Copper‐Catalyzed C(sp3)−H Amidation: Sterically Driven Primary and Secondary C−H Site‐Selectivity

Swimming against the tide: A new β‐diketiminate Cu^I catalyst system has been developed for C−H amidation with aroyl azides via copper nitrene intermediates. Owing to their steric bulk they target stronger, more accessible primary and secondary C−H bonds in the presence of weaker, hindered tertiary C−H bonds.

Abstract

Undirected C(sp³)−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)N₃. Mechanistic and DFT studies indicate that C−H amidation involves H‐atom abstraction from R‐H substrates by nitrene intermediates [Cu](κ²‐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.

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