Regioselective indolization of unsymmetrical phenylhydrazones by reaction, at room temperature, with PCl3

Abstract

Unsymmetrical ketone phenylhydrazones (1)(R¹≠ R²) react with PCl₃, at room temperature to give predominantly one, (2), of the two possible 2,3-disubstituted indoles in good to excellent overall yield. When the R¹ and R² groups are very different (R¹= Ph or Me; R²= alkyl or H) the reaction is highly regioselective leading to exclusive or prevalent formation of the corresponding 3-R¹ indoles (2), whereas when R¹ and R² are very similar (R¹,R²= alkyl chains) the regioselectivity is decreased and the indole having the shorter chain in the 3-position predominates, but only slightly.

Inspection of the results enables the direction of indolization to be predicted and the positions of the substituents in the 2,3-disubstituted indoles to be assigned with certainty, features not inherent in the classical Fischer indolization.