Deoxyfluorination of Hydroxy-Substituted Boronates

Area of Science:

• Organic Chemistry
• Fluorine Chemistry
• Synthetic Methodology

Background:

• Deoxyfluorination is crucial for introducing fluorine into organic molecules.
• Hydroxyalkyl-substituted aryl- and alkenylboronates are valuable synthetic intermediates.
• Developing scalable and practical fluorination methods remains a challenge.

Purpose of the Study:

• To develop a practical and scalable protocol for the deoxyfluorination of hydroxyalkyl-substituted aryl- and alkenylboronates.
• To explore the utility of the resulting fluorinated boronates as building blocks.
• To establish a one-pot strategy for accessing complex fluorinated molecules.

Main Methods:

• Optimized deoxyfluorination using Deoxo-Fluor and TEA·3HF.
• Substrate preconversion to trifluoroborate salts.
• Telescoped one-pot reaction strategy.

Main Results:

• Efficient deoxyfluorination of diverse (homo)-benzylic and allylic alcohols.
• Tolerance of protected carboxyl and amino groups.
• Successful application of fluorinated boronates in oxidation and Suzuki cross-coupling reactions.
• Direct utilization of crude fluorinated intermediates in a one-pot approach.

Conclusions:

• The developed methodology provides a general and efficient route for incorporating monofluorinated aliphatic fragments.
• This approach facilitates the synthesis of complex molecular frameworks relevant to medicinal chemistry and materials science.
• The protocol is practical, scalable, and versatile for late-stage fluorination challenges.