Copper‐Catalyzed C(<i>sp</i><sup>3</sup>)− Functionalization and Annulation of 2‐Bromoaryl Oximes with Active Methylene Compounds towards Synthesis of Isoquinoline <i>N</i>‐Oxides
Chandresh K. Patel, Raghuram Gujjarappa, Kamal Kant, Susanta Ghanta, Virender Singh, Arup K. Kabi, Nabil Al‐Zaqri, Chandi C. Malakar
Abstract
Abstract The established process proceeds through copper (II)‐catalyzed C( sp 3 )− functionalization of β ‐diketones/ β ‐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.