Effect of Terminal Alkylation of Aryl and Heteroaryl Hydrazines in the Fischer Indole Synthesis.

The effect of alkylation on the terminal position of aryl and heteroaryl hydrazines in the Fischer indole synthesis was examined. Compared to their unalkylated counterparts, reactions using alkylated hydrazines provided indole products with higher yields and faster rates. The reactions can be conducted at lower temperatures and are compatible with acid-sensitive functionality. The terminally alkylated hydrazines were readily prepared by a new two-step sequence and held as stable hydrazinium salts. The mild formation of the salts along with the favorable Fischer indole reaction conditions highlights the potential of this approach in later-stage synthetic use.