Brønstead Acid-Catalyzed Regiodivergent Hydroindolation of Indoles: Temperature-Controlled Markovnikov and Anti-Markovnikov Addition

Brønsted acid-catalyzed, regiodivergent hydroindolation of indoles with terminal aryl alkynes was developed, affording bis(indolyl)alkanes in good to excellent yields. Systematic investigations revealed that temperature variation plays a key role in determining the regioselectivity of anti-Markovnikov and Markovnikov addition reactions. The reaction proceeds efficiently under transition metal-free conditions in an environmentally benign water/alcohol solvent system, using readily available and inexpensive <i>p</i>-toluenesulfonic acid (TsOH) as the catalyst. Control experiments and mechanistic studies support distinct reaction pathways for each regioisomer.