DBU-Mediated Diastereoselective Aldol-Type Cyanomethylation of Isatins

An efficient, metal-free
approach to 3-substituted 3-hydroxyoxindole
by DBU-mediated highly diastereoselective addition of aryl acetonitrile
to N-protected isatin under mild conditions has been
developed. The reaction proceeds smoothly to produce respective cyanomethylated
adducts in good yield and excellent diastereoselectivity. Further
transformation of the cyanide group allowed the synthesis of an advance
intermediate of corresponding (±) CPC analogue. The mechanistic
insight toward the aldol-type cyanomethylation of N-tritylisatin with benzyl cyanide was obtained by DFT calculations.