Pd-Catalyzed Synthesis of Indoles via NH₃ Cross-Coupling-Alkyne Cyclization

Significance

Reported is the first use of ammonia in the palladium-catalyzed synthesis of 2-aryl indoles 2 from ortho-bromophenylacetylenes 1. Methylamine was also employed to generate N-methyl indoles directly. A variety of functional groups on the R^² arene ring are tolerated, including EDGs, halogens and heterocycles, although EWGs (CF₃, F) lead to poor yields of products of 2. Only a cursory investigation of substituent effects (R^¹) on the aryl bromide was carried out. Interestingly, 1,6-dibromo substitution in 1 led to mono-coupled product 2 (R^¹ = 4-Br-6-Me), a valuable precursor for further manipulation by cross-coupling methods. In a significant extension to the methodology, hydrazine was also used to generate N-aminoindoles 3 in moderate yields (along with varying amounts of indazoles 4).