An efficient method for the synthesis of mixed phosphine–phosphine oxide ligands via Rh(I)-catalyzed C─H bond alkylation of biarylphosphines was developed. The resulting hemilabile ligands demonstrate high reactivity in Pd-catalyzed Buchwald–Hartwig coupling with ammonia, achieving excellent yields. This work highlights the potential of mixed phosphine–phosphine oxide ligands for catalytic transformations with NH₃ gas.

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.