Oxone mediated epoxidation

Polymer-bound trifluoromethyl aryl ketone 42 was prepared by attaching 4-(trifluoroacetyl)benzoic acid to a suitably functionalized resin and used as a catalyst in Oxone-mediated epoxidations.64 The reactions proceed by in situ generation of the polymer-supported (trifluoromethyl)-dioxirane. A series of epoxides was formed in good to excellent yield. 

Remarkably, simple chiral ammonium salts such as 31 can induce modest enantiomeric excess in the Oxone-mediated epoxidation of tiisubstituted alkenes. While no in-depth mechanistic models have been proposed, the mode of action is believed to be through the formation of chiral salts with Oxone itself <04AGE1460>. 

The epoxide formation is thought to proceed via Oxone-mediated dioxirane formation and inclusion of the aromatic moiety inside the cavity. The influence of the substrate binding inside the CD cavity was evaluated by inhibitory experiments with naphthalene-2-sulfonate, which is known to bind both a- and / -CD with good affinity. As expected, the addition of 2 equivalents of inhibitor to the reaction mixture resulted in a significant decrease in reaction rate. 

L. Bohe, M. Kammoun, Catalytic oxaziridinium-mediated epoxidation of olefins by Oxone . A convenient catalyst excluding common side reactions. Tetrahedron Lett. 43 (2002) 803. 

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]. 

Armstrong has shown that even acyclic iminium salts can mediate epoxidation by Oxone [73] however, enantiomeric excesses are low [74]. By condensing A-trimethylsilylpyrrolidine 23 with a range of aromatic aldehydes in the presence of trimethylsilyltriflate, Armstrong was able to produce a range of substituted exocyclic iminium salts (Scheme 1.28). 

The principal limitation to this system is the restricted range of temperatures in which the epoxidation can be performed (0°C to room temperature). The upper limit is determined by the oxone, which decomposes relatively quickly in the basic medium at room temperature. The lower limit is determined by the use of the aqueous medium the normal ratio of the water and acetonibile solvents used is 1 1, and this mixture freezes at around -8°C. Therefore the development of the TPPP system (tetraphenylphosphonium monoperoxybisulfate) has allowed, for the first time, oxaziridinium salt mediated epoxidation to occur at sub zero temperatures [90]. This has resulted in the highly enantioselective epoxidation of c -alkenes using catalyst 48 (Scheme 1.44) and the asymmetric total syntheses of levcromakalim 49 [91], (-)-(3 5)-lomatin 50, and (-n)-(3 5, 4 i )-trani-khellactone 51 (Fig. 1.9) [92]. 

All the reactions were carried out at 0°C, with the substrate (1 equivalent), ketone (3 equivalents), Oxone (5 equivalents), and NaHCC>3 in CH3CN aqueous EDTA for 2 hours. High enantioselectivity can generally be obtained for trans- and trisubstituted olefins. The favored spiro and planar transition states have been proposed for ketone 130-mediated rrans-stilbene epoxidation (Scheme 4-48). 

Denmark has developed a practical dioxirane-mediated protocol for the catalytic epoxidation of alkenes, which uses Oxone as a terminal oxidant. The olefins studied were epoxidized in 83-96% yield. Of the many reaction parameters examined in this biphasic system, the most influential were found to be the reaction pH, the lipophilicity of the phase-transfer catalyst, and the counterion present. In general, optimal conditions feature 10 mol% of the catalyst l-dodecyl-l-methyl-4-oxopiperidinium triflate (30) and a pH 7.5-8.0 aqueous-methylene chloride biphasic solvent system [95JOC1391]. 

This remains a developing area for the synthesis of chiral oxiranes and has attracted interest from several research groups. As with the use of dioxiranes (above), it is not necessary to form the reactive oxaziridinium salt rather, the epoxidation reaction can be mediated by the corresponding iminium salt and Oxone. 

SCHEME 5.21 The standard conditions applied for catalytic asymmetric epoxidation mediated by Oxone and iminium salts. 

In the realm of epoxidations without the use of transition metals, dioxirane-mediated processes are among the most versatile. While the use of stoichiometric amounts of even the simplest dioxiranes can still be experimentally cumbersome, novel catalytic systems eontinue to emerge. For example, the PEG-immobilized trifluoroacetophenone 17 is a convenient dioxirane precursor that is highly active, soluble in both water and organic solvents, and easily recoverable and reusable. In the presence of Oxone, this ketone mediates the efficient epoxidation of sensitive substrates, such as the BOC-protected aminostyrene 18 04TL6357>. 

Ketones represented by 83 are a new generation of catalysts for mediating asymmetric epoxidation of alkenes by Oxone . Ketone 84 exhibits desirable characteristics in the epoxidation of c/s-alkenes. For example, it does not cause isomerization of the double bond. 

Epoxidations. Combination of Oxone and the iminium salt derived from pyrrolidine and o-trlfluoromethylbenzaldehyde is effective for epoxidation of alkenes. In the case of an active alkene (e.g., trisubstituted alkene), pyrrolidine is an adequate catalyst. Other types of mediators include a-functionalized ketones (e.g., ot-acetaminoacetone) and the A, A -dialkylalloxans 1. ... 

Hypervalent iodine species were demonstrated to have a pronounced catalytic effect on the metalloporphyrin-mediated oxygenations of aromatic hydrocarbons [93]. In particular, the oxidation of anthracene (114) to anthraquinone (115) with Oxone readily occurs at room temperature in aqueous acetonitrile in the presence of 5-20 mol% of iodobenzene and 5 mol% of a water-soluble iron(llI)-porphyrin complex (116) (Scheme 4.57) [93]. 2-ferf-Butylanthracene and phenanthrene also can be oxygenated under similar conditions in the presence of 50 mol% of iodobenzene. The oxidation of styrene in the presence of 20 mol% of iodobenzene leads to a mixture of products of epoxidation and cleavage of the double bond. Partially hydrogenated aromatic hydrocarbons (e.g., 9,10-dihydroanthracene, 1,2,3,4-tetrahydronaphthalene... 

In the search for a new and highly enantioselective system for iminium salt mediated catalytic asynunetric epoxidation, several parameters and catalyst substructures were examined. The method of oxidation, using Oxone, was estabUshed after some experimentation and a possible catalytic cycle for an oxaziridinium ion as the oxidative intermediate is depicted in Scheme 1.36 [80,81]. The first stage is the formation of an... 

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