Chemical consequences of fluorine substitution. Part 1. Experimental and theoretical results on Diels–Alder reactions of α- and β-fluorostyrenes

Abstract

Vinyl fluorides such as α- and β-fluorostyrenes 2 and 3 are poor dienophiles for Diels–Alder reactions. Under thermal conditions these compounds do not react with usual dienes, but with the highly reactive 1,3-diphenylisobenzofuran (4) to give mixtures of the corresponding endo- and exo-products. Kinetic measurements show that the fluorostyrenes 2 and 3 are less reactive than the parent styrene (1a). Additional electron withdrawing as well as electron donating substituents (p-Cl, p-F, m-Me) on the phenyl ring of 2 and 3 slightly accelerate the reaction rate by a maximum factor of 4. DFT calculations (UB3LYP/6-31G(d)) of activation energies for furan and isobenzofuran as model dienes reflect the order of the reaction rates of the kinetic measurements. The charge difference in the double bond carbon atoms of the different dienophiles pre-determines the activation energies for the endo- and exo-transition states. The optimised structures of the transition states show that the reactions are concerted but asynchronous without biradical character. This asynchrony is determined by the differences in the p_z orbital coefficients of the double bond carbon atoms of the fluorostyrenes. The frontier molecular orbitals reveal that all the reactions are cycloadditions with normal electron demand. The calculated small endo/exo preferences are in qualitative agreement with the experimental values. In the transition states of the reactions of 2a and (E)-3a where the fluorine atom and the oxygen atom of furan are syn-orientated with respect to the reaction center, electrostatic repulsion determines the endo/exo selectivity. Semiempirical calculations show that the reactions of 4 are more exothermic with respect to the parent furan and more endothermic with respect to isobenzofuran. However, regarding relative reactivity and diastereoselectivity, the semiempirical methods are less reliable in comparison to either experiment or DFT.