Selective C-H Fluorination of Pyridines and Diazines Inspired by a Classic Amination Reaction

Fier, Patrick S.; Hartwig, John F.

doi:10.1126/science.1243759

Cited by 232 publications

(157 citation statements)

References 49 publications

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“…70) [119,120,123,[133][134][135][136][137][138]176]. The reaction proceeds at room temperature in 1 h and affords 2-fluoropyridines with high selectivity.…”

Section: Reactions Proposed To Proceed Via One-electron Pathwaysmentioning

confidence: 99%

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

Campbell

Hoover

Ritter

2014

Topics in Organometallic Chemistry

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The development of new C-F bond forming reactions from organotransition metal complexes has played a key role in advancing the field of fluorination chemistry and has allowed for improved access to fluorinated organic molecules of interest in medicine, materials, and agrochemicals. In this review, we describe the development of transition metal-mediated and metal-catalyzed fluorination methods over the past decade. Special attention is paid to the variety of organometallic mechanisms by which C-F bond formation can occur and the strengths and limitations of different approaches.

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“…70) [119,120,123,[133][134][135][136][137][138]176]. The reaction proceeds at room temperature in 1 h and affords 2-fluoropyridines with high selectivity.…”

Section: Reactions Proposed To Proceed Via One-electron Pathwaysmentioning

confidence: 99%

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

Campbell

Hoover

Ritter

2014

Topics in Organometallic Chemistry

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“…. [13] The reactions of pyridines, quinolines, and various diazines afford the monofluorination products in good yields with exclusive ortho-position selectivity. This is a useful synthetic approach for the late-stage modification of complex molecules containing heterocycles such as pyridines.…”

Section: Introductionmentioning

confidence: 99%

Chemically oxidative fluorination with fluoride ions

Jiang

Zeng

et al. 2015

Journal of Fluorine Chemistry

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“…The authors 57 proposed a mechanism that involves initial coordination of AgF 2 to pyridine, followed by addition of the [Ag]-F bond across the π system of the pyridine to form an amidosilver(II)-fluoride complex58 (Scheme 12). The authors also observed a KIE of 2.9, suggesting that the coordination of pyridine to AgF 2 and the addition step are reversible.…”

mentioning

confidence: 99%

Fluorination methods in drug discovery

2016

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Fluorination reactions of medicinal and biologically-active compounds will be discussed. Late stage fluorination strategies of medicinal targets have recently attracted considerable attention on account of the influence that the fluorine atom can impart to targets of medicinal importance, such as a modulation of lipophilicity, electronegativity, basicity and bioavailability, this latter as a consequence of membrane permeability. Therefore, the recourse to late-stage fluorine substitution on compounds with already known and relevant biological activity can provide the pharmaceutical industry with new leads with improved medicinal properties. The fluorination strategies will take into account different fluorinating reagents, nucleophilic, electrophilic and of radical nature. Diverse families of organic compounds such as (hetero)aromatic rings, and aliphatic substrates (sp 3 , sp 2 , and sp carbon atoms) will be studied in late-stage fluorination reaction strategies. The omniphobicity/lipophilicity and electrostatic interactions can be considered among the most prominent effects. Thus, introducing fluorine into an organic compound can significantly alter its biological properties.One other subtle but important effect of introducing fluorine into the backbone of a medicinal target is the inflection of acidity and basicity of the parent compound 4 , which can change, inter alia, the binding affinity, and bioavailability. Highly basic groups can have a detrimental effect on the bioavailability of a drug. Thus introducing a fluorine atom next to a basic group can reduce its basicity, enhancing its membrane permeability, and increasing bioavailability. Although the replacement of hydrogen for fluorine does not have a profound steric influence, electrostatic interactions with other groups can change conformations significantly. The replacement of hydrogen for fluorine on aromatic rings is a well-known strategy to decelerate oxidative metabolic processes by Cytochrome P450 monooxygenases. In this respect, the electron-withdrawing properties of fluorine on aromatic rings, which can slow down hydrolytic metabolism, alter reaction rates and stability of intermediates. Fluorine substitution on aromatic rings is also known to increase binding affinity, as a result of enhancing electrostatic interactions.However, it is difficult to predict the influence of fluorine substitution on the overall profile in a given situation.As numerous reports attest 1 , the number of marketed drugs that contain a fluorine atom has increased rapidly. As of 2009, the FDA-had approved >140 fluorine-containing drugs. This review article is intended to present new synthetic methodologies 9 for accomplishing fluorination reactions on molecules (drugs/prodrugs) with pharmacological activity. It is not our aim (Figure 3). would be beneficial to the syntheses. 3a.-Conversion of C Ar -H into C Ar -F BondsXu and co-workers 38 have developed an ortho C-H bond fluorination of 2-phenoxyl pyridine derivatives through a palladium-catalyzed reaction v...

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Selective C-H Fluorination of Pyridines and Diazines Inspired by a Classic Amination Reaction

Cited by 232 publications

References 49 publications

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

Transition Metal-Mediated and Metal-Catalyzed Carbon–Fluorine Bond Formation

Chemically oxidative fluorination with fluoride ions

Fluorination methods in drug discovery

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