Regioselective Fischer Indole Route to 3-Unsubstituted Indoles

Use of Eaton's reagent (P₂O₅/MeSO₃H) as acid catalyst in the Fischer indole reaction using methyl ketones provides unprecedented regiocontrol to form the 3-unsubstituted indoles. In several instances where the harshness of the reagent causes decomposition and low yields, dilution in sulfolane or dichloromethane results in far less degradation and higher yields of indoles. Steric effects and the acidity of the medium are the two major factors that control the regioselectivity. The role of the P₂O₅ in the reagent mixture P₂O₅/MeSO₃H is simply as a drying agent when used as catalyst for the Fischer indole reaction.