Glutarimides, chromatography

Reaction of the nitrile oxide (498) with the enone (499) gave after chromatography the expected isoxazoline (500) plus some of its dehydro derivative (76TL3983). Hydrogenation of (500) using 30% Pd/SrC03 as catalyst yielded an enaminoketone (501) which was further hydrolyzed to the diketone (502 Scheme 110). This compound is a gem-dimethyl isomer of dehydrocycloheximide, a key intermediate in a previously reported synthesis of the glutarimide antibiotic cycloheximide. 

Scheme 52. Reagents a, glutarimide, DEAD, PhsP, THF b, NaBRt, MeOH, -5°C c, TFA, CH2CI2, 0°C d, LiAlHi, THF, reflux e, OSO4 (cat), NajHiIOj, 80% AcOH, 8 C, then flash chromatography.

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