Controllable Reductive Alkylation of Monodentate Phosphine Ligands under Iron Catalysis

Unsymmetrical aryldialkylphosphine ligands, characterized by their electron-rich and sterically hindered nature, play a pivotal role in the fine-tuning of transition-metal catalysts during catalytic processes. However, their synthesis remains challenging via conventional approaches. Herein, we report an iron-catalyzed reductive cross-coupling of aryldialkylphosphine ligands with alkyl bromides under mild conditions and successfully extend this strategy to diarylalkylphosphines. Utilizing a well-designed iron/diboron catalytic system that promotes the selective cleavage of C(alkyl)-P bonds via the alkyl substituent exchange, this method enables the efficient transformation of readily available monophosphines into structurally diverse tertiary phosphine ligands. The protocol accommodates late-stage functionalization of bioactive phosphines and offers a versatile platform for the diversification of sterically hindered ligands, including Buchwald-type scaffolds, thereby highlighting its utility in transition-metal-catalyzed coupling reactions. Mechanistic studies suggest that borylation of the C(alkyl)-P bond governs the selective C-P bond cleavage, driving the reductive alkylation of phosphines. These findings not only deepen our understanding of iron-catalyzed reductive coupling processes but also inspire the development of new carbon-heteroatom bond-forming strategies using iron/diboron catalysis.