Epoxidation with ketone catalysts

Alkenes can be epoxidised by dioxiranes, and this process can be achieved enan-tioselectively if an enantiomerically pure dioxirane is employed. Since 

The choice of ketone is governed by its ability to form a dioxirane quickly (an electron withdrawing group in the a-position is helpful) and not to be prone to either racemisation or Baeyer-Vilhger oxidation. The intermediate dioxirane must also be willing to donate an oxygen to the alkene substrate. 

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Chiral Ketone and Iminium Catalysts for Olefin Epoxidation Table 3 Asymmetric epoxidation with ketone 26... 

A high catalyst loading (typically 20-30 mol%) is usually required for the epoxidation with ketone 26 because Baeyer-Vilhger oxidation presumably decomposes the catalyst during the epoxidation. The fused ketal moiety in ketone 26 was replaced by a more electron-withdrawing oxazohdinone (32) and acetates (33) with the anticipation that these replacements would decrease the amount of decomposition via Baeyer-Villiger oxidation (Fig. 8) [71, 72]. Only 5 mol% (1 mol% in some cases) of ketone 32 was needed to get comparable reactivity and enantioselectivity with 20-30 mol% of ketone 26 [71]. Since dioxiranes are electrophilic reagents, they show low reactivity toward electron-deficient olefins, such as a, 3-unsaturated esters. Ketone 33, readily available from ketone 26, was found to be an effective catalyst towards the epoxidation of a, 3-unsaturated esters [72]. 

In addition to the enantioselective epoxidation of trans- and trisnbstitnted olefins, efforts have also been made for the asymmetric epoxidation of cis- and terminal olefins. Glncose-derived ketone 55 was reported to be a highly enantioselective catalyst for the epoxidation of varions cw-olefins and certain terminal olefins (Fig. 11, Table 4) [97-100]. The resnlts of epoxidation with ketone 55 indicate that a n... 

In 1996, a fructose-derived ketone (39) was reported to be a highly effective epoxidation catalyst for a wide range of olefins (Scheme 3.25) [34]. The synthesis of ketone 39 can be readily achieved in two steps from D-fructose by ketahzation and oxidation [34-37]. The synthesis of the enantiomer of ketone 39 can be performed similarly from L-fructose, which can be prepared from readily available L-sorbose based on a literature procedure [35, 38]. Similar enantioselectivities were observed for the epoxidation with ketone ent-39 prepared in this way. 

The Pacman catalyst selectively oxidized a broad range of organic substrates including sulfides to the corresponding sulfoxides and olefins to epoxides and ketones. However, cyclohexene gave a typical autoxidation product distribution yielding the allylic oxidation products 2-cyclohexene-l-ol (12%) and 2-cyclohexene-1-one (73%) and the epoxide with 15% yield [115]. 

Tertiary butylhydroperoxide (TBHP) is a popular oxidizing agent used with certain catalysts. Because of its size, TBHP is most effective with catalysts containing large pores however, it can also be used with small-pore catalysts. Using first-row transition metals, Cr and V, impregnated into pillared clays, TBHP converts alcohols to ketones, epoxidizes alkenes, and oxidizes allylic and benzylic positions to ketones.83-87... 

The asymmetric epoxidation reaction with polyleucine as catalyst may be applied to a wide range of a, 3-unsaturated ketones. Table 4.1 shows different chalcone derivatives that can be epoxidized with poly-L-leucine. The substrate range included dienes and tctracncs151. Some other examples were reported in a previous edition161 and by M. Lastcrra-Sanchcz171. 

The breakthrough came already in 1996, one year after Curd s prediction, when Yang and coworkers reported the C2-symmetric binaphthalene-derived ketone catalyst 6, with which ee values of up to 87% were achieved. A few months later, Shi and coworkers reported the fructose-derived ketone 7, which is to date still one of the best and most widely employed chiral ketone catalysts for the asymmetric epoxidation of nonactivated alkenes. Routinely, epoxide products with ee values of over 90% may be obtained for trans- and trisubstituted alkenes. Later on, a catalytic version of this oxygen-transfer reaction was developed by increasing the pH value of the buffer. The shortcoming of such fructose-based dioxirane precursors is that they are prone to undergo oxidative decomposition, which curtails their catalytic activity. 

Other advantages include a mechanism that allows one to rationalize and predict the stereochemical outcome for various olefin systems with a reasonable level of confidence utilising a postulated spiro transition state model. The epoxidation conditions are mild and environmentally friendly with an easy workup whereby, in some cases, the epoxide can be obtained by simple extraction of the reaction mixture with hexane, leaving the ketone catalyst in the aqueous phase. 

In a situation where severe steric hindrance (e.g., 16,16-dimethyl-20-keto-pregnanes) prevents enol acetate formation, an alternate scheme has been devised. Condensation of ethyl oxalate at C-21 produces, after hydrolysis, the 21-glyoxylic acid this on treatment with acetic anhydride and a strong acid catalyst such as perchloric acid gives both A17(20)-enol lactone acetates. Epoxidation with peracid, and mild alkaline hydrolysis proceeds to give the 17a-hydroxy-20-ketone in a high overall yield.257... 

Polyfluorooxiranes rearrange to carbonyl compounds in the presence of a wide range of catalysts. The nature of the product carbonyl compound depends on the structure of the epoxide and the catalyst an overview is given in Scheme 8. Monosubstituted perfluorooxiranes generally give acyl fluorides with Lewis bases, and trifluoromethyl ketones with Lewis acids. Symmetrically 2,3-disubstituted perfluorooxiranes give ketones with either Lewis acids or Lewis bases. In the presence of Lewis acids, unsymmetrically 2.3-disubstituted perfluorooxiranes give a 1 1 mixture of the two possible ketones. 

Figure 6B.3. Epoxidation with chiral ketone 4 as a catalyst.

The addition of oxygen nucleophiles (peroxides) to a,(i-unsaturated ketones is also catalyzed by the lanthanoid catalysts, leading to the formation of the corresponding epoxides with up to 96% ee (Scheme 8D.19) [41]. This reaction shall be reviewed in another chapter. 

Many other variations of the basic structure 10 have been explored, including an-hydro sugars and carbocyclic analogs, the latter derived from quinic acid 13 [23-26]. In summary, the preparation of these materials (e.g. 14-16) requires more synthetic effort than the fructose-derived ketone 10. Occasionally, e.g. when using 14, catalyst loadings can be reduced to 5% relative to the substrate olefin, and epoxide yields and selectivity remain comparable with those obtained by use of the fructose-derived ketone 10. Alternative ex-chiral pool ketone catalysts were reported by Adam et al. The ketones 17 and 18 are derived from D-mannitol and tartaric acid, respectively [27]. Enantiomeric excesses up to 81% were achieved in the epox-idation of l,2-(E)-disubstituted and trisubstituted olefins. 

Chiral ketone catalysts of the Yang-type (5a and 5b, see above) and of the Shi-type (10, Scheme 10.2) have been successfully used for kinetic resolution of several racemic olefins, in particular allylic ethers (Scheme 10.4) [28, 29]. Remarkable and synthetically quite useful S values of up to 100 (ketone 5b) and above 100 (ketone 10) were achieved. Epoxidation of the substrates shown in Scheme 10.4 proceeds with good diastereoselectivity. For the cyclic substrates investigated with ketone 10 the trans-epoxides are formed predominantly and cis/trans-ratios were usually better than 20 1 [29]. For the linear substrates shown in Scheme 10.4 epoxidation catalyzed by ketone 5b resulted in the predominant formation of the erythro-epoxides (erythro/threo-ratio usually better than 49 1) [28]. 

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