NHC-Copper Mediated Ligand-Directed Radiofluorination of Aryl Halides

Sharninghausen, Liam S.; Brooks, Allen F.; Winton, Wade; Makaravage, Katarina J.; Scott, Peter J. H.; Sanford, Melanie S.

doi:10.1021/jacs.0c02637

Cited by 43 publications

(28 citation statements)

References 61 publications

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“…1B). Clearly, there is a dearth of methods for the direct radio uorination of electron-rich aryl halides 30 . Such a strategy is highly desirable given the stability and abundance of aryl chlorides and uorides in therapeutics [31][32][33] .…”

Section: Introductionmentioning

confidence: 99%

Arene radiofluorination enabled by photoredox-mediated halide interconversion

et al. 2021

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Positron emission tomography (PET) is a powerful imaging technology that could visualize and measure metabolic processes in vivo and/or obtain unique information about drug candidates at early stages. Identi cation of new and improved molecular probes plays a critical role in PET, but its progress is limited in many situations due to the lack of e cient and simple labeling methods to modify biologically active small molecules and/or drugs. Although various approaches have been reported, current methods to radio uorinate unactivated arenes are still limited. Here we document the discovery of a robust method for constructing C-18F bonds through direct halide/18F conversion in electron-rich halo(hetero)arene substrates. Based on readily available halide precursors and mild photoredox conditions, [18F]F-is e ciently introduced into a broad spectrum of organic molecules, including pharmaceutical compounds in a site-selective manner. Notably, the direct 19F/18F conversion method is demonstrated to be a simple and robust protocol for PET probe screening/preparation: this methodology not only identi es a new cancer imaging agent L-61-18F-COOH after a rapid screening of a tyrosine isomer library; but also allows the simple and high-yielding synthesis of the widely used PET agent L-[18F]FDOPA. Taken together, photoredox-mediated halide/18F interconversion strategies represent an innovative chemical tool to prepare new and clinically signi cant PET agents that are synthetically inaccessible or cumbersome to achieve by traditional methods.

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Section: Introductionmentioning

confidence: 99%

Arene radiofluorination enabled by photoredox-mediated halide interconversion

et al. 2021

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“…Gouverneur reported the application of this method to clinically relevant tracers including 3-[ 18 (Taylor et al 2017) as well as an extensive study providing radiochemists with guidelines on how to apply this radiochemistry to label complex drug candidates featuring multiple functionalities including nitrogen-containing heterocycles and heteroarenes. (Guibbal et al 2020) More recently, Gouverneur also reported the automated radiosynthesis of [ 18 F] (Sharninghausen et al 2020) N-heterocyclic carbene (NHC) Cu-complexes were investigated by Sanford and Scott for the ligand-directed radiofluorination of aryl halides (Ar-X, X = Br, Cl, I); the narrow substrate scope and the need of rigorous air-free and anhydrous conditions limit the applicability of this methodology (Fig. 5C) (Xu et al 2021).…”

Section: Iii122 Coppermentioning

confidence: 99%

Closing the gap between 19F and 18F chemistry

Ajenjo

Destro

Cornelissen

et al. 2021

EJNMMI radiopharm. chem.

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Positron emission tomography (PET) has become an invaluable tool for drug discovery and diagnosis. The positron-emitting radionuclide fluorine-18 is frequently used in PET radiopharmaceuticals due to its advantageous characteristics; hence, methods streamlining access to 18F-labelled radiotracers can make a direct impact in medicine. For many years, access to 18F-labelled radiotracers was limited by the paucity of methodologies available, and the poor diversity of precursors amenable to 18F-incorporation. During the last two decades, 18F-radiochemistry has progressed at a fast pace with the appearance of numerous methodologies for late-stage 18F-incorporation onto complex molecules from a range of readily available precursors including those that do not require pre-functionalisation. Key to these advances is the inclusion of new activation modes to facilitate 18F-incorporation. Specifically, new advances in late-stage 19F-fluorination under transition metal catalysis, photoredox catalysis, and organocatalysis combined with the availability of novel 18F-labelled fluorination reagents have enabled the invention of novel processes for 18F-incorporation onto complex (bio)molecules. This review describes these major breakthroughs with a focus on methodologies for C–18F bond formation. This reinvigorated interest in 18F-radiochemistry that we have witnessed in recent years has made a direct impact on 19F-chemistry with many laboratories refocusing their efforts on the development of methods using nucleophilic fluoride instead of fluorination reagents derived from molecular fluorine gas.

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“…Changing the Cu(I) salt from CuTC to CuI or CuCl resulted in considerable decrease in the yield, indicating the superior catalytic activity of CuTC with Cs2CO3 (Figure 4, entries 2 and 3). In sharp contrast, the reaction with CsF proceeded efficiently irrespective of a counter anion on the Cu(I) salt (Figure 4, entries 8-10), which may be attributable to slow (for Cs2CO3) and fast (for CsF) generation of trasmetalation-active CuOC(O)R [OC(O)R = TC, carbonate] and CuF 36,37 from CuX (X = I, Cl), respectively (trasmetalation-activity: CuTC > CuI, CuCl, see SI, Figure S17). DEE (and DME, see SI, Figure S7 and S8) turned out to be the best medium for the present MKSC, and thus the yield became lower in THF or toluene (Figure 4, entries 4, 5, 11, and 12).…”

Section: Resultsmentioning

confidence: 99%

”Copper Effect” in Migita–Kosugi–Stille Coupling Revisited

Tanaka

Nakamoto

Yoshida

2021

Preprint

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”Copper effect” in Migita–Kosugi–Stille coupling (MKSC) has been well known as acceleration effect by a copper cocatalyst, which has thus far been ascribed to two different actions of copper depending on polarity of solvents, i.e., Sn/Cu transmetalation (in polar solvent such as DMF and NMP) and scavenging of ligands (in less polar ethereal solvent). Herein, we report on reconsideration of the copper effect; MKSC is markedly accelerated based on the Sn/Cu transmetalation in ethereal solvents. In particular, perfluorophenyl- and heteroaryl-stannanes were found to undergo the Sn/Cu transmetalation with excellent site-selectivity in the presence of other Ar–Sn bonds under the ethereal conditions, leading to highly chemoselective, sequential MKSC without masking/unmasking process on a tin center. Moreover, we have also demonstrated that a combination of 119Sn NMR chemical shifts (experimental) and computed FIA (theoretical) provides a quantitative criterion estimating tin-Lewis acidity that is strongly linked to activity toward the present MKSC.

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NHC-Copper Mediated Ligand-Directed Radiofluorination of Aryl Halides

Cited by 43 publications

References 61 publications

Arene radiofluorination enabled by photoredox-mediated halide interconversion

Arene radiofluorination enabled by photoredox-mediated halide interconversion

Closing the gap between 19F and 18F chemistry

”Copper Effect” in Migita–Kosugi–Stille Coupling Revisited

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