Baeyer-Villiger reaction substituent effects

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 accepted two-step mechanism (Scheme 1) for the Baeyer-Villiger reaction is based upon kinetic, isotopic substitution, stereochemical and substituent effect studies. In step 1 of the reaction, addition of... 

RB3LYP calculations indicate that the s-cis conformer of peroxy acids is more stable than the s-trans conformer. Calculations on the reaction of prop-2-enol with some peroxy acids showed that trans-transition states collapse to the epoxide via a 1,2-shift, whereas a 1,4-shift is operable for cis-transition states.195 Quantum mechanical calculations have been performed on the migration step of the Baeyer-Villiger rearrangements of some substituted acetophenones with m-chloroperbenzoic acid (m-CPBA). The energy barriers, charge distributions and frontier molecular orbitals, determined for the aryl migration step, have been used to explain the effects of substituents on the reactivity of the ketones.196... 

The rates of epoxidation of 5,6-disubstituted norborn-2-enes by perbenzoic acid to give 2,3-exo-cis-epoxides are found to increase in the order 5,6-exo-ds < 5,6-trans < 5,6-endo-cis isomer. Substituent electronic effects on reaction rate are discussed. " An interesting report records the use of nitroxide catalysis in the oxidation of alcohols in m-chloroperbenzoic acid. For example, attempted preparation of (515) by direct epoxidation of norbome-2-one gives instead a rearranged Baeyer-Villiger product. Treatment of norborn-5-en-2-ol with one equivalent of the peracid in CHjClj, followed by the addition of a second equivalent and a catalytic amount of 2,2,6,6-tetramethylpiperidine hydrochloride (TMP-HCl) affords (515) in 86 % yield. Likewise... 

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