Ene-ene-yne Reactions: Activation Strain Analysis and Role of Aromaticity

The trend in reactivity of the thermal cycloisomerization reactions of 1,3-hexadien-5-ynes, A=B-C=D-E≡F, were explored and analyzed by using density functional theory at the M06-2X/def2-TZVPP level. These reactions proceed through formally aromatic transition states to form a bent-allene intermediate with relatively high activation barriers. Activation-strain analyses show that the major factor controlling this Hopf cyclization is the geometrical strain energy associated with the rotation of the terminal [A] group. This rotation is necessary for achieving a favorable HOMO-LUMO overlap with the yne-moiety [F] associated with the formation of the new A-F single bond. In addition, the relationship between the aromaticity of the corresponding cyclic transition states (all six-membered rings) and the computed activation barriers were analyzed. The calculations also indicate that the aromatization of the bent-allene structures takes place through two consecutive 1,2-hydrogen shifts, the second one exhibiting negligible energy barriers. Twisted! The barrier of Hopf cyclizations is primarily controlled by the activation strain (see figure, red) associated with twisting the terminal double bond, needed to achieve optimal HOMO-LUMO overlap and single-bond formation between ene and yne terminus (green). Substitution of a heteroatom, for example, NH, for the terminal CH