Recent advances in the selective construction of 1,4-diamine motifs

1,4-Diamines constitute important structural motifs in medicinal chemistry, ligand design, and functional nitrogen-containing compounds. However, synthetic methods for their direct and selective construction are comparatively less developed than those for the extensively studied vicinal 1,2-diamines. The preparation of 1,4-diamines requires the controlled introduction of two nitrogen functionalities at distal carbon centers, often with concurrent control over regioselectivity, chemoselectivity, stereoselectivity, and differentiation of the two nitrogen groups. In recent years, diverse approaches, including conjugated-diene diamination, directed hydroamination, strain-release functionalization, arene dearomatization, C–H diamination, and C–C bond-forming strategies, have expanded the synthetic toolbox for accessing this class of compounds. This review summarizes recent progress in the selective synthesis of 1,4-diamines, with particular attention to reaction design, selectivity control, mechanistic features, substrate scope, and current limitations. Remaining challenges and future opportunities are also discussed, particularly the development of broadly applicable catalytic systems, practical and deprotectable nitrogen sources, asymmetric variants, and late-stage functionalization strategies for complex molecules.