Iron‐Catalyzed Alkynylation of Strong Aliphatic C─H Bonds

The development of synthetic catalysts capable of replicating cytochrome P450's remarkable C─H activation proficiency while suppressing oxygen rebound presents a fundamental challenge in catalysis, yet holds transformative potential for alkane functionalizations. Herein, we report an iron/EtBCMOM (L‐cystine‐based ligand) catalytic system for the selective distal methylene C(sp 3 )‐H alkynylation of alkanes using alkynyl sulfones. This catalytic paradigm establishes a robust platform for the direct transformation of inert C(sp 3 )─H bonds into versatile alkyne functionalities, exhibiting exceptional predictability in regioselectivity and accommodating an expansive substrate scope (>60 structurally diverse examples). The technology unlocks previously inaccessible chemical space, enabling single‐step derivatization of natural products, medicinally relevant molecules, and commodity feedstocks at traditionally unreactive positions.