A mild and regioselective Ullmann reaction of indazoles with aryliodides in water

A mild and regioselective Ullmann reaction of indazoles with aryliodides has been developed as a general method for the synthesis of 1-aryl-1H-indazoles. Water was used as the solvent wherein Tween 20 (2% w/w) was added to form aqueous micelles to improve solubility of starting materials and accelerate reaction rate. This aqueous protocol allows the Ullmann reaction to proceed at a mild temperature (60 °C) within a short reaction time (2 h), which typically requires high temperatures (≥100 °C) and prolonged duration (≥24 h). The protocol demonstrated broad substrate scopes with good isolated yields and high regioselectivity (N-1 arylation over N-2 arylation) for 25 examples examined.