Synthesis of Isoquinoline N-Oxides via Hypervalent Iodine-Mediated Oxidative Cyclization of Ketoximes with Alkenes
Aurapat Ngamnithiporn1,2, Padon Chuentragool1,2, Supakarn Punnita1
1Laboratory of Medicinal Chemistry, Chulabhorn Research Institute, 54 Kamphaeng Phet 6 Road, Bangkok 10210, Thailand.
Abstract:
Reported herein is the development of an intramolecular oxidative cyclization of ketoximes with alkenes for the preparation of isoquinoline N-oxides. The reaction, which utilizes phenyliodine bis(trifluoroacetate) (PIFA) as an oxidant and 2,2,2-trifluoroethanol (TFE) as a solvent, proceeds to afford various N-heterocyclic products, including aryl/heteroaryl-fused pyridine N-oxides, isoindole N-oxides, and 2-benzazepine derivatives. Preliminary experimental and computational mechanistic studies suggest that the ionic pathway is the primary mechanism. The synthetic utility of the developed method was highlighted via several product transformations.
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