Direct Alkynylation of 3H-Imidazo[4,5-b]pyridines Using gem-Dibromoalkenes as Alkynes Source
Jessy Aziz1, Tom Baladi1, Sandrine Piguel2
1Institut Curie, PSL Research University, CNRS, INSERM, UMR9187-U1196 , F-91405, Orsay, France.
Abstract:
C2 direct alkynylation of 3H-imidazo[4,5-b]pyridine derivatives is explored for the first time. Stable and readily available 1,1-dibromo-1-alkenes, electrophilic alkyne precursors, are used as coupling partners. The simple reaction conditions include an inexpensive copper catalyst (CuBr·SMe2 or Cu(OAc)2), a phosphine ligand (DPEphos) and a base (LiOtBu) in 1,4-dioxane at 120 °C. This C-H alkynylation method revealed to be compatible with a variety of substitutions on both coupling partners: heteroarenes and gem-dibromoalkenes. This protocol allows the straightforward synthesis of various 2-alkynyl-3H-imidazo[4,5-b]pyridines, a valuable scaffold in drug design.
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