Controllable Reductive Alkylation of Monodentate Phosphine Ligands under Iron Catalysis
Qiu‐Jin Wu, Shasha Geng, Adong Qiao, Siyu Wang, Jinping Yuan, Yun He, Feng Zhang
Abstract
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.