Improved Synthetic Route to Heteroleptic Alkylphosphine Oxides

A new method for the synthesis of heteroleptic alkylphosphine oxides (R2R1PO, where R ≠ R1) from secondary phosphine oxides (or SPOs, R2HPO) is presented. These reactions were fast at room temperature, sterically selective, high yielding, and >95% pure after an aqueous wash. Deprotonation of an SPO generates a phosphinite anion ([R2P–O]−) that was found to be highly selective for nucleophilic P–C bond formation (as opposed to O–C bond formation) with alkyl halides. Surprisingly, most strong organometallic bases failed to deprotonate SPOs to their respective phosphinite anions (pK as for most SPOs are