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.