Transition-Metal-Catalyzed C–C Bond Macrocyclization via Intramolecular C–H Bond Activation

Macrocycles are commonly synthesized via late-stage macrolactamization and macrolactonization. Strategies involving C–C bond macrocyclization have been reported, and examples include the transition-metal-catalyzed ring-closing metathesis and coupling reactions. In this mini-review, we summarize the recent progress in the direct synthesis of polyketide and polypeptide macrocycles using a transition-metal-catalyzed C–H bond activation strategy. In the first part, rhodium-catalyzed alkene–alkene ring-closing coupling for polyketide synthesis is described. The second part summarizes the synthesis of polypeptide macrocycles. The activation of indolyl and aryl C(sp²)–H bonds followed by coupling with various coupling partners such as aryl halides, arylates, and alkynyl bromide is then documented. Moreover, transition-metal-catalyzed C–C bond macrocyclization reactions via alkyl C(sp³)–H bond activation are also included. We hope that this mini-review will inspire more researchers to explore new and broadly applicable strategies for C–C bond macrocyclization via intramolecular C–H activation.