“…Encouragingly, installing a directing group (DG) at the C3 position of indoles could increase the activity of the proximal C4 site and hence lead to the desired C4–H functionalization. − The success of this strategy relies on the selective formation of a six-membered metallacycle including the C4 site. , However, this strategy is challenged by the possible formation of a thermodynamically more favorable five-membered metallacycle at the C2 site. ,, Thus, to deliver exclusive C4 selectivity, readily tailored DGs and efficient TM catalysts are required to overcome the competing C2 metalation. ,− Most of the DGs on the C3 site arise from the carbonyl-based groups, e.g., aldehyde, ketone, carboxyl, and acylamide. In general, C4 functionalization of indole could be achieved by the weak coordinating DGs, e.g., −CHO, −COCF 3 , and −CO t Bu, , while strong coordinating DGs, e.g., −CONHMe, −COMe, and −COPh, prefer C2-site reactions .…”