Fluorine-Retentive Strategies for the Functionalization of gem-Difluoroalkenes

Abstract

gem-Difluoroalkenes are readily available fluorinated building blocks, and the fluorine-induced electronic perturbations of the alkenes enable a wide array of selective functionalization reactions. However, many reactions of gem-difluoroalkenes result in a net C–F functionalization to generate monofluorovinyl products or addition of F to generate trifluoromethyl-containing products. In contrast, fluorine-retentive strategies for the functionalization of gem-difluoroalkenes remain less generally developed and is now becoming a rapidly developing area. This review will present the development of fluorine-retentive strategies including electrophilic, nucleophilic, radical, and transition metal catalytic strategies with an emphasis on key physical organic and mechanistic aspects that enable reactivities.

1 Introduction

2 Two-Electron Processes

2.1 Elimination of Allyl Groups

2.2 Electrophilic Addition

2.3 Halonium and Thiiranium Intermediates

2.4 Kinetic Quench of Anionic Intermediates

2.5 Concerted Cycloadditions

3 Radical Processes

3.1 Thermal Activation

3.2 Photoactivation

3.3 Transition-Metal-Mediated

4 Reductions

5 Cross-Coupling Reactions

6 Conclusions

Key words

synthetic methodology - fluorination - gem-difluoroalkene - organofluorine

Publication History

Received: 13 May 2021

Accepted after revision: 12 July 2021

Accepted Manuscript online:
12 July 2021

Article published online:
25 August 2021

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