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

Area of Science:

• Physical Chemistry
• Organic Chemistry
• Spectroscopy

Background:

• The Diels-Alder reaction is a fundamental carbon-carbon bond-forming reaction in organic chemistry.
• Understanding the nature of pre-reactive intermediates is crucial for controlling reaction stereoselectivity.
• Noncovalent interactions play a significant role in stabilizing reaction transition states and intermediates.

Purpose of the Study:

• To experimentally characterize the pre-reactive intermediates in the furan-acrolein Diels-Alder reaction.
• To investigate the influence of noncovalent interactions, specifically π-π stacking and hydrogen bonding, on intermediate structure and stability.
• To explore the effect of solvent on the reaction's stereoselectivity.

Main Methods:

• High-resolution rotational spectroscopy was employed for experimental characterization.
• Computational methods, including the XYG3 and CCSD(T) levels of theory, were used for validation and energetic analysis.
• Microsolvation models were applied to study solvent effects.

Main Results:

• Three distinct pre-reactive isomers were identified experimentally.
• π-π stacking interactions were found to be more significant than hydrogen bonding in stabilizing the intermediates.
• The exo isomer was determined to be slightly more stable than the endo isomer.
• Computational methods accurately predicted the energetic ordering of the isomers.
• Hexafluoro-2-propanol was shown to preserve π-π stacking and enhance exo selectivity through hydrogen-bonding networks.

Conclusions:

• π-π stacking is a key noncovalent interaction governing the stereochemistry of the furan-acrolein Diels-Alder reaction.
• Solvent choice can significantly influence noncovalent interactions and thus control reaction stereoselectivity.
• These findings offer molecular-level insights into stereocontrol mechanisms applicable to a broader range of Diels-Alder reactions.