Abstract
Imidazo[1,5-a]pyridines are core motifs in bioactive compounds, drugs and photofunctional materials. In addition to the well-known organic synthetic methods, Pd-catalyzed C3 functionlization via C−H activation has recently been reported. To the best of our knowledge, there are no reports on Ni-catalyzed C−H functionalization of imidazo[1,5-a]pyridines. Herein, we discover the Ni-catalyzed C3 alkenylation of imidazo[1,5-a]pyridines with internal alkynes under mild conditions at ambient temperature. Regioselectivity can be switched to C5 alkenylation in the presence of Lewis acid. In addition, the present methodology is also applied to C5 alkylation of imidazo[1,5-a]pyridines with various alkenes upon heating. In summary, we have first demonstrated Ni-catalyzed C−H activation of imidazo[1,5-a]pyridines to perform alkenylation or alkylation with high regioselectivity. It is worth mentioning that this is the first example for C5 functionalization of imidazo[1,5-a]pyridines by using nickel and a Lewis acid.