Epoxidation of chalcone

In studies of the asymmetric epoxidation of olefins, chiral peroxycarboxylic acid induced epoxidation seldom gives enantiomeric excess over 20%.1 Presumably, this is due to the fact that the controlling stereocenters in peroxycarboxylic acids are too remote from the reaction site. An enantiomeric excess of over 90% has been reported for the poly-(Y)-alanine-catalyzcd epoxidation of chalcone.2 The most successful nonmetallic reagents for asymmetric epoxidation have been the chiral TV-sulfonyloxaziridincs3 until asymmetric epoxidation reactions mediated by chiral ketones were reported. Today, the... 

For epoxidation of chalcones using Ender s method, the results depend on the nature of the substrate. For the ( )-benzylideneacetophcnonc (R1, R2 = Ph), the enantiomeric excess was only 60 % using the same procedure as the one described above, whereas the polyleucine method furnished the epoxide with an enantiomeric excess > 95%. Table 4.3 gives some results of the epoxidation of some acyclic enones using Ender s method. 

The amount of molecular sieves 4 A largely influences the product s ee[11]. Usually 100 mg (for the CMHP oxidation) or 1 g (for the TBHP oxidation) of MS 4A for 1 mmol of substrate is enough however, in the case where chemical yield and/or optical yield are not high, use of excess MS 4A often improves them. The addition of achiral ligands such as tributylphosphine oxide, tri-o-tolyl- and tri-/)-tolylphosphine oxides, hexamethylphosphoric triamide, triphenylpho-sphate, lutidine N-oxide, and l,3-dimethyl-2-imidazolidinone were found to be less effective than that of triphenylphosphine oxide in the epoxidation of chalcone. 

The amount of the catalyst can be reduced to 1 mmol% without reducing the enantioselectivity considerably 99% ee (98% yield) of epoxychalcone was obtained in the epoxidation of chalcone with CMHP. 

As shown in Figure 4.5, a remarkably high positive nonlinear effect was observed in the La-BINOL-Ph3PO complex-catalysed epoxidation of chalcone (either with CMHP or with TBHP as an oxidant)1121, which strongly suggests that the active catalyst leading to high enantioselection does not have a monomeric structure but may exist as a thermodynamically stable dinuclear complex. 

Figure 4.5 Nonlinear effect in the epoxidation of chalcone using the La-(i )-BINOL-PI13PO/CMHP system.

Epoxidation of Chalcones Using Chiral Phase-Transfer Catalysts... 

Effect of solvent upon the phase-transfer catalysed epoxidation of chalcones... 

The stereoselective epoxidation of chalcones, followed by acid-catalysed ring closure and concomitant cleavage of the epoxide ring, provides a very efficient route to chiral flavon-3-ols and, subsequently, by borohydride reduction to produce flavan-3,4-diols [13, 14], It has been shown that diastereoselective reduction of the chiral flavon-3-ols by sodium borohydride in methanol yields the trans-2,3-dihydroxy compounds, whereas borohydride reduction in dioxan produces the cis-isomers [14] the synthetic procedure confirms the cis configuration of the 2,3-hydroxy groups of naturally occurring leucodelphinidins [14]. 

It is immediately apparent that the main attraction of the biphasic method is the much shorter reaction times it affords. This is illustrated well by the chalcone system. Using triphasic conditions, the epoxidation of chalcone can take up to 8 hours, while the biphasic reaction (Table 2, Entry 1) is complete in 30 minutes... 

When a poly-(L)-amino acid is used in the epoxidation of chalcone, the predominant optical isomer is laevorotatory [10]. The laevorotatory enantiomer of epoxychalcone has been shown [7] to have absolute configuration 2R, 3S). As anticipated, the use of a poly-(D)-amino acid as the epoxidation catalyst gives rise to the dextrorotatory enantiomer [10]. 

X = 3.9 111a, x = 7.5 111b, x = 11.6 111c, x = 12.2 llld SCHEME 51. Asymmetric epoxidation of chalcone with soluble polyleudne catalyst... 

Hori et have recently reported aza crown ether chiral quaternary ammonium salts for the epoxidation of ( )-chalcone with alkaline hydrogen peroxide as the terminal oxidant. The oxidation proceeded in high yield and good enantio-selectivity the success of the reaction depended on the length of the carbon chain on the nitrogen atom. These PTC catalysts are shown in Figure 1.50. 

Table 6.10 Asymmetric epoxidation of chalcones catalyzed by the azacrown ether-type quaternary ammonium salts as Chiral PTCs (see Figure 6.8).

Some insoluble organic macromolecules catalyze polar organic reactions (7). Asymmetric cyanohydrin formation is catalyzed by ami-nated cellulose with 22% optical yield and is an early example of this type of catalysis (8). Polypeptides that create a unique microenvironment through hydrogen bonding catalyze many organic reactions. Poly-[(S)-amino acids] accelerate the epoxidation of chalcone with alkaline... 

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]. 

Also striking was the discovery, by Julia, Colonna et al. in the early 1980s, of the poly-amino acid (15)-catalyzed epoxidation of chalcones by alkaline hydrogen peroxide [19, 20]. In this experimentally most convenient reaction, enantiomeric excesses > 90% are readily achieved (Scheme 1.6). 

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... 

An example of catalysts which are themselves heterogeneous are the poly-amino acids used for the asymmetric Julia-Colonna-type epoxidation of chalcones using alkaline hydrogen peroxide (Section 10.2) [8]. Because of the highly efficient synthesis of epoxides, this process also has attracted industrial interest (Section 14.3). Since recent work by the Berkessel group revealed that as few as five L-Leu residues are sufficient for epoxidation of chalcone, several solid-phase-bound short-chain peptides have been used, leading to enantioselectivity up to 98% ee [14], For example, (L-Leu)5 immobilized on TentaGel S NH2 , 8, was found to be a suitable solid-supported short-chain peptide catalyst for epoxidations. 

In parallel, the three-phase reaction system was improved. It was found that the reaction was strongly enhanced when performed in the presence of a phase-transfer catalyst as achiral additive [35-40], Epoxidation of chalcone 9 with 10 mol% TBAB led to >99% conversion within 7 min and high enantioselectivity of 94% ee (Scheme 14.3) [35]. In the absence of TBAB the asymmetric poly-L-leucine-catalyzed epoxidation afforded only 2% conversion after 1.5 h. It was also reported that the amount of catalyst could be further reduced. 

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