Metal-Catalyzed Decarboxylative Fluoroalkylation Reactions

Abstract

Metal-catalyzed decarboxylative fluoroalkylation reactions enable the conversion of simple O-based substrates into biologically relevant fluorinated analogues. Herein, we present decarboxylative methods that facilitate the synthesis of trifluoromethyl- and difluoroketone-containing products. We highlight key mechanistic aspects that are critical for efficient catalysis, and that inspired our thinking while developing the reactions.

1 Introduction

2 Copper-Catalyzed Decarboxylative Trifluoromethylation Reactions

2.1 Net Trifluoromethylation of Alcohols

2.2 Mechanism of Decarboxylation Impacts Functional-Group Tolerance

2.3 Allylic Trifluoromethylation Enabled by Activation Protocol

2.4 Generation of Iodide Intermediate Required for Benzylic Trifluoromethylation

2.5 Ligand-Controlled Regiodivergent Trifluoromethylation of Propargylic Electrophiles

2.6 Summary

3 Palladium-Catalyzed Decarboxylative Alkylation of α,α-Difluoroketone Enolates

3.1 Convergent Routes towards α,α-Difluoroketones

3.2 Palladium-Catalyzed Decarboxylative Benzylation of α,α-Difluoroketone Enolates

3.3 Palladium-Catalyzed Decarboxylative Allylation of α,α-Difluoroketone Enolates

3.4 Summary

Key words

fluorine - trifluoromethylation - difluoroketone - decarboxylation - catalysis - copper - palladium

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