A catalytic carbonylative approach to the multicomponent synthesis of benzothiophene derivatives from simple building blocks [1‐(2‐(methylthio)phenyl)prop‐2‐yn‐1‐ols, carbon monoxide, and an alcohol)] is presented. It is based on an S‐cyclization‐demethylation‐alkoxycarbonylation‐reduction sequence promoted by the PdI2/KI catalytic system, occurring under relatively mild conditions (40 atm, 80 °C, 15 h). Benzothiophene‐2‐acetic esters are obtained in moderate to good yields (35–70%) starting from variously substituted substrates in combination with different alcohols as external nucleophiles (17 examples).

We report the first example of iodocyclization of readily available 2‐methylthiophenylacetylenes in a deep eutectic solvent (ChCl/urea 1/2, mol/mol) as recyclable and more sustainable solvent with respect to the classical VOCs employed so far. The process successfully afforded a variety of 3‐iodobenzothiophenes in good to high yields starting from differently substituted substrates, with the possibility to recycle the DES several times without appreciable lowering of the product yield. The 3‐iodothiophenes thus synthesized are known to be important precursors of biologically active molecules and functionalized heterocycles, and were successfully employed for performing representative Sonogashira and Suzuki cross‐coupling reactions. The solvent‐catalyst system could be conveniently recycled several times without any loss of activity in both coupling processes, thus further demonstrating the practical usefulness of our approach.

Polycyclic heterocyclic derivatives have been synthesized in one step by a carbonylative double cyclization approach starting from readily available starting materials. The method is based on a regioselective 6‐endo‐dig heterocyclization – cyclocarbonylation sequence catalyzed by the PdI2/KI catalytic system under oxidative conditions, with CO (5–10 atm) as the carbonylating agent and O2 (from air, 35–70 atm) as the external oxidant and formation of water as benign coproduct. Starting from thiophenecarboxylic acids bearing an ω‐hydroxyalkynyl substituent in vicinal position, previously unknown 1H‐furo[3,4‐b]thieno[3,2‐d]pyran‐1,5(3H)‐diones, 4H‐furo[3,4‐b]thieno[2,3‐d]pyran‐4,8(6H)‐diones, 3,4‐dihydro‐1H,6H‐pyrano[4,3‐b]thieno[3,2‐d]pyran‐1,6‐diones, and 6,7‐dihydro‐4H,9H‐pyrano[4,3‐b]thieno[2,3‐d]pyran‐4,9‐diones were obtained in 45–86% yields over 21 examples. The structures of two representative products have been confirmed by X‐ray diffraction analysis.