Synthesis of Chroman Derivatives by Group Transposition and Atom Swap of 1-Tetralones. Single Atom Editing Enabled by Contractive Oxidation 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 oxi-dation state at each stage, the substrate scope naturally extends: starting from tetralins via 1-tetralones and further via subsequently formed seven-membered lactones, the transformation results in diverse chroman-2-carboxylic acids and chroman-2-ols. The effi-ciency of this synthetic route is governed by the developed new oxidative ring-contractive transformations of tetrahydroben-zooxepinones, enabled by intermediate silylation into ketene acetals. The described carbon-to-oxygen swap is illustrated by 35+ examples, including skeletal editing of natural products and short formal synthesis of Heliannuol E. Formation of chroman-2-ols tentatively proceeds via a rare retro-[2+1]-cycloaddition accompanied by extrusion reaction of carbon monoxide..