Selective Iron Catalyzed Synthesis of N-Alkylated Indolines and Indoles

Whereas iron catalysts usually promote catalyzed C3-alkylation of indole derivatives via a borrowing-hydrogen methodology using alcohols as the electrophilic partners, this contribution shows how to switch the selectivity towards N-alkylation. Thus, starting from indoline derivatives, N-alkylation was efficiently performed using a tricarbonyl(cyclopentadienone) iron complex as the catalyst in trifluoroethanol in the presence of alcohols leading to the corresponding N-alkylated indoline derivatives in 31-99 % yields (28 examples). The one-pot, two-step strategy for the selective N-alkylation of indolines is completed by an oxidation to give the corresponding N-alkylated indoles in 31-90 % yields (15 examples). This unprecedented oxidation methodology involves an iron salt catalyst associated with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) and a stoichiometric amount of t-BuOOH at room temperature.

Automated summary

This study presents a method for switching the selectivity of indole derivatives from C3-alkylation to N-alkylation using a catalyst. By using an iron complex and alcohols in trifluoroethanol, efficient N-alkylation of indole derivatives was achieved with high yields. The method also involves an oxidation step to convert the products into N-alkylated indoles.