Dioxirane formation

By exploiting electrostatic field effects (unfavourable through-space charge-dipole repulsion) to increase the nucleophilic susceptibility of cyclohexanones, more efficient catalysts (16) and (17) for epoxidafion through in situ dioxirane formation have been designed. ... 

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. 

SCHEME 1. The catalytic cycle for dioxirane formation and its oxidation of the substrate (S)... 

When the reaction is carried out at pH 7-8, however, ketone 4 is consumed rapidly because of the undesired Bayer-Villiger (B.V.) reaction of the intermediary hydroxy peroxysulfonate, which competes with the desired dioxirane formation (Scheme 6B.7). The suppression of the undesired B. V. reaction is indispensable for performing the desired epoxidation in a catalytic manner. Shi et al. have found that alkaline reaction conditions accelerate the conversion of the hydroxy peroxysulfonate to dioxirane and the reaction can be carried out with a catalytic amount (0.3 equiv.) of chiral ketone (Fig. 6B.3) [11], Alkaline conditions also bring about enhance-... 

The epoxide formation is thought to proceed via Oxone-mediated dioxirane formation and inclusion of the aromatic moiety inside the cavity. The influence of the substrate binding inside the CD cavity was evaluated by inhibitory experiments with naphthalene-2-sulfonate, which is known to bind both a- and / -CD with good affinity. As expected, the addition of 2 equivalents of inhibitor to the reaction mixture resulted in a significant decrease in reaction rate. 

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). 

The explanation for these experimental results, i.e. the lack of label transfer, is that the tetrahedral species (A) resulting from the addition of HSOf to the carbonyl group is capable of epoxidation. Ring closure of (A) is likely to be the rate-determining step in dioxirane formation. This work is important from a synthetic viewpoint, since it is crucial in the development of chiral ketones for the catalytic asymmetric epoxidation and the design of probes of transition state stereoselectivities that the nature of the oxidizing species is understood. 

The same authors published a detailed report on the calculations of the oxygen insertion into unactivated C-H bonds by dioxiranes using DFT theory and on comparison of the transition structures for stepwise routes via radical pairs with the concerted pathway <2003JOC811>. The articles dealing with the mechanism of OH formation from ozonolysis of isoprene and a- and /3-pinene provide DFT and ab initio calculation results also for the dioxirane formation <2001CPL(358)171, 2002JA2692, 2005JCP114308>. 

The CBS-QB3, MCG3, RRKM/master equation, and transition-state theory (TST) calculations were made for a detailed analysis of cyclopropene ozonolysis, treating all possible conformers of all intermediates and transition structures (TSs). The TST rate constant indicated that approximately 90% of the reaction proceeded through the endo-TS. It was predicted that approximately one-third of activated syn Criegee intermediates (Cls) would cyclize to dioxiranes despite the fact that the barriers to dioxirane formation were higher than the barriers to the 1,4-hydrogen shift that would lead to vinyl hydroperoxides and "OH. This helped to reduce the predicted OH yield for cyclopropene ozonolysis to 44%. It was also predicted that approximately 20% of either the endo-primary ozonide (PO) or its syn Cl derivatives would isomerize to the exo-PO or anti Cls. ... 

The other oxidation reaction of ketones which has recently become important is that of dioxirane formation, described in section 9.3.3.4. 

Dioxiranes for alkene epoxidation may be prepared in situ from a catalytic amount of a ketone and Oxone (potassium peroxymonosulfate triple salt). )V,)V-Dimethyl-and A, A -dibenzylalloxans (20a) and (20b) (Figure 3) have been prepared and used as novel dioxirane catalysts for the epoxidation of a range of di- and tri-substituted alkenes in good to excellent yield. H2O2 (rather than the usual Oxone) has been successfully used as primary oxidant in asymmetric epoxidations with Shi s fructose-derived ketone (21) in acetonitrile. The ketone is converted into the dioxirane, which is responsible for epoxidation and the active oxidant responsible for dioxirane formation is proposed to be peroxyimidic acid formed by combination of H2O2 with acetonitrile. ... 

The oxidation of naphthalic acid (1,8-naphthalenedicarboxylic acid) by peroxide, rather surprisingly, does not proceed by formation of a cyclic peroxide but rather via a dioxirane [53] (a three-membered ring containing a carbon atom and a peroxide group). CL is observed from this reaction. 

Halogen substitution is expected to increase the electrophilicity of the carbenes, and in particular lh with four fluorine substituents is expected to be highly electrophilic and of unusual reactivity. All the carbenes le-g could be matrix-isolated by irradiation of their corresponding quinone diazides 2 in argon at 8-10 K.24 68,62 Again, the thermal reaction in (Vdoped matrices results in the formation of quinone oxides 7, which show the expected photochemical rearrangement to the spiro dioxiranes 8 and finally lactones 9. 

Tetra-n-butylammonium hydrogen sulphate facilitates the enantiomeric epoxida-tion of alkenes by persulphates in the presence of chiral ketones (10.6.8). The reaction proceeds via the initial formation of chiral dioxiranes [23]. 

---