Selective Halogenation of Pyridines Using Designed Phosphine Reagents
2019-08-26T15:36:34Z (GMT) by
Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochemicals, and ligands for metal complexes, but strategies to selectively halogenate pyridine C–H precursors are lacking. We designed a set of heterocyclic phosphines that are selectively installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. The study concludes that both tuning the phosphonium electrophilicity and pyridine substitution patterns influence the efficiency of the carbon-halogen bond-forming step.