Jin Yang

Nickel-catalyzed Suzuki–Miyaura coupling (Ni-SMC) reactions offer a cost-effective approach for active pharmaceutical ingredient (API) synthesis but remain constrained by their limited compatibility with heteroaromatic substrates and the need for high catalyst loadings. Our laboratory recently developed the ProPhos ligand, which significantly addresses these challenges. In this study, we systematically investigate the electronic and steric effects of the ProPhos ligand framework. Evaluation of over 20 ProPhos derivatives, alongside representative monodentate and bidentate phosphine ligands, reveals that the beneficial influence of the tethered hydroxyl group is general. Other nucleophilic substituents were less effective, and variations in the three-carbon linker length compromised the catalytic efficiency. Increased steric bulk on phosphorus decreased reactivity, whereas electron-donating substituents such as para-tolyl enhanced performance; in contrast, replacing aryl groups with cyclohexyl groups proved detrimental. Finally, the application of the optimized ligand, ProPhos*, to a range of previously challenging substrates demonstrated the robustness and efficiency of Ni-SMC at low catalyst loading.

A detailed examination of substrate scope is described for alkene hydrophosphination catalyzed by a series of Cp*Ru complexes. An outer‐sphere mechanism is proposed that involves nucleophilic addition of a Ru phosphido ligand to the alkene and subsequent proton transfer to the resulting phospha‐carbanion from Ru‐bound substrate phosphine. Selected kinetic studies and the observation of catalyst resting state complexes that inevitably contain both a reactive phosphido ligand and substrate phosphine suggest that the conjugate addition is turnover limiting. However, analysis of catalyst activities as a function of the alkene activating group, and observation of off‐cycle alkene oligomerization initiated by the phospha‐carbanion intermediate for some alkene and phosphine substrates point to a more complex situation. These results suggest that alkenes that are “too” activated or substrate phosphines that are not sufficiently P─H acidic cause the intramolecular proton transfer to become turnover‐limiting, with rates sensitive to the conjugate addition “pre‐equilibrium”. This unusual compilation of experimental evidence for the impact of substrate variation on the activity and selectivity of a hydrophosphination catalyst provides insights for guiding future catalyst (re)design, including the challenge of providing a coordination environment that enhances phosphine P─H acidity to achieve a broader substrate phosphine scope.

This study reports that the well-known Co(III) precursor Co(η⁵-Cp*)I₂(CO) (1) is an effective precatalyst for dehydrocoupling reactions of phosphines. Reaction monitoring by NMR, complemented by ESI-MS and EPR, suggests that Co(III) complexes containing secondary and primary phosphine ligands play an important role in this catalysis but that redox chemistry is also facile for these complexes, resulting in paramagnetic species. Representative examples of the mono(phosphine) complexes Co(η⁵-Cp*)I₂(PR₂H) (2) and Co(η⁵-Cp*)I₂(PRH₂) (4) and bis(phosphine) complexes [Co(η⁵-Cp*)I(PR₂H)₂] I (3) have been prepared. The characterization of these complexes through structural, computational, spectroscopic, and electrochemical analysis is reported and serves as a foundation for considering their mechanistic significance in the observed catalytic dehydrocoupling chemistry.