Lewis Acid/Oxidant as Rapid Regioselective Halogenating Reagent System for Direct Halogenation of Fused Bi-/Tri-cyclic Hetero-Aromatic Congeners via C(sp2)-H bond Functionalization

Herein, we report the identification of new and fast halogenating reagent system consisting of Lewis acid AlX3 [X=Cl, Br, I] as a halogen source in the presence of tert-butyl hydroperoxide (TBHP) which has been utilized for the direct regioselective halogenation on various fused bi-/tri-cyclic hetero-aromatic congeners 3 a-q, 7 a-d, 8 and 9 via C-(sp2)-H bond functionalization. The operationally simple protocol is quite fast and does not require the external halogenation source at 110 degrees C in 20-60 minutes and furnished halogenated fused heterocycles 4 a-p, 5 a-k, 6 a-l, 10 a-i, 11 a, 12 a-b in up to 96% yields. The gram-scale synthesis, wide substrate scope, functional group tolerance, control experiments and application to further derivatization/functionalization for C-C bond formation further highlights the versatility of the developed methodology as well as the compatibility of the new catalyst. The combination of Lewis acid (AlX3) as a halogen source and TBHP (oxidant) as a halogenating reagent system is the first account for the direct regioselective halogenation of several fused bi-/tri-cyclic hetero-aromatic congeners via C-(sp2)-H bond functionalization.

Automated summary

In this study, a new and fast halogenating reagent system was developed using Lewis acid AlX3 and tert-butyl hydroperoxide (TBHP) for direct regioselective halogenation, leading to the synthesis of various fused bi-/tri-cyclic hetero-aromatic compounds. The protocol is operationally simple and provides high yields, showcasing the versatility and compatibility of the new catalyst.