Enantioselective Synthesis of 3,4‐Dihydropyranones via Low‐Loading Squaramide Catalysis “on Water”

An organocatalytic “on‐water” cascade reaction of β ‐ketothioesters and β , γ ‐unsaturated α ‐ketoesters, catalyzed by 0.2 mol% proline‐derived squaramide, delivers 3,4‐dihydropyranones in 74–98% yield with 90–99% ee within 4 h at ambient temperature. Combined NMR and computational studies characterize the product's keto‐enol tautomeric behavior, while synthetic applications include the diastereoselective construction of 3,4‐dihydropyranones featuring an all‐carbon quaternary stereocenter.