Enone Julia-Colonna epoxidation

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]. 

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... 

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.

For an overview of the Julia-Colonna epoxidation of enones, see Berkessel, A. Groger, H. Asymmetric Organocatalysis , Wiley-VCH Weinheim, 2005, Chapter 10.2. 

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). 

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... 

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). 

Another important highlight in organocatalysis was also developed in the 1980s. Julia and Colonna reported the epoxidation of enones by H2O2 catalyzed by poly-L-leucine. This example is formally the first use of hydrogen-bonding catalysis in asymmetric synthesis (Scheme 1.7) [19]. 

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