Synthesis 2017; 49(15): 3394-3406
DOI: 10.1055/s-0036-1588489
short review
© Georg Thieme Verlag Stuttgart · New York

Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

Sankarganesh Krishnamoorthy
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California University Park, Los Angeles, CA 90089-1661, USA   Email: [email protected]
,
G. K. Surya Prakash*
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California University Park, Los Angeles, CA 90089-1661, USA   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 03 May 2017

Accepted after revision: 06 June 2017

Publication Date:
17 July 2017 (online)


Dedicated to Professor Herbert Mayr on the occasion of his 70th birthday

Abstract

There have been significant developments in the area of perfluoroalkyl group transfer using silicon reagents, specifically in nucleo­philic trifluoromethylation. The mild and versatile activation conditions bestow significant synthetic prowess to the silicon reagents in the area of fluoroalkylations. Owing to the importance of difluoromethylene (CF2) containing compounds in pharmaceuticals, materials, and agrochemicals, several CF2 group transfer methods using related silicon reagents have been developed and studied in detail. This review summarizes the recent developments and trends in this area.

1 Introduction

2 Trimethyl(trifluoromethyl)silane (Me3SiCF3)

3 (Difluoromethyl)trimethylsilane (Me3SiCF2H)

3.1 Nucleophilic Addition

3.2 Nucleophilic Substitution

3.3 Nucleophilic Difluoromethylation of Electron-Deficient Hetero­cycles

3.4 Metal-Mediated Cross Coupling

3.5 Oxidative Coupling of Terminal Alkynes

4 Post-functionalizable Difluoromethyl Transfer Reagents

4.1 (Chlorodifluoromethyl)trimethylsilane (Me3SiCF2Cl)

4.2 (Bromodifluoromethyl)trimethylsilane (Me3SiCF2Br)

4.3 [Difluoro(iodo)methyl]trimethylsilane (Me3SiCF2I)

4.4 [Difluoro(phenylthio)methyl]trimethylsilane (Me3SiCF2SPh)

4.5 [Difluoro(phenylsulfonyl)methyl]trimethylsilane (Me3SiCF2SO2Ph)

4.6 Diethyl [Difluoro(trimethylsilyl)methyl]phosphonate [Me3SiCF2P(O)(OEt)2]

4.7 Ethyl Difluoro(trimethylsilyl)acetate (Me3SiCF2CO2Et)

4.8 Difluoro(trimethylsilyl)acetamides (Me3SiCF2CONR2)

4.9 Difluoro(trimethylsilyl)acetonitrile (Me3SiCF2CN)

5 Others

6 Conclusions

 
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