Mechanistic Insights into a Chiral Phosphoric Acid-Catalyzed Asymmetric Pinacol Rearrangement.

Area of Science:

• Organic Chemistry
• Catalysis
• Computational Chemistry

Background:

• The first catalytic enantioselective pinacol rearrangement was achieved using chiral phosphoric acid catalysts.
• These reactions can yield products with up to 96% enantiomeric excess (ee).

Purpose of the Study:

• To investigate the reaction mechanism and origins of stereoselectivity in chiral phosphoric acid-catalyzed pinacol rearrangements.
• To elucidate the factors influencing selectivity differences between various catalysts.

Main Methods:

• Density Functional Theory (DFT) calculations were employed to study the reaction mechanism.
• Analysis of transition states and intermediate interactions, including hydrogen bonding.

Main Results:

• The stereoselective [1,2]-aryl shift is stabilized by OH···O and CH···O hydrogen bonds between intermediates and the catalyst.
• A stronger CH···O interaction in the transition state correlates with higher enantioselectivity.
• Bulkier catalysts, such as TRIP, hinder key CH···O interactions, reducing enantioselectivity.

Conclusions:

• Hydrogen bonding interactions are crucial for controlling stereoselectivity in these catalytic rearrangements.
• Catalyst structure significantly impacts the strength of these interactions and, consequently, the observed enantioselectivity.