 in directed c  h activation reactions , nitrogen and sulfur atoms present in heterocyclic substrates coordinate strongly with metal catalysts . this coordination , which can lead to catalyst poisoning or c  h functionalization at an undesired position , limits the application of c  h activation reactions in heterocycle - based drug discovery.15 herein , we report a robust and synthetically useful reaction that overcomes the complications associated with performing c  h functionalization reactions on heterocycles . 
 our approach employs a simple n - methoxy amide group , which serves as both a directing group and an anionic ligand to promote the in situ generation of the reactive pdx2 ( x = arconome ) species from a pd(0 ) source using air as the sole oxidant . in this way 
 , the pdx2 species is inherently anchored in close proximity with the target c  h bond adjacent to conhome group , thus avoiding the interference from various heterocycles . 
 remarkably , this reaction overrides the conventional positional selectivity patterns observed with substrates containing strongly coordinating heteroatoms , including nitrogen , sulfur , and phosphorus . 
 thus , this operationally simple aerobic reaction demonstrates the feasibility of bypassing a fundamental limitation that has long plagued applications of directed c  
 h activation in medicinal chemistry . 
Supplementary Material