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

Abstract

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, [R 3 PX]CX 3 and alkoxy phosphonium cation [R 3 POR]X, validates the reaction pathway mediated by the phosphamides.