Moderation of the Electronic Structure of Phosphamides to Execute the Catalytic Appel Reaction Bypassing Phosphine

A set of structurally analogous, albeit electronically distinct, phosphamides (<b>1aa-10aa</b>) is prepared, and the effect of the electronic amendment due to p-substitution has been tested for the conversion of alcohols to halides via the Appel reaction. The -OMe-substituted diphosphamide (<b>8aa</b>) remains the most active, providing ∼96% conversion of alcohols to halides with a TON of 11 in moderate reaction conditions with a large substrate scope. Halide formation follows a pseudo-first-order rate with a constant rate (<i>k</i>_obs) of 7.13 × 10^-5 s^-1. Temp-dependent kinetics and Eyring analyses reveal the activation parameters Δ<i>H</i>^‡ of 28.95 (±1.6) kcal mol^-1, Δ<i>S</i>^‡ of -70.02 (±0.4) cal K^-1 mol^-1, and Δ<i>G</i>^‡₂₉₈ of 49.81 (±1.2) kcal mol^-1. The deuterium labeling study highlights the O-H dissociation of the alcohol as the rate-determining step, while the Hammett analysis with <i>p</i>-substituted benzyl alcohols indicates a positive charge accumulation at the phosphorus center during the Appel reaction. The HOMO-LUMO energy and NPA analyses show that <i>p</i>-OMe substitutions in <b>8aa</b> make the "P═O" bond more ionic and corresponding aminophosphine is nucleophilic, which are favorable for the Appel reaction. In situ detection of the Appel salt, [R₃PX]CX₃ and alkoxy phosphonium cation [R₃POR]X, validates the reaction pathway mediated by the phosphamides.