Probing substituent effects in aryl-aryl interactions using stereoselective Diels-Alder cycloadditions.

TitleProbing substituent effects in aryl-aryl interactions using stereoselective Diels-Alder cycloadditions.
Publication TypeJournal Article
Year of Publication2010
AuthorsWheeler, SE, McNeil, AJ, M\üller, P, Swager, TM, Houk, KN
JournalJournal of the American Chemical Society
Date Publishedmar
KeywordsAlkynes, Alkynes: chemistry, Anthracenes, Anthracenes: chemistry, Benzene Derivatives, Benzene Derivatives: chemistry, Cyclization, Models, Molecular, Molecular Conformation, Stereoisomerism, Thermodynamics

Stereoselective Diels-Alder cycloadditions that probe substituent effects in aryl-aryl sandwich complexes were studied experimentally and theoretically. Computations on model systems demonstrate that the stereoselectivity in these reactions is mediated by differential pi-stacking interactions in competing transition states. This allows relative stacking free energies of substituted and unsubstituted sandwich complexes to be derived from measured product distributions. In contrast to gas-phase computations, dispersion effects do not appear to play a significant role in the substituent effects, in accord with previous experiments. The experimental pi-stacking free energies are shown to correlate well with Hammett sigma(m) constants (r = 0.96). These substituent constants primarily provide a measure of the inductive electron-donating and -withdrawing character of the substituents, not donation into or out of the benzene pi-system. The present experimental results are most readily explained using a recently proposed model of substituent effects in the benzene sandwich dimer in which the pi-system of the substituted benzene is relatively unimportant and substituent effects arise from direct through-space interactions. Specifically, these results are the first experiments to clearly show that OMe enhances these pi-stacking interactions, despite being a pi-electron donor. This is in conflict with popular models in which substituent effects in aryl-aryl interactions are modulated by polarization of the aryl pi-system.