Pd-Catalyzed Azidation of Aryl (Pseudo)Halides

Organic azides are powerful tools in organic synthesis, chemical biology, and drug discovery. Pd catalysts have become general tools for C–N bond formation from aryl electrophiles, but azide stands out as a rare example of a nitrogen-centered nucleophile for which suitable catalysts have not been identified. Herein, we report the development of an effective Pd-catalyzed method for the synthesis of aryl azides from aryl bromides and aryl triflates using sodium azide as a convenient reagent. A variety of heterocycles, as well as aryl electrophiles incompatible with existing approaches (e.g., triflates), undergo efficient azidation. Experimental and computational mechanistic studies point to three distinct roles of the bulky ancillary phosphine ligands critical to facilitating this reaction. First, the structure of the phosphine lowers the barrier to reductive elimination from LPd(Ar)N3; second, it minimizes the formation of off-cycle Pd2(μ-N3)2 dimer; finally, it affords resistance of the LPd(0) toward inactivation by the aryl azide product.