Dioxirane, chiral

The epoxidation of nonfunctionalized alkenes may also be effected by chiral dioxiranes. These species, formed in situ using the appropriate ketone and potassium caroate (Oxone), can be formed from C-2 symmetric chiral ketones (29)[93], functionalized carbohydrates (30)[94] or alkaloid derivatives (31)[95]. One example from the laboratories of Shi and co-workers is given in Scheme 19. 

Among many other methods for epoxidation of disubstituted E-alkenes, chiral dioxiranes generated in situ from potassium peroxomonosulfate and chiral ketones have appeared to be one of the most efficient. Recently, Wang et /. 2J reported a highly enantioselective epoxidation for disubstituted E-alkenes and trisubstituted alkenes using a d- or L-fructose derived ketone as catalyst and oxone as oxidant (Figure 6.3). 

Epoxidation of alkenes can be effected by potassium persulphate. When the oxidation is conducted in the presence of chiral trifluoroketones, chiral oxiranes (ee 12-22%) are produced [14]. The chirality appears to be achieved via the initial reaction of the persulphate with the ketone to generate chiral dioxiranes, which then interact with the alkenes. 

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]. 

Yang/Shi (1996), Denmark (1997) chiral dioxiranes and chiral oxaziridinium ions H-Bond Cataiysis... 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

Shi and coworkers developed a method using silyl enol ethers and in situ generated chiral dioxirane derivatives. Lopp and coworkers could develop an asymmetric dihydroxy lation method for racemic 2-hydroxymethyl ketones 202a-c, using TBHP as oxygen source in combination with the Sharpless catalytic system Ti(OPr-i)4/DET, yielding... 

The epoxidation of unfunctionalized alkenes by dioxiranes was investigated mainly for mechanistic purposes P . Some representative cases are collected in Scheme 3. Although such unfunctionalized alkenes have not been studied as intensively as the other olefin types, the recent asymmetric epoxidations by dioxirane were performed mainly on this substrate class (vide infra) J P. For this purpose, in-situ-generated dioxiranes in carefully buffered aqueous solutions had to be used, since the chiral dioxiranes cannot be readily isolated. Fortunately, the epoxides of unfunctionalized alkenes are more resistant to... 

These few cases indisputably illustrate the synthetic value of such enantioselective CH insertions, a challenging area of dioxirane chemistry that demands more intensive research activity. For that purpose more reactive and more effective chiral dioxiranes must be designed. 

Chiral ketone-catalyzed asymmetric epoxidation has received intensive interest since the first reported by Curci et al. in 1984. The reaction is performed with oxone (potassium peroxomonosulfate) as the primary oxidant which generates the chiral dioxirane catalytic species in situ, which in turn, transfers the oxygen... 

Chiral dioxiranes, generated in situ from chiral ketones and Oxone , are promising reagents for the asymmetric epoxidation of unfunctionalized alkenes. Chiral ketone catalysts that are easily accessible in both enantiomers are targets for development. 

Chiral dioxirane that was also generated in situ from the corresponding ketone and Oxone was first used for catalytic asymmetric epoxidation by Curd et al., although enantioselectivity was low [7], Later, Yang et al. disclosed that this approach had a bright prospect if used with a combination of Oxone and chiral ketone 3 [8]. Ketone 3 is converted into the corresponding dioxirane in situ, which epoxidizes olefins (Scheme 6B.5). 

Figure 6B.4. Mechanism for asymmetric induction by chiral dioxiranes.

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

A series of meso-dihydrobenzoins was also subjected to oxidative desymmetrization. Three equivalents of the chiral ketone 88 again provided the chiral dioxirane as the active species [138, 139]. As shown in Table 10.14, enantiomeric excesses up to 60% were achieved. In addition to the meso diols themselves, acetonides also proved suitable substrates in two instances (Table 10.14). 

Trisubstituted cyclic alkenes have been kinetically resolved via a chiral dioxirane (4), generated in situ from the ketone and Oxone. A sequential desymmetrization and kinetic resolution of cyclohexa-1,4-dienes has also been achieved. The observed stereochemical results have been rationalized on the basis of a spiro-planar transition state model.93... 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

Fig. 4.104 Catalytic cycle of asymmetric epoxidation via chiral dioxiranes.

Chiral dioxiranes continue to be examined for the synthesis of enantioenriched epoxides. An interesting report details the use of a dioxirane derived from oxazolidinone 7 for the... 

The epoxidation of alkenes is accelerated in fluorinated alcohol solvents the factors responsible for this rate acceleration have been examined <2006JA8421, 2006JA13412>. Chiral dioxiranes can now be used in a catalytic sense for the synthesis of vinyl m-epoxides <2006AGE4475>. 

Recently, Wong and Shi have examined the effect of substitution in the 6- or 8-position in the asymmetric epoxidation of chromenes by chiral dioxiranes derived from ketones 52 and 53. Up to 93% ee was achieved, with higher ee s obtained when substrates are substituted at the 6-position <2006JOC3973>. 

Shing et al. have prepared a number of arabinose (commercially available in both enantiomeric forms) derived 4-uloses and examined their potential as chiral dioxirane precursors. The most successful of these ketones was found to epoxidize phenylcyclohexene in 92% yield and 85% ee (Scheme 24) <2003TL9225>. 

The asymmetric epoxidation of electron-deficient olefins, particularly a,/3-enones, including the use of chiral metal hydroperoxides, asymmetric phase-transfer methods, polyamino acid catalysts, and the chiral dioxiranes, has been reviewed <2000CC1215>. 

Advances in the chemistry of ring-fused oxiranes during the period under review (1995-2007) principally involve new or expanded methods of asymmetric synthesis including metallosalen-catalyzed, and chiral dioxirane- and iminium salt-mediated processes. Developments in the reactivity of such species include extensive work in the area of epoxide ring opening and advances in the chemistry of lithiated epoxides. 

Yang et al. have applied C2-symmetric chiral dioxiranes, generated in situ from corresponding chiral ketones 75 and Oxone, for asymmetric epoxidation of trans-olefins and trisubstituted olefins (33-87% ee) <1996JA491, 1996JA11311>. 

Moreover, in the same work, the 0-labeling experiment confirmed chiral dioxiranes to be the intermediates in chiral ketone-catalyzed epoxidation reactions. Murray et al. reported the synthesis and structural characterization of cyclooctatetraene tetraepoxides 90 and 91 through the oxidation of cyclooctatetraene with excess of DMDO lb... 

---