Efficient Synthesis of Heterocycles with the Aid of Electrophilic Cyclizations and Fluorous Chemistry

Reports: B1 46094-B1: Efficient Synthesis of Heterocycles with the Aid of Electrophilic Cyclizations and Fluorous Chemistry

Roman Dembinski, Oakland University

In pursuit of the synthesis of 3-fluorofurans, 5-endo-dig cycloisomerization of 1,4-, mostly aryl-substituted, 2-monofluorobut-3-yn-1-ones was investigated with the use of metal catalysts. Zinc and silver-containing compounds were ineffective, while palladium catalysts gave moderate results. Finally, 5-endo-dig cyclization reaction was accomplished effectively in the presence of chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (both 5 mol %, dichloromethane) under ambient conditions. These reagents provides a facile method for the preparation of 2,5-diaryl 3-fluorofurans in high yields (89-96%). The structure of 2-(4-bromophenyl)-3-fluoro-5-(4-methylphenyl)furan was confirmed by X-ray crystallography. The key starting materials, 2-fluorobut-3-yn-1-ones, were generated by a newly elaborated fluorination of 1,4-disubstituted tert-butyldimethylsilyl but-1-en-3-yn-1-yl ethers with Selectfluor.

Overall, three undergraduate students were supported by this project and gained valuable synthetic organic chemistry experience during their summer research.