Fluorinated Chiral Pyrans Obtained via Mechanochemical Organocatalytic Michael/oxa‐Michael Cascade

Fluorine‐containing compounds are important in medicine or crop‐protection. Herein, we show asymmetric organocatalytic Michael/oxa‐Michael cascade leading to chiral fluorinated pyrans under mechanochemical conditions. Formal oxa‐Diels‐Alder reaction between fluorine containing unsaturated keto esters and β,γ‐unsaturated ketones afforded a range of drug‐like pyran derivatives in short times and good to high yields. Ball‐milling conveys the reaction in short times and high product yields, while keeping high enantiomeric purities of products. The reaction is diastereodivergent depending on the use of either monofunctional amine catalysts or bifunctional thiourea or squaramide.