Despite extensive efforts by many practitioners in the field, methods for the direct a-C À H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a b-ketoacid under mild conditions to provide valuable b-amino ketones with unprecedented ease. Regioselective a'-alkylation is achieved for substrates with existing asubstituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a S N Ar step.

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.

Relatively unstable cyclic imines, generated in situ from their corresponding alicyclic amines via oxidation of their lithium amides with simple ketone oxidants, engage aryllithium compounds containing a leaving group on an ortho-methylene functionality to provide polycyclic isoindolines in a single operation. The scope of this transformation includes pyrrolidine, piperidine, azepane, azocane, and piperazines.

Despite extensive efforts by many practitioners in the field, methods for the direct a-C À H bond functionalization of unprotected alicyclic amines remain rare. A new advance in this area utilizes N-lithiated alicyclic amines. These readily accessible intermediates are converted to transient imines through the action of a simple ketone oxidant, followed by alkylation with a b-ketoacid under mild conditions to provide valuable b-amino ketones with unprecedented ease. Regioselective a'-alkylation is achieved for substrates with existing asubstituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a S N Ar step.