Oxadiazole alkynylation

Keywords 1,3,4-Oxadiazoles, alkynyl bromides, LiO-t-Bu/CuI/l,10-phenanthroline (phen), toluene, room temperature, C-H activation, direct alkylnylation, heteroaryl-aUcynyl linkage... 

Furoxan and furazans alcohols are relatively uncommon compounds, but they can serve as useful precursors to various new derivatives of 1,2,4-oxadiazole. 3-Hydroxy-4-nitrofurazan 208 reacts with iodosylbenzene to produce a highly reactive intermediate phenyliodonium nitrofurazanylate 209 which can be converted to a series of alkynyl(phenyl)-iodonium nitrofurazanylates and related products (Scheme 48) <2001TL5759>. 

The direct C—H alkynylation of 1,3,4-oxadiazoles with 1,2-dibromo-l-alkenes has been described in an eco-friendly manner by the use of CnBr and LiOt-Bu in PEG-400, a green solvent. High yields were obtained at relatively low temperatures (80°C) in 2 h (Scheme 7.7). 

Cross-coupling. Heteroarenes, such as 1,3,4-oxadiazole and oxazole, efficiently undergo a copper(II) chloride-mediated oxidative coupling with terminal alkynes (eq 34). Electron-rich alkynes effectively coupled with 2-phenyl-1,3,4-oxadiazole, although electron-deficient substrates led to a decreased yield. The 1,3,4-oxadiazoles with various substituents at the 2-position were also suitable substrates, but the slow addition of terminal alkynes was essential to avoid undesired diyne formation. The desired 2-alkynyl-5-aryloxazoles were obtained in DMSO at 150 °C. 

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