Julia-Colonna catalysts

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

Unnatural amino acid backbones can also act as catalysts. Poly-/J-leucines have been evaluated as catalysts for the Julia-Colonna asymmetric epoxidahon of enones the /3-3-isomer was found to be an effective catalyst for the epoxidahon ofchalcone (70% e.e.) and some analogs (Coffey, 2001). 

All these findings serve to illustrate that the Julia-Colonna epoxidahon is not completely understood yet. More importantly in the context of this book, there is not much indication that poly-(amino acid)s as catalysts bear much resemblance to proteins. 

J. Skidmore, and J. A. Smith, beta-Peptides as catalysts poly-beta-leudne as a catalyst for the Julia-Colonna asymmetric epoxidation of enones, Chem. Commun. 2001, (22), 2330-2331. 

Because the catalyst is usually prepared by the polymerization of amino acid N-carboxy anhydrides, induced by water or amines [66, 67], the Julia-Colonna epox-idation was soon recognized as a reaction of great practical value. In the course of exploration of the scope of the Julia-Colonna procedure many enone substrates were successfully epoxidized by use of the original three-phase conditions (Table 10.8). 

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. 

Researchers at Bayer AG addressed these critical issues and developed successful solutions enabling commercial application of Julia-Colonna-type epoxidation [35-40]. Starting with optimization of catalyst preparation, a straightforward synthesis based on inexpensive reagents and requiring a shorter reaction time was developed for the poly-Leu-catalyst [35], In particular, the reaction time for the new polymerization process was only 3 h when the process was conducted at 80 °C in toluene, compared with 5 days under classic reaction conditions (THF, room temperature). Furthermore, the catalyst prepared by the Bayer route is much more active and does not require preactivation [35-40],... 

Preparation and activation of silica-supported poly-L-leucine[150] has been studied under a variety of reaction conditions leading to an efficient procedure for the preparation of material suitable for use in the Julia-Colonna asymmetric epoxidation reaction. Poly-L-leucine, can be added to the list of natural11511 and non-natural[152] oxidation catalysts that benefit from being supported on commercially available silica gel. 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

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,... 

Scheme 16. Monodisperse and solid-phase-bound peptide catalysts for the Julia-Colonna epoxidation.

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. ... 

All the Julia-Colonna catalytic systems presented above are heterogeneous, in which two or three phases are used for obtaining good results. However, homogeneous catalytic systems are generally more attractive for academia and often for applications on industrial scales. Some examples of homogeneous systems have been developed by modifications of the appropriate catalysts [140, 141]. 

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