Ti-Catalyzed Couplings of Halopyridines and Organozinc Reagents

Traditional transition metal-catalyzed coupling of 2-haloaryl metal reagents with halopyridines often results in undesirable side reactions, including further coupling of C-X bonds in 2-(2-haloaryl)pyridines or reactions involving arynes generated from 2-haloaryl metal reagents. Similarly, the coupling of alkyl metal reagents also faces the challenge of branched/linear isomerization. We describe the first titanium-catalyzed couplings of aryl/alkyl zinc reagents with halopyridines, effectively addressing these limitations and providing a versatile synthetic route to challenging pyridine derivatives.