Copper-Catalyzed Radical-Induced Annulation-Halo(bi)cyanomethylation of Indole-Tethered 1,6-Enynes toward Pyrrolo[1,2-a]indoles

A copper-catalyzed radical-induced annulation-halocyanomethylation of indole-linked 1,6-enynes has been established using haloacetonitrile as radical precursors, enabling the synthesis of 21 cyanomethylated pyrrolo[1,2-a]indoles with yields ranging from 42% to 81% and a Z/E ratio up to 19:1. Moreover, by adjusting the reaction temperature, a variation of the annulation-bromobicyanomethylation process was achieved, resulting in the production of 12 bicyanomethylated pyrrolo[1,2-a]indole isomers in yields of 41-68%. The stereoisomeric mixture of bicyanomethylated products could be purified to their pure configurations through recrystallization. The proposed reaction mechanism was formulated through a series of control experiments.