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

The iodolactonization of 3-alkynylthiophene-2-carboxylicacids 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 andpyranopyridinones, respectively, from 6-endo-dig cyclization.The method also worked nicely for the transformation of2-(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-digproducts, it could be still made selective toward the pyranopyridinonecompound working in 1-ethyl-3-methylimidazoliumethyl sulfate as the solvent. On the other hand, the exclusiveformation of the 5-exo-dig product was observed in N-ethyl-Nmethylmorpholiniumdicyanamide starting from 3-(3,3-dimethylbut-1-yn-1-yl)picolinic acid. Some representative iodinatedthienopyridinone products were successfully used as substratesfor Pd-catalyzed Suzuki and Sonogashira reactions.