Chalcones Julia-Colonna epoxidation

Researchers at Degussa AG focused on an alternative means towards commercial application of the Julia-Colonna epoxidation [41]. Successful development was based on design of a continuous process in a chemzyme membrane reactor (CMR reactor). In this the epoxide and unconverted chalcone and oxidation reagent pass through the membrane whereas the polymer-enlarged organocatalyst is retained in the reactor by means of a nanofiltration membrane. The equipment used for this type of continuous epoxidation reaction is shown in Scheme 14.5 [41]. The chemzyme membrane reactor is based on the same continuous process concept as the efficient enzyme membrane reactor, which is already used for enzymatic a-amino acid resolution on an industrial scale at a production level of hundreds of tons per year [42]. 

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... 

Several examples are known of the enantioselective conversion of alkenes into epoxides with the use of polymer-supported oxidation catalysts. This can be traced to the pioneering work by Julia and Colonna in 1980. They demonstrated that highly enantioselective epoxidations of chalcones and related a, 3-unsaturated ketones can be achieved with the use of insoluble poly(a-amino acids) (116, Scheme 10.20) as catalysts [298-301]. The so-called Julia-Colonna epoxidation has been the object of several excellent reviews [302-306]. The terminal oxidant is H202 in aq. NaOH. With lipophilic amino acids as the components, such as (SJ-valine or (SJ-leucine, enantioselectivities as high as 96-97% ee were obtained. The enan-tioselectivity depends of several factors, including the side-chain of the amino acid, the nature of the end groups and the degree of polymerization. Thus, for instance,... 

Fig. 3. Peptide-catalyzed Julia-Colonna epoxidation of chalcone (37) top binding of the substrate enone to the N-terminus of the helical peptide bottom P-hydroperoxy-enolate bound to the N-terminus of the peptide catalyst.

The epoxidation ofa, (3-unsaturated ketones catalysed by polyamino acids is known as the Julia-Colonna epoxidation.This three-phase procedure utilises aqueous hydrogen peroxide as oxidant along with a water immiscible solvent and solid poly-L-leucine as a catalyst and is mainly effective in the epoxidation of chalcone (4.79) and derivatives. ... 

Scheme 7.85 Enantioselective Julia-Colonna epoxidation of chalcones.

Nucleophilic epoxidation (Julia-Colonna epoxidation) of trans-chalcone and derivatives with hydrogen peroxide catalysed by Nagasawa-G (Scheme 23.1) was shown to proceed successfully with a biphasic system consisting of water and toluene. This is a highly atom economical reaction (92% for chalcone). 

Julia-Colonna epoxidation in the synthesis of (+)-clausenamide (638). The y-lactam clausenamide (638) was isolated from the leaves of Clausena lansium, a species that is a liver-protecting Chinese folk medicine and is utilized also in cases of acute and chronic viral hepatitis (549). In their synthesis of 638, Roberts et al. employed a fixed-bed poly-L-leucine catalyst together with DABCO-H2O2 as the oxidant to carry out an early-stage epoxidation of chalcone 639 to obtain epoxide 640 in high enantiomeric excess (>98% ee) (Scheme 132). After five more steps, the total synthesis of (+)-clausenamide (638) was accomplished in an overall yield of 40% (547). 

Berkessel et al. addressed the question of identifying the minimal catalophore (i.e., the minimum peptide length for catalytic activity). For this purpose, they synthesized a library of L-leu oligomers (1-20 mer) on TentaGel, and tested these solid-phase-bound oligopeptides in the Julia-Colonna epoxidation [38]. This work revealed that as few as five L-Leu residues are sufficient for the epoxidation of chalcone to take place with 96-98% enantiomeric excess. The result strongly suggests that one turn of a helical peptide is the minimal structural element required for catalysis. 

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). 

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. 

The Julia-Colonna method, which uses polyleucine, can form an epoxide from a chalcone (Scheme 9.17).126-132 However, the method is limited to aryl-substituted enones and closely related systems, and even then scale up of the procedure has been found to be problematic.133 The product of the epoxidation 14 has been used in a synthesis of (+)-clausenamide (15).134... 

Polyamino acid 8 catalyzed the epoxidation of chalcones in the presence of alkaline hydrogen peroxide. The Julia-Colonna reaction furnished the corresponding oxiranes with excellent enantioselectivities (Equation 10.21) [43]. 

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). 

A research team from Bloemfontein (South Africa) have also taken advantage of the Julia and Colonna oxidation in elegant research aimed at the synthesis of optically active flavonoids. Bezuidenhoudt, Ferreira et al. have oxidised a range of chalcone derivatives using poly-(L)-alanine in the three phase system to afford optically active epoxides 4 which were readily cyclised to target compounds of the dihydroflavinol type 5, (Scheme 3) [16]. 

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... 

In addition, solid-phase bound short-chain peptides have been recently found by the Ber-kessel group to act as highly efficient catalysts in asymmetric epoxidation reactions [17]. In the early 1980s, Julia and Colonna reported that chalcone 11 can be epoxidized asymmetrically by akaline hydrogen peroxide in the presence of poly-amino acids as catalysts [18, 19], The work by Berkessel et al. revealed that in fact as little as five I-Leu residues are sufficient for the epoxidation of the enone 11 with 96-98% ee (Scheme 8). 

Julia and Colonna in the 1980s described the asymmetric epoxidation of chalcones by using polypepbdes such as poly-alanines and poly-leucines [35]. 

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