Epoxidation of Electron-poor Olefins

In 2011 Demizu und Kurihara published stapled and linear helical l-Lcu-based peptides that catalyse enantioselective epoxidation of chalcones with yields up 99% and enantioselectivities up to 99%/ The nucleophilic reaction was carried out with 5 mol% peptide, urea-hydrogen peroxide as oxidant and DBU as base. The most active peptide, which was an efficient catalyst in epoxidation of several a,p-unsaturated ketones, was found to be the stapled heptapeptide containing L-homoserine in the third and seventh positions with a linker in between. 

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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. 

In the presence of cinchona derivatives as catalysts, peroxides or hypochlorites as Michael donors react with electron-deficient olefins to give epoxides via conjugate addition-intramolecular cyclization sequence reactions. Two complementary methodologies have been developed for the asymmetric epoxidation of electron-poor olefins, in which either cinchona-based phase-transfer catalysts or 9-amino-9(deoxy)-epi-dnchona alkaloids are used as organocatalysts. Mechanistically, in these two... 

Deprotonated peroxide coordinates to metals in low- and intermediate-oxidation states tend to bind side-on and display nucleophilic properties. For example, iron(III) porphyrin-peroxo complexes are nucleophilic they did not transfer an oxygen atom to electron-rich substrates (such as electron-rich olefins), but brought about epoxidation of electron-poor olefins or oxidative deformylation of aldehydes.130 Dinuclear... 

JULI A-COLONNA Asymmetric Epoxidation Asymmetric epoxidation of electron-poor olefins catalyzed by poly-a amino acids. 

Acetyl hypofluorite (AcOF) and methyl hypofluorite (MeOF) as fluorinating agents of olefins and aromatics3 HOF-MeCN an oxygen transfer agent in epoxidation of electron poor olefins, in Baeyer-Villiger reaction, in oxidation of a-amino acids to a-nitro acids. 

Scheme 13.31 Epoxidation of electron-poor olefins catalysed by poly-L-leucine catalysts 53-55.

Banfi S, Colonna S, Molinaii H, Julia S, Guixer J (1984) Asymmetrie Epoxidation of Electron-Poor Olefins. 5. Influence rai Stereoselectivity of the Structure of Poly-a-Aminoacids Used as Catalysts. Tetrahedron 40 5207... 

Not only oxidants with nucleophilic character but also intermediates of electrophilic nature can be used in the enantioselective epoxidation of a,p-unsaturated carbonyl compounds. Among the possible candidates, dioxirane reagents have been successfully used for this purpose. Contrary to the usual nucleophilic oxidants, dioxiranes add to double bonds in a concerted manner. These dioxiranes could be easily prepared in situ by reaction of oxone (2KHS05-KHS0 K3S0 ) with chiral ketones. Chiral ketones derived from quinic acid such as compounds 61 [67], which have been successfully used in the enantioselective epoxidation of electron rich olefins, have been also applied to the epoxidation of electron poor olefins such as chalcone 7 or a,P-unsaturated esters 59 (Scheme 4.10) to give the corresponding... 

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. 

The asymmetric epoxidation of several chalcones (39) and other electron-poor olefins in a triphase system (water/organjc solvent/chiral polyamino acid) afford optically active oxirans with optical yields of up to 96%. The influence of the molecular structure of the catalysts and substrates, the solvent, and the temperature on the stereochemistry was investigated by a group of chemists from Italy and Spain 77). 

Another method is to use poly-L-amino acids as catalysts in alkaline media (Julia-Colanna epoxidation) for the asymmetric epoxidation of chalcones and other electron-poor olefins with H202 [287]. SmithKline Beecham workers used this method (see Fig. 4.105) as a key step in the synthesis of a leukotriene antagonist, although it required 20 equivalents of H202 and 12 equivalents of NaOH, based on substrate [288]. The mechanism probably involves the asym-... 

Quaternary ammonium salts of alkaloids have been used for the synthesis of optically active oxiranes from electron-poor olefins under phase-transfer conditions. The enantiomer yield is inversely proportional to the dielectric constant of the solvent,Asymmetric epoxidation in the presence of catalytic amounts of poly-(S)-amino-acids in a triphase system has been described with optical yields up to 96% ... 

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). 

Substituent effects on this kind of concerted, stereospecific epoxidation indicate that the peroxy-acid functions as an electrophile electron-donating groups activate the olefin vhile electron-withdrawing groups strongly deactivate it. When the electron flow at the transition state is reversed by using electron-poor olefins and peroxy anions for epoxidation, the reaction is stepwise and stereo-equilibrating and both cis- and trans-olefins (e.g., benzalacetophenone) yield trans-epoxide. (13. 14)... 

A more efficient agent than peroxy compounds for the epoxidation of fluoro-olefins with nonfluonnated double bond is the hypofluorous acid-acetomtrile complex [22] Perfluoroalkylethenes react with this agent at room temperature within 2-3 h with moderate yields (equation 13), whereas olefins with strongly electron-deficient double bond or electron-poor, sterically hindered olefins, for example l,2-bis(perfluorobutyl)ethene and perfluoro-(l-alkylethyl)ethenes, are practically inert [22] Epoxidation of a mixture of 3 perfluoroalkyl-1-propenes at 0 C IS finished after 10 mm in 80% yield [22] The trifluorovinyl group in partially fluorinated dienes is not affected by this agent [22] (equation 13)... 

Polyoxometalates have been used as homogenous catalysts for a wide variety of thermal organic substrate oxidations37. This involves the epoxidation of relatively electron poor terminal olefins by H2O2 and heteropoly acids, principally H3[PWi2C>4o], using PTC (equation 9). 

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