A palladium/norbornene (NBE) cooperative catalytic system was developed to access C5-aminated indoles, starting from readily available C4-idonated indoles. Good yields and exclusive site selectivity were achieved for a broad substrate scope, including drug molecule core architectures. Control experiments found that both aldehyde on the C3 position and sulfonyl protecting group on the N1 position were vital for the transformation. Preliminary bioactivity evaluation identified a promising leading compound 3af with potent antitumor proliferative activity against several cancer cells.