Chalcone derivatives, asymmetric epoxidation

The asymmetric epoxidation reaction with polyleucine as catalyst may be applied to a wide range of a, 3-unsaturated ketones. Table 4.1 shows different chalcone derivatives that can be epoxidized with poly-L-leucine. The substrate range included dienes and tctracncs151. Some other examples were reported in a previous edition161 and by M. Lastcrra-Sanchcz171. 

The catalytic asymmetric epoxidation of electron-deficient olefins has been regarded as one of the most representative asymmetric PTC reactions, and various such systems have been reported (Scheme 3.12). Lygo reported the asymmetric epoxidation of chalcone derivatives through the use of NaOCl [30,31], while Shioiri and Arai used aqueous H202 as an oxidant, their results indicating hydrogen bonding between the catalyst and substrates because an OH functionality in the catalyst was essential... 

The Wang group also reported the asymmetric epoxidation of chalcone derivatives with their polymer-supported dimeric PTC 61 using fert-butyl hydroperoxide as an oxidant (Scheme 4.18) [23]. 

Chiral monoaza-15-crown-5 derived from D-glucose 92 was shown to be another good catalyst in the asymmetric epoxidation of chalcones with tert-butylhydroper-oxide as the oxidant, with the highest enantioselectivity (94% ee) being reported by Bako (entry 4, Table 11.8) [71]. The tetracyclic C2-symmetric guanidiurn salt 93, which was prepared from (SJ-malic acid by Murphy, also showed excellent enantioselection in the asymmetric epoxidation of chalcone (entry 5) [72]. 

A contrasting example is the peptide-catalyzed asymmetric epoxidation of chalcones, the so-called Julia-Colonna reaction. The latter authors discovered in the early 1980s that poly-amino acids such as poly-L-alanine or poly-L-leucine catalyze the asymmetric epoxidation of chalcone (37) and derivatives using alkaline dihydrogen peroxide as the terminal oxidant (Scheme 15) (49,50). 

The mechanism of the a,a-L-diarylprolinol-catalysed asymmetric epoxidation of enones with TBHP has been studied by second-order Moller-Plesset perturbation theory and DFT calculations. Non-covalent activation of the reactants is shown to initiate an energetically viable pathway, thereby a two-step nucleophilic epoxidation mechanism, with the first oxa-Michael addition being the rate- and stereoselectivity-determining step. Consistent with the experimental findings, the formation of the (2/ ,35)-enantiomer of the epoxide, derived from trani -chalcone, is energetically favoured." ... 

Roberts has shown that the asymmetric epoxidation of chalcone can be catalysed by polyamino acid derivatives under non-aqueous conditions [13]. This improved reaction involves the use of a urea-hydrogen peroxide complex in THF, in the presence of an organic base (DBU) and immobilized poly-(L)-leucine. Under these conditions, the reaction of chalcone derivatives and related substrates provided the corresponding epoxides in 70-99% yield and 83-95% ee within 30 min. Several substrates with enolisable enones have also been epoxidized successfully [14]. 

The asymmetric epoxidation of the chalcone type of substrate has also been accomplished using other types of chiral catalysts [15]. Wynberg was the first to use chiral ammonium salts, and obtained chalcone oxide with 55% ee using alkaline hydrogen peroxide as the stoichiometric oxidant and a quinine-derived quaternary ammonium salt as the chiral phase transfer catalyst [16]. More recently, Lygo... 

Lygo and Wainwright recently reported a detailed study of the asymmetric phase-transfer mediated epoxidation of a variety of acyclic a,P-unsaturated ketones of the chalcone type. The third-generation cinchona-derived quats (8c and 7c), related to those discussed earlier in the alkylation section and Scheme 10.4, gave the best inductions (89% ee, 88 to 89, Scheme 10.13 and 86% ee for the pseudoenantiomeric catalyst 7c to give, as product, the enantiomer of 89). 

The mechanism of the polyleucine-catalyzed epoxidation is still under investigation [74]. Kinetic studies indicate that the reaction proceeds via the reversible addition of chalcone to a polyleucine-bound hydroperoxide [75]. Recent discussions have included studies of asymmetric amplification polyleucine derived from non-enantiopure amino acid shows highly amplified epoxide enantiomeric excess, and the results fit a mathematical model requiring the active catalyst to have five terminal homochiral residues, as rationalized by molecular modeling studies [76]. 

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