The Origin of the Halogen Effect on Reactivity and Reversibility of Diels–Alder Cycloadditions Involving Furan

Abstract

Origin and generality of the halogen effect in Diels–Alder reactions were explored with high‐accuracy CBS–QB3 computations. Halogen substitution increases cycloaddition exergonicities and decreases activation barriers. This effect is attributed to the energetic preference for electronegative halogen substituents to be attached to a more highly alkylated, and therefore more electropositive, carbon framework.

Five‐Membered Heterocycles: Furan

“…This phenomenon is attributed to the decreased activation energy and a greater stabilization of the cycloadduct imparted by the substitution as determined by CBS-QB3 calculations. The same substitution at the 3-position can also provide a similar effect although to a lesser extent than that of the 2-position [231]. In the example shown in Scheme 6.116, the DielsÀAlder reaction occurred mainly at the 3-chloroScheme 6.114 Scheme 6.115 582j 6 Five-Membered Heterocycles: Furan furan ring, which suggests a dominant effect of a 3-halo substituent on intermolecular cycloaddition [232].…”

Recent progress in the use of fluoroorganic compounds in pericyclic reactions

“…69 As Table 3 shows, these substituents and other halogens were found to lower the activation enthalpies, while increasing the exothermicities. In other words, the facilitations are both kinetic and thermodynamic in nature.…”

Addition Reactions: Cycloaddition

“…The trifluoromethyl group shows comparable effects to halogen at the 2-position of furan. 88 Also, the incorporation of a halogen in the 3-or 5-position of N -alkenyl-substituted furanylamides increased the reaction rate of the intramolecular Diels-Alder reactions. 89 In a recent re-examination of the thermolysis of benzocyclobutenes for the in situ generation of o-quinodimethanes, the resultant IMDA diastereoselectivity was highly de dependent on the nature of the hydroxyl protective group.…”

“…96 The Diels-Alder cycloadditions of the natural cyclolignins thuriferic acid and epithuriferic acid with cyclopentadiene have been reinvestigated. In the case of thuriferic acid (86), all four possible α,β-isomers (87)(88)(89)(90) were isolated and characterized, while with epithuriferic acid only the β-isomers were isolated and identified (Scheme 23). 97 The cycloaddition of zirconacyclopentadienes to p-quinones in the presence of CuCl-p-chloranil produced higher p-dihydroquinones in high yields (65-79%).…”