Emerging Fluorinated Motifs

A must-have resource for all the researchers working in the organofluorine and related fields

This timely two-volume set uniquely focuses on emerging fluorinated motifs beyond R-CF3 and R-F, like R-CF2H, R-OCF3, R-SCF3 and R-SF5. It also offers descriptions of the properties, synthesis, and applications of these emerging fluorinated motifs in order to help readers design new chemical entities, while providing new interest for researchers in organofluorine chemistry and new tools for those in other areas.

Emerging Fluorinated Motifs: Synthesis, Properties and Applications begins with a description of carbon-linked fluorine-containing groups that include monofluoromethyl and difluoromethyl groups. It then details combinations of heteroatoms, Oxygen, Sulfur, Selenium, Nitrogen, and Phosphorus with fluorine-containing groups, outlining subsections of the most popular current motifs. Fluoroalkyl ethers, thioethers, and the recent blossoming of the SF5 unit is covered. Other chapters look at: selenium-linked fluorine-containing motifs; construction of N-CF2H, N-CF3, N-CH2CF3 motifs; and the synthesis and applications of P-Rf-containing molecules.

-Focuses on the synthesis, properties, and applications of emerging fluorinated motifs
-Covers carbon-linked fluorine-containing motifs, oxygen-linked fluorine-containing motifs, sulfur-linked fluorine-containing motifs, and more
-Appeals to academic and industrial researchers working in organic chemistry, medicinal chemistry, food chemistry, and materials science
-Edited by world-renowned experts in organofluorine chemistry

Emerging Fluorinated Motifs is intended for academic research institutes, university libraries, researchers, graduate students, postdoctors, and researchers in the chemical industry.

Autorentext

Dominique Cahard, PhD, is Director of Research at the French National Center for Scientific Research, CNRS. His current research interests concern innovative methodologies for asymmetric synthesis of fluorinated molecules and the synthesis of fluorinated biomolecules. Jun-An Ma, PhD, is a Full Professor of organic chemistry at Tianjin University, P. R. of China. His current research efforts are focused on organofluorine chemistry, catalytic asymmetric synthesis, and the rational design & construction of biological molecules.

Inhalt
Preface xiii

Volume 1

Part I CarbonLinked FluorineContaining Motifs 1

**1 Difluoromethylation and Difluoroalkylation of (Hetero)Arenes: Access to Ar(Het)CF2H and Ar(Het)CF2R 3
**YuLan Xiao and Xingang Zhang

1.1 Introduction 3

1.2 Difluoromethylation of (Hetero)aromatics 3

1.2.1 TransitionMetalMediated/Catalyzed Nucleophilic Difluoromethylation of (Hetero)aromatics 3

1.2.2 Catalytic MetalDifluorocarbeneInvolved Coupling (MeDIC) Reaction 10

1.2.3 TransitionMetalCatalyzed Radical Difluoromethylation of (Hetero)aryl Metals/Halides and Beyond 11

1.2.4 Radical CH Bond Difluoromethylation of (Hetero)aromatics 19

1.3 Difluoroalkylation of Aromatics 22

1.3.1 TransitionMetalCatalyzed Phosphonyldifluoromethylation of (Hetero)aromatics 23

1.3.2 TransitionMetalCatalyzed Difluoroacetylation of (Hetero)aromatics and Beyond 26

1.3.3 Other Catalytic Difluoroalkylations of (Hetero)aromatics 37

1.4 Outlook 39

References 42

**2 Difluoromethylation and Difluoroalkylation of Aliphatic Unsaturated C=C, CC, and N=C Bonds 47
**Sebastian BarataVallejo and Al Postigo

2.1 Introduction 47

2.2 Difluoromethylation of CC Double Bonds 49

2.2.1 Intermolecular Difunctionalization of CC Double Bonds 56

2.2.1.1 By Means of BrCF2P(O)(OR)2 56

2.2.1.2 By Means of Ph3P+CF2CO2 59

2.2.1.3 By Means of HCF2R (R = CO2H, SO2NHNHBoc) 62

2.2.1.4 By Means of Selectfluor 65

2.2.1.5 By Means of BrCF2CO2Et 66

2.2.2 Difluoromethylation of CC Double Bonds and Subsequent Cyclization 69

2.2.3 Difluoromethylation of CC Double Bonds with Rearrangements 73

2.3 Difluoromethylation of Isocyanides 76

2.4 Difluoromethylation of Alkynes 79

2.5 Conclusion and Perspectives 82

References 85

3 Difluoromethylation and Difluoroalkylation in C(sp3) Centers and CO, CC, and CN Bonds 89
**Qiqiang Xie and Jinbo Hu

3.1 Nucleophilic Difluoromethylation and Difluoroalkylation 89

3.1.1 By Means of XCF2PO(OEt)2 89

3.1.2 By Means of BrCF2CO2Et and BrCF2CHCH2 89

3.1.3 By Means of Difluoromethylcadmium, Difluoromethylcopper, and Difluoromethylzinc Reagents 90

3.1.4 By Means of Difluoroalkylated Sulfone Reagents (XCF2SO2Ar) and Difluoromethylated Sulfoxides 90

3.1.5 By Means of Difluoroalkylated Silanes and Trifluoromethylsilane Reagents 94

3.1.6 By Means of Difluoromethyl Sulfoximine Reagent 96

3.1.7 Miscellaneous Reagents 96

3.2 Electrophilic Difluoromethylation and Difluoroalkylation 97

3.2.1 By Means of Difluorocarbene Reagents 97

3.2.2 By Means of CF3X (X H, I, TMS) Reagents 99

3.2.3 By Means of I(III)CF2SO2Ph Reagent 100

3.2.4 By Means of S((Phenylsulfonyl)difluoromethyl)thiophenium Salts 100

3.3 Free Radical Difluoromethylation and Difluoroalkylation 101

3.3.1 By Means of Iododifluoroacetates 101

3.3.2 By Means of CF2Br2, CF2BrCl, or TMSCF2Br 102

3.3.3 By Means of Phosphoruscontaining Reagents 103

3.3.4 By Means of BrCF2CO2Et 104

3.3.5 By Means of Halodifluoroketone or Amide 107 3.3.6 By Means of HCF2I and PhCH2&...