Synthesis of fluorinated oxygen- and sulfur-containing heteroaromatics

O’Leary, Eileen M.; Jones, David J.; O'Donovan, Fiona P.; O’Sullivan, Timothy P.

doi:10.1016/j.jfluchem.2015.06.002

Cited by 17 publications

(3 citation statements)

References 115 publications

(82 reference statements)

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“…Meanwhile, the presence of a fluorine atom can further alter binding affinities with receptors, rate of absorption, transport, metabolism, and clearance . An obstacle hampering the extensive applications of 2-fluorobenzofurans in medicinal chemistry is the lack of efficient methods for their preparation . The direct electrophilic fluorination of benzofurans suffers from poor chemo- and regioselectivities and low yields, thus seldom finding practical uses .…”

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confidence: 99%

Synthesis of 2-Fluorobenzofuran by Photocatalytic Defluorinative Coupling and 5-endo-trig Cyclization

Ling

Fang

et al. 2023

J. Org. Chem.

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An alkyl radical-triggered dual C−F bond cleavage of α-CF 3 -ortho-hydroxystyrenes for the synthesis of 2-fluorobenzofurans was developed. The visible-light-induced defluorinative cross-coupling reactions of α-CF 3 -ortho-hydroxystyrenes with a variety of carboxylic acids produced gem-difluoroalkenes, which underwent S N V-type 5-endo-trig cyclization to give 2-fluorobenzofurans. Mechanistic studies indicated that the electron transfer between phenoxyl radicals and carboxylates was the major pathway for the generation of alkyl radicals.

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confidence: 99%

Synthesis of 2-Fluorobenzofuran by Photocatalytic Defluorinative Coupling and 5-endo-trig Cyclization

Ling

Fang

et al. 2023

J. Org. Chem.

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“…70 Isoxazolinone cores are widespread components in numerous biological important molecules such as those depicted in Figure 12. Triazoles substituted with methylpyridine, n-heptyl, methylnaphthalene at the 1-position (and a phenyl group at the 4-position) also afford good yields of 5-fluorotriazole derivatives (products 124-126).…”

Section: A4-isoxazolinone Coresmentioning

confidence: 99%

“…70 Isoxazolinone cores are widespread components in numerous biological important molecules such as those depicted in Figure 12. …”

Section: A4-isoxazolinone Coresmentioning

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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Importance of a Fluorine Substituent for the Preparation of meta‐ and para‐Pentafluoro‐λ⁶‐sulfanyl‐Substituted Pyridines

et al. 2016

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Although there are ways to synthesizeo rtho-pentafluoro-l 6 -sulfanyl (SF 5 )p yridines,m eta-and para-SF 5 -substituted pyridines are rare.W edisclose herein ageneral route for their synthesis.The fundamental synthetic approach is the same as reported methods for ortho-SF 5 -substituted pyridines and SF 5 -substituted arenes,that is,oxidative chlorotetrafluorination of the corresponding disulfides to give pyridylsulfur chlorotetrafluorides (SF 4 Cl-pyridines), followed by chloride/fluoride exchange with fluorides.H owever,t he trick in this case is the presence on the pyridine ring of at least one fluorine atom, which is essential for the successful transformation of the disulfides into m-and p-SF 5 -pyridines.A fter enabling the synthesis of an SF 5 -substituted pyridine,o rtho-F groups can be efficiently substituted by C, N, S, and Onucleophiles through an S N Ar pathway.T his methodology provides access to av ariety of previously unavailable SF 5 -substituted pyridine building blocks.

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Synthesis of fluorinated oxygen- and sulfur-containing heteroaromatics

Cited by 17 publications

References 115 publications

Synthesis of 2-Fluorobenzofuran by Photocatalytic Defluorinative Coupling and 5-endo-trig Cyclization

Synthesis of 2-Fluorobenzofuran by Photocatalytic Defluorinative Coupling and 5-endo-trig Cyclization

Fluorination methods in drug discovery

Importance of a Fluorine Substituent for the Preparation of meta‐ and para‐Pentafluoro‐λ⁶‐sulfanyl‐Substituted Pyridines

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Synthesis of fluorinated oxygen- and sulfur-containing heteroaromatics

Cited by 17 publications

References 115 publications

Synthesis of 2-Fluorobenzofuran by Photocatalytic Defluorinative Coupling and 5-endo-trig Cyclization

Synthesis of 2-Fluorobenzofuran by Photocatalytic Defluorinative Coupling and 5-endo-trig Cyclization

Fluorination methods in drug discovery

Importance of a Fluorine Substituent for the Preparation of meta‐ and para‐Pentafluoro‐λ6‐sulfanyl‐Substituted Pyridines

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Importance of a Fluorine Substituent for the Preparation of meta‐ and para‐Pentafluoro‐λ⁶‐sulfanyl‐Substituted Pyridines