Temporary or removable directing groups enable activation of unstrained C-C bonds

Carbon-carbon (C-C) bonds make up the skeletons of most organic molecules. The selective manipulation of C-C bonds offers a direct approach to editing molecular scaffolds but remains challenging. The kinetic inertness of C-C bonds can be overcome with transition-metal catalysis, which, nevertheless, relies on a substrate being highly strained or bearing a permanent directing group (DG). The driving force for C-C activation in these cases is strain relief and the formation of a stable metallocycle, respectively. Over the past two decades, a strategy has emerged that uses temporary or removable DGs to effect C-C activation of more common and less strained compounds. A variety of C-C bonds in less strained organic molecules are converted into more reactive transition-metal-carbon (M-C) bonds, enabling downstream transformations as part of diverse synthetic methods. This Review highlights catalytic approaches using temporary or removable DGs to help activate unstrained C-C bonds. The content is organized according to the temporary or removable nature of the DGs and includes applications in the synthesis of natural products or bioactive molecules.