Julia-Colonna reaction/epoxidation

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. 

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). 

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]. 

Gerlach, A. and Geller, T. Scale-up Studies for the Asymmetric Julia-Colonna Epoxidation Reaction. Adv. Synth. Catal. 2004, 346, 1247-1249. 

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). 

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). 

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]. 

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. ... 

B.iii. Julia-Colonna Epoxidation. A new and useful innovation involving the hydroperoxide anion epoxidation of conjugated carbonyl compounds modified the procedure so the reaction is done in the... 

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). 

The Julia-Colonna epoxidation uses different polyamino acid derivatives as catalysts [62], However, owing to their very high molecular weight (close to the enzymes) this reaction is not a topic of this article. 

In the early 1980 s Julia and Colonna published a series of papers which, to some extent, filled the gap left by the natural biocatalysts. The Spanish and Italian collaborators showed that a, -unsaturated ketones of type 1 underwent asymmetric oxidation to give the epoxide 2 using a three-phase system, namely aqueous hydrogen peroxide containing sodium hydroxide, an organic solvent such as tetrachloromethane and insoluble poly-(l)-alanine, (Scheme 1) [12]. The reaction takes place via a Michael-type addition of peroxide anion (the Weitz-Scheffer reaction). 

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