Synthesis of allyl vinyl ketone substrates for electrocyclization reactions

CHED 502

Daniel R. Jacobsen, yakelina@plu.edu and Neal A. Yakelis, yakelina@plu.edu. Department of Chemistry, Pacific Lutheran University, 1010 122nd Street South, Tacoma, WA 98447
As a versatile path to allyl vinyl ketone substrates for 6π-electrocylization reactions, the synthesis of 1-(isoxazolidin-2-yl)-2-(trimethylsilyl)prop-2-en-1-one was targeted as a key intermediate. The synthesis of the Weinreb-type urea (bis(N-methyl-O-methyl)hydroxylamine urea) was difficult to isolate by distillation in good yield as a high-boiling oil. A modified version of the urea using isoxazolidine as a N-methyl-O-methylhydroxylamine surrogate was designed to simplify purification and handling procedures. This crystalline bis(isoxazolidinyl) urea was produced using two different carbonyl sources: 1) triphosgene, and 2) 1,1'-carbonyldiimidazole. The latter reagent resulted in higher isolated product yield and observed purity. 13C NMR (CDCl3, 300 MHz) δ 165.4, 68.7, 48.7, and 28.3. Isoxazolidinyl amides and unsymmetrical ketones could then be synthesized using this urea precursor by stepwise organometallic addition reactions.