Synthesis of 2-Aryl-Substituted Indole-3-acetic Acid Derivatives via Intramolecular Imino-Stetter Reaction of Aldimines with Cyanide

A general method to generate umpolung of aldimines with cyanide was developed via the addition of cyanide to aldimines followed by a proton transfer from the carbon atom to the nitrogen atom in the resulting cyanide adducts. This novel method was successfully applied to the first imino-Stetter reaction of aldimines obtained from 2-aminocinnamic acid derivatives and aromatic aldehydes with cyanide, affording 2-aryl-substituted indole-3-acetic acid derivatives. Furthermore, the usefulness of this method was successfully demonstrated by the synthesis of an FPTase inhibitor, one of the biologically important 2-arylindole-3-acetic acid derivatives. (Figure presented.).