TEMPO-Mediated Selective Synthesis of Isoxazolines, 5-Hydroxy-2-isoxazolines, and Isoxazoles via Aliphatic δ-C(sp3)-H Bond Oxidation of Oximes

Chem Asian J. 2021 Sep 1;16(17):2439-2446. doi: 10.1002/asia.202100572. Epub 2021 Jul 29.

Abstract

Selective synthesis of three different bioactive heterocycles; isoxazolines, 5-hydroxy-2-isoxazolines and isoxazoles from the same starting material using TEMPO (2,2,6,6-Tetramethylpiperidin-1-oxyl) as a radical initiator is reported. Selectivity was achieved using different oxidants with TEMPO. The reaction goes through a 1,5-HAT (hydrogen atom transfer) process resulting in products with good yields. This strategy offers a straightforward route to three different heterocycles from oximes via radical-mediated C(sp3 )-H oxidation.

Keywords: divergent synthesis; heterocycles; hydrogen atom transfer (HAT); isoxazoles; isoxazolines.