Iron-Catalyzed Reductive Cross-Coupling of Heterocyclic Bromides

Controlling the reductive coupling of highly reactive heterocycloalkyl and heteroaryl bromides is challenging due to their propensity for side reactions such as dimerization and debromination. Herein, we present an iron-catalyzed reductive cross-coupling protocol for organobromides that effectively balances their high reactivity with selective reaction pathways. Utilizing an iron/diboron catalytic system designed for the controlled regulation of reactive iron species, our method efficiently converts N-heteroaryl and piperidinyl bromides under mild conditions. This protocol allows the late-stage functionalization of biorelevant compounds, offering good opportunities for the diversification of heterocycle derivatives. Mechanistic investigations indicate that an iron(I) complex is likely the key active intermediate, while kinetic studies reveal that substrate concentration critically governs the balance between reactivity and selectivity. These findings offer insights into iron-catalyzed coupling reactions and may pave the way for the design of transformations of organohalides using the iron/diboron catalytic system.