Copper(I) halide-promoted formation of 3-acyl-5-halopyridine moiety from NH-2-(2-acylethynyl)pyrroles and propargylamine

Recent Strides in the Transition Metal-Free Cross-Coupling of Haloacetylenes with Electron-Rich Heterocycles in Solid Media

“…Latter [79] from the reaction of NH-acylethynylpyrroles 59 with propargylamine in the presence of CuX (X = Cl, Br, I), 3-acyl-2-(pyrrol-2-yl)-5-halopyridines 60 were unexpectedly isolated in 4-14% yields along with 3-acyl-2-(pyrrol-2-yl)pyridines 61 (28-61% yields) (Scheme 33). Evidently, the cause of this difference compared to the previous cyclization [78] was the NH-functionality of the starting acylethynylpyrroles.…”

“…Synthesis of pyrrolyl pyridines 60 and 61 from NH-2-acylethynylpyrroles and propargylamine.Under the above conditions, pyrrolyl pyridines 61 were not halogenated with CuX, thus indicating that construction of the halogenated pyridine ring occurred before its closure. It is supposed (Scheme 34)[79] that hydrogen halides, reversibly generated by the interaction of the NH pyrrole moiety of the intermediate N-propargyl(pyrrolyl)aminoenone 57 with CuX, add to the triple bond activated by π-complexing with other CuX molecules to give haloallyl intermediate B(Scheme 34). Afterwards, the intramolecular addition of the CH bond to the allyl moiety takes place to form the intermediate 5-halotetrahydropyridyl intermediate C. Aromatization of the latter is finalized via the reaction with CuX and further oxidation by Cu + cations as previously described for a similar process[78].…”