Nature's Blueprint: Chelation‐Assisted C−H Functionalization for Selective and Efficient Reactions in Aqueous Media

Abstract Efficient and sustainable strategies for C−H functionalization are crucial in organic synthesis. Bioinspired catalytic systems have emerged as promising alternatives to traditional synthetic methods. These systems draw inspiration from nature‘s ability to selectively functionalize complex molecules in water‐based environments. Among these, chelation‐assisted C−H functionalization stands out due to its ability to guide the substrate towards the active site of the catalyst, thereby controlling the selectivity of the reaction. This review focuses on the use of chelation assistance to enhance the efficiency and selectivity of bioinspired C−H functionalization reactions in aqueous media. We cover aliphatic, aromatic, and alkenyl C−H functionalization, as well as tandem C−H activation/cyclization, utilizing metallocycle intermediates. Additionally, we highlight the underlying mechanisms of these reactions for a deeper understanding and development of novel methodologies.