When π–π Stacking Outcompetes Hydrogen Bonding: Pre-Reactive Intermediates in the Furan–Acrolein Diels–Alder Reaction

Abstract

This study presents the experimental characterization of pre-reactive intermediates in the furan–acrolein Diels–Alder reaction using high-resolution rotational spectroscopy. Three distinct isomers were identified, with π–π stacking unexpectedly prevailing over hydrogen-bonded structures, and the exo structure being slightly more stable than endo. The computationally affordable yet accurate XYG3 method, validated against benchmark CCSD(T) calculations, accurately reproduced the energetic ordering of the isomers. Solvent effects were investigated through microsolvation models, revealing that hexafluoro-2-propanol preserves π–π stacking and enhances exo selectivity via strong hydrogen-bond networks. These findings provide molecular-level insights into the stereocontrol of Diels–Alder reactions, outlining a generalizable role of π–π stacking and solvent-induced noncovalent forces in determining stereoselectivity in solution.