Solvent-Controlled Regioselective Switch in Oxidative Cyclization of Biaryl Ketoximes

Abstract

Reported herein is the development of a solvent-controlled, regiodivergent oxidative cyclization for the preparation of N-containing heterocyclic N-oxides. By employing biaryl ketoximes as substrates in the presence of PIFA as an oxidant in HFIP, the reactions proceed to exclusively afford phenanthridine N-oxides. On the other hand, the use of nucleophilic solvents leads to a dearomative functionalization, generating solvent-incorporated spirocyclic isoindole N-oxides. An investigation of the substrate scope reveals that the 6-membered vs. 5-membered ring closure is partially dependent on the substitution pattern on the aryl ring that participates in the C-N bond formation. Finally, the synthetic utility of the developed method was demonstrated through a number of product transformations.