Palladium-Catalyzed Cross-Coupling of Aryl Bromides and Chlorides with Trimethylsilylalkynes under Mild Conditions.

Herein, we disclose a palladium-catalyzed cross-coupling of aryl bromides and chlorides with trimethylsilylalkynes under mild reaction conditions. This method utilizes commercially available and air stable palladium precatalysts and avoids the use of copper cocatalysts. Moreover, it allows for the synthesis of a wide range of disubstituted alkynes in high yields with excellent functional group tolerance.

Direct Arylation of Simple Arenes with Aryl Bromides by Synergistic Silver and Palladium Catalysis.

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.

Site-Selective Silver-Catalyzed C-H Bond Deuteration of Five-Membered Aromatic Heterocycles and Pharmaceuticals.

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.

Diastereoselective Allylation of Aldehydes by Dual Photoredox and Chromium Catalysis.

Herein, we report the redox-neutral allylation of aldehydes with readily available electron-rich allyl (hetero-) arenes, β-alkyl styrenes and allyl-diarylamines. This process was enabled by the combination of photoredox and chromium catalysis, which allowed a range of homoallylic alcohols to be prepared with high levels of selectivity for the anti diastereomer. Mechanistic investigations support the formation of an allyl chromium intermediate from allylic C(sp)-H bonds and thus significantly extends the scope of the venerable Nozaki-Hiyama-Kishi reaction.

DMSO as a Switchable Alkylating Agent in Heteroarene C-H Functionalization.

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.

Visible-Light-Mediated Synthesis of Ketones by the Oxidative Alkylation of Styrenes.

The oxidative coupling of photogenerated alkyl radicals with readily available styrenes is disclosed. This visible-light-mediated method allows rapid access to a wide range of α-alkyl-acetophenones in good yields and with high functional group tolerance. In addition, the developed protocol features room temperature conditions, low photocatalyst loadings, and the use of dimethyl sulfoxide as nontoxic and mild terminal oxidant.

Palladium-Catalyzed Decarboxylative Heck-Type Coupling of Activated Aliphatic Carboxylic Acids Enabled by Visible Light.

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 ) is employed as an inexpensive palladium source and no addition of base or classical photocatalyst is required.

Alkynylation of Csp2 (O)-H Bonds Enabled by Photoredox-Mediated Hydrogen-Atom Transfer.

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.

Multicomponent Oxyalkylation of Styrenes Enabled by Hydrogen-Bond-Assisted Photoinduced Electron Transfer.

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 )-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 -sp bonds across styrene moieties that gives straightforward access to complex alcohol and ether scaffolds.

Visible-Light-Promoted Activation of Unactivated C(sp)-H Bonds and Their Selective Trifluoromethylthiolation.

Selective functionalization of ubiquitous C(sp)-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)-H bonds, followed by their trifluoromethylthiolation, which has high potential as a late-stage functionalization tool.

Merging Visible Light Photoredox and Gold Catalysis.

Since the beginning of this century, π-Lewis acidic gold complexes have become the catalysts of choice for a wide range of organic reactions, especially those involving nucleophilic addition to carbon-carbon multiple bonds. For the most part, however, the gold catalyst does not change oxidation state during the course of these processes and two-electron redox cycles of the kind implicated in cross-coupling chemistry are not easily accessible. In order to address this limitation and expand the scope of gold catalysis beyond conventional hydrofunctionalization, extensive efforts have been made to develop new oxidative reactions using strong external oxidants capable of overcoming the high potential of the Au/Au redox couple.

Oxidative Addition to Gold(I) by Photoredox Catalysis: Straightforward Access to Diverse (C,N)-Cyclometalated Gold(III) Complexes.

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.

Alkyne Difunctionalization by Dual Gold/Photoredox Catalysis.

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.

Dual gold/photoredox-catalyzed C(sp)-H arylation of terminal alkynes with diazonium salts.

The arylation of alkyl and aromatic terminal alkynes by a dual gold/photoredox catalytic system is described. Using aryldiazonium salts as readily available aryl sources, a range of diversely-functionalized arylalkynes could be synthesized under mild, base-free reaction conditions using visible light from simple household sources or even sunlight. This process, which exhibits a broad scope and functional group tolerance, expands the range of transformations amenable to dual gold/photoredox catalysis to those involving C-H bond functionalization and demonstrates the potential of this concept to access Au/Au redox chemistry under mild, redox-neutral conditions.

Synthesis of tetra-substituted imidazoles and 2-imidazolines by Ni(0)-catalyzed dehydrogenation of benzylic-type imines.

Ni(0)-catalyzed dehydrogenation of benzylic-type imines was performed to yield asymmetrical tetra-substituted imidazoles and 2-imidazolines. This was achieved with a single operational step while maintaining good selectivity and atom economy. The catalytic system shows low to moderate tolerance for fluoro-, trifluoromethyl-, methyl-, and methoxy-substituted benzylic-type imines.

On the catalytic hydrodefluorination of fluoroaromatics using nickel complexes: the true role of the phosphine.

Homogeneous catalytic hydrodefluorination (HDF) of fluoroaromatics under thermal conditions was achieved using nickel(0) compounds of the type [(dippe)Ni(η(2)-C6F6-nHn)] where n = 0-2, as the catalytic precursors. These complexes were prepared in situ by reacting the compound [(dippe)Ni(μ-H)]2 with the respective fluoroaromatic substrate. HDF seems to occur homogeneously, as tested by mercury drop experiments, producing the hydrodefluorinated products.