Synthesis of isoquinoline N-oxides via direct annulation with cyclic dicarbonyls

An efficient Rh(III)-catalyzed, regioselective oxidative annulation of substituted aryl ketoximes with cyclic 1,3-dicarbonyl compounds for the divergent synthesis of polysubstituted isoquinoline N -oxides is described. This protocol utilizes PhI(OAc)₂ as a terminal oxidant to generate a highly reactive iodonium ylide intermediate in situ from the dicarbonyl coupling partner. Operating under mild conditions in a practical ethanol solvent, the method features operational simplicity, broad functional group tolerance, and affords diverse polycyclic N -heterocyclic scaffolds in moderate to excellent yields (up to 87%). Furthermore, the reaction is amenable to gram-scale synthesis without significant loss of efficiency. By obviating the need for pre-synthesized diazo precursors, this methodology provides a straightforward route to complex N -oxide motifs that are prevalent in medicinal chemistry.