Ketones unsaturated, Baeyer-Villiger oxidation

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. 

A high catalyst loading (typically 20-30 mol%) is usually required for the epoxidation with ketone 26 because Baeyer-Vilhger oxidation presumably decomposes the catalyst during the epoxidation. The fused ketal moiety in ketone 26 was replaced by a more electron-withdrawing oxazohdinone (32) and acetates (33) with the anticipation that these replacements would decrease the amount of decomposition via Baeyer-Villiger oxidation (Fig. 8) [71, 72]. Only 5 mol% (1 mol% in some cases) of ketone 32 was needed to get comparable reactivity and enantioselectivity with 20-30 mol% of ketone 26 [71]. Since dioxiranes are electrophilic reagents, they show low reactivity toward electron-deficient olefins, such as a, 3-unsaturated esters. Ketone 33, readily available from ketone 26, was found to be an effective catalyst towards the epoxidation of a, 3-unsaturated esters [72]. 

The reduction of the unsaturated ketone (560) can be controlled to give mainly the cw-cyclopentanone (561). Upon treatment with sodium hydroxide isomerization to the trans compound occurs. Both isomers undergo a Baeyer-Villiger oxidation to the corresponding tetrahydropyranones, of which the cis isomer is rather unstable (Scheme 213) (82GJC29). 

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. 

Fig. 14.35. Chemoselective oxidations of an unsaturated ketone the imido peracid A epoxidizes the C=C double bond, while the peracid B reacts with the C=0 double bond causing a Baeyer-Villiger rearrangement...

A number of variations on the system, including the use of the nitroxyl radical of TMP-HCl187 and of perbenzoic acid,188 have been described. Unsaturated substrates are converted to epoxyketones.187 By adding excess peracid, further conversion of ketones to esters via Baeyer-Villiger re-arrangement is possible. MCPBA may be used to oxidize sterically unhindered, acid-stable alcohols in the presence of hydrochloric acid using dimethylformamide or tetrahydrofuran solvents.189... 

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... 

The Baeyer-Villiger rearrangement of cyclohexanone and acetophenone with TS-I/H2O2 proved to be poorly selective [117]. Notably, Ti-P and Sn-P have different chemoselectivities in the oxidation of unsaturated ketones, leading selectively to corresponding epoxides and lactones, respectively [118]. The different oxidation pathways were attributed to the preferential adsorption of hydrogen peroxide on Ti-sites and of the carbonyl group on Sn-sites. 

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). 

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. 

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. 

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