Chiral Bifunctional Guanidine-Catalyzed Enantioselective Aza-Henry Reaction of Isatin-Derived Ketimines

An efficient asymmetric aza-Henry reaction of isatin-derived ketimines has been achieved by using a chiral guanidine–amide organocatalyst. A series of 3-substituted 3-amino-2-oxindoles was obtained with excellent results (up to 99% yield, 94% ee). Other functionalized derivatives were also conveniently transformed. This metal-free system was convenient, practical, and insensitive to air and moisture. On the basis of the crystal structure of the catalyst and NMR spectra analysis, a bifunctional catalytic model was suggested to explain the origin of the asymmetric process.