Stereoselective Baeyer–Villiger oxidation of 3-substituted cyclobu-tanones promoted by flavinium-cinchona alkaloid ion-pair catalyst

The previously reported asymmetric Baeyer–Villiger (BV) oxidation of 3-substituted cyclobutanones promoted by a co-factor flavin derivative was revisited to broaden its scope. The correlation between the stereochemical outcome and the catalyst structure was examined, and only one stereocenter was found to be critical for achieving high stereoselectivity. This observa-tion led to the identification of a new, simpler catalyst with improved selectivity. By positioning a lone pair donor on the substrate, the selectivity was further enhanced to 95% ee using the original catalyst or >99% ee with the new catalyst, among the highest selectivities achieved for the BV reaction using a small-molecule catalyst. This observation supports our hypoth-esis that the H-bonding network is central to the catalyst. This study demonstrates the power of mechanistic investigation to broaden the scope of catalytic systems and aid in catalyst design. We are currently exploring methods to expand the applica-bility of this catalyst and demonstrate its use.