A hemin/t-BuOOH-catalyzed oxidative phenol–enamine formal [3 + 2] cycloaddition has been developed, enabling the environmentally benign synthesis of valuable cyclopenta[b]benzofuran scaffolds under sustainable reaction conditions with excellent atom- and step-economy. Mechanistic studies point to the involvement of a two-electron oxidation pathway. Based on the preliminary biological investigations, compound 3ay displayed moderate anti-cancer activities (IC₅₀ = 27.73 μM) against MCF7 cells (breast cancer cells).