Palladium‐Catalyzed Oxidative Cross‐Coupling of α‐Cyanoketene Dithioacetals with Olefins

Efficient palladium‐catalyzed cross‐coupling reactions of the internal olefins α‐cyanoketene dithioacetals with a variety of olefins were achieved in dioxane/HOAc/DMSO (9:3:1 v/v/v) under air atmosphere or by means of AgOAc as the terminal oxidant. Electron‐deficient terminal olefins reacted to form the linear diene derivatives with air as the oxidant. Styrenes underwent the cross‐coupling to give both the linear and branched dienes when using AgOAc as the oxidant. Unactivated cyclic and linear internal olefin substrates both reacted in the presence of a catalytic amount of benzoquinone in air to produce skipped dienes. The typical products were structurally confirmed by X‐ray crystallography.     

Rhodium‐Catalyzed Annulative Coupling of 3‐Phenylthiophenes with Alkynes Involving Double C‐H Bond Cleavages

Double C?H bond activation took place efficiently upon treatment of 3‐phenylthiophenes with alkynes in the presence of a rhodium catalyst and a copper salt oxidant to form the corresponding naphthothiophene derivatives. Dehydrogenative coupling with alkenes was also found to occur on the phenyl moiety rather than the thiophene ring. These reactions provide straightforward synthetic methods for π‐conjugated molecules involving a thiophene unit from readily available, simple building blocks.     

Quadracyclic Adenine: A Non‐Perturbing Fluorescent Adenine Analogue

Fluorescent‐base analogues (FBAs) comprise a group of increasingly important molecules for the investigation of nucleic acid structure and dynamics as well as of interactions between nucleic acids and other molecules. Here, we report on the synthesis, detailed spectroscopic characterisation and base‐pairing properties of a new environment‐sensitive fluorescent adenine analogue, quadracyclic adenine (qA). After developing an efficient route of synthesis for the phosphoramidite of qA it was incorporated into DNA in high yield by using standard solid‐phase synthesis procedures. In DNA qA serves as an adenine analogue that preserves the B‐form and, in contrast to most currently available FBAs, maintains or even increases the stability of the duplex. We demonstrate that, unlike fluorescent adenine analogues, such as the most commonly used one, 2‐aminopurine, and the recently developed triazole adenine, qA shows highly specific base‐pairing with thymine. Moreover, qA has an absorption band outside the absorption of the natural nucleobases (>300 nm) and can thus be selectively excited. Upon excitation the qA monomer displays a fluorescence quantum yield of 6.8 % with an emission maximum at 456 nm. More importantly, upon incorporation into DNA the fluorescence of qA is significantly less quenched than most FBAs. This results in quantum yields that in some sequences reach values that are up to fourfold higher than maximum values reported for 2‐aminopurine. To facilitate future utilisation of qA in biochemical and biophysical studies we investigated its fluorescence properties in greater detail and resolved its absorption band outside the DNA absorption region into distinct transition dipole moments. In conclusion, the unique combination of properties of qA make it a promising alternative to current fluorescent adenine analogues for future detailed studies of nucleic acid‐containing systems.     

Dimethylzinc‐Initiated Radical Coupling of β‐Bromostyrenes with Ethers and Amines

A new coupling reaction has been developed in which β‐bromostyrenes react with ethers and tertiary amines to introduce the styryl group in the α‐position. The transformation is mediated by Me₂Zn/O₂ with 10 % MnCl₂ and is believed to proceed by a radical addition–elimination mechanism. The ether and the amine are employed as solvent and the coupling takes place through the most stable α radical for unsymmetrical substrates. The products are obtained in moderate to good yields as the pure E isomers. The coupling can be achieved with a range of smaller cyclic and acyclic ethers/amines as well as various substituted β‐bromostyrenes.     

Salt‐Free Reduction of Nonprecious Transition‐Metal Compounds: Generation of Amorphous Ni Nanoparticles for Catalytic C–C Bond Formation

A salt‐free procedure for the generation of a wide variety of metal(0) particles, including Fe, Co, Ni, and Cu, was achieved using 2,3,5,6‐tetramethyl‐1,4‐bis(trimethylsilyl)‐1,4‐diaza‐2,5‐cyclohexadiene ( 1 ), which reduced the corresponding metal precursors under mild conditions. Notably, Ni particles formed in situ from the treatment of Ni(acac)₂ (acac=acetylacetonate) with 1 in toluene exhibited significant catalytic activity for reductive C? C bond‐forming reactions of aryl halides in the presence of excess amounts of 1 . By examination of high‐magnification transmission electron microscopy images and electron diffraction patterns, we concluded that amorphous Ni nanoparticles (Ni aNPs) were essential for the high catalytic activity.     

Palladium‐Catalyzed/Norbornene‐Mediated CH Activation/ N‐Tosylhydrazone Insertion Reaction: A Route to Highly Functionalized Vinylarenes

A straightforward method for the synthesis of highly functionalized vinylarenes through palladium‐catalyzed, norbornene‐mediated C?H activation/carbene migratory insertion is described. Extension to a one‐pot procedure is also developed. Furthermore, this method can also be used to generate polysubstituted bicyclic molecules. The reaction proceeds under mild conditions to give the products in satisfactory yields using readily available starting materials. This is a Catellani–Lautens reaction that incorporates different types of coupling partners. Additionally, this reaction is the first to demonstrate the possibility of combining Pd‐catalyzed insertion of diazo compounds and Pd‐catalyzed C?H activation.     

Self‐Assembled Nanocomposite Organic Polymers with Aluminum and Scandium as Heterogeneous Water‐Compatible Lewis Acid Catalysts

While water‐compatible Lewis acids have great potential as accessible and environmentally benign catalysts for various organic transformations, efficient immobilization of such Lewis acids while keeping high activity and without leaching of metals even under aqueous conditions is a challenging task. Self‐assembled nanocomposite catalysts of organic polymers, carbon black, aluminum reductants, and scandium salts as heterogeneous water‐compatible Lewis acid catalysts are described. These catalysts could be successfully applied to various C? C bond‐forming reactions without leaching of metals. Scanning transmission electron microscopy analyses revealed that the nanocomposite structure of Al and Sc was fabricated in these heterogeneous catalysts. It is noted that Al species, which are usually decomposed rapidly in the presence of water, are stabilized under aqueous conditions.     

Unprecedented Transformation of a Directing Group Generated In Situ and Its Application in the One‐Pot Synthesis of 2‐Alkenyl Benzonitriles

An unprecedented protocol for the transformation of benzoyl azides into benzonitrile derivatives via iminophosphoranes generated in situ is described. The strategy was successfully applied to the de‐novo synthesis of 2‐alkenylated benzonitrile derivatives from benzoyl azides through ortho C?H activation/alkenylation followed by subsequent rearrangement. The salient features of this protocol involve incorporation of two important functionalities through cyanation and olefination in one pot under mild reaction conditions by using a less expensive Ru catalyst. The mechanism was established by isolating and characterising (using ³¹P NMR) an intermediate with two ortho functionalities, iminophosphorane and olefin, under specific reaction conditions.     

The Cross‐Dehydrogenative Coupling of CH Bonds: A Versatile Strategy for CC Bond Formations

Over the last decade, substantial research has led to the introduction of an impressive number of efficient procedures which allow the selective construction of C? C bonds by directly connecting two different C? H bonds under oxidative conditions. Common to these methodologies is the generation of the reactive intermediates in situ by activation of both C? H bonds. This strategy was introduced by the group of Li as cross‐dehydrogenative coupling (CDC) and discloses waste‐minimized synthetic alternatives to classic coupling procedures which rely on the use of prefunctionalized starting materials. This Review highlights the recent progress in the field of cross‐dehydrogenative C? C formations and provides a comprehensive overview on existing procedures and employed methodologies.     

Visible‐Light‐Induced Decarboxylative Functionalization of Carboxylic Acids and Their Derivatives

Visible‐light‐induced radical decarboxylative functionalization of carboxylic acids and their derivatives has recently received considerable attention as a novel and efficient method to create C? C and C? X bonds. Generally, this visible‐light‐promoted decarboxylation process can smoothly occur under mild reaction conditions with a broad range of substrates and an excellent functional‐group tolerance. The radical species formed from the decarboxylation step can participate in not only single photocatalytic transformations, but also dual‐catalytic cross‐coupling reactions by combining photoredox catalysis with other catalytic processes. Recent advances in this research area are discussed herein.     

Dehydrogenative Carbon–Carbon Bond Formation Using Alkynyloxy Moieties as Hydrogen‐Accepting Directing Groups

In the presence of a catalyst system consisting of Pd(OAc)₂, PCy₃, and Zn(OAc)₂, the reaction of alkynyl aryl ethers with bicycloalkenes, α,ß‐unsaturated esters, or heteroarenes results in the site‐selective cleavage of two C? H bonds followed by the formation of C? C bonds. In all cases, the alkynyloxy group acts as a directing group for the activation of an ortho C? H bond and as a hydrogen acceptor, thus rendering the use of additives such as an oxidant or base unnecessary.     

Water‐Promoted Generation of a Diazairida Homobarrelene by CC Coupling Between an Iridacyclic Alkylidene and Acetonitrile

The stable cationic iridacyclopentenylidene [Tp^Me2Ir(?CHC(Me)?C(Me)C H₂(NCMe)]PF₆ ( A ; Tp^Me2=hydrotris(3,5‐dimethylpyrazolyl)borate) has been obtained by α‐hydride abstraction from the iridacyclopent‐2‐ene [Tp^Me2Ir(CH₂C(Me)?C(Me)C H₂)(NCMe)]. Complex A exhibits Brønsted–Lowry acidity at the Ir? CH₂ and proximal (relative to Ir? CH₂) methyl sites. The coordination of an extra molecule of acetonitrile to the iridium center initiates the reversible isomerization of the chelating carbon chain of A to the monodentate butadienyl ligand of complex [Tp^Me2Ir(CH?C(Me)C(Me)?CH₂)(NCMe)₂]PF₆, which is capable to engage in a water‐promoted C? C coupling with the MeCN co‐ligands. The product is an aesthetically appealing bicyclic structure that resembles the hydrocarbon barrelene.     

A Highly Efficient Gold‐Catalyzed Photoredox α‐C(sp3)H Alkynylation of Tertiary Aliphatic Amines with Sunlight

A new α‐C(sp³)? H alkynylation of unactivated tertiary aliphatic amines with 1‐iodoalkynes as radical alkynylating reagents in the presence of [Au₂(μ‐dppm)₂]²⁺ in sunlight provides propargylic amines. Based on mechanistic studies, a C? C coupling of an α‐aminoalkyl radical and an alkynyl radical is proposed for the C(sp³)? C(sp) bond formation. The mild, convenient, efficient, and highly selective C(sp³)? H alkynylation reaction shows excellent regioselectivity and good functional‐group compatibility. A scale‐up to gram quantities is possible with sunlight used as a clean and sustainable energy source.     

Modular Synthesis of Phenanthro[9,10‐c]thiophenes by a Sequence of CH Activation,Suzuki Cross‐Coupling and Photocyclization Reactions

A total number of 15 different 3,4‐diarylthiophenes were synthesized, which bear a chlorine atom in ortho‐position of one of the aryl substituents. One aryl group was introduced by an oxidative cross‐coupling reaction, involving a C?H activation at C4(3) of the thiophene core. The other aryl group was in most cases introduced by a Suzuki cross‐coupling reaction, which succeeded the oxidative cross‐coupling step. Photocyclization reactions of the 3,4‐diarylthiophenes were performed in a solvent mixture of benzene and acetonitrile (50:50 v/v) at λ=254 nm and proceeded to the title compounds in yields of 60–82 %. The selectivity of the photocyclization was determined at the ortho‐chloro‐substituted aryl ring by the position of the chlorine substituent. At the other ring, a single regioisomer was observed for phenyl and para‐substituted phenyl groups. For 2‐naphthyl and ortho‐substituted phenyl rings a clear preference was observed in favor of a major regioisomer, while meta‐substitution in the phenyl ring led to a about 1:1 mixture of 5‐ and 7‐substituted phenanthro[9,10‐c]thiophenes. Mechanistically, the photocyclization is likely to occur as a photochemically allowed, conrotatory [(4n+2)π] process accompanied by elimination of HCl. It was shown for two phenanthro[9,10‐c]thiophene products that they can be readily brominated in positions C1 and C3 (74–77 %), which in turn allows for further functionalization at these positions, for example, in the course of halogen–metal exchange and polymerization reactions.     

Metal‐Free Oxidative CC Bond Formation through CH Bond Functionalization

The formation of C?C bonds embodies the core of organic chemistry because of its fundamental application in generation of molecular diversity and complexity. C?C bond‐forming reactions are well‐known challenges. To achieve this goal through direct functionalization of C?H bonds in both of the coupling partners represents the state‐of‐the‐art in organic synthesis. Oxidative C?C bond formation obviates the need for prefunctionalization of both substrates. This Minireview is dedicated to the field of C?C bond‐forming reactions through direct C?H bond functionalization under completely metal‐free oxidative conditions. Selected important developments in this area have been summarized with representative examples and discussions on their reaction mechanisms.     

Palladium‐Catalyzed Synthesis of Phenanthridine/Benzoxazine‐Fused Quinazolinones by Intramolecular CH Bond Activation

A highly efficient synthesis of phenanthridine/benzoxazine‐fused quinazolinones by ligand‐free palladium‐catalyzed intramolecular C?H bond activation under mild conditions has been developed. The C?C coupling provides the corresponding N‐fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance.     

Metal‐Catalyzed Reductive Coupling Reactions of Organic Halides with Carbonyl‐Type Compounds

Metal‐catalyzed reductive coupling reactions of aryl halides and (pseudo)halides with carbonyl‐type compounds have undergone an impressive development within the last years. These methodologies have shown to be a powerful alternate strategy, practicality aside, to the use of stoichiometric, well‐defined, and, in some cases, air‐sensitive organometallic species. In this Minireview, the recent findings in this field are summarized, with particular emphasis on the mechanistic interpretation of the results and future aspects of this area of expertise.     

Light‐Harvesting Nanoparticle Probes for FRET‐Based Detection of Oligonucleotides with Single‐Molecule Sensitivity

Controlling the emission of bright luminescent nanoparticles by a single molecular recognition event remains a challenge in the design of ultrasensitive probes for biomolecules. Herein, we developed 20‐nm light‐harvesting nanoantenna particles, built of a tailor‐made hydrophobic charged polymer poly(ethyl methacrylate‐co‐methacrylic acid), encapsulating circa 1000 strongly coupled and highly emissive rhodamine dyes with their bulky counterion. Being 87‐fold brighter than quantum dots QDots 605 in single‐particle microscopy (with 550‐nm excitation), these DNA‐functionalized nanoparticles exhibit over 50 % total FRET efficiency to a single hybridized FRET acceptor, a highly photostable dye (ATTO665), leading to circa 250‐fold signal amplification. The obtained FRET nanoprobes enable single‐molecule detection of short DNA and RNA sequences, encoding a cancer marker (survivin), and imaging single hybridization events by an epi‐fluorescence microscope with ultralow excitation irradiance close to that of ambient sunlight.