Oxidation of Unsaturated Ketones

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]. 

3-Cyclohexen-l-one oxide is obtained from 2-cyclohexen-l-one on treatment with hydrogen peroxide [151] or rert-butyl hydroperoxide [220] (equation 438). 1,4-Naphthoquinone is oxidized with sodium [691] or cal- 

In a-ionone, peroxybenzoic acid and peroxyphthalic acid epoxidize solely the endocyclic double bond to give 3,4-epoxy-a-ionone in 96.5 and 66% yields, respectively [299]. Alkaline hydrogen peroxide, on the other hand, epoxidizes only the double bond conjugated with carbonyl to give a 28-31% yield of a-ionone-ot, p -epoxide [332] (equation 440). 

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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. 

The results of oxidation of unsaturated ketones depend on the position of the double bond with respect to the carbonyl group and on the oxidant. 

Oxidation of unsaturated ketones such as mesityl oxide, methyl vinyl ketone, isopropenyl methyl ketone, chalcone, and 2-cyclohexenone to the corresponding epoxides can also be effected by tert-butyl hydroperoxide in the presence of Triton B 50 and similar conditions have been used for epoxidation of [Pg.280]

Sn-beta (68,151,235) shows extraordinary chemoselectivity for the BV oxidation of unsaturated ketones using aqueous hydrogen peroxide as... 

Photolysis of epoxy ketone 54, obtained upon oxidation of unsaturated ketone 53 with m-chloroperbenzoic acid (MCPBA) in dry benzene, afforded the aldehydoketene 55. The ketene cis-55, firstly undergoes photochemical isomerization to the trans-isomer on prolonged irradiation, and then undergoes an intramolecular [4 - - 2] cycloaddition on heating to afford the bicyclic lactone 56 (Scheme 19) (1978JOC3314). 

V.C.8.1. Alkenes and Alcohol Functions. Although TS-1 and other titanosi-licates oxidize alcohols to the corresponding aldehydes and ketones, the rates are suppressed in the presence of compounds containing C=C bonds. CH3OH, for example, is not oxidized at all during epoxidations of alkene reactants. Higher alcohols, however, are partially oxidized. The oxidation of unsaturated alcohols in the presence of TS-1 is shown in Table XVII (193). 

More recently, the Noyori group described an organic solvent- and haUde-free oxidation of alcohols with aqueous H202 . The catalyst system typically consists of Na2W04 and methyltrioctylammonium hydrogen sulfate, with a substrate-to-catalyst ratio of 50-500. Secondary alcohols are converted to ketones, whereas primary alcohols, in particular substituted benzyUc ones, are oxidized to aldehydes or carboxylic acid by selecting appropriate reaction conditions This system also catalyzed the chemoselective oxidation of unsaturated alcohols, the transformation exemplified in equation 65, with a marked prevalence for the hydroxy function. 

The efficient formation of diaryliodo-nium salts during the electrolysis of arylio-dides has been reported by Peacock and Fletcher [166]. The electroiodination of a 3D-aromatic molecule, dodecahydro-7,8-dicarba-nido-undecaborate has also been reported [167]. The iodination (and bromi-nation) of dimedone has been reported to yield 2-iododimedone, which formally is an electrophilic substitution reaction [123]. In a similar process, the indirect electrochemical oxidation of aliphatic ketones in an alkaline Nal/NaOH solution environment has been shown to yield a,a-diiodoketones, which rapidly rearrange to give unsaturated conjugated esters [168]. Dibenzoylmethane has been converted into dibenzoyliodomethane [169]. Terminal acetylenes have been iodinated in the presence of Nal. However, this process was proposed to proceed via oxidation of the acetylene [170]. 

Fatty Acid Oxidation Yields Large Amounts of ATP Additional Enzymes Are Required for Oxidation of Unsaturated Fatty Acids in Mitochondria Ketone Bodies Formed in the Liver Are Used for Energy in Other Tissues Summary of Fatty Acid Degradation Biosynthesis of Saturated Fatty Acids... 

Nomially, dry solvents are employed in the oxidation of unsaturated alcohols with DDQ. This is done because DDQ is decomposed by water.94c On the other hand, the use of wet solvents may not be deleterious, as a mixture of CH2CI2 and water is routinely employed for the deprotection of p-methoxybenzyl (PMB)10S and 3, 4-dimethoxybenzyl (DMPM)106 ethers with DDQ, and, when this deprotection leads to an unsaturated alcohol, a prolonged reaction allows a successful oxidation of the alcohol to a ketone.107... 

Another situation is observed in the case of oxidative cyclization of unsaturated ketones 58 with phenylhydrazine 33 in the presence of iodine [61]. The reaction passes through the initial formation of pyrazoline 59, which is oxidized in the presence of iodine to pyrazole 60 (Scheme 2.14). 

In [210, 211] the solid-phase reaction of unsaturated ketones and anilines on a surface of silica gel in the presence of indium chloride under microwave irradiation was described. The library consists of 15 quinolines in yields of 55-87% which were generated quickly and characterized. Ranu et al. [211] showed that dihydro derivatives of qiunolines (e.g., 270 and 273) can also be synthesized, but in this case one component of the reaction must be a 4,4-disubstituted methyl vinyl ketone, for example, mesityl oxide 52 or l-(2-methylcyclopent-l-enyl)ethanone 272 (Scheme 3.75). 

Exercises 15 and 17 show that rule 2 should be applied cautiously in nucleophilic reactions of unsaturated ketones. This is true also for electrophilic reactions for example, osmium tetraoxide selectively oxidizes 40 at the isolated double bond (yield -90%),52 despite the fact that its HOMO is lower in energy. 

Like its homogeneous analogue, 3 shows high activity in both the oxidation of unsaturated hydrocarbons and the transfer hydrogenation of ketones, representative examples being shown in Table 1. For comparative purposes, reported yields for the analogous reactions using 6 are also shown. 

Ishiyama et al. observed that reduced cobalt oxide or Raney Co is the most selective of the transition metals investigated for the preferential hydrogenation of unsaturated ketones to unsaturated alcohols.145 146 The hydrogenation of unsaturated ketones 18a, 18f, and 18g over cobalt catalyst gave the corresponding unsaturated alcohols in 100%... 

Oxidation of unsaturated intermediate 153 with RuCl3/NaI04 <1998JA5943> or its ozonolysis <1997TA2921> resulted in the ketone dioxonine 21 (Scheme 28). 

In the first approach shown in Scheme 9, ketoester 77 was alkylated successively with 4-bromobutene and 1,3-dibromopropene. After decarboxylation, 78 was converted into iV-aziridinylimine 79 in good yield. The pivotal radical cyclization reaction proceeded smoothly to produce a mixture of isomeric propellane compounds 80, which was purified after the epoxidation step. For the synthesis of modhephene, the mixture of epoxides was rearranged into the corresponding allylic alcohols 81 and then the allylic alcohols were oxidized, giving a separable mixture of unsaturated ketones 82a and 82b. The major product 82a possessed the correct stereochemistry of the methyl group of modhephene. Since 82a had already been converted into modhephene, a formal total synthesis of dZ-modhephene has thus been completed. The isomeric ratio of 80 reflects the stereoselectivity during the radical cyclization reaction. The selectivity was very close to the ratio reported by Sha in his radical cyclization reaction. ... 

Wiberg and Saegebarth also obtained fair yields of cyclopentane-13-dialddiyde from the oxidation of bicyclo[2.2.1]hept-2-ene under mild conditions (equation 18). However, the oxidation of unsaturated tertiary carbons to the corresponding ketones is much more typical. The reaction depicted in equation (19), where a trisubstituted double bond is cleaved to a ketone and a carboxylic acid, is exertqrlaty of the products that are normaUy produced when alkenes react with aqueous permanganate. ... 

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... 

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. 

Oxidation with chromium(VI) oxide, t-butyl chromate or chromyl chloride may also take place at the allylic position with the formation of unsaturated ketones. The alkene may enhance the rate of displacement of an allylic halide, and the reaction may even take place with the participation of the double bond, so leading to an allylic rearrangement (Scheme 3.25). 

Quinones are cyclic unsaturated diketones in which the carbon atoms are derived from the oxidation of an aromatic system. Although the underlying reactivity of quinones is that of unsaturated ketones (cyclohexadi-enediones), it is tempered by this relationship to aromatic compounds and in particular by their reduction to dihydroxyphenols (quinols). 

Although Smh is more chemoselective than traditional dissolving metal reagents, it does react with sulfoxides, epoxides, the conjugated double bonds of unsaturated ketones, aldehydes and esters, alkyl bromides, iodides and p-toluenesulfonates. It does not, however, reduce carboxylic acids, esters, phosphine oxides or alkyl chlorides. In common with most dissolving metal systems, ketones with an a-hetero substituent suffer loss of the substituent rather than reduction of the carbonyl group. ... 

The combination of silicon hydrides and a Pd° catalyst is essentially useless for reduction of electron-deficient alkenes. However, addition of catalytic amounts of zinc chloride creates a new three-component mixture that enables rapid conjugate reduction of a,p-unsaturated ketones and aldehydes. In fact, soluble palladium complexes of various oxidation states were equally efficient catalysts, an obvious practical advantage of this approach. The generality of the method with respect to the substrate, its experimental simplicity, and its easy applicability to large-scale work make it a method of choice for conjugate reduction of unsaturated ketones and aldehydes. 

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 oxidative cleavage of unsaturated ketones takes place under the same conditions as that of alkenes or other unsaturated derivatives. The fate of the primary fission product depends on the position of the double bond with respect to the carbonyl group and on the subsequent reactions. Ozonization of A -cholestenone in acetic acid and ethyl acetate, followed by treatment with 30% hydrogen peroxide, gives a keto acid, evidently resulting from the decomposition of the primarily formed diketo acid (equation 444) [1176]. 

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