I have this stubborn starting material that is quite reluctant to react the way I need it to, under typical Sonogashira conditions with propargyl alcohol (PdCl2(PPh3)2, CuI, pyrrolidine, heat).
I am unfortunately not at liberty to disclose the exact structure, but what I can say is that the arylbromide is quite electron-rich (FGs = several e-donating groups, R = alkyl chain). The corresponding aryliodide does unfortunately not exist and would be pretty demanding to synthesize, so that is not really an option. The molecule also contains a silyl protection group, but that should not matter.
What conditions might get the desired reaction going? I now see a very slow conversion of the starting material over several days, and the isolated yield of the desired product is below 10 %. There is an annoying side-reaction too, which is not plain reduction, that consumes most of the arylbromide.
I am counting on your cross-coupling expertise here! Any obvious quick-fix? I should also say that this is on gram scale, so glove box-ish conditions are not acceptable. Do you think an NHC palladium catalyst would perform better? If so, which one? Conditions? The catalyst/ligand has to be commercial. Please include Sigma-Aldrich item numbers and/or DOIs 🙂