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Updated: Jan 8, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Switchable Access to Quinolines and Isoquinolines via the Diverse Behavior of Transient Directing Groups
Xianwen Zeng1, Wen Fu1, Xiaoxiao Huang1
1Gannan Innovation and Translational Medicine Research Institute, Gannan Medical University, Ganzhou 341000, China.
Abstract:
A hydroxylamine-O-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.
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