Regioselectivity of Larock Heteroannulation: A Contribution from Electronic Properties of Diarylacetylenes

A series
of 2,3-diarylindoles were synthesized from 2-iodoaniline
and unsymmetrical diarylacetylenes using the Larock heteroannulation.
Diarylacetylenes bearing electron-withdrawing substituents lead to
2,3-diarylindoles with substituted phenyl moieties at the 2-position
as major products, while those with electron-donating groups preferably
yield indole products with substituted phenyl moieties at the 3-position.
The regioisomeric product ratios exhibit a clear correlation with
Hammett σp values. DFT calculations reveal the origin
of this effect, displaying smaller activation energy barriers for
those pathways leading to the major regioisomer.