Transition Metal‐Catalyzed Directing Group‐Assisted Site‐Selective Di‐ Ortho CH Functionalizations via Double CH Activation

The directing group (DG)‐assisted transition metal (TM)‐catalyzed site‐selective CH activation and functionalization has become a popular approach in the synthesis of natural products, pharmaceuticals, and late‐stage functionalization. In particular, the ortho ‐selective CH functionalization is frequently addressed. One DG generally directs the mono‐CH functionalization. However, over the years, there are some exceptional reactions that have been reported where one DG directs di‐ ortho ‐CH functionalization, offering extra functionalization in one pot. There is no generalization in this type of reaction. In this comprehensive report, the di‐ ortho ‐CH functionalization reactions reported in the recent two decades (2004–2024) are summarized, and the current status and future perspective for further modifications are provided. This discussion covers DG‐assisted site‐selective di‐ ortho ‐arylation, di‐ ortho ‐alkylation, di‐ ortho ‐alkenylation, di‐ ortho ‐alkynylation, di‐ ortho ‐cyanation, di‐ ortho ‐amination, di‐ ortho ‐thiolation/selenation, di‐ ortho ‐carbonylation, di‐ ortho ‐halogenation, di‐ ortho ‐oxygenation, and unsymmetrical di‐ ortho CH functionalization of inert aryl and heteroaryl CH bonds.