Impact of Multiple Hydrogen Bonds with Fluoride on Catalysis: Insight from NMR Spectroscopy

Area of Science:

• Catalysis
• Organic Chemistry
• Supramolecular Chemistry

Background:

• Hydrogen bonding is crucial in catalysis, enabling complex chemical transformations.
• BINAM-derived bisurea catalysts facilitate enantioselective nucleophilic fluorination using alkali metal fluorides.
• These catalysts solubilize fluoride sources and create chiral environments for selective reactions.

Purpose of the Study:

• To elucidate hydrogen-bonding networks between BINAM-derived bisurea catalysts and fluoride ions in solution using NMR spectroscopy.
• To understand how these hydrogen-bonding arrangements influence the efficiency and enantioselectivity of nucleophilic fluorination reactions.
• To investigate the impact of catalyst structure and counterions on fluoride complexation and catalytic performance.

Main Methods:

• Utilized ¹H/¹⁹F NMR spectroscopy to study hydrogen-bonding interactions in solution.
• Analyzed diagnostic coupling constants (^1hJ_NH···F) to quantify hydrogen bonds to fluoride.
• Investigated catalyst behavior with different fluoride sources (e.g., TBAF, CsF) and counterions in dichloromethane-d₂.

Main Results:

• Determined the number and strength of hydrogen bonds to fluoride for thirteen bisurea catalysts.
• Observed that nonalkylated catalysts have lower enantioselectivity, while N-alkylated catalysts form rigid, trifurcated fluoride complexes.
• Identified that three hydrogen bonds to fluoride contribute unequally to catalytic efficacy, with counterion effects also characterized.

Conclusions:

• Catalyst structure significantly impacts hydrogen-bonding networks and catalytic outcomes in nucleophilic fluorination.
• Dynamically rigid, trifurcated hydrogen-bonded complexes are key for efficient enantioselective fluoride delivery.
• Tuning the electronic environment of catalysts offers a strategy to optimize phase-transfer and enantioselectivity.