Radical Fluoroalkylation Reactions

Recent protocols and reactions for catalytic radical perfluoroalkylations will be described. The production of perfluoroalkyl radicals (RF = CnF2n+1, n ≥ 2), which effect both addition and substitution reactions on organic substrates, can be realized through a range of diverse methods such as the well-established visible-light transition-metal-mediated photocatalysis, organic-dye-photocatalyzed reactions, electron donor-acceptor complexes, and more recently frustrated Lewis pairs. Thus, perfluoroalkylation reactions of carbon-carbon multiple bonds, isocyanides, nitrones, hydrazones, β-keto esters, α-cyano arylacetates, sulfides, and (hetero)arenes will be described. Special emphasis will be placed on examples published after 2015, where higher fluorinated series of fluoroalkylating reagents are studied.Fil: Barata Vallejo, Sebastian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cooke, María Victoria. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Postigo, A.. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentin

Palladium-catalyzed difluoromethylation of heteroaryl chlorides, bromides and iodides.

A palladium-catalyzed difluoromethylation of a series of heteroaryl chlorides, bromides and iodides under mild conditions is described. A wide range of heteroaryl halides such as pyridyl, pyrimidyl, pyrazyl, funanyl, thienyl, pyazolyl, imidazolyl, thiazolyl, and oxazolyl halides were efficiently difluoromethylated, thus providing medicinal chemists an alternative choice for the preparation of drug candidates with the difluoromethylated heteroarene unit

N-Дифлуорометиліндазоли

Aim. To study the possibility of the N-difluoromethylation and separation of 1-difluoromethyl and 2-difluoromethyl isomers of C-substituted indazoles, as well as some possibilities of functionalization of such molecules.Results and discussion. The N-difluoromethylation of indazole derivatives containing bromine, iodine, and nitro groups in various positions of the heterocyclic ring was studied. In all cases, the conditions for the separation of isomers – N-difluoromethylation products – in positions 1 and 2 were found. The corresponding amines, esters of carboxylic and boric acids were obtained as a result of further functionalization of 1- and 2-difluoromethylindazole derivatives.Experimental part. The structure of the compounds synthesized was proven by 1H and 19F NMR spectroscopy methods, as well as by the elemental analysis. The structure of isomeric difluoromethylindazoles was finally confirmed by the SELNOESY and 1H-13C HMBC experiments.Conclusions. A convenient method for the difluoromethylation of substituted indazoles has been found; difluoromethyl derivatives in positions 1 and 2 of the indazole ring have been obtained in high yields. The method for the efficient separation of isomeric difluoromethylindazoles has been found; some possibilities of their further functionalization have been described.Мета. Вивчити можливість N-дифлуорометилювання та розділення ізомерних 1-дифлуорометил- і 2-дифлуорометил С-заміщених індазолів, а також деякі можливості функціоналізації таких молекул.Результати та їх обговорення. Досліджено N-дифлуорометилювання похідних індазолу, що містять атоми брому, йоду та нітрогрупу в різних положеннях гетероциклічного циклу. У всіх випадках визначено умови розділення ізомерів – продуктів N-дифлуорометилювання за положеннями 1 і 2. У результаті подальшої функціоналізації похідних 1- та 2-дифлуорометиліндазолу одержано відповідні аміни, естери карбонової та борної кислот.Експериментальна частина. Структуру синтезованих сполук підтверджено методами 1H і 19F ЯМР-спектроскопії, а також елементним аналізом. Остаточне підтвердження структури ізомерних дифлуорометиліндазолів здійснено в експериментах SELNOESY та 1H-13C HMBC.Висновки. Знайдено зручний метод дифлуорометилювання заміщених індазолів та одержано дифлуорометильні похідні за положеннями 1 та 2 індазольного ядра з високими виходами. Знайдено метод ефективного розділення ізомерних дифлуорометиліндазолів та досліджено деякі можливості їх подальшої функціоналізації

New N-difluoromethylindoles: features of N-difluoromethylation of indoles with electron-donor or electron-withdrawing substituents

The study of the difluoromethylation of various indole derivatives containing both electron-donating and electron-withdrawing groups was carried out. N-Difluoromethyl derivatives of indole with methoxy, methyl, nitro, cyano, amino groups and bromine atom were isolated and fully characterized

Photocatalytic Difluoromethylation Reactions of Aromatic Compounds and Aliphatic Multiple C-C Bonds

Among the realm of visible light photocatalytic transformations, late-stagedifluoromethylation reactions (introduction of difluoromethyl groups in the last stages of syntheticprotocols) have played relevant roles as the CF2X group substitutions exert positive impacts on thephysical properties of organic compounds including solubility, metabolic stability, andlipophilicity, which are tenets of considerable importance in pharmaceutical, agrochemical, andmaterials science. Visible-light-photocatalyzed difluoromethylation reactions are shown to beaccomplished on (hetero)aromatic and carbon?carbon unsaturated aliphatic substrates under mildand environmentally benign conditions.Fil: Barata Vallejo, Sebastian. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Postigo, Jose Alberto. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Orgánica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin

Introduction of Fluorine and Fluorine-Containing Functional Groups

Over the past decade, the most significant, conceptual advances in the field of fluorination were enabled most prominently by organo- and transition-metal catalysis. The most challenging transformation remains the formation of the parent C[BOND]F bond, primarily as a consequence of the high hydration energy of fluoride, strong metal—fluorine bonds, and highly polarized bonds to fluorine. Most fluorination reactions still lack generality, predictability, and cost-efficiency. Despite all current limitations, modern fluorination methods have made fluorinated molecules more readily available than ever before and have begun to have an impact on research areas that do not require large amounts of material, such as drug discovery and positron emission tomography. This Review gives a brief summary of conventional fluorination reactions, including those reactions that introduce fluorinated functional groups, and focuses on modern developments in the field.Chemistry and Chemical Biolog

Part I: Design, synthesis, and studies of novel age-inhibitors and age-breakers; Part II: Novel synthetic methods for organofluorine compound

Novel small molecule inhibitors and breakers of advanced glycation end-products (AGEs) have been synthesized and their in vitro inhibitory activities have been studied by 13C NMR, fluorescence, and UV-visible spectroscopy. We have demonstrated that these AGE-inhibitors and AGE-breakers were found to be more effective in their sequestration of AGE intermediates, such as dehydroascorbate (DHA) than the state-of-the art phenacylthiazolium bromide (PTB)-based AGE-inhibitors and AGE-breakers. Citric acid and other polyphenolic antioxidants have substantial AGE inhibitory effects in the D-glucose/leucine or benzylamine Maillard reaction model systems, and thus they are suitable as dietary additives for ameliorating AGE-induced complications. Organofluorine compounds have found numerous applications as pharmaceutically interesting compounds, and toward developing novel synthetic methods for organofluorine compounds, we have investigated synthetic strategies for gem-difluoro and trifluormethyl compounds. gem-Difluorination of 1,3-dithiolanes, obtained from the corresponding ketones, form gem-difluoromethylene compounds through the photoredox catalysis, using photocatalyst 9-fluorenone in the presence of visible light (household bulb 13W CFL). This reaction proceeds under mild conditions and is applicable to gem-difluorination of variously substituted diaryl 1,3-dithiolanes. We have also developed a novel NHC-catalyzed trifluoromethylation of aromatic N-tosyl aldimines with electron-withdrawing as well as electron-donating groups on the aryl ring. We have synthesized a series of novel purine-based triazole derivatives as potential CDK-inhibitors and characterized their structures using high-field 1H- and 13C-NMR spectroscopy”--Abstract, page iii

Tri- and difluoromethoxylated N-based heterocycles − Synthesis and insecticidal activity of novel F3CO- and F2HCO-analogues of Imidacloprid and Thiacloprid

International audienc