Julia-Colonna

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]. 

The improved Julia-Colonna epoxidation conditions have been successfully employed for poly-(D)-leucine. 

Julia-Colonna, Dolling phase transfer reactions Agami enamine-based reactions I Inoue, Upton peptide-based reactions... 

TABLE 14. Epoxidation results obtained under Julia-Colonna and Roberts conditions... 

EnQy o R R2 Method s Julia-Colonna conditions Roberts conditions Ref- erence... 

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

Adger, B.M., Barkley, J V. Bergeron, S., Cappi, M.W., Elowerdew, B.E., Jackson, M. R, McCague, R., Nugent, T.C. and Roberts, S.M. Improved Procedure for Julia-Colonna Asymmetric Epoxidation of a,/l-Unsaturated Ketones Total Synthesis of Diltiazem and Taxol Side-chain. J. Chem. Soc., Perkin Trans. 1 1997, 23, 3501-3507. 

The Julia - Colonna asymmetric epoxidation of electron-deficient unsaturated ketones to the corresponding epoxides with high yields and high ee is well known. This technique produces chiral chemical entities from the clean oxidant, hydrogen peroxide, without the use of a toxic or water sensitive transition metal additive. 

Entry 0 R1 R2 R2 Method Julia-Colonna conditions yield ee (%) (%) Roberts conditions yield ee (%) (%) Ref- erence... 

The Julia-Colonna epoxidation uses poly-L-leucine and hydrogen peroxide to effect enantioselective epoxidation of chalconc derivatives such as 12. In a pair of back-to-back papers (Tetrahedron Lett. 2004,45, 5065 and 5069), H.-Christian Militzer of Bayer Healthcare AG, Wuppertal, reports a detailed optimization of this procedure. In the following paper (Tetrahedron Lett. 2004,45,5073), Stanley Roberts of the University of Liverpool reports the extension of this procedure to unsaturated sulfones such as 14. 

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. 

D. Reichert, A. Kuhnle, H.-P. Krimmer and K. Drauz, Julia-Colonna asymmetric epoxidation in a continuously operated chemzyme membrane reactor, Synlett 2002, (5), 707-710. 

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). 

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. 

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