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.
Table of Contents
Preface xiii
Volume 1
Part I Carbon‐Linked Fluorine‐Containing Motifs 1
1 Difluoromethylation and Difluoroalkylation of (Hetero)Arenes: Access to Ar(Het)-CF2H and Ar(Het)-CF2R 3
Yu‐Lan Xiao and Xingang Zhang
1.1 Introduction 3
1.2 Difluoromethylation of (Hetero)aromatics 3
1.2.1 Transition‐Metal‐Mediated/Catalyzed Nucleophilic Difluoromethylation of (Hetero)aromatics 3
1.2.2 Catalytic Metal‐Difluorocarbene‐Involved Coupling (MeDIC) Reaction 10
1.2.3 Transition‐Metal‐Catalyzed Radical Difluoromethylation of (Hetero)aryl Metals/Halides and Beyond 11
1.2.4 Radical C─H Bond Difluoromethylation of (Hetero)aromatics 19
1.3 Difluoroalkylation of Aromatics 22
1.3.1 Transition‐Metal‐Catalyzed Phosphonyldifluoromethylation of (Hetero)aromatics 23
1.3.2 Transition‐Metal‐Catalyzed 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, C≡C, and -N=C Bonds 47
Sebastian Barata‐Vallejo and Al Postigo
2.1 Introduction 47
2.2 Difluoromethylation of C═C Double Bonds 49
2.2.1 Intermolecular Difunctionalization of C═C 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 C═C Double Bonds and Subsequent Cyclization 69
2.2.3 Difluoromethylation of C═C 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 C═O, C═C, and C═N 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 BrCF2CH═CH2 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 Phosphorus‐containing 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 PhCH2CF2I 107
3.3.7 By Means of HCF2SO2Cl and HCF2SO2Na or Zn(SO2CF2H)2 108
3.3.8 By Means of Difluoromethylated Sulfones, Sulfoximines, Thioethers, and Sulfonium Salts 109
3.3.9 By Means of TMSCF2CO2Et and ArCF2CO2H 112
References 112
4 Monofluoromethylation Reactions of Aliphatic Substrates and (Hetero)Arenes 119
Qiqiang Xie and Jinbo Hu
4.1 Nucleophilic Monofluoromethylation 119
4.1.1 By Means of Fluoromalonates 119
4.1.2 By Means of Fluoromethyl Phenyl Sulfone 119
4.1.3 By Means of Fluorobis(phenylsulfonyl)methane 121
4.1.4 By Means of 2‐Fluoro‐2‐Sulfonylketone 122
4.1.5 By Means of 2‐Fluoro‐1,3‐benzodithiole‐1,1,3,3‐tetraoxide (FBDT) 123
4.1.6 By Means of TMSCF(SO2Ph)2 (TFBSM) 123
4.1.7 By Means of PhSO(NTBS)CH2F 123
4.1.8 By Means of CH2FI 124
4.1.9 By Means of Monofluoromethyl Phosphonium Salts 124
4.2 Electrophilic Monofluoromethylation 125
4.2.1 By Means of CH2FX (X = Cl, Br, I, OTf, OTs, OMs) 125
4.2.2 By Means of S‐(monofluoromethyl)diarylsulfonium Tetrafluoroborate 125
4.2.3 By Means of Monofluoromethylsulfoxinium Salts 126
4.2.4 By Means of Monofluoromethylsulfonium Ylides 127
4.2.5 By Means of Monofluoromethyl Phosphonium Salts 127
4.3 Free Radical Monofluoromethylation 128
4.3.1 By Means of (PhSO2)2CFI 128
4.3.2 By Means of (H2FCSO2)2Zn (MFMS) 128
4.3.3 By Means of CH2FSO2Cl 128
4.3.4 By Means of PhSO(NTs)CH2F 129
4.3.5 By Means of Monofluoromethyl Sulfone 130
4.4 Transition‐Metal‐Catalyzed/Mediated Monofluoromethylation 130
4.4.1 By Means of CH2FI 130
4.4.2 By Means of PhSO2CHFI 131
4.4.3 By Means of CH2FBr 131
4.4.4 By Means of PTSO2CH2F 132
References 132
5 Synthesis of gem‐Difluorocyclopropanes 135
Dmitriy M. Volochnyuk and Oleksandr O. Grygorenko
5.1 Introduction 135
5.2 Intramolecular Wurtz (Freund) Reaction 140
5.3 Nucleophilic Fluorination of Pre‐existing Ring System 140
5.4 Cyclopropanation of 1,1‐Difluoroalkenes 142
5.5 Difluorocyclopropanation of Alkenes and Alkynes 143
5.5.1 Fragmentation of Trihalomethyl Anions CF2X- (X = Cl, Br) 145
5.5.2 Reduction of CF2Br2 with Zn or Other Reductants 146
5.5.3 Decarboxylative Difluorocarbene Generation 149
5.5.4 Difluorocarbene Generation by Nucleophilic Cleavage of a Carbene Precursor 153
5.5.5 Decomposition of CF3‐substituted Organometallic Derivatives 164
5.5.6 Lewis Base‐promoted Cleavage of the Ruppert-Prakash‐type Reagents XCF2SiMe3 (X = F, Cl, Br) 169
5.5.7 Photodissociation of Difluorodiazirine 182
5.5.8 Thermal Decomposition of Hexafluoropropene Oxide 183
5.6 Michael‐induced Ring Closure (MIRC) 183
5.7 Reactions at the Double Bond of gem‐Difluorocyclopropenes 185
5.8 Conclusions 187
References 187
Part II Oxygen‐Linked Fluorine‐Containing Motifs 195
6 Indirect Construction of the OCF3 Motif 197
Pingping Tang and Xiaohuan Jiang
6.1 Introduction 197
6.2 Fluorination of Trichloromethyl Ethers 197
6.3 Deoxyfluorination of Fluoroformates 198
6.4 Oxidative Fluorodesulfurization 198
6.5 Decarboxylative Fluorination 199
6.6 Direct Trifluoromethylation 200
6.7 Intramolecular OCF3 Migration 202
References 204
7 Reagents for Direct Trifluoromethoxylation 207
Pingping Tang and Xiaohuan Jiang
7.1 Introduction 207
7.2 Trifluoromethyl Hypofluorite (FTM) 207
7.3 Chloroxytrifluoromethane 209
7.4 Bistrifluoromethyl Peroxide (BTMP) 210
7.5 Bis(trifluoromethyl) Trioxide 210
7.6 N‐Trifluoromethoxy Benzimidazole 211
7.7 N‐Trifluoromethoxypyridinium 213
7.8 N‐Trifluoromethoxy Triazolium Salts 214
7.9 Trifluoromethyl Trifluoromethanesulfonate (TFMT) 215
7.10 Organometallic Trifluoromethoxides 217
7.11 Perfluoroalkylsulfurane 219
7.12 Perfluoroalkylsulfurane Oxide 219
7.13 2,4‐Dinitro(trifluoromethoxy)benzene (DNTFB) 221
7.14 Trifluoromethyl Sulfonates (TFMS) 221
7.15 Trifluoromethyl Benzoate (TFBz) 222
References 223
8 Direct Trifluoromethoxylation of Aromatics and Heteroaromatics 225
Johnny W. Lee, Katarzyna N. Lee, and Ming‐Yu Ngai
8.1 Introduction 225
8.2 Direct Anionic Trifluoromethoxylation 226
8.3 Direct Radical Trifluoromethoxylation 239
8.4 Conclusion and Future Perspective 249
References 249
9 Direct Trifluoromethoxylation of Aliphatic Compounds 251
Chaohuang Chen and Guosheng Liu
9.1 Direct Trifluoromethoxylation of Alkenes 251
9.1.1 Radical Trifluoromethoxylation of Alkenes 251
9.1.2 Pd(II)‐Catalyzed Oxidative Trifluoromethoxylation of Alkenes 252
9.1.3 Silver(I)‐catalyzed Trifluoromethoxylation of Alkenes 255
9.1.4 Direct Trifluoromethoxylation at sp3‐Carbon Atoms 258
9.1.4.1 Trifluoromethoxylation of Alkyl Halides and Alkyl Triflates 258
9.1.4.2 Trifluoromethoxylation of Alkyl Alcohols and Alkyl Silanes 259
9.1.4.3 Trifluoromethoxylation of C-H Bonds 260
9.1.4.4 Nucleophilic Trifluoromethoxylation of Epoxides 262
9.2 Trifluoromethoxylation of α‐Diazo Esters 263
9.3 Summary and Outlook 264
References 265
10 Extension to the Construction of ORf Motifs (OCF2H, OCFH2, OCH2CF3, OCFHCH3) 267
Jin‐Hong Lin and Ji‐Chang Xiao
10.1 Introduction 267
10.2 Construction of the OCF2H Group 269
10.2.1 Insertion of Difluorocarbene into O─H Bond 269
10.2.2 Decarboxylative Fluorination 272
10.2.3 Direct Electrophilic Difluoromethylation 272
10.2.4 Difluoromethoxylation 273
10.2.5 Nucleophilic Fluorination 274
10.3 Construction of the OCFH2 Group 275
10.3.1 Monofluoromethylation 275
10.3.2 Fluorination 278
10.4 Construction of the OCH2CF3 Group 280
10.4.1 Trifluoroethoxylation 281
10.4.2 Trifluoroethylation 283
10.5 Construction of the OCFHCH3 Group 285
10.6 Conclusions and Perspectives 285
References 285
Volume 2
Preface xvii
Part III Sulfur‐Linked Fluorine‐Containing Motifs 289
11 Indirect Trifluoromethylthiolation Methods 291
Xiu‐Hua Xu and Feng‐Ling Qing
12 Reagents for Direct Trifluoromethylthiolation 309
He Liu, Hangming Ge, and Qilong Shen
13 Trifluoromethylthiolation of Aromatic and Heteroaromatic Compounds 343
Wenbin Yi, Zhidong Song, Jie Liu, Yasir Mumtaz, and Wei Zhang
14 Synthesis of Trifluoromethylthiolated Alkenes and Alkynes 373
Matthew N. Hopkinson
15 Direct Trifluoromethylthiolation Toward C(sp3)-SCF3 Compounds 403
Yumeng Liang, Dominique Cahard, and Norio Shibata
16 Extension to the SCF2H, SCH2F, and SCF2R Motifs (R = PO(OEt)2, CO2R, Rf) 449
Tatiana Besset and Thomas Poisson
17 Synthesis and Applications of Fluorinated Sulfoxides (RSORF) and Sulfones (RSO2RF) 477
Vinayak Krishnamurti, Colby Barrett, and G.K. Surya Prakash
18 Pentafluorosulfanylation of Aromatics and Heteroaromatics 551
Petr Beier
19 Pentafluorosulfanylation of Aliphatic Substrates 571
Günter Haufe
20 Extension to SF4CF3 and SF4FG Groups 611
Peer Kirsch
21 Properties and Applications of Sulfur(VI) Fluorides 621
Nicholas D. Ball
22 Construction of S-RF Sulfilimines and S-RF Sulfoximines 675
Emmanuel Magnier
Part IV Selenium‐Linked Fluorine‐Containing Motifs 691
23 When Fluorine Meets Selenium 693
Thierry Billard and Fabien Toulgoat
Part V Nitrogen‐Linked Fluorine‐Containing Motifs 723
24 Construction of N‐CF2H, N‐CF3, and N‐CH2CF3 Motifs 725
Thierry Milcent and Benoit Crousse
Part VI Phosphorus‐Linked Fluorine‐Containing Motifs 763
25 Synthesis and Applications of P-Rf‐Containing Molecules 765
Fa‐Guang Zhang and Jun‐An Ma
Index 809
