I'm trying to stannylate a thiophene at the 2-position with an amide side chain already at the 3-position. I've tried both metalation with n-BuLi and lithium-halogen exchange by first brominating and the quenching with trimethyltin chloride. I've also attempted Stille coupling with hexamethylditin and the brominated version of the thiophene. In all cases I regain the starting material with nothing at the 2 position. It appears the insertion of the metal is occurring (whether it's lithium or palladium) but the reaction refuses to go forward to convert to the final product. Is it possible that the amide chain is somehow interfering? This is all so that I can eventually couple the organotin with an aryl halide. I'd appreciate a solution for this synthesis, or perhaps a workaround to the eventual coupling.
I would recommend a different synthetic route if the amide side chain at the 3-position is detrimental for your reactions. You can run a Stetter reaction to form a 1,4-dicarbonyl precursor (with the desired aryl already in place), and then follow up with a Paal-Knorr thiophene synthesis using Lawesson's reagent. This would circumvent the need for lithiation/Li-halogen exchange chemistry.
For more reading see enclosed linked.
http://pubs.acs.org/doi/abs/10.1021/ja401511r
http://pubs.acs.org/doi/abs/10.1021/ol060208a
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