Developing organoboranes as phase transfer catalysts for nucleophilic fluorination using CsF

Area of Science:

• Organometallic Chemistry
• Fluorination Reactions
• Catalysis

Background:

• Boron compounds typically exhibit high affinity for fluorine.
• Organohalide fluorination is crucial for synthesizing fluorinated organic molecules.
• Phase-transfer catalysis is essential for reactions involving immiscible phases.

Purpose of the Study:

• To investigate the efficacy of organoboranes as phase-transfer catalysts for CsF-mediated fluorination.
• To explore chiral induction in nucleophilic fluorination using oxazaborolidine precatalysts.
• To establish structure-activity relationships between borane properties and fluorination efficiency.

Main Methods:

• Screening of various boranes as phase-transfer catalysts for CsF fluorination.
• Calculation of fluoride affinities for different boranes.
• Investigation of cesium cation (Cs+) ligation effects on catalysis.
• Chiral induction studies using oxazaborolidine precatalysts.

Main Results:

• Organoboranes, including triethylborane (BEt3) and 3,5-bis(trifluoromethyl)phenylboronic acid pinacol ester (3,5-(CF3)2C6H3-BPin), were effective phase-transfer catalysts for CsF fluorination.
• Significant enantioselectivity (up to 30% e.e.) was achieved in the synthesis of β-fluoroamines.
• A correlation was found between calculated fluoride affinity and catalytic activity; optimal activity requires moderate affinity.
• Cesium cation ligation influences CsF phase transfer and the Cs⋯F-B interaction, impacting B-F bond strength and fluoride transfer.

Conclusions:

• Organoboranes can serve as effective phase-transfer catalysts for nucleophilic fluorination with CsF.
• Borane fluoride affinity and Cs+ ligation are critical parameters for optimizing fluorination reactions.
• Optimal borane-mediated fluorination involves robust boranes with a fluoride affinity around 105 kJ mol−1 (relative to Me3Si+) and a persistent Cs⋯F-B interaction.