Direct S-difluoromethylation of thiols using the Ruppert–Prakash reagent

Prakash, G. K. Surya; Krishnamoorthy, Sankarganesh; Kar, Sayan; Oláh, George A.

doi:10.1016/j.jfluchem.2015.09.011

Cited by 40 publications

(22 citation statements)

References 31 publications

(14 reference statements)

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“…Additionally, use of NaH as a base instead of LiH, led to decomposition of TMSCF 3 into several unidentified products along with CF 3 H and TMSF, and no expected product was formed. Moreover, no tetrafluoroethylene and related products were observed under the reaction conditions, clearly ruling out the involvement of free singlet difluoromethylene . In 2016, Besset and collaborators published a review article describing the synthesis of molecules containing the SCF 2 H and SCF 2 FG functionality.…”

Section: Late‐stage Introduction Of Cf2h and Cf2y Groups Into Organicsupporting

confidence: 81%

Difluoromethylation Reactions of Organic Compounds

Yerien

Barata‐Vallejo

Postigo

2017

Chemistry A European J

405

153

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The relevance of the -CF H moiety has attracted considerable attention from organic synthetic and medicinal chemistry communities, because this group can act as a more lipophilic isostere of the carbinol, thiol, hydroxamic acid, or amide groups. Being weakly acidic, the CF H moiety can establish hydrogen-bonding interactions to improve the binding selectivity of biologically active compounds. Therefore, the hydroxyl, amino, and thio substituents of lead structures are routinely replaced by a CF H motif in drug discovery, with great benefits in the pharmacological activity of drugs and drug candidates and agrochemicals. Consequently, the late-stage introduction of CF H is a sought-after strategy in designing bioactive compounds. Secondly, but nonetheless relevant and meaningful, is the study of synthetic pathways to introduce a CF -Y moiety (Y≠H, F) into organic substrates because compounds that contain a CF -Y functionality have also found vast applications in medicinal chemistry and in other areas, such as that of fungicides, insecticides, etc., and thus, this functionality deserves special attention. Although emphasis is made on difluoromethylation strategies to functionalize different families of organic compounds, three main methodological protocols will be presented in this review article for the late-stage introduction of a CF H or CF Y moieties into organic substrates: i) a metal-photoredox catalysis; ii) through transition metal-catalyzed thermal protocols; and iii) from transition-metal-free strategies.

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Section: Late‐stage Introduction Of Cf2h and Cf2y Groups Into Organicsupporting

confidence: 81%

Difluoromethylation Reactions of Organic Compounds

Yerien

Barata‐Vallejo

Postigo

2017

Chemistry A European J

405

153

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“…Previously, we disclosed that the Li + ion could prevent such runaway reactions by controlling the amount of soluble free nucleophilic fluoride that is present in the reaction solution . These results led us to re‐examine the conditions reported by Hu and co‐workers (Scheme ) .…”

Section: Resultsmentioning

confidence: 87%

“…Thus, NaI was replaced by LiI to determine the effect of the Li + ion on the reaction. As the LiI required higher temperatures to activate the TMSCF 3 , our previously developed conditions[16a] of LiI/diglyme/170 °C were employed along with the use of PPh 3 . The first experiment carried out in the presence of LiI/PPh 3 produced 2a in 74 % yield (Table , Entry 3), and prolonging the reaction time increased the production of 2a to 81 % (Table , Entry 4).…”

Section: Resultsmentioning

confidence: 99%

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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“…This served as a further evidence to support the Li + control of the fluoride ion reactivity in these reactions. 22 However, the protocol failed to provide the expected product with electron-deficient thiols such as 4-nitrothiophenol. Based on these observations, 1-2 migratory substitution of the thiolate and Li + -assisted fluoride elimination to yield the ArSCF 2 SiMe 3 product were proposed.…”

Section: Scheme 5 N-difluoromethylation Of Nitrogen Heterocyclesmentioning

confidence: 99%

Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

Krishnamoorthy

Prakash

2017

Synthesis

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There have been significant developments in the area of perfluoroalkyl group transfer using silicon reagents, specifically in nucleophilic trifluoromethylation. The mild and versatile activation conditions bestow significant synthetic prowess to the silicon reagents in the area of fluoroalkylations. Owing to the importance of difluoromethylene (CF2) containing compounds in pharmaceuticals, materials, and agrochemicals, several CF2 group transfer methods using related silicon reagents have been developed and studied in detail. This review summarizes the recent developments and trends in this area.1 Introduction2 Trimethyl(trifluoromethyl)silane (Me3SiCF3)3 (Difluoromethyl)trimethylsilane (Me3SiCF2H)3.1 Nucleophilic Addition3.2 Nucleophilic Substitution3.3 Nucleophilic Difluoromethylation of Electron-Deficient Heterocycles3.4 Metal-Mediated Cross Coupling3.5 Oxidative Coupling of Terminal Alkynes4 Post-functionalizable Difluoromethyl Transfer Reagents4.1 (Chlorodifluoromethyl)trimethylsilane (Me3SiCF2Cl)4.2 (Bromodifluoromethyl)trimethylsilane (Me3SiCF2Br)4.3 [Difluoro(iodo)methyl]trimethylsilane (Me3SiCF2I)4.4 [Difluoro(phenylthio)methyl]trimethylsilane (Me3SiCF2SPh)4.5 [Difluoro(phenylsulfonyl)methyl]trimethylsilane (Me3SiCF2SO2Ph)4.6 Diethyl [Difluoro(trimethylsilyl)methyl]phosphonate [Me3SiCF2P(O)(OEt)2]4.7 Ethyl Difluoro(trimethylsilyl)acetate (Me3SiCF2CO2Et)4.8 Difluoro(trimethylsilyl)acetamides (Me3SiCF2CONR2)4.9 Difluoro(trimethylsilyl)acetonitrile (Me3SiCF2CN)5 Others6 Conclusions

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Direct S-difluoromethylation of thiols using the Ruppert–Prakash reagent

Cited by 40 publications

References 31 publications

Difluoromethylation Reactions of Organic Compounds

Difluoromethylation Reactions of Organic Compounds

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

Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

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Direct S-difluoromethylation of thiols using the Ruppert–Prakash reagent

Cited by 40 publications

References 31 publications

Difluoromethylation Reactions of Organic Compounds

Difluoromethylation Reactions of Organic Compounds

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

Silicon-Based Reagents for Difluoromethylation and Difluoromethylenation Reactions

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