(Dimethoxy‐ and Dihalopyridyl)boronic Acids and Highly Functionalized Heteroarylpyridines by Suzuki Cross‐Coupling Reactions

Abstract We report the synthesis of (2,6‐dimethoxy‐3‐pyridyl)boronic acid (2), (2,3‐dimethoxy‐4‐pyridyl)boronic acid (4), (2,6‐difluoro‐3‐pyridyl)boronic acid (6), (2,6‐dichloro‐3‐pyridyl)boronic acid (8) and (2,3‐dichloro‐4‐pyridyl)boronic acid (10) by directed ortho‐metalation reactions on the corresponding disubstituted pyridine precursor, followed by the reaction with triisopropyl borate (TPB) or trimethyl borate. Thereactivity of the pyridylboronic acids with heteroaryl halides in Suzuki–Miyaura cross‐coupling reactions has been evaluated. New highly functionalized heteroarylpyridine derivatives have thereby been obtained in moderate to high yields. The reaction of 8 and 3‐amino‐2‐chloropyridine yielded the rare 5H‐pyrrolo[2,3‐b:4,5‐b′]dipyridine (i.e. 1,5‐diazacarbazole) ring system by sequential cross‐coupling and intramolecular cyclisation reactions. The X‐ray crystal structures are reported for the pyridylboronic acids 2, 4, 8 and 10. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)