Direct ortho-Arylation of Pyridinecarboxylic Acids: Overcoming the Deactivating Effect of sp2-Nitrogen

Direct arylations of pyridines are challenging transformations due to the high Lewis basicity of the sp²-nitrogen. The use of carboxylates as directing groups is reported, facilitating the Pd-catalyzed C–H arylation of this difficult class of substrates. This methodology allows regioselective C3/C4 arylation, without the need to use solvent quantities of the pyridine, and using low-cost chloro- and bromoarenes as coupling partners. Furthermore, carboxylates could be employed as traceless directing groups through a one-pot C–H arylation/Cu(I)-mediated decarboxylation sequence, thereby accessing directing-group-free pyridine biaryls.