Organofluorine Chemistry

Kálmán J. Szabó is professor at the Department of Organic Chemistry at the Arrhenius Laboratory, Stockholm University (Sweden), since 2003. His major research interests are method development in organic synthesis, catalytic reactions, organoboron and organofluorine (including fluorine-18) chemistry. He is a member of the Royal Swedish Academy of Sciences and has authored over 150 publications. He is the editor of the book Pincer and Pincer-Type Complexes (Wiley-VCH).Nicklas Selander is an assistant professor at the Department of Organic Chemistry at Stockholm University (Sweden), since 2018. His research interests include organic synthesis methodology, catalysis, and radical chemistry.

• Preface xiii1 The Development of New Reagents and Reactions for Synthetic Organofluorine Chemistry by Understanding the Unique Fluorine Effects 1Qiqiang Xie and Jinbo Hu1.1 Introduction 11.2 The Unique Fluorine Effects in Organic Reactions 31.2.1 Fluorine-Enabled Stability of “CuCF3” inWater, and the Unusual Water-Promoted Trifluoromethylation 31.2.2 Fluorine Enables β-Fluoride Elimination of Organocopper Species 41.2.3 The “Negative Fluorine Effect” Facilitates the α-Elimination of Fluorocarbanions to Generate Difluorocarbene Species 51.2.4 Tackling the β-Fluoride Elimination of Trifluoromethoxide Anion via a Fluoride Ion-Mediated Process 91.3 The Relationships Among Fluoroalkylation, Fluoroolefination, and Fluorination 91.3.1 From Fluoroalkylation to Fluoroolefination 91.3.2 From Fluoroolefination to Fluoroalkylation 131.3.3 From Fluoroalkylation to Fluorination 181.4 Conclusions 20References 202 Perfluoroalkylation Using Perfluorocarboxylic Acids and Anhydrides 23Shintaro Kawamura and Mikiko Sodeoka2.1 Introduction 232.2 Perfluoroalkylation with Perfluorocarboxylic Acids 232.2.1 Electrochemical Reactions 242.2.1.1 Reactions of Alkenes and Alkynes 242.2.1.2 Reaction of Aromatic Compounds 302.2.2 Reactions Using XeF2 302.2.3 Reactions Using Copper and Silver Salts 312.2.3.1 Using Copper Salts 312.2.3.2 Using Silver Salts 352.2.4 Photochemical Reactions 362.2.5 Other Methods 382.2.5.1 Hydro-Trifluoromethylation of Fullerene 382.2.5.2 Metal-Free Aryldifluoromethylation Using S2O8 2− 392.3 Perfluoroalkylation with Perfluorocarboxylic Anhydride 392.3.1 Reactions Using Perfluorocarboxylic Anhydride/Urea⋅H2O2 402.3.2 Photocatalytic Reactions Using Perfluorocarboxylic Anhydride/Pyridine N-oxide 422.4 Summary and Prospects 43References 433 Chemistry of OCF3, SCF3, and SeCF3 Functional Groups 49Fabien Toulgoat, François Liger and Thierry Billard3.1 Introduction 493.2 CF3O Chemistry 493.2.1 De Novo Construction 493.2.1.1 Trifluorination of Alcohol Derivatives 493.2.1.2 Fluorination of Difluorinated Compounds 503.2.2 Indirect Methods 513.2.2.1 O-(Trifluoromethyl)dibenzofuranium Salts 513.2.2.2 Hypervalent Iodine Trifluoromethylation Reagents 513.2.2.3 CF3SiMe3 513.2.3 Direct Trifluoromethoxylation 523.2.3.1 Difluorophosgene and Derivatives 533.2.3.2 Trifluoromethyl Hypofluorite and Derivatives 533.2.3.3 Trifluoromethyl Triflate (TFMT) 533.2.3.4 Trifluoromethoxide Salts Derived from TFMT or Difluorophosgene 553.2.3.5 Trifluoromethyl Arylsulfonates (TFMSs) 573.2.3.6 Trifluoromethylbenzoate (TFBz) 603.2.3.7 2,4-Dinitro(trifluoromethoxy)benzene (DNTFB) 603.2.3.8 (Triphenylphosphonio)difluoroacetate (PDFA) 613.2.3.9 N-Trifluoromethoxylated Reagents 623.3 CF3S Chemistry 633.3.1 Indirect Methods 633.3.2 Direct Trifluoromethylthiolation 643.3.2.1 CF3SAg, CF3SCu, CF3SNR4 653.3.2.2 Trifluoromethanesulfenamides 653.3.2.3 N-Trifluoromethylthiophthalimide 663.3.2.4 N-Trifluoromethylthiosaccharin 673.3.2.5 N-Trifluoromethylthiobis(phenylsulfonyl)amide 683.4 CF3Se Chemistry 693.4.1 Introduction 693.4.2 Indirect Synthesis of CF3Se Moiety 703.4.2.1 Ruppert–Prakash Reagent (CF3SiMe3) 713.4.2.2 Fluoroform (HCF3) 723.4.2.3 Other Reagents Involved in CF3 − Anion Generation 733.4.2.4 Sodium Trifluoromethylsulfinate (CF3SO2Na) 733.4.3 Direct Introduction of the CF3Se Moiety 743.4.3.1 Trifluoromethyl Selenocopper DMF Complex 743.4.3.2 Trifluoromethyl Selenocopper Bipyridine Complex: [bpyCuSeCF3]2 753.4.3.3 Tetramethylammonium Trifluoromethylselenolate [(NMe4)(SeCF3)] 763.4.3.4 In Situ Generation of CF3Se− Anion from Elemental Selenium 793.4.3.5 Trifluoromethylselenyl Chloride (CF3SeCl) 803.4.3.6 Benzyltrifluoromethylselenide (CF3SeBn) 813.4.3.7 Trifluoromethylselenotoluenesulfonate (CF3SeTs) 833.4.3.8 Benzylthiazolium Salt BT-SeCF3 853.5 Summary and Conclusions 85References 864 Introduction of Trifluoromethylthio Group into Organic Molecules 99Hangming Ge, He Liu and Qilong Shen4.1 Introduction 994.2 Nucleophilic Trifluoromethylthiolation 994.2.1 Preparation of Nucleophilic Trifluoromethylthiolating Reagent 994.2.1.1 Preparation of Hg(SCF3)2, AgSCF3, and CuSCF3 994.2.1.2 Preparation of MSCF3 (M = K, Cs, Me4N, and S(NMe2)3) 1004.2.1.3 Preparation of Stable Trifluoromethylthiolated Copper(I) Complexes 1004.2.2 Formation of C(sp2)-SCF3 by Nucleophilic Trifluoromethylthiolating Reagents 1014.2.2.1 Reaction of CuSCF3 with Aryl Halides 1014.2.2.2 Sandmeyer-Type Trifluoromethylthiolation 1024.2.2.3 Transition Metal-Catalyzed Trifluoromethylthiolation 1034.2.2.4 Oxidative Trifluoromethylthiolation 1074.2.2.5 Transition Metal-Catalyzed Trifluoromethylthiolation of Arenes via C–H Activation 1084.2.2.6 Miscellaneous Methods for the Formation or Aryl Trifluoromethylthioethers via Nucleophilic Trifluoromethylthiolating Reagents 1104.2.3 Formation of C(sp3)-SCF3 by Nucleophilic Trifluoromethylthiolating Reagents 1124.2.3.1 Reaction of CuSCF3 with Activated Alkylated Halides 1124.2.3.2 Reaction of MSCF3 with Unactivated Alkyl Halides 1144.2.3.3 Nucleophilic Dehydroxytrifluoromethylthiolation of Alcohols 1144.2.3.4 Nucleophilic Trifluoromethylthiolation of Alcohol Derivatives 1164.2.3.5 Nucleophilic Trifluoromethylthiolation of α-Diazoesters 1164.2.3.6 Formation or Alkyl Trifluoromethylthioethers via In Situ Generated Nucleophilic Trifluoromethylthiolating Reagent 1184.2.3.7 Formation of Alkyl Trifluoromethylthioethers via C—H Bond Trifluoromethylthiolation 1204.3 Electrophilic Trifluoromethylthiolating Reagents 1204.3.1 CF3SCl 1204.3.2 CF3SSCF3 1214.3.3 Haas Reagent 1214.3.4 Munavalli Reagent 1234.3.5 Billard Reagent 1284.3.6 Shen Reagent 1314.3.7 Shen Reagent-II 1364.3.8 Optically Active Pure Trifluoromethylthiolation Reagents 1404.3.9 Lu–Shen Reagent 1414.3.10 α-Cumyl Bromodifluoromethanesulfenate 1444.3.11 Shibata Reagent 1454.3.12 In Situ-Generated Electrophilic Trifluoromethylthiolating Reagents 1464.3.12.1 AgSCF3 +TCCA 1464.3.12.2 AgSCF3 +NCS 1484.3.12.3 Langlois Reagent (CF3SO2Na) with Phosphorus Reductants 1484.3.12.4 Use of CF3SO2Cl with Phosphorus Reductants 1494.3.12.5 Reagent Based on CF3SOCl and Phosphorus Reductants 1514.4 Radical Trifluoromethylthiolation 1514.4.1 Trifluoromethylthiolation by AgSCF3/S2O8 2− 1524.4.2 Electrophilic Reagents Involved in Radical Trifluoromethylthiolation 1584.4.3 Visible Light-Promoted Trifluoromethylthiolation by Using Electrophilic Reagents 1594.5 Summary and Prospect 165References 1655 Bifunctionalization-Based Catalytic Fluorination and Trifluoromethylation 173Pinhong Chen and Guosheng Liu5.1 Introduction 1735.2 Palladium-Catalyzed Fluorination, Trifluoromethylation, and Trifluoromethoxylation of Alkenes 1735.2.1 Palladium-Catalyzed Fluorination of Alkenes 1745.2.2 Palladium-Catalyzed Trifluoromethylation of Alkenes 1795.2.3 Palladium-Catalyzed Trifluoromethoxylation of Alkenes 1805.3 Copper-Catalyzed Trifluoromethylative Functionalization of Alkenes 1835.3.1 Copper-Catalyzed Trifluoromethylamination of Alkenes 1845.3.2 Copper-Catalyzed Trifluoromethyloxygenation of Alkenes 1855.3.3 Copper-Catalyzed Trifluoromethylcarbonation of Alkenes 1875.3.4 Enantioselective Copper-Catalyzed Trifluoromethylation of Alkenes 1905.4 Summary and Conclusions 197References 1976 Fluorination, Trifluoromethylation, and Trifluoromethylthiolation of Alkenes, Cyclopropanes, and Diazo Compounds 201Kálmán J. Szabó6.1 Introduction 2016.2 Fluorination of Alkenes, Cyclopropanes, and Diazocarbonyl Compounds 2026.2.1 Application of Fluoro-Benziodoxole for Fluorination of Alkenes 2026.2.1.1 Geminal Difluorination of Styrene Derivatives 2036.2.1.2 Iodofluorination of Alkenes 2056.2.1.3 Fluorocyclization with C—N, C—O, and C—C Bond Formation 2056.2.2 Fluorinative Cyclopropane Opening 2076.2.3 Fluorine-18 Labeling with Fluorobenziodoxole 2076.3 Fluorination-Based Bifunctionalization of Diazocarbonyl Compounds 2096.3.1 Rhodium-Catalyzed Geminal Oxyfluorination Reactions 2096.3.2 [18F]Fluorobenziodoxole for Synthesis of α-Fluoro Ethers 2106.4 Trifluoromethylation of Alkenes, Alkynes, and Diazocarbonyl Compounds with the Togni Reagent 2126.4.1 Bifunctionalization of C—C Multiple Bonds 2136.4.1.1 Oxytrifluoromethylation of Alkenes and Alkynes 2136.4.1.2 Cyanotrifluoromethylation of Styrenes 2146.4.1.3 C–H Trifluoromethylation of Benzoquinone Derivatives 2156.4.2 Geminal Oxytrifluoromethylation of Diazocarbonyl Compounds 2176.5 Bifunctionalization-Based Trifluoromethylthiolation of Diazocarbonyl Compounds 2186.5.1 Multicomponent Approach for Geminal Oxy-Trifluormethylthiolation 2186.5.2 Simultaneous Formation of C—C and C—SCF3 Bonds via Hooz-Type Reaction 2196.6 Summary 220References 2217 Photoredox Catalysis in Fluorination and Trifluoromethylation Reactions 225Takashi Koike and Munetaka Akita7.1 Introduction 2257.2 Fluorination 2267.2.1 Fluorination Through Direct HAT Process by Excited Photocatalyst 2267.2.2 Fluorination Through Photoredox Processes 2287.3 Trifluoromethylation 2347.3.1 Trifluoromethylation of Aromatic Compounds 2347.3.2 Trifluoromethylative Substitution of Alkyl Bromides 2387.4 Summary and Outlook 239References 2398 Asymmetric Fluorination Reactions 241Edward Miller and F. Dean Toste8.1 Introduction 2418.2 Electrophilic Fluorination 2428.2.1 Stoichiometric Asymmetric Fluorination 2428.2.1.1 Chiral Auxiliary 2428.2.1.2 Chiral Reagents 2438.2.2 Catalytic Electrophilic Fluorination 2448.2.2.1 Organocatalytic Fluorination 2448.2.2.2 Transition Metal-Catalyzed Fluorinations 2598.3 Nucleophilic Fluorination 2698.3.1 Metal-Catalyzed Nucleophilic Fluorination 2708.3.1.1 Ring Opening of Strained Ring Systems 2708.3.1.2 Allylic Functionalization 2728.3.2 Organocatalytic Nucleophilic Fluorination 2738.4 Summary and Conclusions 274References 2769 The Self-Disproportionation of Enantiomers (SDE): Fluorine as an SDE-Phoric Substituent 281Jianlin Han, Santos Fustero, Hiroki Moriwaki, Alicja Wzorek, Vadim A. Soloshonok and Karel D. Klika9.1 Introduction 2819.2 General Concepts and the Role of Fluorine in the Manifestation of the SDE 2839.3 The SDE Phenomenon 2859.3.1 SDE via Distillation 2859.3.2 SDE via Sublimation 2869.3.3 SDE via Chromatography 2889.3.3.1 SDEvC for Compounds Containing a –CF3 Moiety 2899.3.3.2 SDEvC for Compounds Containing a Cq–F1/2 Moiety 2909.3.3.3 SDEvC for Compounds Containing a –COCF3 Moiety 2919.4 The SIDA Phenomenon 2949.5 Conclusions and Recommendations 296References 29910 DFT Modeling of Catalytic Fluorination Reactions: Mechanisms, Reactivities, and Selectivities 307Yueqian Sang, Biying Zhou, Meng-Meng Zheng, Xiao-Song Xue and Jin-Pei Cheng10.1 Introduction 30710.2 DFT Modeling of Transition Metal-Catalyzed Fluorination Reactions 30810.2.1 Ti-Catalyzed Fluorination Reaction 30810.2.2 Mn-Catalyzed Fluorination Reactions 30910.2.3 Fe-Catalyzed Fluorination Reactions 31010.2.4 Rh-Catalyzed Fluorination Reactions 31210.2.5 Ir-Catalyzed Fluorination Reactions 31610.2.6 Pd-Catalyzed Fluorination Reactions 31710.2.6.1 Pd-Catalyzed Nucleophilic Fluorination 31710.2.6.2 Pd-Catalyzed Electrophilic Fluorination 32210.2.7 Cu-Catalyzed Fluorination Reactions 32810.2.7.1 Cu-Catalyzed Nucleophilic Fluorination 32810.2.7.2 Cu-Mediated Radical Fluorination 33110.2.8 Ag-Catalyzed Fluorination Reactions 33310.2.9 Zn-Catalyzed Fluorination Reactions 33910.3 DFT Modeling of Organocatalytic Fluorination Reactions 34010.3.1 Fluorination Reactions Catalyzed by Chiral Amines 34010.3.1.1 Chiral Secondary Amines-Catalyzed Fluorination Reactions 34010.3.1.2 Chiral Primary Amines-Catalyzed Fluorination Reactions 34210.3.2 Tridentate Bis-Urea Catalyzed Fluorination Reactions 34510.3.3 Hypervalent Iodine-Catalyzed Fluorination Reactions 34710.3.4 N-Heterocyclic Carbene-Catalyzed Fluorination Reactions 35110.4 DFT Modeling of Enzymatic Fluorination Reaction 35410.5 Conclusions 357Acknowledgments 357References 35811 Current Trends in the Design of Fluorine-Containing Agrochemicals 363Peter Jeschke11.1 Introduction 36311.2 Role of Fluorine in the Design of Modern Agrochemicals 36311.3 Fluorinated Modern Agrochemicals 36511.3.1 Herbicides Containing Fluorine 36611.3.1.1 Acetohydroxyacid Synthase/Acetolactate Synthase Inhibitors 36611.3.1.2 Protoporphyrinogen Oxidase Inhibitors 36611.3.1.3 Cellulose Biosynthesis Inhibitors 36711.3.1.4 Very Long-Chain Fatty Acid Synthesis Inhibitors 36811.3.1.5 Auxin Herbicides 36811.3.1.6 Hydroxyphenylpyruvate Dioxygenase Inhibitors 36911.3.1.7 Selected Fluorine-Containing Herbicide Development Candidates 37011.3.2 Fungicides Containing Fluorine 37111.3.2.1 Fungicidal Succinate Dehydrogenase Inhibitors 37111.3.2.2 Complex III Inhibitors 37311.3.2.3 Sterolbiosynthesis (Sterol-C14-Demethylase) Inhibitors 37411.3.2.4 Polyketide Synthase Inhibitors 37411.3.2.5 Oxysterol-Binding Protein Inhibitors 37611.3.2.6 Selected Fluorine-Containing Fungicide Development Candidates 37711.3.3 Insecticides Containing Fluorine 37811.3.3.1 Nicotinic Acetylcholine Receptor Competitive Modulators 37811.3.3.2 Ryanodine Receptor (RyR) Modulators 38211.3.3.3 GABA-Gated CI-Channel Allosteric Modulators 38311.3.3.4 Selected Fluorine-Containing Insecticide Development Candidates 38511.3.4 Acaricides Containing Fluorine 38611.3.4.1 Mitochondrial Complex II Electron Transport Inhibitors 38611.3.4.2 Selected Fluorine-Containing Acaricide Development Candidates 38711.3.5 Nematicides Containing Fluorine 38711.3.5.1 Nematicides with Unknown Biochemical MoA 38711.3.5.2 Nematicidal Succinate Dehydrogenase Inhibitors 38811.3.5.3 Selected Fluorine-Containing Nematicide Development Candidates 38811.4 Summary and Prospects 389References 39012 Precision Radiochemistry for Fluorine-18 Labeling of PET Tracers 397Jian Rong, Ahmed Haider and Steven Liang12.1 Introduction 39712.2 Electrophilic 18F-Fluorination with [18F]F2 and [18F]F2-Derived Reagents 39812.3 Nucleophilic Aliphatic 18F-Fluorination 39912.3.1 Transition Metal-Free Nucleophilic Aliphatic Substitution with [18F]Fluoride 39912.3.2 Transition Metal-Mediated Aliphatic 18F-Fluorination 40312.4 Nucleophilic Aromatic 18F-Fluorination with [18F]Fluoride 40512.4.1 Transition Metal-Free Nucleophilic Aromatic 18F-Fluorination with [18F]Fluoride 40512.4.2 Transition Metal-Mediated Aromatic 18F-Fluorination 41312.5 18F-Labeling of Multifluoromethyl Motifs with [18F]Fluoride 41812.6 Summary and Conclusions 421References 421Index 427