Fructose-derived chiral ketone catalyst

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 asymmetric oxidation of a variety of differently substituted, acyclic and cyclic enol phosphates using the Sharpless AD (asymmetric dihydroxylation)-reagents, AD-mix-a and AD-mix- 0, and a fructose-derived chiral ketone as a catalyst, with PMS was a terminal oxidant, afforded the corresponding a-hydroxy ketones in good yield and with high enantioselectivity. The influence of substrate steric and electronic factors on the facial stereoselectivity has been studied. Kinetic and activation parameters for copper(II)-catalysed and -uncatalysed oxidation of ornithine with PMS have been determined. Cyclic voltammetric and absorption studies confirmed the formation of a copper-ornithine-PMS complex and ESR spectral studies ruled out the participation of free radical intermediates. Kinetic and activation parameters for the oxidation of aspartic acid and nicotinic acid with PMS have been determined and plausible mechanisms have been proposed. 

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. 

Ge, H. Q. Chiral ketone catalysts derived from D-fructose. Synlett 200A, 2046-2047. 

The asymmetric oxidation of a variety of acyclic (89) and cyclic (90) substituted enol phosphates using commercially available Sharpless reagent (93), and a fructose derived chiral (94) as a catalyst, afforded the corresponding a-hydroxy ketones (91) and (92) in high enantioselectivily and good yields (Scheme 30). The influence of steric and electronic... 

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). 

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. ... 

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. 

Mechanism of Shi epoxidation was probed for synthesis of (+)-(R,R) epoxide 20 in the reaction of frans-2-methylstyrene 18 with peroxymonosulphate (Oxone) in the presence of catalyst 19, chiral ketone derived from fructose (Scheme 5).74... 

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]. 

Alkenes, Allies, Arenes, and Alkanes. One of the most common apphcations of Oxone in organic synthesis is the in situ formation of dioxiranes fromketones (eq 1). Dioxrrane chemistry has grown significantly in recent years, particularly in the area of enantioselective epoxidation, and a wide variety of chiral ketones have been designed for this purpose. Notably, ketones (5 and 6) derived from fructose and glucose, respectively, have been shown to be effective catalysts for enantioselective epoxida-tions of a variety of trans-, trisubstituted, cis-, and terminal olefins with Oxone as primary oxidant (eqs 38 and 39). ... 

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 7.64 Chiral fructose-derived ketone catalyst 376...

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