Iterative and regioselective cross-couplings of 2-chloro-3,4-diiodopyridine leading to 2,3,4-triheteroarylpyridines

A one-pot synthesis of 2-chloro-3,4-diiodopyridine from 2-chloropyridine is described via a Directed ortho Metallation (DoM)/Halogen Dance (HD) mechanism in 26–28% yields. By performing sequential, iterative Suzuki–Miyaura cross-couplings using a variety of functionalised heteroaryl and arylboronic acids, a series of novel 2,3,4-triheteroarylpyridine scaffolds have been accessed in synthetically viable yields, including sterically hindered derivatives. 2-Chloro-4-heteroaryl-3-iodopyridines and 2-chloro-3,4-diheteroarylpyridines are also reported. The synthesis of 5-[3,4-bis(2-phenylethynyl)pyridin-2-yl]-2-fluoropyridine via a two-step Sonogashira/Suzuki–Miyaura reaction sequence from 2-chloro-3,4-diiodopyridine, phenylacetylene and 6-fluoropyridin-3-yl-3-boronic acid has been achieved in 48% overall yield.