Primary amine catalyzed aldol reaction of isatins and acetaldehyde

Several cinchona alkaloid-derived chiral primary amines were applied as the catalyst for the cross aldol reaction of isatins with acetaldehyde. With the quinine-derived amine catalyst 3, the desired aldol products were obtained in high yields and good enantioselectivities (up to 93% ee) under the optimized conditions. Although other enolizable aldehydes and ketones may also be applied in this reaction, the ee values obtained are usually low. A mechanism was proposed to account for the formation of the major enantiomer in this reaction.