Ketones fructose-derived catalysts

However, it was the development of the fructose-derived ketone catalyst 5, reported by Shi in 1996, that offered the most useful organocatalyst for asymmetric epoxidations [12-14]. Now commercially available, the catalyst 5 can be produced... 

Scheme 7.64 Chiral fructose-derived ketone catalyst 376...

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). 

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. 

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. 

The epoxidation procedure described herein utilizes the fructose-derived ketone (1) as catalyst and Oxone" j or H,0, as oxidant. The procedure provides a valuable method for... 

The ability of non-C2 symmetric ketones to promote a highly enantioselective dioxirane-mediated epoxidation was first effectively demonstrated by Shi in 1996 [114]. The fructose-derived ketone 44 was discovered to be particularly effective for the epoxidation of frans-olefins (Scheme 17 ). frans-Stilbene, for instance, was epoxidized in 95% ee using stoichiometric amounts of ketone 44, and even more impressive was the epoxidation of dialkyl-substituted substrates. This method was rendered catalytic (30 mol %) upon the discovery of a dramatic pH effect, whereby higher pH led to improved substrate conversion [115]. Higher pH was proposed to suppress decomposition pathways for ketone 44 while simultaneously increasing the nucleophilicity of Oxone. Shi s ketone system has recently been applied to the AE of enol esters and silyl enol ethers to provide access to enantio-enriched enol ester epoxides and a-hydroxy ketones [116]. Another recent improvement of Shi s fructose-derived epoxidation reaction is the development of inexpensive synthetic routes to access both enantiomers of this very promising ketone catalyst [117]. 

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]. 

Fructose-derived ketone 42 has been shown to be a highly general ketone catalyst (typically 20-30 mol% used) for epoxidation of a wide variety of trans and trisubsti-... 

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. ... 

In 1996, Shi et al. [75] developed a fructose-derived ketone (Epoxone ) 183 as a highly effective asymmetric epoxidation catalyst. Shi s epoxidation is known to be the best for the asymmetric epoxidation of tramolefms and tri-substituted olefins. Shi s ketone is readily available and an efficient and selective oxidant that requires mild conditions. Ketone 183 could be synthesized [88] from inexpensive chiral starting material D-fructose, by ketalization and oxidation (Scheme 9.48). The enantiomer of 183 can be synthesized from L-fructose, which in turn could be obtained from commereially available L-sorbose. Chemists at DSM developed a scalable process for the preparation of Epoxone 183 in large quanities. 

SCHEME 35.16. Enantioselective epoxidation of trans-disubstituted and trisubstituted olefins with fructose-derived ketone 62 as a highly reactive and enantioselective catalyst. 

In 1996, a fructose-derived ketone was identified by Shi and co-workers to be a highly reactive and enantioselective epoxidation catalyst for frtz 5-disubstituted and trisubstituted olefins." Good yields and high enantioselec-tivities can be obtained with 30 mol% of ketone 62 for a wide range of unfunctionalized ira 5-disubstituted and trisubstituted olefins (Scheme 35.16). The epoxidation is typically performed at pH around 10.5 by adding either potassium carbonate or potassium hydroxide into the... 

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. 

Fructose-derived ketone 39 is readily available, and is a highly general and enantio-selective catalyst for the epoxidation of trans- and trisubstituted olefins. Its utilization in synthesis has been reported by other researchers [70]. For example, recently Corey and coworkers reported that (R)-2,3-dihydroxy-2,3-dihydrosqualene (47) was enantio-... 

More recently Shi has reported several highly enantioselective epoxidation systems based on the oxazolidinone catalysts 13 and 14, modified from the original fructose-derived ketone 10 [47]. Highly chemo- and enantioselective epoxidation of cw-enynes was achieved using oxone as the stoichiometric oxidant (Scheme 1.17). In a separate report ketone 14 has been used in the epoxidation of a variety of substrates using hydrogen peroxide as the stoichiometric oxidant, for example the... 

In 1996, Shi et al. reported fructose-derived ketone 376 as a highly reactive and enantioselective (<90% ee) catalyst for the epoxidation of tran -olefins, trisubsti-tuted olefins, fluorooleflns, conjugated enynes, and silyl enol ethers with20-30mol% catalyst loading at an elevated pH of 10 [256]. This ketone can be prepared from... 

Subsequently, high chemoselectivity and enantioselectivity have been observed in the asymmetric epoxidation of a variety of conjugated enynes using fructose-derived chiral ketone as the catalyst and Oxone as the oxidant. Reported enantioselectivities range from 89% to 97%, and epoxidation occurs chemoselectively at the olefins. In contrast to certain isolated trisubstituted olefins, high enantioselectivity for trisubstituted enynes is noticeable. This may indicate that the alkyne group is beneficial for these substrates due to both electronic and steric effects. 

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

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. ... 

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