Switchable Access to Quinolines and Isoquinolines via the Diverse Behavior of Transient Directing Groups

A hydroxylamine-<i>O</i>-sulfonic acid (HOSA)-enabled, switchable C-H functionalization/annulation of acetophenones with α,β-unsaturated ketones is disclosed, providing a tunable one-pot route to either quinoline or isoquinoline derivatives. The identity of the HOSA-derived transient directing group, coupled with solvent and temperature control, dictates the divergent reaction pathway with high selectivity. This strategy features a broad substrate scope and excellent functional group tolerance. Its utility is demonstrated by a significantly streamlined three-step synthesis (formerly nine) of the antianemic drug roxadustat. This work establishes HOSA as a powerful catalytic transient directing group for selective C-H annulation, offering a new paradigm for heterocycle synthesis.