Among the transition metals, copper-based catalyst systems enable the widest range of N-containing reagents in C−H amination to allow for the direct incorporation of versatile N-based functionalities via ubiquitous C−H bonds. In addition to nitrene-based approaches involving sulfonyliminoiodinanes (PhINSO 2 R), diverse non-nitrene protocols have been developed that allow for the direct use of organic amides, nitrosoarenes, and hydroxylamines, strained heterocycles such as oxaziridines, acetonitrile, secondary sulfonylamines, and even alkylamines and arylamines. Synthetic, mechanistic, and theoretical studies reveal discrete copper nitrenes [Cu]NR and copper amides [Cu]−NHR to be key reactive intermediates in C−H amination. Copper-catalyzed sp 3 C−H amination is reviewed, connecting catalytic reactivity patterns with likely copper intermediates wherever possible, with the goal to stimulate the further development of C−H functionalization reactions with copper which possess significant sustainability advantages over other contemporary approaches involving noble metals.

En route to catalysis: Two equivalents of the three‐coordinate copper(II) amide [(Cl2NN)Cu]‐NHAd participate in stoichiometric CH amination by a H‐atom abstraction/radical capture sequence. This active species may be generated through a copper(II) tert‐butoxide intermediate to allow for the unprecedented catalytic amination of sp3‐CH bonds with unactivated alkylamines. This method greatly expands the range of amines for catalytic CH amination since most protocols require N‐based electron‐withdrawing groups.

Kinetic analysis of the reaction of the copper(I) β-diketiminate [Cl(2)NN]Cu ([Cu(I)]) with (t)BuOO(t)Bu to give [Cu(II)]-O(t)Bu (1) reveals first-order behavior in each component implicating the formation of free (t)BuO(•) radicals. Added pyridine mildly inhibits this reaction indicating competition between (t)BuOO(t)Bu and py for coordination at [Cu(I)] prior to peroxide activation. Reaction of [Cu(I)] with dicumyl peroxide leads to [Cu(II)]-OCMe(2)Ph (3) and acetophenone suggesting the intermediacy of the PhMe(2)CO(•) radical. Computational methods provide insight into the activation of (t)BuOO(t)Bu at [Cu(I)]. The novel peroxide adduct [Cu(I)]((t)BuOO(t)Bu) (4) and the square planar [Cu(III)](O(t)Bu)(2) (5) were identified, each unstable toward loss of the (t)BuO(•) radical. Facile generation of the (t)BuO(•) radical is harnessed in the catalytic C-H etherification of cyclohexane with (t)BuOO(t)Bu at rt employing [Cu(I)] (5 mol %) to give the ether Cy-O(t)Bu in 60% yield.

Aniline joins the club: A β-diketiminato copper(I) catalyst enables C-H amination of anilines employing low catalyst loadings to preclude oxidation to the diazene ArN=NAr. Electron-poor anilines are particularly resistant towards diazene formation and participate in the amination of strong and unactivated C-H bonds. N-alkyl anilines also take part in C-H amination.

Auf dem Weg zur Katalyse: Zwei Äquivalente des Kupfer(II)‐amids [(Cl2NN)]Cu‐NHAd nehmen über eine Sequenz aus H‐Abstraktion und Radikaleinfang an stöchiometrischen C‐H‐Aminierungen teil (siehe Schema). Diese aktive Spezies entsteht vermutlich über ein Kupfer(II)‐tert‐butoxid‐Zwischenprodukt und sorgt für eine beispiellose katalytische Aktivierung von sp3‐C‐H‐Bindungen mit nichtaktivierten Alkylaminen. Die Methode erweitert enorm die Bandbreite von Aminen für katalytische C‐H‐Aminierungen, da die meisten bisherigen Protokolle elektronenziehende N‐Substituenten erfordern.