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.