Synthesis of Mixed Phosphine–Phosphine Oxide Ligands by Rh(I)‐Catalyzed C─H Bond Alkylation

Abstract

The design of phosphine ligands is pivotal in transition metal catalysis, enabling fine‐tuning of catalytic activity, selectivity, and stability. Hemilabile ligands, particularly mixed phosphine–phosphine oxide ligands, offer dynamic coordination, stabilizing reactive intermediates, and enhancing catalytic performance. Herein, we report an efficient Rh(I)‐catalyzed method for synthesizing these ligands via selective C─H bond alkylation of biarylphosphines, allowing the introduction of one or two hemilabile phosphine oxide side arms. The synthesized ligands exhibit remarkable reactivity in Pd‐catalyzed Buchwald–Hartwig coupling between 2‐chlorotoluene and gaseous ammonia, a challenging reaction due to ammonia's strong Lewis basicity. Among the ligands tested, DavePhosO showed complete conversion and 97% yield, highlighting the role of the hemilabile phosphine oxide unit in preventing formation of inactive palladium complexes.