Organofluorine Chemistry: Synthesis and Applications

Description

Organofluorine Chemistry: Synthesis and Applications gives a comprehensive outlook on modern synthetic methodologies for organofluorine compounds. It illustrates chemical, biochemical, and materials applications of fluorine-containing compounds, including synthesis and applications of fluorinated nanoscopic materials for drug delivery and catalysis. This book is of use to practitioners working in interdisciplinary areas such as chemical-, biochemical-, and biomedical engineering, as well as those involved in materials science and medicinal chemistry. It is also a useful reference for researchers and graduate students in working in organofluorine chemistry. Cover Organofluorine Chemistry: Synthesis and Applications Copyright Dedication Contents Preface 1 Nucleophilic reactions in the synthesis of organofluorine compounds 1.1 Introduction 1.2 Reagents for nucleophilic fluorinations 1.3 Nucleophilic deoxyfluorination 1.4 Nucleophilic fluorination of pyridines and diazines 1.5 Nucleophilic gem-difluorination of carbonyl compounds 1.6 Nucleophilic fluoroalkylations 1.6.1 Nucleophilic difluoromethylation of aldehydes 1.6.2 Ruppert–Prakash reagent (CF3SiMe3) for trifluoromethylation 1.6.2.1 Enantioselective trifluoromethylation 1.6.2.2 Synthesis of trifluoromethyl ketones 1.6.2.3 Trifluoromethylation of imines 1.6.3 Fluoroacetone hydrates for the nucleophilic fluoroalkylations 1.6.4 Trifuoromethylations using fluoroform (CHF3) 1.6.5 Borazine-mediated trifluoromethylation and difluoroalkylation 1.6.6 N-Trifluoromethylation of amines 1.6.7 Tetrakis(dimethylamino)ethylene-mediated fluoroalkylations 1.6.7.1 Trifluoromethylation of acyl chlorides 1.6.7.2 Synthesis of gem-(difluoromethyl)thioethers 1.7 Nucleophilic trifluoromethylthiolation 1.8 Trifluoromethoxylations 1.8.1 Trifluoromethyl benzenesulfonate–mediated vicinal (bromo)trifluoromethoxylation 1.8.2 Trifluoromethyl benzoate–mediated trifluoromethoxylation References 2 Electrophilic reactions in the synthesis of organofluorine compounds 2.1 Introduction 2.2 Reagents for electrophilic fluorination 2.2.1 Fluorinated bioisosteres of phosphate esters 2.3 Enantioselective electrophilic fluorination 2.3.1 Enantioselective α-fluorination of aldehydes 2.3.2 Enantioselective α-fluorination of amides 2.3.3 Enantioselective fluorination of allylsilanes and enolsilyl ethers 2.3.4 Enantioselective α-fluorination of ketones and 1,3-dicarbonyl compounds 2.4 Electrophilic fluorination in the synthesis of α-fluorinated amino acids 2.5 Electrophilic fluoroalkylation 2.5.1 Reagents for electrophilic trifluoromethylation 2.5.2 NHC-catalyzed electrophilic trifluoromethylation 2.5.3 Electrophilic difluoromethylation 2.6 Electrophilic trifluoromethylthiolation and trifluoromethoxylation 2.6.1 Synthetic methods for O-trifluoromethylation 2.7 Synthetic methods for trifluoromethylthiolation 2.7.1 Reagents for electrophilic trifluoromethylthiolation 2.7.1.1 Munavalli’s reagent 2.7.1.2 Asymmetric trifluoromethylthiolation 2.7.2 Billard’s reagents 2.7.2.1 Synthesis of the Billard’s reagents 2.7.2.2 Trifluoromethylthiolation of alkynes and Grignard reagents 2.7.3 Diethylaminosulfur trifluoride–mediated trifluoromethylthiolation of silylenol ethers and β-naphthols 2.8 Difluoromethylthiolation References 3 Free-radical reactions in the synthesis of organofluorine compounds 3.1 Introduction 3.2 Reagents for the free-radical trifluoromethylation 3.3 Decarboxylative fluoroalkylation 3.3.1 Decarboxylative trifluoromethylation 3.3.2 Decarboxylate difluoromethylation 3.4 β-Amino-fluoroalkylation of alkenes 3.4.1 Cu(I)-catalyzed amino-fluoroalkylation 3.4.2 Fe(II)-catalyzed azido- and amino-trifluoromethylation 3.4.3 Ru(II)-catalyzed amino-fluoroalkylation 3.5 Fluoroalkylation using sodium triflinate (Langlois reagent) 3.5.1 Aromatic trifluoromethylation 3.5.2 Hydro-trifluoromethylation of alkenes 3.5.3 Trifluoromethylation of arylboronic acids 3.5.4 Azido-fluoroalkylation of alkenes 3.5.5 Electrochemical oxy- and amino-trifluoromethylation 3.5.6 Selective trifluoromethylation of proteins 3.6 Photoredox-catalyzed S-fluoroalkylation and arylation 3.7 Radical fluoroalkylation of enolates References 4 Organotransition metal catalysis in the synthesis of organofluorine compounds 4.1 Introduction 4.2 Pd-catalyzed fluorination of aryl halides and triflates 4.3 Transition metal–catalyzed C–H fluorination 4.3.1 Aryl fluorination 4.3.2 Benzylic fluorination 4.3.2.1 Mn(III)-catalyzed benzylic fluorination 4.3.2.2 Pd(II)-catalyzed benzylic fluorination 4.3.3 Fluoroalkylation of hydrazones 4.3.3.1 Difluoroalkylation of hydrazones 4.3.3.2 Trifluoromethylation of hydrazones 4.4 Au(I)-catalyzed hydrofluorination of alkenes and alkynes 4.5 Ni-catalyzed fluoroalkylation of aromatics 4.5.1 Fluoroalkylation of arylsilanes 4.5.2 Aryl difluoromethylation 4.6 Ag(II)-catalyzed oxidative ring-opening fluorination of cyclic amines 4.7 Ag(I)-catalyzed decarboxylative fluorination 4.8 Cu(I)-mediated dediazoniative difluoromethylation 4.9 Fluoroalkylation of arylboronic acids and esters 4.9.1 Copper-mediated trifluoromethylation 4.9.2 Cu(I)-catalyzed trifluoromethylation of arylboronate esters 4.9.3 Pd(0)-catalyzed difluoroalkylation of arylboronic acids 4.10 Cu(I)-catalyzed fluoroalkylation of aryl halides 4.11 Ni-catalyzed trifluoromethylthiolation 4.12 Pd(II)-catalyzed (amino)trifluoromethoxylation References 5 Pharmaceutical applications of organofluorine compounds 5.1 Introduction 5.1.1 Blood–brain permeability 5.1.2 Metabolic stability and bioavailability 5.1.3 π–π Stacking interactions 5.2 Antibacterial pharmaceuticals 5.2.1 Fluoroquinolones 5.2.1.1 Mechanism of action of fluoroquinolones 5.2.2 Tetracyclines 5.3 Antidiabetic pharmaceuticals 5.3.1 Sitagliptin 5.3.1.1 Synthesis of sitagliptin 5.3.2 Carmegliptin 5.3.2.1 Synthesis of carmegliptin 5.3.3 Canagliflozin 5.4 Anti-Alzheimer pharmaceuticals 5.4.1 BACE-1 inhibitors 5.4.1.1 CNP520 as an Alzheimer’s disease–preventive drug 5.4.1.2 Verubecestat, a BACE-1 inhibitor 5.4.2 γ-Secretase inhibitors and modulators 5.4.2.1 Nonsteroidal antiinflammatory drugs as γ-secretase modulators 5.5 Anti-HIV pharmaceuticals 5.5.1 Bictegravir 5.5.2 Doravirine 5.6 Antimalarial pharmaceuticals 5.6.1 Tafenoquine 5.6.2 Mefloquine 5.7 Anticancer pharmaceuticals 5.7.1 Dacomitinib 5.7.2 Lorlatinib 5.7.3 Cobimetinib 5.7.4 Abemaciclib 5.7.5 PARP inhibitors: rucaparib (Rubraca) and olaparib (Lynparza) 5.7.6 Taxoid anticancer agents 5.7.6.1 Tumor-targeted drug delivery of the fluorinated taxoids 5.7.6.2 Drug delivery through aptamer–drug conjugates 5.7.7 Fulvestrant 5.7.7.1 Synthesis of fulvestrant 5.7.8 Enasidenib 5.7.9 Nonsteroidal antiandrogens (apalutamide, bicalutamide, and flutamide) 5.7.9.1 Enzalutamide 5.7.10 BRAF and mitogen-activated protein kinase kinase enzyme inhibitors in cancer treatment 5.8 Antiviral pharmaceuticals 5.8.1 Tecovirimat 5.8.1.1 Synthesis of tecovirimat 5.8.2 Sofosbuvir 5.8.3 Ledipasvir 5.8.3.1 Synthesis of ledipasvir 5.8.4 Glecaprevir and pibrentasvir 5.8.5 Voxilaprevir 5.8.6 Letermovir (Prevymis) 5.9 Fluorinated pharmaceuticals for cardiovascular diseases 5.9.1 Statin drugs 5.9.2 Ezetimibe 5.9.3 Nebivolol 5.9.4 Antiplatelet drugs 5.9.4.1 Cangrelor 5.9.4.2 Riociguat 5.10 Antiinflammatory pharmaceuticals 5.10.1 Nonsteroidal antiinflammatory agents 5.10.2 Celecoxib 5.10.3 Corticosteroids 5.11 Antidepressants References 6 Synthesis and applications of 18F-labeled compounds 6.1 Introduction 6.2 Synthetic methods for radiofluorination 6.2.1 Synthesis of 18F-labeled reagents 6.3 Sharpless click reactions for positron emission tomography tracers 6.3.1 Protein and oligonucleotide triazole positron emission tomography tracers 6.3.2 18F-octreotate positron emission tomography tracers for tumor imaging 6.3.3 Strain-promoted click chemistry 6.4 Staudinger ligation reactions for positron emission tomography tracers 6.5 Radiofluorination via aromatic nucleophilic substitution 6.5.1 [18F]fluoro-(+)-biotin 6.5.2 l-3,4-Dihydroxy-6-[18F]fluorophenylalanine (6-[18F]l-DOPA) 6.5.3 γ-Aminobutyric acid transporter positron emission tomography tracers 6.5.4 Radiofluorination of phenolic compounds 6.6 Transition metal–mediated radiofluorination 6.6.1 Mn(III)-catalyzed radiofluorinations 6.6.2 Pd-catalyzed radiofluorinations 6.6.3 Au(III) catalysis for the synthesis of [18F]trifluoromethyl compounds 6.6.4 Ni(II)-catalyzed radiofluorinations 6.6.5 Cu(I)-catalyzed radiofluorinations 6.7 Radiofluorination via diaryliodonium salts 6.7.1 Cu(I)-catalyzed radiofluorination of diaryliodonium salts 6.7.2 Radiofluorination via iodonium ylides 6.8 Enzymatic fluorination reactions for [18F]-labeled positron emission tomography tracers 6.8.1 5′-Fluoro-5′-deoxyadenosine and 5-fluororibose 6.8.2 Fluorinase-catalyzed synthesis of [18F]5′-deoxy-5′-fluoroadenosine-biotin conjugate 6.8.3 5′-Fluoro-5′-deoxyadenosine-RGD conjugate in cancer detection 6.9 Positron emission tomography tracers in Alzheimer’s disease 6.9.1 [18F]Flortaucipir (a neurofibrillary tangle biomarker) 6.9.1.1 Synthesis of [18F]flortaucipir 6.9.2 2-(4-Aminoaryl)quinoline-based 18F-labeled positron emission tomography tracers (THK series) 6.9.3 Tropomyosin receptor kinase targeted 18F-positron emission tomography 6.10 18F-positron emission tomography tracers in cancer diagnosis 6.10.1 [18F]-(R)-lorlatinib 6.10.2 Cyclic RGDYK (arginine-glycine-aspartic acid-tyrosine-lysine) dimer-derived positron emission tomography tracers 6.10.2.1 FPPRGD2 (dimeric cyclic RGDYK peptide) 6.10.2.2 [18F]FAl-NOTA-PRGD2 (18F-alfatide) and [68Ga]-NOTA-PRGD2 6.10.2.3 NOTA-conjugated linear peptides 18F-AlF-NOTA-IF7 and 18F-Al-NOTA-MATBBN 6.10.2.4 Folate-NOTA-Al18F 6.10.2.5 18F-fluciclovine (Axumin) 6.10.2.5.1 Synthesis of 18F-fluciclovine References 7 Materials applications of organofluorine compounds 7.1 Introduction 7.2 Fluorinated surfactants 7.2.1 Perfluorocarbon nanomaterials 7.2.2 Fluorous catalysis 7.2.3 Environmentally benign perfluorosurfactants 7.3 Fluoropolymers 7.3.1 Poly(tetrafluoroethylene) 7.3.2 Poly(vinylidene fluoride) 7.4 Fluorinated π-conjugated polymeric materials in photovoltaic devices 7.4.1 π–π Stacking interactions in polyfluoroaromatics 7.4.2 π-Conjugated polymers 7.4.3 Synthesis of the fluorinated donor–acceptor polymers for fullerene–polymer solar cells 7.4.4 π-Conjugated benzodithiophene–quinoxaline copolymers 7.4.5 Fluorinated polymers in fullerene-free, all-polymer (organic) solar cells 7.5 Fluorinated poly(aryl thioethers) in organic electronic materials 7.6 Polymer electrolytes 7.7 Fluorinated ionomers as proton-exchange membranes in fuel cells 7.8 Fluorinated carbon nanoparticles and nonaqueous electrolytes in lithium- and lithium-ion batteries 7.9 Fluorinated hyperbranched dendrimers: synthesis and applications 7.10 Fluorinated compounds in drug delivery and magnetic resonance imaging 7.10.1 Fluorinated curcumin analogs as 19F MRI agents 7.10.2 Polyfluorinated dendrimer amphiphiles as 19F MRI probes and drug delivery agents 7.11 Organofluorine liquid crystal materials 7.11.1 Fluorinated dendrimer-based liquid crystals 7.12 Organofluorine compounds in high-energy materials 7.12.1 N,N-Difluoramine (NF2) compounds 7.12.1.1 Synthesis of HNFX 7.12.1.2 Synthesis of RNFX 7.12.1.3 Synthetic methods for the gem-difluoramination 7.12.2 Pentafluorosulfanyl (SF5) compounds References Index Back Cover