Tetramethylphosphorinones as Functional Alternatives to Di- <i>tert</i> -butylphosphino Substituents in Ligand Design

Bulky phosphino substituents, such as tBu2P, are key components of ligands in homogeneous catalysis, yet few options exist to tune their electronic properties while retaining comparable steric environments. Here, we report the synthesis of oxo-tetramethylphosphinane (oxo-TMPhos), a 2° phosphorinone scaffold that incorporates a γ-ketone substituent into the tetramethylphosphinane framework. The ketone handle enables broad derivatization, including reduction, amination, and C–C bond formation, while the 2° phosphine can be used to construct a variety of ligands. Systematic donor strength evaluation using the Huynh electronic parameter (HEP) confirmed that phosphorinones are weaker donors than tetramethylphosphinane (TMPhos) and tBu2PH, reflecting the electron-withdrawing C═O substituent. From this scaffold, we prepared a series of phosphorinone ligands, including Buchwald-type, bidentate phosphines with propyl (BPP) or butyl (BPB) linkers, bulky PCP and PNP pincer ligands, and a new scalable route to bis(2,2,6,6-phosphorin-4-one)-o-xylene (BPX). In Pd-catalyzed isomerizing methoxycarbonylation of 4-octene, BPP delivered over an order of magnitude higher turnover numbers (TONs) than the corresponding di-tert-butylphosphino analogue. It could be applied across a broad substrate scope, including internal, branched, cyclic, and styrenic alkenes. This work highlights phosphorinones as a practical and tunable alternative to classical bulky alkylphosphines, with significant potential for applications in homogeneous catalysis.