Copper-Catalyzed C(sp3)? Functionalization and Annulation of 2-Bromoaryl Oximes with Active Methylene Compounds towards Synthesis of Isoquinoline N-Oxides

Abstract

The established process proceeds through copper (II)-catalyzed C(sp3)? functionalization of ?-diketones/?-ketoesters with 2-bromobenzaldehyde oximes followed by the intramolecular cyclization of in situ generated acylated intermediates to deliver isoquinoline N-oxides. The copper(II) acetate catalyzed C?H functionalization showed maximum efficacy at 60 �C in methanol/toluene as solvent. The described reaction conditions were applicable over a wide range of substrates with a variety of functional groups to yield isoquinoline N-oxides in yields up to 85%. The developed approach was further elucidated by means of control experiments and DFT calculations. � 2023 Wiley-VCH GmbH.