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Updated: Sep 2, 2025

Syntheses, Crystallization, and Spectroscopic Characterization of 3,5-Lutidine N-Oxide Dehydrate
Published on: April 24, 2018
Substituted pyridines from isoxazoles: scope and mechanism
Seokjoo Lee1, Rashmi Jena1, Aaron L Odom1
1Michigan State University, Department of Chemistry, 578 S. Shaw Ln, East Lansing, Michigan 48824, USA. odoma@msu.edu.
Abstract:
Treatment of isoxazoles with enamines leads to an inverse electron-demand hetero-Diels-Alder reaction that produces substituted pyridines in the presence of TiCl4(THF)2 and titanium powder. The reaction is highly regioselective with only a single isomer of the product observed by GC/MS and tolerant of many common functional groups. The transformation was examined computationally, and it was found that TiCl4 (or a similar Lewis acid) likely acts to catalyze the reaction. After the initial [4 + 2]-cycloaddition, the oxaza-[2.2.1]-bicycle produced likely ring opens before amine loss to give an N-oxide. The pyridine is then obtained after reduction with TiCl4 and titanium powder.
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