Diversifying fluoroalkanes: light-driven fluoroalkyl transfer via vinylboronate esters.
Kaushik Chakrabarti1, Chandana Sunil1, Benjamin M Farris1
1Department of Chemistry, University of Michigan 930N. University Ann Arbor Michigan 48109 USA nszym@umich.edu.
Chemical Science
|March 26, 2025
Summary
A novel synthetic strategy enables the creation of tertiary difluoromethylene molecules using fluoroalkane precursors and vinyl-pinacol boronic ester reagents. This method offers a versatile, one-pot protocol tolerant to various functional groups and reaction conditions.
Area of Science:
- Organic Synthesis
- Fluorine Chemistry
- Radical Reactions
Background:
- Tertiary difluoromethylene motifs are valuable in pharmaceuticals and materials science.
- Existing synthetic methods often lack versatility or require stringent conditions.
- Efficient and robust methods for introducing -CF2- groups are highly sought after.
Purpose of the Study:
- To develop a new, versatile synthetic strategy for tertiary difluoromethylene-containing molecules.
- To establish a one-pot protocol utilizing readily available fluoroalkanes and vinyl-pinacol boronic ester reagents.
- To investigate the reaction mechanism and scope of the developed method.
Main Methods:
- Photochemical conjugate radical addition of fluoroalkyl(vinyl)pinacol boronate esters.
- One-pot synthesis employing fluoroalkane precursors (RCF2H) and vinyl-pinacol boronic ester (vinyl-BPin) reagents.
- Experimental and theoretical mechanistic studies including radical initiation and ionic rearrangement.
Main Results:
- Successful synthesis of tertiary difluoromethylene molecules from fluoroalkane precursors.
- Demonstrated tolerance to oxygen and nitrogen heterocycles, and common functional groups.
- Versatile application using HFC-23, HFC-32, and difluoromethyl heteroarenes as precursors.
- Elucidation of a reaction mechanism involving radical initiation and a 1,2-boronate rearrangement.
Conclusions:
- A new, efficient, and versatile synthetic strategy for tertiary difluoromethylene compounds has been established.
- The developed one-pot protocol offers a practical approach using accessible starting materials and mild conditions.
- The mechanistic insights provide a foundation for further development and application of this methodology.
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