, an oxidation involving the carbonyl group. 

By controlling reaction conditions and by proper choice of the peroxy acid, it is often possible to favor the Baeyer-Villiger reaction over epoxidation. An illustrative example of the usefulness of the Baeyer-Villiger reaction is the stereospecific, and regio- and chemoselective conversion of the unsaturated bicyclic ketone shown below to a cyclopentene containing three consecutive stereogenic centers. 

Since the polyleucine epoxidation conditions are only favourable for highly electron-deficient unsaturated systems (i. e. ketones), use of the Baeyer-Villiger oxidation subsequent to the epoxidation reaction allows access to the optically active epoxyesters. 

Two different modes of reaction have been reported for steroidal A -3-ketones 20). Potassium persulphate in sulphuric acid gave the 4 0xa"3 ketone (23), considered to arise by an initial Baeyer-Villiger oxidation to the unsaturated lactone (21) as an enol lactone of the C(g)-aldehyde (22) this could suffer further degradation through a second Baeyer-Villiger attack on the aldehyde group [64], Other. workers [6 ] used peroxytrifluoroacetic acid and obtained the 5a-carboxy--4"Oxa 3-ketone (25) and the bridged product (26), apparently derived by an internal aldol condensation of the intermediate lactone-aldehyde (24). 

Alkaline hydrogen peroxide reacts with a jS-unsaturated ketones by a different reaction sequence, exemplified by the behaviour of "A-nor-testosterone 27) [7 ]. The reagent first converts the steroid into the corresponding epoxy-ketone 28) by the mechanism discussed on p. 201, and only then brings about a Baeyer-Villiger oxidation of the ketone function to give the epoxy-lactone (29) as the major product. 

A combination of known reactions has been used for the a -alkoxycarbonylmethyl-ation of a/3-unsaturated ketones, (146), by photochemical [2 + 2] addition of ketene dimethyl acetal and subsequent Baeyer-Villiger oxidation to give a mixture of the expected lactone and the derived unsaturated acid, arising from hydrolysis of the lactone and dehydration. A final alkylation step serves to convert both compounds into the desired ester (147). The enol acetate of acetaldehyde can be used in place of the ketene, although here of course, an extra oxidation step is required. ... 

The epoxidation of the unsaturated ketone limits the scope of the reaction and impacts the yield, since a Baeyer-Villiger oxidation is competing. However, at a 100-kilogram scale, the yield ranges around 84%, based on 50% conversion of starting material. Another way around this problem is peracid epoxidation of the corresponding allyl alcohol, and oxidation with chromium trioxide the conversion is then quantitative. 

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