Iodolactonization of 3-Alkynylthiophene-2-Carboxylic and 3-Alkynylpicolinic Acids for the Synthesis of Fused Heterocycles

The iodolactonization of 3-alkynylthiophene-2-carboxylic acids and 3-alkynylpicolinic acids has been investigated. Using I2 as the iodine source and NaHCO3 as the base in MeCN, the process took place smoothly to afford thienopyranones and pyranopyridinones, respectively, from 6-endo-dig cyclization. The method also worked nicely for the transformation of 2-(phenylethynyl)thiophene-3-carboxylic acid and 3-(phenylethynyl)isonicotinic acid into 7-iodo-6-phenyl-4H-thieno[3,2-c]pyran-4-one and 4-iodo-3-phenyl-1H-pyrano[4,3-c]pyridin-1-one, respectively. Although with some 3-alkynylpicolinic acids the process led to a mixture of the 6-endo-dig and 5-exo-dig products, it could be still made selective toward the pyranopyridinone compound working in 1-ethyl-3-methylimidazolium ethyl sulfate as the solvent. On the other hand, the exclusive formation of the 5-exo-dig product was observed in N-ethyl-N-methylmorpholinium dicyanamide starting from 3-(3,3-dimethylbut-1-yn-1-yl)picolinic acid. Some representative iodinated thienopyridinone products were successfully used as substrates for Pd-catalyzed Suzuki and Sonogashira reactions.