Baeyer-Villiger oxidation reaction kinetics

The stereochemistry of the C(3) hydroxy was established in Step D. The Baeyer-Villiger oxidation proceeds with retention of configuration of the migrating group (see Section 12.5.2), so the correct stereochemistry is established for the C—O bond. The final stereocenter for which configuration must be established is the methyl group at C(6) that was introduced by an enolate alkylation in Step E, but this reaction was not very stereoselective. However, since this center is adjacent to the lactone carbonyl, it can be epimerized through the enolate. The enolate was formed and quenched with acid. The kinetically preferred protonation from the axial direction provides the correct stereochemistry at C(6). 

The Ti-silicalite catalysed Baeyer-Villiger oxidation of cyclohexanone by H2O2 in aqueous solution promotes a high concentration of OH radicals, which accelerate the reaction and the consecutive formation of adipic acid (and of lighter diacids as well) as the kinetically preferred product. In the absence of the catalyst, the primary reaction product is e-caprolactone, which quickly undergoes consecutive transformations to form adipic acid even when a stoichiometric amount of the oxidant is used, since it is more reactive than cyclohexanone. The choice of solvent, which could act as a radical scavenger, also allows control over the reaction rates. ° ... 

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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