Practical Ligand-Enabled C-H Halogenation of (Hetero)Benzoic and (Hetero)Aryl Acetic Acids.

ABSTRACT: For over half a century, ortho-halogenated arenes, widely used in cross-coupling reactions, are mainly synthesized and manufactured by stoichiometric-directed ortho-lithiation/halogenation technology. While catalytic C-H halogenation has emerged as a potentially environmentally friendly method, the need for stoichiometric bases, expensive oxidants, and installation of directing groups prevented its adoption in scalable synthesis. In addition, the ligandless Pd(II)-catalyzed C-H halogenation is incompatible with heterocyclic substrates, thus limiting its use in medicinal chemistry substantially. By the discovery and development of three bifunctional bidentate pyridone ligands, we categorically removed these four detrimental drawbacks, rendering C-H halogenation technology subs

SUBMITTER: Zhao H 

PROVIDER: S-EPMC12767750 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature