We report a metal-free selective synthesis of 2-iodo-3-alkyl-1-arylbut-2-en-1-ones from propargylic alcohols that is enabled by N-iodosuccinimide. A variety of substituted propargylic alcohols are amenable to delivering the selective 2-iodoenone products in very good yields. The utility of the α-iodoenone derivatives is further extended by developing an efficient, novel, and new synthetic methodology for the synthesis of 3,5,6-trisubstituted 2H-pyran-2-ones. To the best of our knowledge, this protocol is the first of its kind to accomplish 3,5,6-trisubstituted 2H-pyran-2-ones through an unprecedented domino (formation of two C-C bonds and one C-O bond) one-pot process via intermolecular Heck coupling, base-driven Michael addition, and base-mediated double bond isomerization followed by cyclo-condensation. This protocol showed good compatibility with a wide range of iodoenones (18 examples) and 2H-pyran-2-ones (42 examples). Mechanistic studies indicate that palladium is only involved in the Heck coupling; the base solely drives the rest of the steps. © 2022 American Chemical Society. All rights reserved.