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.