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

Abstract

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.