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

A set of structurally analogous, albeit electronically distinct, phosphamides (1aa-10aa) 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 (8aa) 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 (k_obs) of 7.13 × 10^–5 s^–1. Temp-dependent kinetics and Eyring analyses reveal the activation parameters ΔH^‡ of 28.95 (±1.6) kcal mol^–1, ΔS^‡ of −70.02 (±0.4) cal K^–1 mol^–1, and ΔG^‡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 p-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 p–OMe substitutions in 8aa 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.