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Fluorous Chemistry pp 25–44Cite as

Selective Fluoroalkylation of Organic Compounds by Tackling the “Negative Fluorine Effect”

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Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 308))

Abstract

The presence of fluorine on a carbanion center will dramatically influence the nucleophilic alkylation reactions. Based on our own experience, we noticed that the fluorine substitution on the carbanionic carbon poses a negative effect in many nucleophilic fluoroalkylation reactions [we propose this effect as “negative fluorine effect (NFE)”]. Two factors were believed to contribute to the NFE: (1) thermal instability of fluorinated carbanions caused by α-elimination (self-decomposition) and (2) the intrinsic nucleophilicity of fluorinated carbanion influenced by the fluorine atoms (such as hard/soft nature of the fluorinated carbanions). By tackling the NFE, our research group has attempted to design nucleophilic fluoroalkylation reactions with fluorinated sulfones and related reagents. These results were summarized as four methods to modulate the fluoroalkylation reactions: (1) changing the number of fluorine atoms, (2) slightly changing the neighboring groups, (3) changing the metal counterion, including using carbon-metal covalent bond to tune the reactivity, and (4) enhancing the generation of carbene species.

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Abbreviations

Bn:

Benzyl

DFT:

Density functional theory

dr :

Diastereomeric ratio

ee :

Enantiomeric excess

i-Pr:

iso-Propyl

KHMDS:

Potassium bis(trimethylsilyl)amide

LiHMDS:

Lithium bis(trimethylsilyl)amide

NaHMDS:

Sodium bis(trimethylsilyl)amide

Ph:

Phenyl

Py:

Pyridine

TBAT:

Tetrabutylammonium triphenyldifluorosilicate

t-Bu:

tert-Butyl

TMS:

Trimethylsilyl

Ts:

Tosyl (p-toluenesulfonyl)

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Acknowledgments

We are grateful to the following agencies for financial support: the National Natural Science Foundation of China (20825209, 20772144, 20832008) and the Chinese Academy of Sciences.

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Authors and Affiliations

  1. Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China

    Wei Zhang, Chuanfa Ni & Jinbo Hu

Authors
  1. Wei Zhang
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  2. Chuanfa Ni
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  3. Jinbo Hu
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Corresponding author

Correspondence to Jinbo Hu .

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Editors and Affiliations

  1. , Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, China, People's Republic

    István T. Horváth

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Zhang, W., Ni, C., Hu, J. (2011). Selective Fluoroalkylation of Organic Compounds by Tackling the “Negative Fluorine Effect”. In: Horváth, I. (eds) Fluorous Chemistry. Topics in Current Chemistry, vol 308. Springer, Berlin, Heidelberg. https://doi.org/10.1007/128_2011_246

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