Quaternary Phosphonium Salts Enable Palladium‐Catalyzed Annulative C─H Activation of Aminophosphines with Alkynes

Abstract Quaternary phosphonium salts, despite their extensive historical study, have remained unexplored as key additives in transition metal catalysis until our current investigation. Here, we present a groundbreaking palladium‐catalyzed system for P(III)‐directed C─H activation of aminophosphines, followed by annulation with alkynes. By utilizing P‐stereogenic aminophosphines, we have achieved the stereospecific synthesis of chiral phosphacycles. This innovative process, facilitated by deprotonative isomerization, efficiently yields a wide range of P‐heterocycles. The pivotal breakthrough of our methodology lies in the identification of phosphonium salts as effective additives, which undertake multiple functions: they not only reduce the energy barrier of pivotal steps but also regenerate the palladium catalyst while safeguarding the P(III) directing group from oxidation. Through systematic experimental investigations, particularly by comparing transition states with and without quaternary phosphonium salts, we have elucidated the unique reaction pathway, thereby explaining the critical role of the salts.