Charge-Transfer-Regulated Site-Selective Activation: Divergent On-Surface Coupling Pathways of Multi-Reactive-Site Amide Precursors on Au(111) and Ag(111).

Controlling the reaction selectivity of multi-reactive-site precursors and understanding its underlying mechanism are crucial for on-surface synthesis. However, directing the activation of different functional groups toward specific reaction pathways remains a fundamental challenge. Herein, we report a comprehensive investigation of the substrate-dependent reactivity of 2,8-dibromo-5H-dibenzo[b,e]azepin-5-one (2,8-DBDA), a multi-reactive-site precursor containing both C-Br bonds and amide groups, on Au(111) and Ag(111) surfaces using scanning tunneling microscopy and density functional theory (DFT) calculations. On Au(111), selective activation of C-Br bonds triggers Ullmann-type C-C coupling, yielding zigzag chains, cyclic trimers, and S-shaped oligomers, while the amide groups remain intact to mediate hydrogen bonding. In contrast, on Ag(111), C-Br cleavage together with N-H deprotonation leads to the formation of N-Ag-N and N-Ag-C intermediates, which further evolve into N-C and C-C cross-coupled heterocycles. The strong electronic interactions and interfacial charge redistribution on Ag(111) substantially lower the energy barriers for both C-Br and N-H bond activation, enabling multisite reactivity, as confirmed by DFT calculations. This work demonstrates that the choice of metal substrate is a powerful strategy to steer the reactivity of multi-reactive-site precursors, providing fundamental insights into the rational design of on-surface synthetic pathways for complex functional nanostructures.