Recent Advances in the Synthetic Application of Difluorocarbene

Abstract

Difluorocarbene is a versatile, reactive intermediate for use in organic synthesis. Over the past decade, significant progress has been made in difluorocarbene chemistry owing to the increasing demand for various fluorinated molecules. Not only the substrate scope for some classical difluorocarbene reagents has been largely expanded, but also new and environmentally friendly difluorocarbene reagents for difluoromethylation and gem-difluorocyclization have been developed. This review summarizes the difluoromethylation, gem-difluorocyclopropanation, gem-difluorocyclopropenation, gem-difluoroolefination, and trifluoromethylation achieved in the last decade using both the classical and the new difluorocarbene sources.

1 Introduction

2 Difluorocarbene Sources

3 Difluoromethylation

3.1 O-Difluoromethylation

3.2 S-Difluoromethylation

3.3 N-Difluoromethylation

3.4 Difluoromethylation of Ambident N,O- and N,S-Nucleophiles

3.5 Se- and P-Difluoromethylation

3.6 C-Difluoromethylation

3.7 Sn-Difluoromethylation

4 gem-Difluorocyclization

4.1 gem-Difluorocyclopropanation

4.2 gem-Difluorocyclopropenation

5 gem-Difluoroolefination and Related Reactions

6 Trifluoromethylation

7 Miscellaneous

8 Conclusions

Key words

difluorocarbene - difluoromethylation - cycloaddition - gem-difluoroolefination - trifluoromethylation

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