Reductive functionalization of N-heteroarenes remains to date a challenge due to the easy occurrence of direct reduction of such substances into non-coupling saturated cyclic amines. Herein, by developing an unprecedented manganese catalyst ligating with an unsymmetrical 2-aminotetrahydronaphthyridyl PNP-ligand, we have achieved a new reductive cross-coupling of indoles/pyrroles and N-heteroarenes. Mechanistic investigations show that the catalyst-enabled in situ capture of the partially reduced intermediates by interruption of the second transfer hydrogenation of N-heteroarenes constitutes the key to success for the present reaction. The developed chemistry proceeds with good substrate and functional group compatibility, high step and atom efficiency, excellent chemo and regioselectivity, and applicable for late-stage modification of pyridine-containing biomedical molecules, which has established a new platform allowing the linkage of aromatic systems into functional frameworks, and further development of unsymmetrical PNP organometallic complexes and related catalytic transformations. (C) 2020 Elsevier Inc. All rights reserved.