Fused Thienopyranones via Sonogashira-Based Heteroannulation

Significance

Reported is the selective synthesis of 4- and 7-unsubstituted and alkynyl-substituted thieno[2,3-c]pyran-7-ones and thieno[3,2-c]py­ran-4-ones from halothiophene carboxylic acids in fair to good yields. The selectivity is determined by altering the Pd catalyst and the solvent. Fair substrate scope is presented as aliphatic alcohol, aniline, thiophenyl, nitro and indole functionality and ring systems are tolerated. For the tandem process, a mechanism is suggested involving HPd(II) acetylide mediated carboxylate 6-endo-dig heteroannular cyclization and carbopalladation followed by reductive elimination, which is based on an earlier proposal (B. M. Trost, C. Chan, G. Ruhter J. Am. Chem. Soc. 1987, 109, 3486-3487). Interestingly but not surprisingly, it was also shown that CuI itself promotes the 6-endo-dig ­cyclization in these systems, a fact which may suggest the operation of alternative mechanisms (S. Raju et al. Tetrahedron Lett. 2006, 47, 83-88).