Abstract3‐Fluorofuran‐2(5H)‐one (1) and three 3,4‐difluorofuran‐2(5H)‐ones 2–4, α,β‐unsaturated lactones possessing fluorinated double bonds, were applied as dienophiles in Diels–Alder reactions with normal electron demand using diphenylisobenzofuran or cyclopentadiene as dienes. In the same reactions, furan or 2,3‐dimethylbuta‐1,3‐diene were completely unreactive. Three structural factors of furan‐2(5H)‐ones appeared to have an effect on the reactivity, regioselectivity and diastereoselectivity of the [4+2] cycloadditions: the number of fluorine atoms attached to the double bond and the number and the bulkiness of alkyl substituents at the 5‐position of the furan‐2(5H)‐one system. The monofluorinated furan‐2(5H)‐one 1 was generally more reactive than the difluorinated furan‐2(5H)‐ones 2–4. While the reactions of the furan‐2(5H)‐ones 2–4 with isobenzofuran exclusively gave exo products, those of the monofluorinated lactone 1 led to mixtures of endo and exo diastereoisomeric [4+2] cycloadducts. All fluorinated furan‐2(5H)‐ones 1–4 formed mixtures of diastereoisomeric 1:1 and 1:2 adducts with cyclopentadiene. DFT calculations of the transition states of the above Diels–Alder reactions using the BMK functional, a third‐generation hybrid functional tailored for transition state calculations, together with the polarization consistent aug‐pc‐2 basis set, confirmed the preferential formation of the exo adducts from difluorinated furan‐2(5H)‐ones, while for nonfluorinated analogues a small but significant preference for the endo adducts was confirmed.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)