18F‐Labeling of Aryl‐SCF3, ‐OCF3 and ‐OCHF2 with [18F]Fluoride

Khotavivattana, Tanatorn; Verhoog, Stefan; Tredwell, Matthew; Pfeifer, Lukas; Calderwood, Samuel; Wheelhouse, Katherine M. P.; Collier, Thomas Lee; Gouverneur, Véronique

doi:10.1002/anie.201504665

Cited by 97 publications

(76 citation statements)

References 88 publications

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“…We were naturally eager to extend the methodology to other fluoroalkylsulfonyl chlorides as radical precursors for the synthesis of the potentially useful chiral β-difluoromethyl or difluoroacetyl amines. To our delight, the reaction of N -alkenyl urea substrate 1a with 2b under the otherwise identical reaction conditions delivered difluoroacetyl-containing product 4A in 97% yield with 85% ee, which containing an acetyl structure is especially appealing because further transformations of the acetyl group in the obtained product would give access to a more diverse class of structures5960. Further improvement of the stereoselectivity indicated that lowering the reaction temperature was obviously beneficial for such a process, giving 4A in 95% yield with 97% ee at 0 °C (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

et al. 2017

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Although great success has been achieved in asymmetric fluoroalkylation reactions via nucleophilic or electrophilic processes, the development of asymmetric radical versions of this type of reactions remains a formidable challenge because of the involvement of highly reactive radical species. Here we report a catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes with commercially available fluoroalkylsulfonyl chlorides as the radical sources, providing a versatile platform to access four types of enantioenriched α-tertiary pyrrolidines bearing β-perfluorobutanyl, trifluoromethyl, difluoroacetyl and even difluoromethyl groups in excellent yields and with excellent enantioselectivity. The key to success is not only the introduction of the CuBr/chiral phosphoric acid dual-catalytic system but also the use of silver carbonate to suppress strong background and side hydroamination reactions caused by a stoichiometric amount of the in situ generated HCl. Broad substrate scope, excellent functional group tolerance and versatile functionalization of the products make this approach very practical and attractive.

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Section: Resultsmentioning

confidence: 99%

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

et al. 2017

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“…The specific activity of the quinoline 2 s was determined to be about 21 mCi mmol À1 at the end of synthesis (see the Supporting Information for details), which is comparable with the recently reported arylÀ [ 18 F]CF 3 [5a] and arylÀ[ 18 F]SCF 3 labeling. [15] In summary, we have successfully developed an efficient, fast, and transition-metal-free trifluoromethylthiolation method with a wide substrate scope and applicability. This strategy has been successfully applied to [ 18 F]trifluoromethylthiolation of alkyl electrophiles, and is the first example of [ 18 F]CF 3 S labeling.…”

Section: Methodsmentioning

confidence: 99%

Difluorocarbene‐Derived Trifluoromethylthiolation and [¹⁸F]Trifluoromethylthiolation of Aliphatic Electrophiles

et al. 2015

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The first trifluoromethylthiolation and [ 18 F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external (radioactive) fluoride ion is described. This transition metal-free approach is high yielding, compatible with variety of functional groups and operated under mild conditions. The conceptual advantage of this exogenous fluoride mediated transformation enables unprecedented syntheses of [ 18 F]CF 3 Slabeled molecules from most commonly used [ 18 F]fluoride ion. The rapid radiochemical reaction time (≤ 1 min) and highly functional group tolerance allow this method to access a variety of aliphatic [ 18 F]CF 3 S compounds in high yields. Keywordstrifluoromethylthiolation; difluorocarbene; fluorine-18; positron emission tomography; metal free Correspondence to: Ji-Chang Xiao, jchxiao@sioc.ac.cn. † These authors contributed equally to this work.Supporting information for this article is given via a link at the end of the document. Recently, outstanding accomplishments have been made for the incorporation of CF 3 S group via non-radioactive methods. [7] Two general strategies have been well established, including direct trifluoromethylthiolation by constructing C-SCF 3 bond [8] or squential constructing of S-CF 3 and C-SCF 3 bonds [8c, 9] (eq. 1, Scheme 1), and trifluoromethylation of sulfur-containing compounds to form RS-CF 3 bond [10] (eq. 2, Scheme 1). In both strategies, CF 3 S scaffold are derived from CF 3 S-or CF 3 -containing reagents without the involvement of external fluoride, which makes it not applicable or difficult for translation into 18 F-radiolabeling. Difluorocarbene has served as a powerful reaction intermediate in organic synthesis. [11] On the basis of our previous studies that difluorocarbene can be readily trapped by fluoride to generate trifluoromethyl anion (CF 3 − ) [12] and the recent studies that trifluoromethyl anion can react with elemental sulfur (S 8 ) to produce trifluoromethylthio anion (CF 3 S − ), [8c] we speculated that the reaction of difluorocarbene with fluoride in the presence of elemental sulfur may give trifluoromethylthio anion, which is a key intermediate for trifluoromethylthiolation reaction. This trifluoromethylthiolation protocol would sequentially construct F-CF 2 , S-CF 3 and C-SCF 3 bonds, and involve the use of external fluoride for the formation of CF 3 S functionality. Due to the time constraint of PET radiochemistry, if the reaction occurs fast enough, this trifluoromethylthiolation strategy may be able to be applied in 18 F-labeled trifluoromethylthiolation. Herein we describe the first trifluoromethylthiolation and [ 18 F]trifluoromethylthiolation of alkyl electrophiles with in situ generated difluorocarbene in the presence of elemental sulfur and external fluoride ion under transition metal-free conditions (eq. 3, Scheme 1). HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptWe have previously shown that difluoromethylene phospho...

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“…[2] As ac onsequence,c onsiderable efforts have been devoted to the development of efficient methods for the preparation of 18 Flabeled PET radiotracers. [3] Them ajority of 18 F-labeling methods reported to date have focused on the direct [ 18 F]fluorination of pre-functionalized arenes and alkanes, [4] while radiosynthetic routes towards 18 F-labeled molecules with functional groups such as [ 18 F]CF 3 , [5] [ 18 F]CF 2 H, [6] [ 18 F]SCF 3 , [7,8] [ 18 F]OCF 2 H, [8b] and [ 18 F]OCF 3 [8b] have appeared only more recently.Within this series,the trifluoromethylthiol group (-SCF 3 )h as gained much attention in the context of medicinal chemistry,d ue to its beneficial effects on pharmacokinetic and physicochemical properties,i ncluding metabolic stability and lipophilicity. [9] In 2015, Gouverneur and co-workers reported the first radiosynthetic route towards [ 18 F]arylSCF 3 via halogen exchange (halex) of ArSCF 2 Br with cyclotron-produced 18 Ffluoride ( Figure 1A).…”

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confidence: 99%

Synthesis and Reactivity of α‐Cumyl Bromodifluoromethanesulfenate: Application to the Radiosynthesis of [¹⁸F]ArylSCF₃

Zhao

Wilson

et al. 2019

Angew Chem Int Ed

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Ah ighly reactive electrophilic bromodifluoromethylthiolating reagent, a-cumyl bromodifluoro-methanesulfenate 1,was prepared to allowfor direct bromodifluoromethylthiolation of aryl boron reagents.T his coupling reaction takes place under copper catalysis,a nd affords al arge range of bromodifluoromethylthiolated arenes.T hese compounds are amenable to various transformations including halogen exchange with [ 18 F]KF/K 222 ,aprocess giving access to [ 18 F]arylSCF 3 in two steps from the corresponding aryl boronic pinacol esters.Positron Emission Tomography (PET) is al eading noninvasive imaging modality enabling the study of physiological processes in vivo.T he technique has found aw ide range of applications in the clinic, and serves as an aid to drug discovery by providing valuable information on the pharmacokinetic and pharmacodynamic properties of lead compounds. [1] Among the commonly used positron-emitting isotopes for PET,fluorine-18 is advantageous in part because of its relatively long half-life (t1 = 2 = 109.7 min). [2] As ac onsequence,c onsiderable efforts have been devoted to the development of efficient methods for the preparation of 18 Flabeled PET radiotracers. [3] Them ajority of 18 F-labeling methods reported to date have focused on the direct [ 18 F]fluorination of pre-functionalized arenes and alkanes, [4] while radiosynthetic routes towards 18 F-labeled molecules with functional groups such as [

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¹⁸F‐Labeling of Aryl‐SCF₃, ‐OCF₃ and ‐OCHF₂ with [¹⁸F]Fluoride

Cited by 97 publications

References 88 publications

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

Difluorocarbene‐Derived Trifluoromethylthiolation and [¹⁸F]Trifluoromethylthiolation of Aliphatic Electrophiles

Synthesis and Reactivity of α‐Cumyl Bromodifluoromethanesulfenate: Application to the Radiosynthesis of [¹⁸F]ArylSCF₃

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18F‐Labeling of Aryl‐SCF3, ‐OCF3 and ‐OCHF2 with [18F]Fluoride

Cited by 97 publications

References 88 publications

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

Catalytic asymmetric radical aminoperfluoroalkylation and aminodifluoromethylation of alkenes to versatile enantioenriched-fluoroalkyl amines

Difluorocarbene‐Derived Trifluoromethylthiolation and [18F]Trifluoromethylthiolation of Aliphatic Electrophiles

Synthesis and Reactivity of α‐Cumyl Bromodifluoromethanesulfenate: Application to the Radiosynthesis of [18F]ArylSCF3

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¹⁸F‐Labeling of Aryl‐SCF₃, ‐OCF₃ and ‐OCHF₂ with [¹⁸F]Fluoride

Difluorocarbene‐Derived Trifluoromethylthiolation and [¹⁸F]Trifluoromethylthiolation of Aliphatic Electrophiles

Synthesis and Reactivity of α‐Cumyl Bromodifluoromethanesulfenate: Application to the Radiosynthesis of [¹⁸F]ArylSCF₃