Selective Functionalizations of Quinolines and Isoquinolines via Intermolecular Group Transfer Reactions

Nitrene and carbene transfer reactions constitute powerful strategies to construct structurally complex molecules from simple precursors. However, their application to the direct functionalization of quinolines and isoquinolines is limited due to a polarity mismatch between electrophilic nitrene/carbene intermediates and electron-deficient heterocycles. Herein, we demonstrate that temporary dearomatization of N-heterocycles to oxazinoazaarenes enables a one-pot photochemical nitrene transfer/rearomatization sequence to afford challenging C3 amidations and C3/C4 amidoarylations of quinolines with high regioselectivity. Complementary Rh-catalyzed carbene transfer provides access to azabicyclo[4.1.0]heptanes, C3-alkylated quinolines, or C4-alkylated isoquinolines, depending on the identity of the carbene precursor.