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Catalytic methods for the direct introduction of hydrogen isotopes into organic molecules are essential to the development of improved pharmaceuticals and to the alteration of their absorption, distribution, metabolism, and excretion (ADME) properties. However, the development of homogeneous catalysts for selective incorporation of isotopes in the absence of directing groups under practical conditions remains a long-standing challenge. Here, we show that a phosphine-ligated, silver-carbonate complex catalyzes the site-selective deuteration of C-H bonds in five-membered aromatic heterocycles and active pharmaceutical ingredients that have been resistant to catalytic H/D exchange. The reactions occur with CH3OD as a low-cost source of the isotope. The silver catalysts react with five-membered heteroarenes lacking directing groups, tolerate a wide range of functional groups, and react in both polar and nonpolar solvents. Mechanistic experiments, including deuterium kinetic isotope effects, determination of kinetic orders, and identification of the catalyst resting state, support C-H bond cleavage from a phosphine-ligated, silver-carbonate intermediate as the rate-determining step of the catalytic cycle.

The direct, catalytic arylation of simple arenes in small excess with aryl bromides is disclosed. The developed method does not require the assistance of directing groups and relies on a synergistic catalytic cycle in which phosphine-ligated silver complexes cleave the aryl C-H bond, while palladium catalysts enable the formation of the biaryl products. Mechanistic experiments, including kinetic isotope effects, competition experiments, and hydrogen-deuterium exchange, support a catalytic cycle in which cleavage of the C-H bond by silver is the rate-determining step.

The development of new hydrogen-atom transfer (HAT) strategies within the framework of photoredox catalysis is highly appealing for its power to activate a desired C−H bond in the substrate leading to its selective functionalization. Reported here is the first photoredox-mediated hydrogen-atom transfer method for the efficient synthesis of ynones, ynamides, and ynoates with high regio- and chemoselectivity by direct functionalization of C [ABSTRACT FROM AUTHOR]

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Herein, we report the oxidative addition of aryldiazonium salts to ligand-supported gold(I) complexes under visible light photoredox conditions. This method provides experimental evidence for the involvement of such a process in dual gold/photoredox-catalyzed reactions and delivers well-defined ( C,N)-cyclometalated gold(III) species. The remarkably mild reaction conditions and the ability to widely vary the ancillary ligand make this method a potentially powerful synthetic tool to access diverse gold(III) complexes for systematic studies into their properties and reactivity. Initial studies show that these species can undergo chloride abstraction to afford Lewis acidic dicationic gold(III) species. [ABSTRACT FROM AUTHOR]

Herein, we report a novel strategy for the activation of DMSO to act as a versatile alkylating agent in heteroarene C-H functionalization. This direct, simple, and mild switch between methylation/trideuteromethylation and methylthiomethylation of heteroarenes was achieved under reagent-controlled photoredox catalysis conditions. The proposed mechanism is supported by both experimental and computational studies., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The palladium-catalyzed coupling reaction of N-hydroxyphthalimide esters and styrenes to deliver exclusively (E)-substituted olefins under irradiation with visible light is reported. This method tolerates N-hydroxyphthalimide esters derived from primary, secondary, tertiary as well as benzylic carboxylic acids. Notably, Pd(PPh 3 ) 4 is employed as an inexpensive palladium source and no addition of base or classical photocatalyst is required. Mechanistic studies suggest a light-mediated single-electron reduction of the activated acid by a photoexcited palladium(0) species to access alkyl radicals through decarboxylation., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The development of new hydrogen-atom transfer (HAT) strategies within the framework of photoredox catalysis is highly appealing for its power to activate a desired C-H bond in the substrate leading to its selective functionalization. Reported here is the first photoredox-mediated hydrogen-atom transfer method for the efficient synthesis of ynones, ynamides, and ynoates with high regio- and chemoselectivity by direct functionalization of Csp2 (O)-H bonds. The broad synthetic application of this method has been demonstrated by the selective functionalization of C(O)-H bonds within complex molecular scaffolds., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Herein, we disclose a strategy for the activation of N-(acyloxy)phthalimides towards photoinduced electron transfer through hydrogen bonding. This activation mode enables efficient access to C(sp 3 )-centered radicals upon decarboxylation from bench-stable and readily available substrates. Moreover, we demonstrate that the formed alkyl radicals can be successfully employed in a novel redox-neutral method for constructing sp 3 -sp 3 bonds across styrene moieties that gives straightforward access to complex alcohol and ether scaffolds., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Selective functionalization of ubiquitous C(sp 3 )-H bonds using visible light is a highly challenging yet desirable goal in organic synthesis. The development of such processes relies on both rational design and serendipitous discoveries from innovative tools such as screening technologies. Applying a mechanism-based screening strategy, we herein report photoredox-mediated hydrogen atom transfer catalysis for the selective activation of otherwise unactivated C(sp 3 )-H bonds, followed by their trifluoromethylthiolation, which has high potential as a late-stage functionalization tool. The generality of this method is exhibited through incorporation of the trifluoromethylthio group in a large number of C(sp 3 )-H bonds with high selectivity without the need for an excess of valuable substrate.

Highly selective tandem nucleophilic addition/cross-coupling reactions of alkynes have been developed using visible-light-promoted dual gold/photoredox catalysis. The simultaneous oxidation of Au(I) and coordination of the coupling partner by photo-generated aryl radicals, and the use of catalytically inactive gold precatalysts allows for high levels of selectivity for the cross-coupled products without competing hydrofunctionalization or homocoupling. As demonstrated in representative arylative Meyer-Schuster and hydration reactions, this work expands the scope of dual gold/photoredox catalysis to the largest class of substrates for gold catalysts and benefits from the mild and environmentally attractive nature of visible-light activation., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)