Baeyer-Villiger oxidation kinetic resolution

TABLE 8-1. Yeast-Mediated Kinetic Resolution of 2-Substituted Ketones via Baeyer-Villiger Oxidation... 

SCHEME 169. Chiral Pt complexes 231 employed as asymmetric inductors in the kinetic resolution of racemic cyclic ketones formed by enantioselective Baeyer-Villiger oxidation... 

Preparation of optically active P-ionone epoxide by a solid state kinetic resolution in the presence of the chiral host 10a is also possible. When a mixture of 10a, P-ionone (66) and m-chloroperbenzoic acid (MCPBA) is ground by mortar and pestle in the solid state, (+)-67 of 88% ee was obtained.29 Mechanism of the kinetic resolution is shown below. Of course, all processes proceed in the solid state. Firstly, oxidation of 66 with MCPBA gives rac-P-ionone epoxide (67). Secondly, enantioselective inclusion of (+)-67 with 10a occurs. Thirdly, uncomplexed (-)-67 is oxidized to give the Baeyer- Villiger oxidation product (-)-68 of 72% ee. This is the first example of the resolution by an enantioselective inclusion complexation in the solid state. 

Dynamic kinetic resolution process was also applied to biocatalytic Baeyer-Villiger oxidations. The recombinant E. coli expressing the cyclohexanone monooxygenase from A. calcoaceticus was used for the oxidation of racemic... 

Figure 32. Kinetic resolutions of ketones through Baeyer-Villiger oxidation...

Application of dynamic kinetic resolution has also been reported in a whole-cell enzymatic Baeyer-Villiger process. While this was initially done using slightly basic conditions, Furstoss and Alphand have more recently reported the use of a weakly basic anion exchange resin to promote racemization of the slow oxidizing enantiomer 99 to the fast enantiomer 100.53 Baeyer-Villiger oxidation using recombinant E. coli to overexpress the CHMO from A. calcoaceticus provided excellent yield and % ee of lactone 101. 

Baeyer-Villiger oxidation. In kinetic resolutions of chiral ketones (as racemic mixtures) up to 58% ee has been observed. The configuration of the migrating carbon is retained. 

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

The substrates, ( )-E-caprolactones 1, 2 and 3 (Figure 1) were synthesized by Baeyer-Villiger oxidation of the corresponding cyclohexanones and kinetic resolutions were examined using Novozym-43S (immobilized lipase-B from Candida antarctica catalyzed ring-opening of the lactones 1, 2, and 3 with 1.5 molar equivalents of n-butanol (Scheme-1). Authentic samples of the racemic... 

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. 

Gutierrez M-C, Furstoss R, Alphand V (2005) Microbiological transformations 60. Enantioconvergent Baeyer-Villiger oxidation via a combined whole cells and ionic exchange resin-catalysed dynamic kinetic resolution process. Adv Synth Catal 347(7-8) 1051-1059. doi 10.1002/adsc.200505048... 

N. Berezina, V. Alphand, R. Furstoss, Microbiological transformations. Part 51 The first example of a dynamic kinetic resolution process applied to a microbiological Baeyer-Villiger oxidation. Tetrahedron Asymmetry 13 (2002) 1953-1955. 

Bolm et al. (130) reported the asymmetric Baeyer-Villiger reaction catalyzed by Cu(II) complexes. Aerobic oxidation of racemic cyclic ketones in the presence of pivalaldehyde effects a kinetic resolution to afford lactones in moderate enan-tioselectivity. Aryloxide oxazolines are the most effective ligands among those examined. Sterically demanding substituents ortho to the phenoxide are necessary for high yields. Several neutral bis(oxazolines) provide poor selectivities and yields in this reaction. Cycloheptanones and cyclohexanones lacking an aryl group on the a carbon do not react under these conditions. 

The Baeyer-Villiger (B V) oxidation reaction is a very old chemical transformation that converts ketones into the corresponding esters or lactones hy inserting an oxygen atom from the oxidant between the carbonyl carbon and the one next to it The first report on the asymmetric BV oxidation appeared about fifteen years ago thanks to the pioneering work of Bolm and Strukul. These authors independently demonstrated, with two different catalysts and oxidant combinations, that a certain degree of stereocontrol of the process was possible, with ee up to 92% on chiral cyclobu-tanones and 58% in the kinetic resolution of chiral-substituted cyclohexanones, respectively. After these seminal contributions, a series of different catalysts have been proposed. 

The mechanism shown uses m-chloroperoxybenzoic acid (mCPBA) as the oxidant. The enzymatically catalyzed reaction uses molecular oxygen. The reaction is considered a kinetic resolution, discussed further in Section 3.4. The enzyme reacts faster with the S enantiomer, allowing formation of the S lactone and separation of the unreacted R ketone, which can be converted to the R lactone using traditional Baeyer-Villiger conditions [36]. 

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