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A two-stepprotocol has been developed for the introduction ofcyanomethylene groups to metalated aromatics through the intermediacyof substituted isoxazoles. Apalladium-mediated cross-coupling reaction was used to introduce theisoxazole unit, followed by release of the cyanomethylene functionunder thermal or microwave-assisted conditions. The intermediate isoxazoleswere shown to be amenable to further functionalization prior to deprotectionof the sensitive cyanomethylene motif, allowing access to a wide rangeof aryl- and heteroaryl-substituted acetonitrile building blocks. [ABSTRACT FROM AUTHOR]

The osmium-catalyzed oxidative cyclization of amino alcohol initiators formally derived from 1,4-dienes is an effective method for the construction of pyrrolidines, utilizing a novel reoxidant (4-nitropyridine N-oxide = NPNO). The cyclization of enantiopure syn- and anti-amino alcohols gives rise to enantiopure cis- and trans-2,5-disubstituted pyrrolidines, respectively. Moreover, the cyclization of bis-homoallylic amines bearing an exocyclic chelating group is shown to be a complementary method for trans-pyrrolidine formation. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

This communication describes a method for the nucleophilic radiofluorination of electron-rich arenes. The reaction involves the initial C(sp²)-H functionalization of an electron-rich arene with MesI(OH)OTs to form a (mesityl)(aryl)iodonium salt. This salt is then used in situ in a Cu-mediated radiofluorination with [18F]KF. This approach leverages the stability and availability of electron-rich arene starting materials to enable mild late-stage radiofluorination of toluene, anisole, aniline, pyrrole, and thiophene derivatives. The radiofluorination has been automated to access a 41 mCi dose of an 18F-labeled nimesulide derivative in high (2800 ± 700 Ci/mmol) specific activity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

A practical, rapid, and highly regioselectiveCu-catalyzed radiofluorinationof (mesityl)(aryl)iodonium salts is described. This protocol utilizes[18F]KF to access 18F-labeled electron-rich,-neutral, and -deficient aryl fluorides under a single set of mildconditions. This methodology is applied to the synthesis of protectedversions of two important radiotracers: 4-[18F]fluorophenylalanineand 6-[18F]fluoroDOPA. [ABSTRACT FROM AUTHOR]