Abstract

This paper presents a theoretical study on the distinguishable regiodivergent C2-C7 Myers-Saito and C2-C6 Schmittel routes of benzannelated enyne-allene cycloaromatizations, in which substitutions on the terminal alkyne by alkyl (-CH3, -CH2CH3, -CH(CH3)2 and -C(CH3)3) and aryl (-C6H5 and -C6H2(CH3)3) groups were included. Mechanistic differences were found between substituents attached to alkynes with and without alpha-H, whereas in the former the Schmittel cyclization proceeds together with 1,8-H migration, in the latter it does so as the sole primitive event. It was also observed that bulky substituents preferentially favor the C2-C6 Schmittel route, and the statistical prediction of regioselectivity is greatly affected when the ratio of accessible vibrational microstates of the transition states is included, especially in highly competing routes, i.e., Delta Delta G double dagger -> 0. Aiming to gain a deeper understanding, an analysis based on reaction force F(xi) and reaction force constant kappa(xi) was performed to gain insights into the competing routes. The reactive normal modes were unveiled by means of the correlation between kappa(xi) and the force constant of reaction modes kappa i(xi), given by a statistical protocol based on the partial least square with vector importance in projection (PLS-VIP) method. These findings suggest how the vibrational energy can be reorganized in competing paths from a static approach.