Enones, 367. peroxides

The diol function of 130 was protected as its acetonide 131 (88 %). Next, the enone function was installed by a-selenation of the enoxysilane, followed by peroxide oxidation and elimination (57 % over two steps). Finally, the unsaturated ketone 132 was homologated by 1,4-addition of trimethylsilylmethyl magnesium chloride, trapping with chlorotrimethylsilane, and reoxidation, to afford the target 117 (88 %). 

Exposure of 93 to dry oxygen furnished the corresponding ethyl peroxide complex, which is highly active for the expoxidation of enones, and crystallizes dimeric with bridging Zn-O bonds.153... 

Isoxazolines 79, obtained from aromatic nitrile oxide cycloadditions to cyclohex-2-enone, reacted with nickel peroxide to give 3-aryl-6,7-dihydro[l] benzoisoxazol-4(5// )-ones 80. In contrast, the corresponding 2-bromocyclohex-2-enone underwent nitrile oxide cycloaddition, followed by dehydrobromination, to afford the regioisomeric 3-aryl-4,5-dihydro[l]benzoisoxazol-7(6//)-ones 81 (Scheme 1.23) (242). 

Cycloaddition of 5,6-dihydropyran-2-one with aromatic nitrile oxides leads to 3-aryl-3a,6,7,7a-tetrahydropyrano[3,4-d]isoxazol-4(47/)-ones 98. The latter react with nickel peroxide to give the corresponding dihydropyranoisoxazolones 99. Similar to 2-bromocyclohex-2-enone, 3-bromo-5,6-dihydropyran-2-one undergoes nitrile oxide cycloaddition, followed by dehydrobromination, to form regioi-someric 3-aryl-5,7-dihydropyrano 4,3-c/ isoxazol-7(4//)-ones 100 (Scheme 1.24) (242). 

Conjugate addition of RN02 to enones. Primary nitroalkanes and a, (3-enones when activated by alumina form conjugate addition products that are oxidized in situ by alkaline hydrogen peroxide to 1,4-diketones. A similar reaction of nitromethane with a vinyl ketone provides 1,4,7-triketones. 

Cyclic enone, 12 185 Cyclic ethers, 10 567, 569 12 663 polymerization, 14 271 Cyclic fatigue, in ceramics, 5 633-634 Cyclic gas generators, 6 786-787, 789, 827 Cyclic halides, 19 56 Cyclic hexakis(thio-l,4-phenylene), melt polymerization of, 23 705 Cyclic hydrocarbons, 13 687 Cyclic hydroxyalkyl alkyl peroxide, 18 454 Cyclic ion exchange operation, 14 408-413 Cyclic ketones, 12 176, 177 14 590-592. See also Cyclic 1,2-diketones physical properties of, 14 591t hydroxyalkyl hydroperoxides from, 18 450... 

One of the first synthetic applications of organoboranes in radical chemistry is the conjugate addition to enones (Scheme 23, Eq. 23a) and enals reported by Brown [58-61]. Addition to -substituted enones and enals are not spontaneous and initiation with the oxygen [62], diacetyl peroxide [63], or under irradiation [63] is necessary (Eq. 23b). A serious drawback of this strategy is that only one of the three alkyl groups is efficiently transferred, so the method is restricted to trialkylboranes derived from the hydroboration of easily available and cheap alkenes. To overcome this limitation B-alkylboracyclanes have been used but this approach was not successful for the generation of tertiary alkyl radicals [64,65]. 

Cyclic enones can be oxidatively cleaved by a range of reagents to yield keto acids. As ozonolysis can be quite hazardous for large-scale preparations with the build up of ozonides, the procedure has been modified using quaternary ammonium salts to catalyse the transfer of peroxide anion for a rapid oxidative work-up [32]. Two methods are available but, in the safer procedure (10.7.15.A), there is no effective build-up of the ozonide. 

Direct phase-transfer catalysed epoxidation of electron-deficient alkenes, such as chalcones, cycloalk-2-enones and benzoquinones with hydrogen peroxide or r-butyl peroxide under basic conditions (Section 10.7) has been extended by the use of quininium and quinidinium catalysts to produce optically active oxiranes [1 — 16] the alkaloid bases are less efficient than their salts as catalysts [e.g. 8]. In addition to N-benzylquininium chloride, the binaphthyl ephedrinium salt (16 in Scheme 12.5) and the bis-cinchonidinium system (Scheme 12.12) have been used [12, 17]. Generally, the more rigid quininium systems are more effective than the ephedrinium salts. 

Basic solid liquid two-phase conditions with f-butyl peroxide and N-benzylquininium chloride convert cyclohex-2-enone preferentially into the 2(S),3(S)-oxirane (20% ee) which, upon purification and treatment with hydrazine, yields (S)-cyclohex-2-enol [7]. This reaction contrasts with the direct reduction of cyclohex-2-enone to the /J-isomer by lithium aluminium hydride in the presence of quinine [20]. 

Metal alkyl peroxides can be used for the epoxidation of electron-deficient alkenes such as enones. The use of a combination of diethylzinc, oxygen, and A-methylephedrine gave epoxides in very high yield and generally high enantio-selectivity (Figure 11.8). " ... 

One or both of the disadvantages are Hkely to be overcome in due course. It is obvious that a clearer picture of the mechanism of the oxidation is mandatory before much progress can be made. Once it is understood how this very simple protein folds, in the presence of organic solvent, to form a chiral cavity or chiral surface that activates the peroxide and/or enone to accomplish the desired asymmetric oxidation then the reaction may be extended to other substrates, e.g. a, unsaturated esters, nitroalkenes, perhaps (under different conditions) electron-rich alkenes. 

The introduction of the double bond of rac-14 was performed by conversion of rac-13 into its a-phenylselenide, subsequent peroxide oxidation, and elimination. Following the synthesis reported by Mehta and Srinivas, an alkylative enone transposition was used as the last step towards irradiation... 

An alternative method for the epoxidation of enones was developed by Jackson and coworkers in 1997 , who utilized metal peroxides that are modified by chiral ligands such as diethyl tartrate (DET), (5,5)-diphenylethanediol, (—)-ephedrine, ( )-N-methylephedrine and various simple chiral alcohols. The best results were achieved with DET as chiral inductor in toluene. In the stoichiometric version, DET and lithium tert-butyl peroxide, which was generated in situ from TBHP and n-butyllithium, were used as catalyst for the epoxidation of enones. Use of 1.1 equivalent of (-l-)-DET in toluene as solvent afforded (2/f,35 )-chalcone epoxide in 71-75% yield and 62% ee. In the substo-ichiometric method n-butyllithium was replaced by dibutylmagnesium. With this system (10 mol% Bu2Mg and 11 mol% DET), a variety of chalcone-type enones could be oxidized in moderate to good yields (36-61%) and high asymmetric induction (81-94%), giving exactly the other enantiomeric epoxide than obtained with the stoichiometric system (equation 37). 

Although arteflene 5 is not a 1,2,4-trioxane, its mechanism of action is believed to be very similar to trioxanes dne to the presence of the peroxide bond. Indeed, when radioactive C-arteflene was incnbated with P. falciparum, several alkylated parasitic proteins were identified . The O Neill gronp carried out the first iron(II) degradation studies of arteflene using iron(II) chloride in aqneons acetonitrile they isolated enone 63a (in tandem with radical 63b) and diol 64a (Scheme 19A). The degradation with heme (generated from hemin chloride by A-acetylcysteine) was observed to be slower, but afforded the same products although in different ratio. 

The proposed mechanism for the degradation involves SET to the peroxide resulting in homolytic cleavage of the 0—0 bond. An Ol-centred radical led to the formation of the enone, while an 02-centred radical afforded the diol. 

The product (6-2) from the reaction of thebaine with hydrogen peroxide can be viewed as the result from fromal 1,4 addition of two hydroxyl groups across the diene. The perspective depiction of thebaine reveals that the addition in fact occurs at the far more open face of the molecule. The product from this oxidation incorporates a new hydroxyl group at the 14(3 position and a hemiacetal at the 6 position. Treatment with a nuld acid leads to the hydrolysis of this last function and the formation of enone (6-3). 

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