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Recent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate the fate of molecules in complex biological systems. A bioorthogonal uncaging strategy is presented, which is triggered by heterogeneous gold catalysis and facilitates the activation of a structurally diverse range of therapeutics in cancer cell culture. Furthermore, this solid-supported catalytic system enabled locally controlled release of a fluorescent dye into the brain of a zebrafish for the first time, offering a novel way to modulate the activity of bioorthogonal reagents in the most fragile and complex organs., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Biaryls (two directly connected aromatic rings, Ar(1)-Ar(2)) are common motifs in pharmaceuticals, agrochemicals, and organic materials. Current methods for establishing the Ar(1)-Ar(2) bond are dominated by the cross-coupling of aryl halides (Ar(1)-X) with aryl metallics (Ar(2)-M). We report that, in the presence of 1 to 2 mole percent of a gold catalyst and a mild oxidant, a wide range of arenes (Ar(1)-H) undergo site-selective arylation by arylsilanes (Ar(2)-SiMe(3)) to generate biaryls (Ar(1)-Ar(2)), with little or no homocoupling (Ar(1)-Ar(1)/Ar(2)-Ar(2)). Catalysis proceeds at room temperature and tolerates a broad range of functional groups, including those incompatible with cross-coupling. These features expedite biaryl preparation, as demonstrated by synthesis of the nonsteroidal anti-inflammatory diflunisal.

1-Hydroxy-1,2-benziodoxol-3(1H)-one (IBA) is an efficient terminal oxidant for gold-catalysed, three-component oxyarylation reactions. The use of this iodine(III) reagent expands the scope of oxyarylation to include styrenes and gem-disubstituted olefins, substrates that are incompatible with the previously reported Selectfluor-based methodology. Diverse arylsilane coupling partners can be employed, and in benzotrifluoride, homocoupling is substantially reduced. In addition, the IBA-derived co-products can be recovered and recycled., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Arylsilanes are efficient reagents for the gold-catalyzed oxyarylation of alkenes (21 examples, up to 85% isolated yield). Using commercially available Ph(3)PAuCl and readily prepared, benign arylsilanes, these two- and three-component reactions proceed smoothly in air. The oxidant, Selectfluor, not only facilitates entry to the Au(I/III) manifold but also provides a fluoride anion for silane activation, thereby avoiding the need for addition of a stoichiometric base.

Recent advances in bioorthogonal catalysis are increasing the capacity of researchers to manipulate the fate of molecules in complex biological systems. A bioorthogonal uncaging strategy is presented, which is triggered by heterogeneous gold catalysis and facilitates the activation of a structurally diverse range of therapeutics in cancer cell culture. Furthermore, this solid-supported catalytic system enabled locally controlled release of a fluorescent dye into the brain of a zebrafish for the first time, offering a novel way to modulate the activity of bioorthogonal reagents in the most fragile and complex organs. [ABSTRACT FROM AUTHOR]

Tailoring of the pre-catalyst, the oxidant and the arylsilane enables the first room-temperature, gold-catalysed, innate C−H arylation of heteroarenes. Regioselectivity is consistently high and, in some cases, distinct from that reported with palladium catalysis. Tolerance to halides and boronic esters, in both the heteroarene and silane partners, provides orthogonality to Suzuki-Miyaura coupling. [ABSTRACT FROM AUTHOR]

Thiole sind allgegenwärtig in lebenden Systemen, und ihre starke Bindung an Goldoberflächen hält andere funktionelle Gruppen fast vollständig von diesen fern. In ihrer Zuschrift auf S. 12727 berichten J. Santamaría, A. Unciti ‐ Broceta et al. über Gold ‐ Heterogenkatalysatoren für die bioorthogonale Aktivierung zugelassener Tumortherapeutika (durch O/N ‐ Depropargylierung) in Krebszellkulturen und die erste Aktivierung einer bioorthogonalen Sonde im Gehirn von Zebrafischen. [ABSTRACT FROM AUTHOR]

Thiols are ubiquitous in living systems where they bind strongly to gold surfaces and render interactions with other functional groups basically non‐existent. In their Communication on page 12548 ff., J. Santamaría and A. Unciti‐Broceta et al. describe heterogeneous gold catalysts that enable bioorthogonal uncaging (by O/N‐depropargylation) of clinically approved anticancer drugs in cancer cell culture, and the first intracranial activation of a bioorthogonal probe in a zebrafish. [ABSTRACT FROM AUTHOR]