Direct π‐Activation vs. O‐Activation in Halogen‐Bonding Catalysis

• Published in: Angewandte Chemie Vol. 135; no. 16
• Main Authors: Robidas, Raphaël, Legault, Claude Y.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 11.04.2023
• Subjects: Carbonyl compounds; Carbonyl groups; Carbonyls; Catalysis; Catalysts; Chemistry; Computer applications; Halogen Bonding; Iodine; Mechanism; Molecular Iodine; Polarity; Solvents; Substrates
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202301190

Halogen bond donors had an increasing impact on catalysis in recent years, and their development is highly active. In particular, numerous iodine‐based halogen bond donors have been developed and used to promote various reactions through coordinating carbonyl groups, a ubiquitous mode of activation in catalysis. We now report computational data which strongly suggests that an alternative activation mode, through direct π‐complexation, is operative for unsaturated carbonyl substrates. Calculations also suggest that solvent polarity could have a clear impact on the preference of the mode of activation, raising the possibility of a mechanistic manifold switch through solvent variation. These findings could profoundly impact the development of the next generation of halogen‐bond donor catalysts. Halogen Bond (XB) donors are under active development in organocatalysis. In analogy to Hydrogen Bond (HB) donors, they have been considered to activate most organic substrates through the O‐complexation of carbonyl groups. Our results suggest that direct π‐activation (i.e., of the π‐bond involved in the reaction) can be dominant in many cases of XB catalysis, largely altering our view on this type of catalysis.