Copper-Catalyzed C(sp )-H Amidation: Sterically Driven Primary and Secondary C-H Site-Selectivity.

Undirected C(sp )-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 . Mechanistic and DFT studies indicate that C-H amidation involves H-atom abstraction from R-H substrates by nitrene intermediates [Cu](κ -N,O-NC(O)Ar) to provide carbon-based radicals R and copper(II)amide intermediates [Cu ]-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.