Iron-Catalyzed Cross-Electrophile Coupling of Inert C-O Bonds with Alkyl Bromides

An example of iron-catalyzed cross-electrophile coupling of inert C-O bonds with alkyl bromides via an iron/B(2)pin(2) catalytic system has been developed. Aryl and heteroaryl carbamates can smoothly undergo this transformation under mild conditions, delivering the alkylated products with good efficiency. This protocol exhibits good functional group compatibility and enables the late-stage functionalization of biorelevant compounds, thus providing excellent opportunities for applications in medicinal chemistry. Control experiments and computational studies reveal that a high spin Fe(I/II/III) catalytic mechanism might be involved in this reaction through single electron transfer to activate alkyl bromides, oxidative addition of aryl carbamates, and reductive elimination to form Csp(2)-Csp(3) bonds. [GRAPHICS] .

Automated summary

This study developed an iron-catalyzed cross-electrophile coupling method using an iron/B(2)pin(2) catalytic system to couple inert C-O bonds with alkyl bromides. The reaction showed good efficiency in generating alkylated products from aryl and heteroaryl carbamates under mild conditions. The protocol exhibited good functional group compatibility and allowed late-stage functionalization of biorelevant compounds, making it suitable for applications in medicinal chemistry.