Ketones fructose-derived chiral

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. 

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

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. ... 

An asymmetric epoxidation using fructose-derived chiral ketone. 

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 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... 

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). 

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). 

Epoxidation using a chiral fructose-derived ketone is easy to carry out, as it occurs in aqueous conditions. The reactions were performed without any modification of the published procedure. The glassware has to be free of trace metal, which can decompose the oxone the use of a plastic spatula is recommended and the volumes must be measured using glass-graduated cylinders. Table 6.2 gives different examples of epoxides which can be obtained using the method prescribed. 

In order to test these assumptions Heathcock prepared different chiral ketones. Thus, the aldol condensation of the fructose-derived ketone and the acetonide of (/ )-glyceraldehyde gave poor results in the double stereodifferentiation, since an almost equal mixture of the two jyn-aldols 68a and 68b were obtained. However, the reaction with the (5)-aldehyde gave only one syn adduct (69a) (Scheme 9.22) ... 

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. ... 

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. 

Whereas the chiral TEMPO analog 87 was used to resolve racemic secondary alcohols, the D-fructose-derived ketone 88 [137] proved useful for oxidative resolution of racemic diols (Table 10.13) [138, 139], Persulfate in the form of Oxone, Curox, etc., served as the final oxidizing agent, and the dioxirane generated from the ketone 88 is the chiral active species. Because of the relatively low conversions (except for unsubstituted dihydrobenzoin) at which the ee stated were achieved, the method currently seems to be of less practical value. Furthermore, typically 3 equiv. ketone 88 had to be employed [138, 139]. 

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... 

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

R " = H, alkyl, aryl, substituted alkyl and aryl SIRs = SIMes, SiMe2(t-Bu), SIEts solvent CHoCH. pentane, toluene n = 1-3 chiral oxidant Davis chiral oxaziridine, Shi s D-fructose derived ketone/Oxone, (Salen)manganese(lll)-complexes/NaOCI or PhIO... 

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

These ketone precursors can also serve as chiral auxiliaries. The dioxirane from the fructose-derived ketone 20 converts trisubstituted and rram-disubstitued alkenes (e.g., 22) to the corresponding epoxides in very good yields and enantioselectivities, but is less effective for terminal and cis-disubstituted substrates. Fortunately, the oxazolidino analog 21 exhibits a complementary scope, providing high enantioselectivities for these latter olefins (e.g., 24). The stereochemical outcome of the reaction has been rationalized on the basis of a spiro transition... 

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