Copper‐Mediated Aminoquinoline‐Directed Radiofluorination of Aromatic C−H Bonds with K18F

A Cu‐mediated ortho‐C−H radiofluorination of aromatic carboxylic acids that are protected as 8‐aminoquinoline benzamides is described. The method uses K18F and is compatible with a wide range of functional groups. The reaction is showcased in the high specific activity automated synthesis of the RARβ2 agonist [18F]AC261066.Late‐stage fluorination: K18F is applied in a newly developed Cu‐mediated ortho‐C(sp2)−H radiofluorination of aromatic carboxylic acids that are protected as 8‐aminoquinoline benzamides. Fluorination of 18 examples in up to 62 % radiochemical yield and high specific activity is reported, including the automated synthesis of [18F]AC261066.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148216/1/anie201812701_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148216/2/anie201812701-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148216/3/anie201812701.pd

Copper‐Mediated Aminoquinoline‐Directed Radiofluorination of Aromatic C−H Bonds with K18F

A Cu‐mediated ortho‐C−H radiofluorination of aromatic carboxylic acids that are protected as 8‐aminoquinoline benzamides is described. The method uses K18F and is compatible with a wide range of functional groups. The reaction is showcased in the high specific activity automated synthesis of the RARβ2 agonist [18F]AC261066.Späte Fluorierung: Mit K18F gelingt die Cu‐vermittelte ortho‐C(sp2)‐H‐Radiofluorierung von aromatischen Carbonsäuren, die als 8‐Aminochinolinbenzamide geschützt sind. Die Fluorierung von 18 Beispielen mit bis zu 62 % radiochemischer Ausbeute und hoher spezifischer Aktivität wird beschrieben, einschließlich der automatisierten Synthese [18F]AC261066.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148266/1/ange201812701-sup-0001-misc_information.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148266/2/ange201812701.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148266/3/ange201812701_am.pd

Copper-Mediated Radiofluorination of Arylstannanes with [¹⁸F]KF

A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [¹⁸F]­KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [¹⁸F]­F-phenylalanine and [¹⁸F]­F-DOPA. In addition, an automated synthesis of [¹⁸F]­MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol

Copper(II)-Mediated [¹¹C]Cyanation of Arylboronic Acids and Arylstannanes

A copper-mediated method for the transformation of diverse arylboron compounds and arylstannanes to aryl-[¹¹C]-nitriles is reported. This method is operationally simple, uses commercially available reagents, and is compatible with a wide variety of substituted aryl- and heteroaryl substrates. This method is applied to the automated synthesis of high specific activity [¹¹C]­perampanel in 10% nondecay-corrected radiochemical yield (RCY)

Synthesis of [¹⁸F]Arenes via the Copper-Mediated [¹⁸F]Fluorination of Boronic Acids

A copper-mediated radiofluorination of aryl- and vinylboronic acids with K¹⁸F is described. This method exhibits high functional group tolerance and is effective for the radiofluorination of a range of electron-deficient, -neutral, and -rich aryl-, heteroaryl-, and vinylboronic acids. This method has been applied to the synthesis of [¹⁸F]­FPEB, a PET radiotracer for quantifying metabotropic glutamate 5 receptors