Transition Metal‐Catalyzed Directing Group‐Assisted Site‐Selective Di‐ortho C−H Functionalizations via Double C−H 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 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 reactions. In this comprehensive report, we have summarized the di‐ortho‐C−H functionalization reactions reported in the recent two decades (2004‐2024) and provided the current status and future perspective for further modifications. 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.