Diversification of Unprotected Alicyclic Amines by C-H Bond Functionalization: Decarboxylative Alkylation of Transient Imines

Despite extensive efforts by many practitioners in the field, methods for the direct alpha-C-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 beta-ketoacid under mild conditions to provide valuable beta-amino ketones with unprecedented ease. Regioselective alpha '-alkylation is achieved for substrates with existing alpha-substituents. The method is further applicable to the convenient one-pot synthesis of polycyclic dihydroquinolones through the incorporation of a SNAr step.

Automated summary

Despite efforts by practitioners, direct alpha-C-H bond functionalization of unprotected alicyclic amines is rare. A new method utilizing N-lithiated alicyclic amines has been developed, providing a convenient approach to achieve functionalization reactions under mild conditions. This method offers a new pathway for the synthesis of beta-amino ketones with regioselective alpha'-alkylation, and potential for one-pot synthesis of polycyclic dihydroquinolones.