Palladium-Catalyzed C-H Acetoxylation Of 2-Arylindazoles

Acetoxy compounds are ubiquitous in varieties of natural products,pharmaceutical molecules,and synthetic intermediates.On the other hand,2H-indazole is an important class of nitrogen-containing heterocycles due to their wide existence in many therapeutic agents,some of which have been commercialized.Herein,an efficient Pd(Ⅱ)-catalyzed direct acetoxylation of 2-arylindazoles has been successfully developed under air atmosphere via chelation-assisted strategy.The main research contents are as follows:We commenced our investigation with 2-phenyl-2H-indazole la to optimize the reaction conditions:2-phenyl-2H-indazole la(0.1 mmol)as the substrate,(diacetoxyiodo)benzene(PIDA)(0.2 mmol)as the oxidant and acetoxy source,10 mol%of palladium(Ⅱ)acetate as the catalyst,1 mL of acetic acid/1,4-dioxance(10/1,v/v)as the mixture solvent,and at 90℃ for 3 h under air.With the optimized conditions in hand,a broad range of substituted 2-arylindazoles was employed to give 25 orthoacetoxylated arylindazoles 2 and 3 in up to 88%yield with good regioselectivity.The current methodology exhibits several unique characteristics,including broad substrate scope,good functional group tolerance,operational convenience,and short reaction time.Meanwhile,a gram-scale production of acetoxylated indazole was successfully achieved,which could further be transformed to the corresponding hydroxyl derivative.Furthermore,a series of control experiments,including H/D exchange experiment and kinetic isotope effect(KIE)were conducted to gain insight in the acetoxylation mechanism,and a possible catalytic cycle was proposed.