Cationic Cascade Strategy for the Synthesis of Dihydrobenzofuran and Isochromane Scaffolds

Oxygen heterocycles are valued for their prevalence in bioactive molecules and their metabolic stability. We report a Brønsted-acid-promoted, oxygen-interrupted <i>halo</i>-Prins/<i>halo</i>-Nazarov cascade that enables the stereospecific construction of dihydrobenzofuran and isochromane scaffolds from simple enyne and carbonyl precursors. This approach unites <i>de novo</i> heterocycle construction with late-stage functionalization, providing access to complex oxygen heterocycles of relevance to medicinal chemistry.