Dioxiranes methyl trifluoromethyl

The synthetically most useful method for the preparation of dioxiranes is the reaction of appropriate ketones (acetone, trill uoroacetone, 2-butanone, cyclohexanone etc.) with Caroate, commercially available as the triple salt of potassium monoperoxysul-fate (KHSOs). The catalytic cycle of the dioxirane formation and oxidation is shown in Scheme 1 in general form. For acetone as the ketone, by simple distillation at a slightly reduced pressure ca 100 torr) at room temperature ca 20 °C), Jeyaraman and Murray successfully isolated dimethyldioxirane (DMD) as a pale yellow solution in acetone (maximally ca 0.1 M). This pivotal achievement in 1985 fomented the subsequent intensive research activity in dioxirane chemistry, mainly the synthetic applications but also the mechanistic and theoretical aspects. The more reactive (up to a thousandfold ) fluorinated dioxirane, methyl(trifluoromethyl)dioxirane (TFD), was later isolated in a similar manner by Curd, Mello and coworkers". For dioxirane derived from less volatile ketones, e.g. cyclohexanone, the salting-out technique has been developed by Murray and coworkers to obtain the corresponding dioxirane solution. 

This was also accomplished with BaRu(0)2(OH)3. The same type of conversion, with lower yields (20-30%), has been achieved with the Gif system There are several variations. One consists of pyridine-acetic acid, with H2O2 as oxidizing agent and tris(picolinato)iron(III) as catalyst. Other Gif systems use O2 as oxidizing agent and zinc as a reductant. The selectivity of the Gif systems toward alkyl carbons is CH2 > CH > CH3, which is unusual, and shows that a simple free-radical mechanism (see p. 899) is not involved. ° Another reagent that can oxidize the CH2 of an alkane is methyl(trifluoromethyl)dioxirane, but this produces CH—OH more often than C=0 (see 14-4). ... 

Aryl-l,2,4,5-tetrazines are oxidised by methyl(trifluoromethyl)dioxirane to their previously unknown iV-oxides 96. NMR studies have shown that N-l is oxidised regioselectively <96X2377 >. 

CgoO (1) can also be prepared by allowing toluene solutions of CgQ to react with dimethyldioxirane (Scheme 8.3) [28], The so-obtained product is identical to that prepared by photochemical epoxidation [15], Upon treatment of CgQ with dimethyldioxirane, a second product is formed simultaneously (Scheme 8.3), which was identified to be the 1,3-dioxolane 6. Upon heating 6 in toluene for 24 h at 110 °C, no decomposition could be observed by HPLC, implying that 1 and 6 are formed by different pathways. Replacement of dimethyldioxirane with the more reactive methyl(trifluoromethyl)dioxirane allows much milder reaction conditions [29]. At 0 °C and a reaction time of only some minutes this reaction renders a CgQ conversion rate of more than 90% and higher yields for CgoO as well as for the higher oxides. 

FIGURE 13. B3LYP/6-311- -G(3df,2p)-optimized stractures of dioxirane (DO), dimethyldioxirane (DMDO) and methyl(trifluoromethyl)dioxirane (TFDO). Bold numbers for DO are experimental microwave-stractural data. ... 

Part of the mystique surrounding the often assumed high reactivity of dioxiranes stems from the observation that dioxiranes such as methyl(trifluoromethyl)dioxirane (TFDO) are capable of oxidizing saturated hydrocarbons to their alcohols at relatively low temperatures in high yields and with impressive stereoselectivities (equation 8). 

The NMR data of dimethyldioxirane 36 have already been reviewed, but the closely related spectrum of methyl(trifluoromethyl)dioxirane 37 was not reviewed and a comparison of its experimental data with the computed values for the parent dioxirane 38 and of difluorodioxirane 39 can be of interest. Experimental and computed data are gathered in Table 9. 

Methyl(trifluoromethyl)dioxirane (TFD) was isolated by Curd and coworkers . 

Two new reactive, very powerful organic peroxides, dimethyldioxirane and methyl(trifluoromethyl)dioxirane (4), have been introduced.81-83 The latter is more reactive and can be used more conveniently.84 85 Acyclic alkanes give a mixture of isomeric ketones on oxidation with methyl(trifluoromethyl)dioxirane,84,85 while cyclohexanone is the sole product in the oxidation of cyclohexane (99% selectivity at 98% conversion).85 With the exception of norbomane, which undergoes oxidation at the secondary C-2 position, highly selective tertiary hydroxylations can be carried out with regioselectivities in the same order of magnitude as in oxidations by peracids.85-87 A similar mild and selective tertiary hydroxylation by perfluorodialkyloxaziridines was also reported.88 Oxidation with dioxiranes is highly stereoselective 85... 

An efficient oxidizing reagent for oxyfunctionalization of saturated hydrocar bons, methyl(trifluoromethyl)dioxirane, can be prepared from aqueous potassium peroxomonosulfale and 1,1,1-tnfluoropropanone [752] The reaction of this reagent with adamantane gives the corresponding tris(hydroxy)adamantane in high yield [755] (equation 80)... 

Dimethyldioxirane (7) and methyl(trifluoromethyl)dioxirane (8) are the two most effective reagents mainly used in preparative organic chemistry. 

R. Mello, M. Fiorentino, C. Fusco, and R. Curci, Oxidations by methyl (trifluoromethyl)-dioxirane. 2-Oxyfunctionalization of saturated hydrocarbons, J. Am. Chem. Soc., Ill (1989) 6749-6757. 

Curci, R. On the isolation and characterization of methyl(trifluoromethyl)dioxirane./. Org. Chem. 1988, 53, 3890-3891. 

Oxygenation of 2-substituted adamantanes with methyl(trifluoromethyl)dioxirane showed a reaction constant, p = -2.31, consistent with a strongly electron-demanding transition state. Analysis of the effect of solvents on the rate yielded a positive regression coefficient with Dimroth-Reichardt Ej solvent polarity parameter. A mechanism involving an electrophilic O atom insertion has been postulated for the formation of alcohols and carbonyl compounds.201... 

DMD is suitable for the oxidation of most substrates with substances that are resistant to oxidation, however, the more reactive but also more expensive methyl (trifluoromethyl)dioxirane (TFD) is necessary. The oxidation is stereoselective for both dioxiranes and proceeds with complete retention of configuration at the oxidized carbon atom (Scheme 1) [20-22]. The reactivity follows the usual order of electrophilic oxidation-primary < secondary < tertiary < benzylic < allylic C-H bonds. Except for tertiary C-H bonds, which produce the oxidatively inert tertiary alcohols, further oxidation of the primary product (an alcohol) to a ketone or aldehyde (the latter is readily further oxidized to the corresponding acid) is possible, because the a-hydrogen of the alcohol is usually more reactive than that of the unactivated alkane, especially for allylic C-H bonds. 

Scheme 1. C-H Insertions by dimethyldioxirane (DMD) and methyl(trifluoromethyl)dioxirane (TFD).

E)-3-Arylidenethiochroman-4-oncs possess thioether and oi,[)-unsaturatcd ketone functionalities both of which are susceptible to oxidation by DMD. In fact, chemoselective oxidation at sulfur is observed with a separable mixture of the sulfoxide and sulfone being produced in >5 1 ratio. A similar situation holds for the related thioflavanones. Epoxidation of the alkenic double bond in the thiochromanone 1,1-dioxides alone can be achieved using methyl(trifluoromethyl)-dioxirane (Scheme 65) <1994T13113>. However, reaction of NaOCl with 3-arylidenethioflavanones gives the epoxide and subsequent oxidation with DMD then gives a mixture of the sulfoxide and sulfone <2003MRC193>. 

The most commonly employed ketone is acetone, however a more powerful alternative is methyl trifluoromethyl ketone.148 The source of the peroxymonosulfate is either the triple salt (2KHSO5-K.HSO4-K.2SO4) or neutralized Caro s acid (nominally NaHS05).149 The scope of the method is limited by the tendency of many ketones to undergo Baeyer-Villiger oxidation in the presence of dioxirane formation (Figure 2.47). 

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