Application of Primary Phosphine Oxides in Domino-Phospha-Aldol Reactions of Diketones

An approach for the preparation and stabilization of primary phosphine oxides is presented complementing previous methods of in situ generation. Specifically, RP(O)H₂ where R=benzyl (Bn), cyclohexyl (Cy), 2-naphthyl (2-Naph), phenyl (Ph), tert-butyl (t-Bu) was prepared by controlled oxidation of the corresponding primary phosphine in presence of ferrocene as stabilizing reagent. The primary phosphine oxides were characterized using NMR and MS and studied in twofold hydrophosphorylation of diketones. The domino-phospha-aldol reaction catalysed with 5 mol% of sodium methoxide yielded five-, six- and seven-membered heterocyclic tertiary phosphine oxides with a high degree of stereoselectivity, as confirmed by single X-ray diffraction.