Copper‐Catalyzed C(sp 3 )−H Amidation: Sterically Driven Primary and Secondary C−H Site‐Selectivity

Undirected C(sp 3 )−H functionalization reactions often follow site‐selectivity patterns that mirror the corresponding C−H bond dissociation energies (BDEs). This often results in the functionalization of weaker tertiary C−H bonds in the presence of stronger secondary and primary bonds. An important, contemporary challenge is the development of catalyst systems capable of selectively functionalizing stronger primary and secondary C−H bonds over tertiary and benzylic C−H sites. Herein, we report a Cu catalyst that exhibits a high degree of primary and secondary over tertiary C−H bond selectivity in the amidation of linear and cyclic hydrocarbons with aroyl azides ArC(O)N 3 . Mechanistic and DFT studies indicate that C−H amidation involves H‐atom abstraction from R‐H substrates by nitrene intermediates [Cu](κ 2 ‐ N , O ‐NC(O)Ar) to provide carbon‐based radicals R . and copper(II)amide intermediates [Cu II ]‐NHC(O)Ar that subsequently capture radicals R . to form products R‐NHC(O)Ar. These studies reveal important catalyst features required to achieve primary and secondary C−H amidation selectivity in the absence of directing groups.