Direct C-H trifluoromethylthiolation of (hetero)arenes: A review

Hamzehloo, Majid; Hosseinian, Akram; Ebrahimiasl, Saeideh; Monfared, Aazam; Vessally, Esmail

doi:10.1016/j.jfluchem.2019.05.004

Cited by 59 publications

(12 citation statements)

References 68 publications

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“…Due to the unique electron-negativity and high lipophilicity, the introduction of a trifluoromethylthio group (SCF 3 ) into pharmaceutical candidates can significantly protect against in vivo enzymatic metabolism and increase the cell membrane permeability 8 . As a consequence, the development of organic synthetic strategies accessing trifluoromethylthiolated compounds has gained considerable momentum in recent years 9–15 . Although several trifluoromethylthiolated drugs (e.g., tiflorex, toltrazuril and tiflorex in Fig.…”

Section: Introductionmentioning

confidence: 99%

Late-stage trifluoromethylthiolation of benzylic C-H bonds

Wang

Liu

et al. 2019

Nat Commun

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The benzylic positions in drugs are sites that readily react with cytochrome P450 oxidases via single-electron oxidation. New synthetic methodologies to incorporate a fluoroalkyl group at the benzylic site are continually being developed, and in this paper, we report a metal-free and site-selective organophotoredox-catalyzed trifluoromethylthiolation of benzylic C-H bonds for a wide variety of alkyl arenes and heteroarenes. The precise and predictive regioselectivity among various C(sp3)-H bonds originates from an inner-sphere benzylic radical initiation mechanism, and avoids the use of external oxidants or hydrogen atom abstractors. Its practicality stems from the trifluoromethylthiolation of a series of drugs and complex organic molecules, which is overwhelmingly selective for benzyl groups. This operationally simple protocol can provide a general and practical access to structurally diverse benzylic trifluoromethyl sulfides produced from ubiquitous benzylic C-H bonds. Large scale trifluoromethylthiolation can be achieved with continuous flow photoredox technology.

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Section: Introductionmentioning

confidence: 99%

Late-stage trifluoromethylthiolation of benzylic C-H bonds

Wang

Liu

et al. 2019

Nat Commun

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“…The incorporation of fluorine-containing moieties has profound impact on the structure, reactivity, and function of the parent molecules, because of the unique properties of fluorine element, thus offering a wide range of applications in pharmaceutical, agrochemical, and material sciences. − As one of the fluoroalkyl groups, the trifluoromethylthio group (−SCF 3 ) is recognized to present an extremely large lipophilicity (Hansch’s hydrophobic parameter π = 1.44) and strong electron-withdrawing (Hammett constant: σ m = 0.40 and σ p = 0.50) properties which could improve the chemical and metabolic stability and enhance the cell-membrane permeability for a drug molecule. As a result, this characterization has stimulated the investigation of trifluoromethylthiolation and earned considerable interest of interdisciplinary fields of fluorine chemistry, medicinal chemistry, and chemical biology in the past decades. − The development of efficient methodologies for introducing this important motif into small molecules to generate the structurally well-defined trifluoromethylthiolated products for further investigations lies at the heart of this field.…”

Section: Introductionmentioning

confidence: 99%

Recent Progress on Trifluoromethylthiolation of (Hetero)Aryl C–H Bonds with Electrophilic Trifluoromethylthiolating Reagents

Wang

Shen

2022

ACS Sustainable Chem. Eng.

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The incorporation of trifluoromethylthio group (−SCF 3 ) into small molecules has attracted considerable attention recently, because of its unique properties, which are beneficial for drug discovery. The preparation of trifluoromethylthiolated (hetero)arenes, a leading class of trifluoromethylthiolated compounds, is one of the hot topics in organic chemistry frontiers, and much effort have been exerted to access them. In this review, special attention is given to the preparation of (hetero)aryl C−H bonds by Friedel−Crafts-type trifluoromethylthiolation and transition-metal-catalyzed aromatic C− H bond activation/trifluoromethylthiolation with electrophilic trifluoromethylthiolating reagents.

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“…6,8 However, the literature review reveals that no comprehensive review article is available covering vicinal halo-triuoromethylation of alkenes. In connection with our recent works on organouorine chemistry [9][10][11][12][13] and modern organic synthesis, 14 herein, we will summarize recent discoveries and developments in the arena of halotriuoromethylation of alkenes, although we occasionally mention earlier work when relevant. For clarity, the reactions were organized according to the type of halogen atoms.…”

Section: Introductionmentioning

confidence: 99%