Ketone catalyst

The main drawback of the system is that the ketone catalyst slowly decomposes during the reaction, which means that 0.2-0.3 equivalents are needed for complete conversion. More robust catalysts, which can be used in 1-3 mol%, have recently been reported, but have not as yet been widely applied [8]. Ketone 1 is commercially available, or can easily be synthesized in large scale in two steps from d-fructose. Ent-1 is obtained in a similar way from L-sorbose. 

The ketone catalyst is readily prepared from D-fructose by ketalization and oxidation. The other enantiomer of this ketone, prepared from L-sorbose,... 

Figure 6.4 Mechanism of epoxidation by a chiral ketone catalyst.

Ketone catalyst derived from fructose, 77.4mg, 0.3 mmol, 0.3 eq ... 

The ketone catalyst was kindly provided by Professor Y. Shi (Colorado State University, Fort Collins, Colorado)... 

In a 50 mL three-necked flask with a magnetic stirrer bar was dissolved (E)-stilbene (181 mg) in acetonitrile-dimethoxymethane (15mL, 1/2, v/v). Buffer (10 mL), tetrabutylammonium hydrogensulfate (15 mg) and ketone catalyst (77.4mg) were added with stirring. 

Mixed donor chiral tetradentate PNNP diaminodiphosphines 83 (Scheme 4.35) have found application in the ATH of ketones, catalyzed by iridium. The results showed that, in the presence of [IrCl-(R,R)-83], chiral alcohols could be obtained with high activity (up to 99.4% yield) and excellent enanhoselectivihes (up to 99.0% ee) under mild conditions using a ketone catalyst raho of 5000 with KOH in PrOH. In the case of propiophenone, the TON reached 4780mol product per mole iridium, while the TOP was as high as 1593 h at 55 °C [72]. 

Should the substrate to be oxidized and its oxidation product be hydrolytically resistant and thermally persistent, the oxidation with in-situ-generated dioxirane is recommended. The advantages include that more ketone catalyst is available, the generation of the... 

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. 

Essentially concurrently, the C2-symmetric ketone catalysts 8-10 were reported . In regard to the enantioselectivity, the TADDOL (o ,Q ,Q , Q -tetraaryl-l,3- oxolane-4,5-dimethanol)-derived ketone 10 performs better than the binaphthalene-based ketone 6, but not as well as the fructose-modified ketone 7, whereas 10 is more resistant than 7 in regard to oxidative degradation. ... 

These encouraging results have led to a surge of activity in this promising area, such that numerous ketone catalysts have been developed for asymmetric epoxidations. A... 

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. 

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. 

AN OXAZOLIDINONE KETONE CATALYST FOR THE ASYMMETRIC EPOXIDATION OF cis-OLEFINS... 

The work on the AlR3-aeid amide catalyst system has its origin in the studies on the AlR3-ketone catalyst system (35). In the course of studies on the latter catalyst, we speculated that the dialkylaluminum monoenolate [X] might be superior to dialkylaluminum monoalcoholate [XI] as a stereospecific polymerization catalyst (35). Although the speculation on the active species of the AlR3-ketone catalyst system was disproved later by our more detailed studies, fortunately we could find out about the AlR3-acid amide catalyst system (35). 

H. Q. Tian, X. G. She, and Y. Shi, Electronic probing of ketone catalysts for asymmetric epoxidation. Search for more robust catalysis, Org. Lett. 2001, 3, 715-718. 

Oxidative degradation of the catalyst (e.g. lactone formation by Baeyer-Villiger oxidation) competes with oxygen transfer and is the reason a relatively high catalyst loading is required. In their search for more robust, yet (comparatively) readily available ketone catalysts, Shi et al. prepared the carbamates 12a-c [20-22], Use... 

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]. 

Cavallo et al. from (+)-dihydrocarvone and evaluated in the asymmetric epoxida-tion of several silyl enol ethers [32]. Enantiomeric excess up to 74% was achieved in the epoxidation of the TBDMS trans-enol ether of desoxybenzoin with the fluoro ketone 19d (30 mol% of the ketone catalysts). In earlier work Solladie-Cavallo et al. had shown that the fluoro ketones 19a and 19e can be used to epoxidize trans-stilbene with up to 90% ee (30 mol% ketone catalyst) [33], Asymmetric epoxidation of trans-methyl 4-para-methoxycinnamate using ketone 19e as catalyst is discussed in Section 10.2. 

In the course of their exploration of structure-activity relationships for ketone catalysts, Denmark et al. noted that oxoammonium salts such as 29-33 are very efficient catalysts of the epoxidation of olefins [34a]. Unfortunately, enantiomeric excesses achieved with this class of ketone catalyst have not yet exceeded 40% (30, epoxidation of tram-fl-rn eth yI styrene . With the fhiorinated oxoammonium catalyst 23 already mentioned, however, 58% ee was achieved in the asymmetric epoxidation of trans-stilbene [34b]. 

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