Iodocyclization, Followed by Palladium-Catalyzed Coupling: A Versatile Strategy for Heterocyclic Library Construction

Anton      V. Dubrovskiy; Nataliya      A. Markina; Richard      C. Larock

Abstract

The iodocyclization of functionally-substituted alkynes provides an excellent way to prepare a wide range of iodoheterocycles, which can then be readily elaborated through palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck, Hartwig-Buchwald, and carbonylation processes into libraries of medicinally relevant heterocycles. The synthesis of libraries of indoles, benzofurans, benzothiophenes, isocoumarins and pyrones, cyclic imidates, isoxazoles, furans using this approach is reviewed. This technology is very versatile, proceeds under mild reaction conditions in high yields, and tolerates considerable functionality.

Keywords: High throughput screening, iodocyclization, library construction, palladium-catalyzed cross-couplings, iodoheterocycles, heterocycles, synthetic transformations, iodoheterocycles, nucleophilic center, Lipinski’s empirical rules