Facile synthesis of chiral 2-functionalized tetrahydroquinolines via Pd/Cu-catalyzed cascade -C(sp³)-H arylation/C-N coupling of amides derived from amino acids and their derivatives

In this work, we explored the precise modification of amides derived from commercially available natural amino acids and their derivatives via Pd/Cu-catalyzed cascade & gamma;-C(sp(3))-H arylation/C-N coupling, and thus successfully constructed a one-pot strategy to synthesize valuable chiral 2-functionalized tetrahydroquinoline motifs with good maintenance of chirality. This methodology offers an alternative route for facile access to valuable chiral tetrahydroquinolines with good regioselectivity and broad functional group compatibility for drug discovery. The synthetic applications of this methodology to the late-stage functionalization of natural products, drugs, and biomolecules have also been well demonstrated.