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Treatment of isoxazoles with enamines leads to an inverse electron-demand hetero-Diels–Alder reaction that produces substituted pyridines in the presence of TiCl 4 (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 TiCl 4 (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 TiCl 4 and titanium powder.more » « less
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Hou, Zhilin; Jena, Rashmi; McDaniel, Tanner J.; Billow, Brennan S.; Lee, Seokjoo; Barr, Hannah I.; Odom, Aaron L. (, ACS Catalysis)
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