Selectivity in the Addition of Electron‐Deficient Radicals to the C2 Position of Indoles

The addition of electron-deficient radicals to theC2position of indoles has been described in the literature as opposed to electrophilic addition at theC3 position. Density functional theory calculations were used to understand the switch in regioselectivity fromC3toC2for indole to undergo radical additions. Electron deficient radicals have a lower barrier for the reaction atC2 and a lower energy radical intermediate that benefits from benzylic radical stabilization. Trifluoromethyl radical addition has a lower energy barrier than acetonitrile radical, and theC3 addition transition state is just 0.8 kcal/mol higher thanC2. This is supported by experimental observations.