Weitz-Scheffer epoxidation

Compared to metal-catalyzed asymmetric epoxidation reactions, asymmetric versions of this reaction without the need of a catalyst (apart from a base) are rarely known. In 2000 Adam and coworkers reported a method for the asymmetric Weitz-Scheffer epoxidation of substituted enones 91 by the secondary, optically active hydroperoxide (5 )-(l-phenyl)ethyl hydroperoxide (equation 27, Table 10). ... 

TABLE 10. Enantioselective Weitz-Scheffer epoxidation of substituted enones p-XC6H4C(0)CH= CR with (5)-(l-phenyl)ethyl hydroperoxide... 

One of the early examples for organocatalysis is the asymmetric Weitz-Scheffer epoxidation of electron-deficient olefins, which can be effected either by organic chiral phase transfer catalysts (PTC) under biphasic conditions or by polyamino acids. This reaction has gained considerable attention and is of great synthetic use. 

SCHEME 49. Weitz-Scheffer epoxidation of isoflavones 101 by various hydroperoxides and the chiral PTCs 103h-k... 

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

In the early 1980s, Julia and Colonna reported that the Weitz-Scheffer epoxidation of chalcone (45a) can be catalyzed by poly-amino acids such as poly-L-alanine, and that the resulting epoxide is formed with enantiomeric excesses > 90% (Scheme 10.8) [66]. In the original three-phase procedure the enone is dissolved in an... 

Finally, it should be mentioned that poly-amino acid catalysts have been used either to enhance or override substrate-induced diastereoselectivity in the Weitz-Scheffer epoxidation of chiral enones (Scheme 10.12) [90]. 

In the 1980s, Julia and Colonna discovered that the Weitz-Scheffer epoxidation of enones such as chalcone (4, Scheme 2) by alkaline hydrogen peroxide is catalyzed in a highly enantioselective fashion by poly-amino acids such as poly-alanine or poly-leucine (Julia et al. 1980, 1982). The poly-amino acids used for the Julia-Colonna epoxidation are statistical mixtures, the maximum length distribution being around 20-25 mers (Roberts et al. 1997). The most fundamental question to be addressed refers to the minimal structural element (i.e. the minimal peptide length) required for catalytic activity and enantioselectiv-ity. To tackle this question, we have synthesized the whole series of L-leucine oligomers from 1- to 20-mer on a solid support (Berkessel... 

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

Another reaction where amino acids play a key role is the Julia-Golonna epoxidation of a,P-unsaturated ketones [52], which involves the use of a catalytic amount of polymeric amino acids, able to catalyze the Weitz-Scheffer epoxidation of chalcone using basic hydrogen peroxide, with high enantioselectivity (Scheme 8.17 Equation a). 

In 2007, the Lygo group surveyed the optimal oxidant for the asymmetric Weitz-Scheffer epoxidation of chalcone 50 through use of various oxidants in the presence of catalyst 8p. Among the oxidants, they found that aqueous sodium hypochlorite was the most effective oxidant for the epoxidations under mild phase-transfer catalytic conditions (Scheme 16.38). ... 

Scheme 16.38 Research of Weitz-Scheffer epoxidation under phase-transfer catalytic conditions.

The epoxidation of a,P-unsaturated carbonyl compounds with hydrogen peroxide under basic biphase condition, known as the Weitz-Scheffer epoxidation (Scheme 64) is a very convenient and efficient method for giving the epoxides. 

Adam W, Rao PB, Degen HG, Levai A, Patonay T, Saha-Moller CR. Asymmetric Weitz-Scheffer epoxidation of iso-flavones with hydroperoxides mediated by optically active phase-transfer catalysts. J. Org. Chem. 2002 67(l) 259-264. 

The asymmetric epoxidation of electron deficient alkenes like a,p-unsaturated esters, ketones and nitriles often is not efficient with the reagents suitable for electron rich systems. Prominent examples for the successful epoxidation of a,P-enones are the well-known Weitz-Scheffer epoxidation using alkaUne hydrogen peroxide or... 

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