Air-Stable Zr(IV) Catalysts for Asymmetric Mannich Reactions

Significance

The development of a Zr(IV)-catalyzed Mannich-type reaction led to the discovery of an air-stable Lewis acid catalyst which can be reisolated and reused with virtually no erosion of activity and enantioselectivity. Silyl enol ethers, silyl ketene acetals, and silyl ketene thioacetals are all suitable nucleophilic precursors for the Mannich-type reaction with 2-aminophenol-derived imines. Both aliphatic and aromatic imines work well, affording products in good to quantitative yields and good to excellent enantioselectivities. Interestingly, the catalysts derived from (R)-6,6′-dibromo BINOL and (S)-6,6′-(C₂F₅)₂ BINOL appear to afford the identical product enantiomer.