Three-Component Radical-Initiated Annulation-Bifunctionalization of Indole-Linked 1,6-Enynes for the Synthesis of Stereodefined Pyrrolo[1,2- <i>a</i> ]indoles

Two separate classes of three-component radical-initiated annulation-bifunctionalization reactions involving indole-linked 1,6-enynes have been successfully established under mild reaction conditions. The oxidant-mediated annulation-iodonitration employs <i>tert</i>-butyl nitrite and iodoform as reagents, while the palladium-catalyzed annulation-aryldifluoroalkylation utilizes difluoroiodoacetate and arylboronic acids as starting materials. In combination, these two reaction models have promoted the synthesis of functionalized pyrrolo[1,2-<i>a</i>]indoles, with stereoselectivity values varying from a 1:1 ratio to a 19:1 ratio. A total of 30 examples are provided to validate the efficacy of these methods. Furthermore, the obtained products exhibit excellent potential for subsequent modifications. The proposed reaction mechanisms have been thoroughly clarified through a series of meticulously designed control experiments. These newly devised protocols open up promising new pathways for the rapid construction of functionalized pyrrolo[1,2-<i>a</i>]indole frameworks with generally acceptable yields.