Quaternary Carbon Centers by Cinchonine-Catalyzed Mannich Reactions

Significance

Herein, the scope of the cinchona alkaloid catalyzed Mannich reaction has been expanded. Also α-quaternary β-amino esters (acids) can now be prepared. Employing cyclic β-diketones 2 as the nucleophile and several acyl imines 3 as the electrophile, cinchonine (1) promoted the formation of β-keto ester products 4 in high yields (90-98%), diastereoselectivities (90-99% de) and enantioselectivities (90-99%). In addition, aryl-propenyl acyl imines 3 (R³= CH=CHAr) could be introduced as a new class of electrophiles for this reaction. The high selectivity of the catalyst is explained by its bifunctionality: the quinoline ring is able to shield the si-face of the enolized β-diketone, which can only be enolized if there is a hydroxyl group present in the catalyst.