Substituted
2-iodoaniline derivatives were prepared and utilized
as reactants, along with asymmetric diarylacetylenes, to synthesize
a series of 6-substituted-2,3-diarylindole derivatives via the Larock
heteroannulation reaction. Electron-donating substituents on the 2-iodoaniline
derivatives retarded the reaction, while electron-withdrawing substituents
provided a complete conversion to the indole products. In addition,
the electronic properties of the substituted 2-iodoaniline reactants
displayed no influence toward regioselectivity. On the contrary, the
electronic effect from unsymmetrical diarylacetylenes significantly
influenced the regiochemical outcome of the reaction. Density functional
theory calculations of the oxidative addition and carbopalladation
steps revealed the electronic influences of the substituted 2-iodoaniline
derivatives toward the overall rate of the reaction. In contrast,
the electronic properties of the asymmetric diarylacetylene remained
the critical product-determining factor of regioselectivity.