Alkene epoxidation with chiral ketone

Table 3.1 Representative Asymmetric Epoxidation of Aryl Alkenes with Chiral Ketones.

Scheme 3.8 Examples of epoxidation of alkenes with chiral ketones.

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

Epoxidation of alkenes can be effected by potassium persulphate. When the oxidation is conducted in the presence of chiral trifluoroketones, chiral oxiranes (ee 12-22%) are produced [14]. The chirality appears to be achieved via the initial reaction of the persulphate with the ketone to generate chiral dioxiranes, which then interact with the alkenes. 

Several methods for the asymmetric epoxidation of electron-poor alkenes rely on the use of metal peroxides associated with chiral ligands . Enders and coworkers reported that ( )-a,/ -unsaturated ketones may be epoxidized using stoichiometric quantities of diethylzinc and a chiral alcohol, in the presence of molecular oxygen (equation 33). The best enantioselectivities were found using (/ ,/ )-Af-methylpseudoephedrine 54 as R OH... 

The dioxirane epoxidation of a prochrral alkene will produce an epoxide with either one new chirality center for terminal alkenes, or two for internal aUcenes. When an optically active dioxirane is nsed as the oxidant, expectedly, prochiral alkenes should be epoxi-dized asymmetrically. This attractive idea for preparative purposes was initially explored by Curci and coworkers in the very beginning of dioxirane chemistry. The optically active chiral ketones 1 and 2 were employed as the dioxirane precursors, but quite disappointing enantioselectivities were obtained. Subsequently, the glucose-derived ketone 3 was used, but unfortunately, this oxidatively labile dioxirane precursor was quickly consumed without any conversion of the aUcene . After a long pause (11 years) of activity in this challenging area, the Curci group reported work on the much more reactive ketone... 

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. 

One highly attractive feature of ketone-catalyzed epoxidation via chiral dioxir-anes is that reliable models can be developed to rationalize the observed enantio-selectivities. For the reaction of a dioxirane with an alkene, two extreme transition states can be envisaged the so-called spiro and planar modes (Fig. 12.3). 

Enantioselective epoxidation of pro-chiral alkenes with dioxiranes generated from optically active ketones affords optically active epoxides with enantiomeric excesses (ee) in the 9-12.5% range <84CC155>. In the late 1980s values up to 24% have been observed when employing 4,4,4-trifluoro-3-phenyl-3-methoxybutan-2-one as the ketone <89ACR205>. 

The first example of the immobilization of a chiral ketone to promote the enan-tioselective epoxidation of alkenes with Oxone has been reported by Sartori and coworkers [322]. They anchored a-fhiorotropinone on KG-60 silica, MCM-41 and a Merrifield resin. The catalysts were tested for the epoxidation of 1-phenylcyclo-hexene but the polymer-supported fhiorotropinone 121 showed a low activity and selectivity. The catalyst immobilized on inorganic supports promoted the stereoselective epoxidation of alkenes with ee values up to 80% and could be reused with the same performance for three runs. 

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). ... 

The pioneering work by Curd offered one of the first examples of the use of chiral catalysts in the asymmetric epoxidation of alkenes with Oxone. In this early example the use of chiral ketone (-l-)-isopinocamphone (3, Figure 19.1) afforded low enantioselectivities (<15% ee) and reaction rates in a biphasic solvent system [9]. Subsequently, Yang developed a class of C2-symmetrical ketones 4 that in a monophasic (CH3CN/H2O) solvent system gave improved enantioselectivity [47% ee for the epoxidation of ( )-stilbene] [10, 11],... 

In 1996 Yang first reported the asymmetric epoxidation of olefins mediated by a symmetric dioxirane generated from the corresponding ketone [22]. The chiral ketone was derived from BINAP, and exhibited enantioselectivities typically between 5% and 50% ee under stoichiometric conditions, and 87% ee in the epoxidation of trans-4,4 - diphenylstilbene. With modification of the original C2 symmetric ketone and development of the reaction to run catalytically, Yang was able to increase the enantioselectivity of the process [23, 24], With very hindered alkenes, such as frans-4,4 -diterf-butylstilbene, enantioselectivities of up to 95% ee were achieved (Scheme 1.9). 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

The epoxidation of electron-deficient alkenes with either vanadium or titanium catalysts give syw-epoxides347 a free hydroxy group and a ketone or ester function are necessary for the reaction to take place, and a modest level of asymmetric induction can be achieved with y-hydroxy enone substrates and chiral titanium catalysts348. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

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