Regioselective One-Pot Synthesis of Isocoumarins and Phthalides from 2-Iodobenzoic Acids and Alkynes by Temperature Control

Copper-catalyzed coupling reaction of 2-iodobenzoic acids and alkynes such as terminal acetylenes, alkynyl carboxylic acids, and trimethylsilylacetylene selectively afforded isocoumarins and phthalides in the presence of cesium carbonate (Cs2CO3) and dimethyl sulfoxide (DMSO). Among the regioselective products, only the 6-endo-dig product, isocoumarin, was formed at 100 degrees C, and the 5-exo-dig product, phthalide, was formed as a major product at 25 degrees C. A variety of alkynes produced the corresponding isocoumarins and phthalides in good yields. A mechanism is suggested in which the formation of 2-alkynylbenzoic acid as an intermediate via Sonogashira-type coupling was ruled out in the reaction pathway.