Trisubstituted alkenes asymmetric epoxidation

Further variations on the epoxyketone intermediate theme have been reported. In the first (Scheme 9A) [78], limonene oxide was prepared by Sharpless asymmetric epoxidation of commercial (S)-(-)- perillyl alcohol 65 followed by conversion of the alcohol 66 to the crystalline mesylate, recrystallization to remove stereoisomeric impurities, and reduction with LiAlH4 to give (-)-limonene oxide 59. This was converted to the key epoxyketone 60 by phase transfer catalyzed permanganate oxidation. Control of the trisubstituted alkene stereochemistry was achieved by reaction of the ketone with the anion from (4-methyl-3-pentenyl)diphenylphosphine oxide, yielding the isolable erythro adduct 67, and the trisubstituted E-alkene 52a from spontaneous elimination by the threo adduct. Treatment of the erythro adduct with NaH in DMF resulted... 

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. 

We recently reported our results on the asymmetric epoxidation of trans-disubstituted and trisubstituted alkenes, using Oxone as oxidant, catalyzed by readily available arabinose-derived 4-uloses containing tunable steric blockers that control the enantioselectivity of the epoxidation.Ulose (3), containing a 2, 3 -diisobutyl acetal unit, was the most efficient catalyst and displayed good enantioselectivity. 

The preparation is easy to reproduce and since d- and L-arabinose are commercially available in large quantities, both enantiomers of ulose (3) are readily accessible. The enantioselectivity of the asymmetric epoxidation using ulose (3) towards frawi-disubstituted and trisubstituted alkenes is shown in Table 6.4. 

The preparation of the silica supported a-fluorotropinone is easy to reproduce as a commercially available solid support was employed the asymmetric epoxidation has been applied to trans- and trisubstituted alkenes affording the corresponding... 

The rigid, chiral salen complexes of Mn(III) shown below catalyze the asymmetric epox-idation of alkenes when treated with commercial bleach (NaOCl). This synthesis of enan-tio-enriched epoxides is particularly powerful since the method is applicable to unfunctionalized olefins. In general, (Z)-l,2-disubstituted alkenes afford higher enantioselectiv-ities than do the ( )-isomers or trisubstituted alkenes. The reaction mechanism is com-plex and proceeds via the formation of a Mn(III,IV) dinuclear species. ... 

The methodology described above allows the asymmetric epoxidation of allylic alcohols or cis-substituted conjugated alkenes and the resolution of terminal epoxides. The asymmetric synthesis of trans-di- and trisubstituted epoxides can be achieved with the dioxirane formed from the fructose-derived ketone 64, developed by Shi and co-workers. The oxidizing agent potassium peroxomonosulfate... 

A more recent alternative approach, developed by Jacobsen and co-workers, concerns the catalytic asymmetric epoxidation of unfunctionalized olefins using cheap NaOCl as oxidant in the presence of Mn complexes of chiral Schiff bases as catalysts, the so-called salene (Fig. 3-4). Values of 97% e.e. have been achieved using cis-disubstituted or trisubstituted alkenes. Equation 3-15 describes the Jacobsen epoxidation of olefins schematically. 

The diaryl prolinol/TBHP system has been found to be suitable for the asymmetric epoxidation of a variety of poorly investigated trans-disubstituted or trisubstituted electron-poor alkenes (Scheme 7.5). ... 

In 1996, Shi made a huge development in this area, reporting the asymmetric epoxidation of alkenes using chiral dioxiranes generated in situ. The epoxidation works well for disubstituted tra s-olefins, and trisubstituted olefins using a fructose-derived ketone as a catalyst and oxone as an oxidant (Scheme 1.9) [26]. 

The highest stereoselectivities are reached with disubstituted (Z) -alkenes (with ee-values up to 99%) as well as trisubstituted alkenes, whereas mono-substituted olefins are poorer substrates. Concerning the mechanism of the Jacobsen epoxidation (see Ref. [21]), asymmetric epoxidation of non-activated olefins can be performed with numerous other transition-metal catalysts [22]. 

This catalytic system provides high enantioselectivities for a range of epoxides (Figure 19.2), including those derived from trisubstituted and traus-1,2-disubstituted alkenes, with complete stereospecificity (retention of the alkene geometry in the epoxide product) [17]. The reaction has been shown to be chem-oselective for the alkene of enynes [18], provided monoepoxides upon reaction with conjugated trans-dienes [19] and afforded up to 93% ee for the asymmetric epoxidation of fluoro-olefins [20]. However, decreased enantioselectivity was observed for both cis- and terminal alkenes. The catalytic system has also been applied to the resolution and desymmetrization of cyclic trisubstituted alkenes [21]. 

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