Palladium-Catalyzed Asymmetric Carbonylative Sonogashira Reaction of Cyclopropenes: Simultaneous Construction of Ynone Skeleton and Central Chirality

Abstract Ynones are fundamental structural motifs found in a broad spectrum of bioactive molecules and pharmaceuticals. Owing to their intrinsic conjugated reactivity, centrally chiral ynones serve as versatile building blocks in organic synthesis. However, the current access to centrally chiral ynones relies predominantly on the stepwise asymmetric functionalization of pre-existing ynone derivatives. In this study, we present a palladium-catalyzed asymmetric carbonylative Sonogashira reaction of cyclopropenes, which enables the simultaneous construction of the ynone framework and the establishment of central chirality, thereby eliminating the need for post-functionalization. The protocol features mild reaction conditions, high atom economy, and a broad substrate scope. Moreover, its practical utility is demonstrated through gram-scale synthesis and diverse product derivatizations, offering a valuable perspective for the construction of centrally chiral ynones.