Synthesis of Chroman Derivatives by Group Transposition and Atom Swapping in 1‐Tetralones: Single‐Atom Editing Enabled by Oxidative Ring Contraction of Benzoxepine Silyl Ketene Acetals

Single-atom editing of complex molecules is steadily filling the chemical toolbox with site-selective modification reactions. Herein, a stepwise scheme for carbon-to-oxygen swap in tetralins leading to privileged chroman scaffolds is presented. Increasing the oxidation state at each stage, the substrate scope naturally extends: starting from tetralins via 1-tetralones and further via seven-membered lactones, the transformation results in diverse chroman-2-carboxylic acids and chroman-2-ols. The efficiency of this synthetic route is governed by the developed new oxidative ring-contractive transformations of tetrahydrobenzooxepinones, enabled by intermediate silylation into ketene acetals. The described carbon-to-oxygen swap is illustrated by 40+ examples, including skeletal editing of natural products and short formal synthesis of Heliannuol E. Formation of chroman-2-ols tentatively may proceed via original mechanism with extrusion of carbon monoxide.