Fructose ketone derivatives, asymmetric

Chiral Ketone from Carbohydrate. Tu et al.100 reported a dioxir-ane-mediated asymmetric epoxidation based on the ketones derived from the low cost material D-fructose (Scheme 4-47). 

Previously, some fluorocyclohexanones were used in a catalytic amount with Oxone for asymmetric epoxidation reaction, but they gave a poor ee . It was found later that chiral ketones derived from fructose work well as asymmetric epoxidation catalysts and show high enantioselectivity in reactions of /rani-disubstituted and trisubsti-tuted olefins ". Cis and terminal olefins show low ee under these reaction conditions. Interestingly, the catalytic efficiency was enhanced dramatically upon raising the pH. Another asymmetric epoxidation was also reported using Oxone with keto bile acids. ... 

Wang, Z.X. et al. Asymmetric Epoxidation by Chiral Ketones Derived from Carbocyclic Analogues of Fructose. 3.2 3.4.2 2001 [191]... 

Scheme 1.12 Shi s fructose derived ketone for asymmetric epoxidation...

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. 

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. 

Unlike epoxidations, the enantioselective CH oxidation is still a virgin field in dioxirane chemistry. The first (and to date only ) enantioselective C—H oxidation has been reported for vic-diols. Thus, the oxidation with the fructose-derived dioxirane of ketone 7 (Shi s ketone) yields the optically active a-hydroxy ketones in ee values of up to 75% °. A typical example of this asymmetric CH oxidation is shown in equation 32 °. 

Tu Y, Wang ZX, Shi Y (1996) An efficient asymmetric epoxidation method for irans-olefins mediated by a fructose-derived ketone. J Am Chem Soc 118 9806... 

They found that the erythrolthreo-% i,cX N Xtj is X-substituent dependent, acting through H-bonding, which was demonstrated by the TFDO Ic epoxidation of 73. An example of cyclohexene epoxidation by dioxiranes derived from various ketones grafted on solid supports has also appeared <1996MI273>. Shi and co-workers reported <1996JA9806> excellent ee s of asymmetric epoxidation of different /ra t-olefms by fructose-derived ketones 74 before then, only low enantioselectivities (9-20%) have been reported on this type of reaction. 

ASYMMETRIC EPOXIDATION OF trans-p-METHYLSTYRENE AND 1-PHENYLCYCLOHEXENE USING A D-FRUCTOSE-DERIVED KETONE (R,R)-trans-P-METHYLSTYRENE OXIDE AND (R,R)-l-PHENYLCYCLOHEXENE OXIDE... 

Tu, Y., Wang, Z.-X., Shi, Y. An Efficient Asymmetric Epoxidation Method fortrans-Olefins Mediated by a Fructose-Derived Ketone. J. Am. Chem. Soc. 1996,118, 9806-9807. 

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... 

An asymmetric epoxidation using a fructose-derived chiral ketone. It is an organocatalyst with Oxone typically used as the primary oxidant. 

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]. 

Besides the secondary amine-catalyzed oxygenation reactions (see Sects. 2.3.1. and 3.2.5.) and phase-transfer catalyzed epoxidations (Chap. 6.) already mentioned, asymmetric epoxidation reactions using the method developed by Shi et al. (530) have found to be highly useful in complex total syntheses (531-535). The Shi epoxidation employs the fructose-derived ketone 629 as an easily available namral... 

Professor Yian Shi at the Colorado State University first reported the use of a fructose-derived chiral ketone 2 for the asymmetric epoxidation in 1996. This ketone is conveniently synthesized from an inexpensive chiral starting material D-fructose via ketalization and oxidation. The enantiomer of ketone 2, ent-2, can be prepared by the same methods from L-fructose, which is derived from L-sorbose. ... 

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. ... 

An asymmetric epoxidation using fructose-derived chiral ketone. 

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. 

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... 

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