Synthesis of Optically Active α-Hydroxy Carbonyl Compounds by the Catalytic, Enantioselective Oxidation of Silyl Enol Ethers and Ketene Acetals with (Salen)manganese(III) Complexes

A set of silyl enol ethers and ketene acetals 1a − h with α- and/or β-phenyl as well as alkyl substituents of different steric bulk has been submitted to the enantioselective catalytic oxidation by chiral (salen)MnIII complexes 3. Highest conversions and best enantioselectivities have been obtained with bleach rather than iodosobenzene as oxygen source for the active oxo−metal species. With regard to substrate structure, ee values up to 89% have been achieved for enol ethers with short and unbranched alkyl substituents at the siloxy position. While β-phenyl groups are beneficial for enantiofacial control, phenyl substituents α to the siloxy functionality result in lower ee values, while the diphenyl-substituted derivative 1d displays the lowest stereoselectivity. The fact that β- versus α-phenyl substituents exhibit not only differences in the magnitude but also in the sense (opposite absolute product configuration) of the stereoselectivity may be utilized as a valuable mechanistic probe to assess steric and electronic effects in the substrate and the catalyst as a function of the type and pattern of substitution. Our results display that steric interactions between the substrate and the oxo−metal complex are mainly responsible for the observed stereochemical preferences. Indeed, significantly increased enantioselectivities are achieved even for the remote siloxy group when bulkier derivatives are employed. In contrast, primarily electronic effects operate in the (salen)MnIII catalyst 3 since electron-donating groups in the 5,5‘ positions of the salicylaldehyde ligand afford higher ee values in this catalytic oxidation. The skewed side-on approach (trajectory b) of the substrate onto the oxo−metal catalyst is favored, the metallaoxetane mechanism adequately accounts for the observed enantioselectivities. Herewith a synthetically valuable method for the preparation of optically active α-hydroxy carbonyl products 2 has been made available through the catalytic, enantioselective oxidation of the silyl enol ethers 1 by (salen)MnIII complexes.