Pd-Catalyzed Asymmetric Aza-Heck Cyclization/Sonogashira Reaction of Alkene-Tethered Oxime Esters and Alkynes

Over the past few decades, Narasaka–Heck-type difunctionalization of tethered alkenes has emerged as a powerful strategy to produce heterocyclic scaffolds. However, asymmetric synthesis has rarely been explored. Herein, we report a robust palladium-catalyzed enantioselective Narasaka–Heck cyclization–Sonogashira reaction of alkene-tethered oxime esters and terminal alkynes. By employing the new Ming-Phos ligand, we obtain high yields of pyrrolines with a quaternary stereocenter and high enantioselectivities under mild reaction conditions. Density functional theory (DFT) study reveals the weak interaction between the aromatic ring of the substrate fragment and the naphthyl group in the ligand, which probably accounts for the high stereoselectivity.