Nucleophilic Difluoromethylation Using (Bromodifluoromethyl)trimethylsilane

Trifonov, Alexey L.; Zemtsov, Artem A.; Levin, Vitalij V.; Стручкова, Марина И.; Dilman, Alexander D.

doi:10.1021/acs.orglett.6b01641

Cited by 57 publications

(21 citation statements)

References 48 publications

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“…[19] Consequently, 10 % of the expected product along with the 38 % of TMS-protected intermediate 4 was observed according to the NMR analysis (Scheme 3 and Supporting Information). [20] We speculate that the formation of the oxaphosphetane is hindered, and, therefore, the betaine picks up a TMS group leading to the formation of 4. Our attempts to increase the conversion by increasing the temperature resulted in little improvement in the yield.…”

Section: Resultsmentioning

confidence: 90%

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

et al. 2016

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A deoxygenative difluoromethylenation of carbonyl compounds has been developed by using readily available, inexpensive trifluoromethyltrimethylsilane, LiI, and PPh3. The presence of the Li+ ion prevents the unproductive exhaustion of trifluoromethyltrimethylsilane (TMSCF3) by keeping the soluble free fluoride concentration in the reaction medium under control. The strategy of combining solvents to increase the reactivity and thereby reduce the reaction temperature and time is disclosed.

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Section: Resultsmentioning

confidence: 90%

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

et al. 2016

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“…228 Aromatic, heteroaromatic, vinyl methyl ketones and nitro alkenes provided the respective corresponding compounds in moderate to good yields. Further treatment with potassium hydroxide (KOH) enables the protodephosphorylation.…”

Section: Synthetic Approaches To Mitochondria-targeted Compoundsmentioning

confidence: 99%

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

Zielonka¹,

Joseph²,

et al. 2017

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Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the potentials of cell and mitochondrial membranes, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

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“…TMSCF 2 Br, a difluorocarbene precursor developed by us,‐ is now commercially available and is one of the most versatile difluorocarbene reagents . It has been applied in the difluoromethylation of (thio)phenols, alcohols, thiols, and amines, as well as the cyclopropanation or cyclopropenation of alkenes and alkynes, among other applications –. In continuation of our effort to develop TMSCF 2 Br as a versatile and robust difluorocarbene reagent, we report herein our recent success in the difluoromethylation of carbon acids with TMSCF 2 Br (Scheme c).…”

Section: Methodsmentioning

confidence: 99%

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF₂Br

Xie

Zhu

et al. 2019

Angew Chem Int Ed

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An efficient method for the selective C‐difluoromethylation of carbon acids with the reagent TMSCF2Br has been developed. A variety of structurally diverse sp3‐ and sp‐hybridized carbon nucleophiles, including esters, amides, fluorenes, terminal alkynes, β‐ketoesters, malonates, and other activated C−H nucleophiles, could be efficiently and selectively transformed into the corresponding C‐difluoromethylated products under mild conditions. This protocol is also effective for the late‐stage difluoromethylation of pharmaceutically relevant molecules and can be readily scaled up. Moreover, ambident substrates with more than one reactive site towards difluorocarbene can be difluoromethylated orthogonally using TMSCF2Br.

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Nucleophilic Difluoromethylation Using (Bromodifluoromethyl)trimethylsilane

Cited by 57 publications

References 48 publications

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF₂Br

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Nucleophilic Difluoromethylation Using (Bromodifluoromethyl)trimethylsilane

Cited by 57 publications

References 48 publications

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF3: The Right Conditions

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF3: The Right Conditions

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF2Br

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Product

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Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

Direct Difluoromethylenation of Carbonyl Compounds by Using TMSCF₃: The Right Conditions

A General Protocol for C−H Difluoromethylation of Carbon Acids with TMSCF₂Br