Fluorinated furan-2(5H)-ones:: Reactivity and stereoselectivity in Diels-Alder reactions

3 -Fluorofuran-2(5H)-one (1) and three 3,4-difluorofuran-2(5H)-ones 2-4, alpha,beta-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 f uran-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. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)