Cationic Chiral Fluorinated Oxazaborolidines. More Potent, Second-Generation Catalysts for Highly Enantioselective Cycloaddition Reactions

The coordination of chiral ligands to Lewis acid metal derivatives, a useful strategy for enantioselective, electrophilic catalysis, generally leads to a lower level of catalytic activity than that of the original uncomplexed compound. Activation by further attachment of a proton or strong Lewis acid to the complex provides a way to overcome the deactivating effect of a chiral ligand. The research described herein has demonstrated that further enhancement of catalytic activity is possible by the judicious placement of fluorine substituents in the chiral ligand. This approach has led to a new, second-generation family of chiral oxazaborolidinium cationic species which can be used to effect many Diels–Alder reactions in >95% yield and >95% ee using catalyst loadings at the 1–2 mol % level. The easy recovery of the chiral ligand makes the application of these new catalysts especially attractive for large-scale synthesis.