Baeyer-Villiger desymmetrization

The high chemoselectivity for the Baeyer-Villiger process was utilized in the synthetic elaboration of another hetero-bicyclic substrate. The biooxidation only provides the expected unsaturated lactone in a desymmetrization reaction without compromising the olefin functionality. The biotransformation product was then converted to pivotal intermediates for C-nucleosides like showdomycin, tetrahydro-furan natural products like kumausyne, and goniofufurone analogs in subsequent chemical operations (Scheme 9.17) [161]. 

Camell and co-workers have recently applied lipase-catalysed resolution to formally desymmetrize prochiral ketones that would not normally be considered as candidates for enzyme resolution, through enantioselective hydrolysis of the chemically prepared racemic enol acetate. " For example, an NK-2 antagonist was formally desymmetrized by this approach using Pseudomonas fluorescens hpase (PFL) (Scheme 1.40). By recychng the prochiral ketone product, up to 82 % yields of the desired (5)-enol acetate (99 % ee) could be realized. This method offers a mild alternative to methodologies such as base-catalysed asymmetric deprotonation, which requires low temperature, and biocatalytic Baeyer-Villiger oxidation, which is difficult to scale up. 

Although the use of asymmetric Baeyer-Villiger reactions for desymmetrization of several types of prochiral ketone using enzymes or metal-catalyzed systems is well established [81], few studies have been conducted on organocatalytic variants. An interesting organocatalytic Baeyer-Villiger reaction has been reported in which the planar-chiral bisflavin 32 (Fig. 12.12) promotes desymmetrization... 

Stereoselective epoxidation of alkenes, desymmetrization of maso-TV-sulfonylaziri-dines, Baeyer-Villiger oxidation of cyclobutanones, Diels-Alder reactions of 1,2-dihydropyridines, and polymerization of lactides using metal complexes of chiral binaphthyl Schiff-base ligands 03CCR(242)97. 

Katsuki recently reported the use of Zr-salen complexes to promote the oxidative desymmetrization of 2-Ph-cyclobutanone 64. Katsuki utilized UHP and the C2-symmetric salen ligand, Zr-salen, which proved to be the best ligand screened. Reaction of ketone 64 with 5 mol% Zr-salen and UHP provided lactone 65 in good yield and 87% ee. These conditions also worked well with racemic bicyclooctanone 66 which provided a mixture of normal 67 and abnormal 68 Baeyer-Villiger products.34 The remaining ketone was recovered in 92% ee. 

Scheme 2.161 Desymmetrization of prochital ketones via enzymatic Baeyer-Villiger oxidation...

Scheme 2.165 Regio- and enantioselective Baeyer-Villiger oxidation using cloned Baeyer-Villigerases exhibiting desymmetrization, and classic and nonclassic kinetic resolution...

Zhou, L., Liu, X., Ji, J., Zhang, Y, Hu, X., Lin, L., Feng, X. (2012). Enantioselective Baeyer-Villiger oxidation desymmetrization of meso cyclic ketones and kinetic resolution of racemic 2-arylcyclohexanones. Journal of the American Chemical Society, 134, 17023-17026. 

Mihovilovic and coworkers have utilized a microbial Baeyer-Villiger oxidation to desymmetrize readily available 8-oxabicyclo[3.2.1]octene 218. Their key reaction used E. coli in a whole-cell oxidation to give multi-gram quantities of 219 in high optical purity (Scheme 59) [67], To demonstrate its utility they transformed 219 into 220, 221, and 222 thus intercepting intermediates that had previously been converted into the namral products (+)-trani-kumausyne, goniofufurone, and (+)-showdomycin. 

---