This Graphical Review provides a concise overview of the manifold and mechanistically diverse methods that enable the functionalization of sp3 C–H bonds in amines and their derivatives.

A simple one-pot procedure enables the sequential, regioselective, and diastereoselective introduction of the same or two different substituents to the α- and α′-positions of unprotected azacycles. Aryl, alkyl, and alkenyl substituents are introduced via their corresponding organolithium compounds. The scope of this transformation includes pyrrolidines, piperidines, azepanes, and piperazines.

Secondary alicyclic amines are converted to α-aminonitriles via addition of TMSCN to their corresponding imines, intermediates that are produced in situ via the oxidation of amine-derived lithium amides with simple ketone oxidants. Amines with an existing α-substituent undergo regioselective α′cyanation even if the C−H bonds at that site are less activated. Amine α-arylation can be combined with α′-cyanation to generate difunctionalized products in a single operation.