Epoxidation of Electron-Poor Alkenes

FIGURE 17.61 Epoxidation of enones with alkaline hydrogen peroxide. 

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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 epoxidation of electron-poor alkenes (Scheme 4) is more cumbersome, such that usually an excess of the dioxirane is required, prolonged reaction times (up to several days) and elevated temperatures (up to 60 °C), to achieve good conversions alternatively, the more reactive TFD may be employed . Again, the epoxide products of these substrates are hydrolytically more robust, so that the in-situ mode is a good choice for these substrates. It must be stressed that the dioxirane epoxidation of electron-poor alkenes offers an effective... 

Electrochemical epoxidation of electron-poor alkenes can be accomplished by the use of silver(III) bipyridine-based redox mediators79. The reaction proceeds in aqueous... 

Asymmetric Weitz-Scheffer epoxidation is commonly used for the epoxidation of electron-poor alkenes. Cinchona-derived phase-transfer catalysts, initially used... 

The stereoselective synthesis of epoxide 28 appears to be the major advantage of this route, since it generates an intermediate already involved in an industrial synthesis of diltiazem. The recent development of basic research methods for the catalytic enantioselective epoxidation of electron poor alkenes [54] can provide a new entry to 26 that is more practical than the approaches of both DSM and others [55]. 

Oxirans.—A simple four-stage preparation of (5)-propylene oxide from ethyl L-( —)-maleate has been described (Scheme 2). This work is of importance for the synthesis of nonactin carboxylic acid. Another synthesis of optically-active propylene oxide involves the cyclization of OL-propylene chlorohydrin with a variety of bases in the presence of a cobalt complex the highest optical purity was 27%. Wynberg and co-workers have shown that the base-catalysed epoxidation of electron-poor alkenes is subject to catalytic asymmetric induction hydrogen peroxide and t-butyl hydroperoxide were used as oxidants in the presence of quaternary... 

Epoxidation of electron-poor alkenes may be accomplished using the anion of hydrogen peroxide as a source of oxygen. 

Good yields are generally observed for this type of reaction however, it is non-stereospedlic, due to the extended life time of the intermediate enolate anion, which has time to rotate around the alpha and beta carbon-carbon bond. Oxides of transition metals are often used as catalysts with hydrogen peroxide to afford the epoxides of electron poor alkenes. 

The epoxidation of alkenes is one of the most impoi4ant oxidation methods. Electrochemical epoxidation of electron-poor olefins such as enoates (154 155) and enones has been accomplished by using silver(III)oxo bis(2,2 -bipyridine) and similar complexes (Scheme 61) [241], )-Dimethyl glutaconate is electrolyzed in an MeCN-LiCl04/Ag0Ac)(bpy)-(Pt) system to give the trans-epoxide in 90% yield. 

Polyamino acids are easy to prepare by nucleophUe-initiated polymerisation of amino acid JV-carboxyanhydrides. Polymers such as poly-(L)-leucine act as robust catalysts for the epoxi-dation of a wide range of electron-poor alkenes, such as y-substituted a,Ji-unsaturated ketones. The optically active epoxides so formed may be transformed into heterocyclic compounds, polyhydroxylated materials and biologically active compounds such as dUtiazem and taxol side chain. 

Benzylic C-H bonds undergo oxidative esterification with TBHP in the presence of tetrabutylammonium iodide as catalyst and carboxylic acids in good to excellent yields. A free radical process has been proposed. Asymmetric epoxidation of electron-poor terminal alkenes bearing different carbonyl groups has been achieved with a cinchona thiourea/TBHP system. The corresponding epoxides, containing a quaternary stereocentre, were isolated in yields up to 98% and enantioselectivity up to 99%. A direct oxidative CDC of indole with A-aryltetrahydroisoquinolines in the 0 presence of a gold catalyst and TBHP resulted in the formation of a variety of alkylated heteroarenes (Scheme 24). ... 

The rate of epoxidation of alkenes is increased by alkyl groups and other ERG substituents and the reactivity of the peroxy acids is increased by EWG substituents.72 These structure-reactivity relationships demonstrate that the peroxyacid acts as an electrophile in the reaction. Decreased reactivity is exhibited by double bonds that are conjugated with strongly electron-attracting substituents, and more reactive peroxyacids, such as trifluoroperoxyacetic acid, are required for oxidation of such compounds.73 Electron-poor alkenes can also be epoxidized by alkaline solutions of... 

Historically, the asymmetric synthesis of epoxides derived from electron-poor alkenes, for example a, (3-unsaturated ketones, has not received as much attention as the equivalent reaction for electron-rich alkenes (vide supra). However, a recent flurry of research activity in this area has uncovered several... 

The oxidation of organic substances by cyclic peroxides has been intensively studied over the last decades , from both the synthetic and mechanistic points of view. The earliest mechanistic studies have been carried out with cyclic peroxides such as phthaloyl peroxide , and more recently with a-methylene S-peroxy lactones and 1,2-dioxetanes . During the last 20 years, the dioxiranes (remarkable three-membered-ring cyclic peroxides) have acquired invaluable importance as powerful and mild oxidants, especially the epoxidation of electron-rich as well as electron-poor alkenes, heteroatom oxidation and CH insertions into alkanes (cf. the chapter by Adam and Zhao in this volume). The broad scope and general applicability of dioxiranes has rendered them as indispensable oxidizing agents in synthetic chemistry this is amply manifested by their intensive use, most prominently in the oxyfunctionalization of olefinic substrates. 

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... 

Other electron-poor alkenes generally require nucleophilic epoxidation conditions. These reactions usually proceed via non-concerted pathways (nucleophilic addition followed by epoxide ring closure), and so do not have the advantage of retaining the alkene geometry. Nevertheless, for the trans-epoxide, which is usually the predominant product, several methods exist that afford excellent levels of enantio-selectivity. 

Diols are directly converted into oxiranes with Ph3P or other phosphines in the presence of diisopropyl azodicarboxylate (Mitsunobu reaction). Simple alkenes can be converted into nonracemic epoxides in high yields and with excellent ee values via a two-step sequence of asymmetric dihydroxylation and Mitsunobu cyclodehydration of the intermediate diol (Scheme 18) <20010L2513>. These reactions give best results using electron-poor alkenes . 

The group of Strukul [134,175] has developed a class of electron-poor Pt(II) complexes which are efficient catalysts for the epoxidation of terminal alkenes with H2O2 (Table 1.6). The complexes have general structure [(P-P)Pt(CfTt)(H2O)] [X] where (P-P) is a diphosphine and X is BF4 or OTf. Kinetic studies showed that the complexes owed their reactivity to their ability to increase the nucleophilicity of the olefin by coordination, thereby changing the traditional electrophile/ nucleophile roles of the system [176] (see Chapter 2). 

Simple alkenes can also provide non-raccmic epoxides via a two-step sequence of asymmetric dihydroxylation (AD) and Mitsunobu cyclodehydration of the intermediate diol. For example, the styrene derivative 26 was converted to the corresponding (S)-epoxide in excellent yield and enantiomeric excess by standard AD conditions, followed by a combination of tricyclohexylphosphinc l(C6Hi])3PJ and diisopropyl azodicarboxylale (DIAD). The best optical yields were obtained with electron-poor alkenes, presumably due to the stabilization of the secondary alkoxidc intermediate (Scheme 2) <01OL2513>. 

The diaryl prolinol/TBHP system has been found to be suitable for the asymmetric epoxidation of a variety of poorly investigated trans-disubstituted or trisubstituted electron-poor alkenes (Scheme 7.5). ... 

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