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Synthesis 2021; 53(21): 3935-3950
DOI: 10.1055/a-1547-9270
short review

Fluorine-Retentive Strategies for the Functionalization of gem-Difluoroalkenes

Jacob P. Sorrentino
a   Department of Medicinal Chemistry, The University of Kansas, Lawrence, Kansas 66045, USA
,
Ryan A. Altman  ∗
b   Department of Medicinal Chemistry and Molecular Pharmacology and Department of Chemistry, Purdue University, West Lafayette, Indiana 47906, USA
› Author Affiliations
Generous financial support from the National Institute of General Medical Sciences of the National Institutes of Health (R35 GM124661) is gratefully acknowledged. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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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

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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