Cross-dehydrogenative Coupling Reaction Research Articles

Electrocatalytic dehydrogenative and defluorinative coupling between aldehyde-derived N,N-dialkylhydrazones and fluoromalonates: synthesis of 2-pyrazolines.

An electrocatalytic synthesis of 2-pyrazolines via dehydrogenative and defluorinative cross-coupling reactions between (hetero)arylaldehyde-derived N,N-dialkylhydrazones and fluoromalonates is disclosed. Salient features of this work include (i) readily available starting materials, (ii) practical reaction conditions, and (ii) a formal oxidative (4 + 1)-cycloaddition via triple C-H bond functionalization. Cyclic voltammetry analyses support the electrocatalytic formation of an α-fluoromalonyl radical.

A Robust Pyrazolate Metal-Organic Framework for Efficient Catalysis of Dehydrogenative C-O Cross Coupling Reaction.

Construction of robust heterogeneous catalysts with atomic precision is a long-sought pursuit in the catalysis field due to its fundamental significance in taming chemical transformations. Herein, we present the synthesis of a single-crystalline pyrazolate metal-organic framework (MOF) named PCN-300, bearing a lamellar structure with two distinct Cu centers and one-dimensional (1D) open channels when stacked. PCN-300 exhibits exceptional stability in aqueous solutions across a broad pH range from 1 to 14. In contrast, its monomeric counterpart assembled through hydrogen bonding displays limited stability, emphasizing the role of Cu-pyrazolate coordination bonds in framework robustness. Remarkably, the synergy of the 1D open channels, excellent stability, and the active Cu-porphyrin sites endows PCN-300 with outstanding catalytic activity in the cross dehydrogenative coupling reaction to form the C-O bond without the "compulsory" ortho-position directing groups (yields up to 96%), outperforming homogeneous Cu-porphyrin catalysts. Moreover, PCN-300 exhibits superior recyclability and compatibility with various phenol substrates. Control experiments reveal the synergy between the Cu-porphyrin center and framework in PCN-300 and computations unveil the free radical pathway of the reaction. This study highlights the power of robust pyrazolate MOFs in directly activating C-H bonds and catalyzing challenging chemical transformations in an environmentally friendly manner.

Salicylaldehyde-Cobalt(II)-Catalyzed C-H Alkoxylation of Indoles with Secondary Alcohols.

A straight and efficient protocol for the synthesis of hindered indole-ethers via C-H alkoxylation of indoles was developed by a cobalt-catalyzed cross-dehydrogenative coupling reaction with secondary alcohols. The selection of the salicylaldehyde-Co(II) catalyst enables the reaction to proceed under conditions without acid or base addition in the presence of limited alcohols. The protocol has broad substrate scope for both indole and secondary alcohols and exhibits good functional tolerance. The synthetic applications are proven by gram-scale reaction and further diversification of the product. Preliminary mechanistic investigations indicate that the activation of C-H bonds is not the rate-determining step of the reaction.

Aromatic Amine Catalysts for the O2-Mediated Cross-Dehydrogenative Phenothiazination Reaction?

AbstractMetal-free aromatic amines have been utilized recently as redox-active catalysts in various oxidative coupling reactions. In this study, we investigated a series of aromatic amines and their potential redox catalytic activity, in particular compared to our previously reported amino-Te(II) catalysts. The O2-mediated cross-dehydrogenative phenothiazination of phenols was utilized as a benchmark test reaction, as well as the O2-mediated cross-dehydrogenative coupling of indoles. We thus identified a proton sponge as an effective aromatic amine redox catalyst. It was moreover found that although the proton sponge displays clear catalytic activity, it is generally less active than previously reported phenotellurazine catalysts. The insights provided by this study should guide future research efforts for the development of innovative redox-catalyzed cross-dehydrogenative coupling reactions.

Rose‐Bengal‐Photocatalyzed Cross‐Dehydrogenative Coupling Reactions under Visible Light

AbstractOver the past few years, organic chemistry has used the organic dye rose bengal‘s ability to absorb visible light. In present‐day research, the innovation of environmentally friendly processes for carbon‐carbon/carbon‐heteroatoms (Nitrogen, Oxygen, Sulphur, and Phosphorus) bond formation has great importance. The photocatalyzed cross‐dehydrogenative coupling (CDC) reactions using rose bengal (RB) is a promising technique for creating carbon‐carbon/carbon‐heteroatom bonds directly from readily available compounds. Our review focuses on the current advancement in rose bengal that uses photocatalyzed carbon‐carbon/carbon‐heteroatom bond‐making reactions to synthesize various important organic molecules via CDC reactions.

Pd-Catalyzed Oxidative Functionalization of Alkenes, Arenes, and 1,3-Dienes Using Molecular Oxygen as the Terminal Oxidant

AbstractThis Account presents palladium-complex-catalyzed oxidative couplings mainly developed by the author’s group, including oxidative amination and silylation of terminal alkenes, direct oxidative arylation of aromatic compounds, and oxidative difunctionalization of 1,3-dienes. The catalytic cycles in these representative reactions feature re-oxidation of the palladium species with molecular oxygen as the terminal oxidant. Varying the combination of palladium catalyst and re-oxidant enables the formation of a variety of bonds through dehydrogenative cross-coupling reactions.1 Introduction2 Oxidative Amination of Terminal Alkenes3 Direct Oxidative Arylation of Aromatic Compounds4 Oxidative Silylation of Terminal Alkenes5 Oxidative Difunctionalization of 1,3-Dienes6 Conclusions and Perspectives

Direct Formation of C-C, C-N, and C-O Bonds in Dihydroquinazolines via Hypervalent Iodine(III)-Mediated sp3 C-H Functionalization.

A hypervalent iodine(III)-mediated cross-dehydrogenative coupling reaction for the direct formation of C-C, C-N, and C-O bonds in dihydroquinazolines has been developed. This one-pot method allows for the synthesis of C4-disubstituted dihydroquinazolines as well as C4-spirolactam, spirolactone, and spiroindene dihydroquinazolines in moderate to high yields.

Enones from aldehydes and alkenes by carbene-catalyzed dehydrogenative couplings

Enones are widely explored in synthetic chemistry as fundamental building blocks for a wide range of reactions and exhibit intriguing biological activities that are pivotal for drug discovery. The development of synthetic strategies for highly efficient preparation of enones thereby receives intense attention, in particular through the transition metal-catalyzed coupling reactions. Here, we describe a carbene-catalyzed cross dehydrogenative coupling (CDC) reaction that enables effective assembly of simple aldehydes and alkenes to afford a diverse set of enone derivatives. Mechanistically, the in situ generated aryl radical is pivotal to “activate” the alkene by forming an allyl radical through intermolecular hydrogen atom transfer (HAT) pathway and thus forging the carbon-carbon bond formation with aldehyde as the acyl synthon. Notably, our method represents the first example on the enone synthesis through coupling of “non-functionalized” aldehydes and alkenes as coupling partners, and offers a distinct organocatalytic pathway to the transition metal-catalyzed coupling transformations.

Rapid modular synthesis of indole ethers via dehydrogenative cross-coupling reaction of indoles and alcohols

Indole ethers are commonly found in pharmaceuticals, enzymes, and many bioactive compounds.

Hollow anatase TiO2 tetrakaidecahedral crystals with an active {001}/{110} redox interface toward high-performance photocatalytic activity.

The existence of the oxidation/reduction interface can promote the performance of a photocatalyst, due to its effect on the separation of photogenerated carriers and the surface reactivity. However, it is difficult to construct two sets of oxidation/reduction interfaces in a single crystal and compare their separation efficiency for photogenerated carriers. Introducing a high proportion of active facets into the co-exposed facets is even more challenging. Herein, a hollow anatase TiO2 tetrakaidecahedron (HTT) with two sets of oxidation/reduction interfaces ({001}/{101} and {001}/{110}) is synthesized by directional chemical etching. Theoretical and experimental results indicate that the {001}/{110} interface is a dominant oxidation/reduction interface, showing a better promotion on the separation of photogenerated carriers than the {001}/{101} interface. In the HTT, the ratio of dominant {001}/(110) is increased and the proportion of the active {110} facet is about 40% (generally about 15%). Therefore, the HTT shows excellent catalytic activity for photocatalytic reductive (hydrogen production) and oxidative (selective oxidation of sulfides) reactions. The HTT also demonstrates favorable photocatalytic activity for the cross-dehydrogenative coupling reaction, where both photogenerated electrons and photogenerated holes are involved, further verifying its high separation efficiency of photogenerated carriers and surface reactivity. This work provides an important guideline for developing advanced structures with a predetermined interface toward desired applications.

Copper-catalyzed room-temperature cross-dehydrogenative coupling of secondary amides with terminal alkynes: a chemoselective synthesis of ynamides.

A copper-catalyzed aerobic oxidative cross-dehydrogenative coupling reaction between secondary amides and terminal alkynes has been developed. With the aid of ligands and 3 Å molecular sieves, ynamides can be efficiently synthesized at room temperature and conveniently scaled up. A legitimate mechanism involving nitrogen-centred radicals and copper trivalent intermediates has been proposed.

Correction: Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives

Correction for ‘Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives’ by Jingbo Yu et al., Green Chem., 2024, https://doi.org/10.1039/d4gc00947a.

Enantioselective cross-dehydrogenative coupling enabled by organocatalysis

Organocatalytic enantioselective cross-dehydrogenative coupling reaction provides a great opportunity for the synthesis of highly enantioenriched molecules. In this review, recent progress in this field is summarized.

Ethanol-assisted mechanochemical asymmetric cross-dehydrogenative coupling reaction with recoverable chiral amine/NaCl for accessing chiral α-alkyl α-glycine derivatives

Chiral α-alkyl α-glycine acids are a prevalent structural motif found in pharmaceuticals and natural products, making them a significant dimension for exploration in modern pharmaceutical and medicinal chemistry. However, the...

Low-Valent-Tungsten-Catalyzed Aerobic Oxidative Cross-Dehydrogenative Coupling Reaction.

A straightforward and convenient protocol was established for the synthesis of thiophosphates and 3-sulfenylated indoles via low-valent-tungsten-catalyzed aerobic oxidative cross-dehydrogenative coupling reactions. These reactions occur under mild conditions and simple operations with commercially available starting materials, processing the advantage of excellent atom and step economy, broad substrate scope, and good functional groups tolerance. Moreover, this transformation could be practiced on the gram scale, which exhibits great potential in the preparation of drug-derived or bioactive molecules.

Chemical Synthesis of Substituted Naphthalene Derivatives: A Review

AbstractThis review outlines progress in the synthesis of substituted naphthalene derivatives. Naphthalene and its derivatives exhibit various biological activities such as anti-inflammatory, anticancer, antiviral, antitubercular, antimicrobial, antihypertensive, antidiabetic, etc. Several strategies have been developed for the construction of naphthalene derivatives, primarily focused on metal-catalyzed reactions (palladium, copper, zinc, rhodium, platinum, nickel, etc.,) and Lewis acid catalyzed transformations. This review discusses the preparations of naphthalene derivatives using various salts such as gallium chlorides, gold chlorides, gold bromides, various gold complexes as well as Brønsted acids like triflic acid and trifluoroacetic acid, and Lewis acids such as boron trifluoride etherate. Additionally, miscellaneous types of reactions are explored involving both metal and Lewis acids. The transformational approaches covered in this review include cycloadditions, carboannulations, benzannulations, electroannulations, rearrangements, and cross-dehydrogenative coupling reactions. Overall this review provides a comprehensive and up-to-date account of the current state of preparations of substituted naphthalenes, highlighting their medicinal and industrial importance.1 Introduction1.1 Medicinal Importance of Naphthalenes2 Synthesis of Substituted Naphthalenes2.1 Metal-Catalyzed Reactions2.1.1 Palladium-Catalyzed Reactions2.1.2 Copper-Catalyzed Reactions2.1.3 Zinc-Catalyzed Reactions2.1.4 Iron-Catalyzed Reactions2.1.5 Rhodium-Catalyzed Reactions2.1.6 Platinum-Catalyzed Reactions2.1.7 Nickel-Catalyzed Reactions2.1.8 Other Metal-Catalyzed Reactions3 Lewis Acid Catalyzed Reactions4 Miscellaneous Reactions5 Conclusion

Green approach to the synthesis of α-aminophosphonate-tetrahydroisoquinoline hybrids and their anti-cholinesterase activity

A series of 19 novel α-aminophosphonate-tetrahydroisoquinoline hybrids were synthesized through a cross dehydrogenative coupling reaction between N-aryl-tetrahydroisoquinolines and dialkylphosphites, using tert-butyl hydroperoxide as oxidazing agent. This simple procedure provided products with high atom economy and moderate to high yields. In vitro cholinesterase inhibitory activity of these compounds was evaluated. All the synthesized compounds showed good to excellent selective inhibition against butyrylcholinesterase. Compound 3bc was found to be the most active derivative with an IC50 of 9 nM. Molecular modelling studies suggested that the inhibitor is located in the peripheral anionic site (PAS) of the enzyme and interacts with some residue of the catalytic anionic site. Kinetic studies revealed that 3bc acts as a non-competitive inhibitor. Predicted ADME showed good pharmacokinetics and drug-likeness properties for most hybrids. Each newly synthesized compound was characterized by IR, 1H NMR, 13C NMR, 31P NMR spectral studies and also HRMS. The results of this study suggest that α-aminophosphonate-tetrahydroisoquinoline hybrids can be promising lead compounds in the discovery of new and improved drugs for the treatment of Alzheimer’s disease and related neurodegenerative disorders.

Highly efficient oxidative C–H/C–H cross coupling of xanthines over bimetallic Ni/Ag@titania: The key role of surface polymorphism and mechanism by surface-enhanced Raman scattering

A new effiecient protocol for the cross dehydrogenative coupling (CDC) of C8(sp2)-H/C(sp2)-H of xanthines and aromatic compounds over nanosized bimetallic Ni/Ag@titania catalyst is presented. The notable properties of Ni/Ag bimetallic nanoparticles (NPs) facilitate the 2-fold activation of classically inert C(sp2)-H bonds. Molecular level study for the catalyst efficiency was determined, by performing the model reaction between caffeine and vanillin, on different catalysts, synthesised by varying the loading of two component metals, on four polymorphic forms of titania, brookite, rutile, anatase and mesoporous. Among the 63 catalyst systems, 5:1 Ni/Ag@anatase showed excellent catalytic activity in dry DMSO with 88% product formation. Tert-butyl hydroperoxide (TBHP) and H2O2 were used as oxidant. The regioselectivity of the CDC reaction depends on the nature of peroxide used. Non-covalent surface π-stacking interaction occurring between peroxide modified titania (PMT) and aromatic ring(s) is the key for the observed regioselectivity. Catalysts were characterised by UV–Vis, FT-IR, powder XRD, XPS, SEM, TEM, etc. The catalytic system showed good operational stability, functional group tolerance, robustness and recyclability. We identified the intermediate(s) through real time monitoring of SERS and proposed the most plausible catalytic cycle as well. Further, a possible energy profile diagram involving the transition states was obtained computationally by DFTB calculations. Almost all the products were afforded in good to excellent yields. Thus, the present process constitutes one straightforward and clean approach to a class of much sought organic transformation.

Diastereoselective Cross-Dehydrogenative Coupling Reactions of Amides with Diarylmethanes Using DDQ through Oxidative C–H Benzylic Activation

AbstractThis study reports the chiral-auxiliary-controlled diastereoselective dehydrogenative coupling of diarylmethanes with amides by using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone as the oxidant. The scope of the proposed reaction is very broad, with a wide variety of substrates and nucleophiles being applicable. The chiral induction can be attributed to the coordination of the oxygen atom on the chiral auxiliary with the carbocation intermediates.

Synthesis of Organic Optoelectronic Materials Using Direct C-H Functionalization.

Small molecules and polymers with conjugated structures can be used as organic optoelectronic materials. These molecules have conventionally been synthesized by cross-coupling reactions; however, in recent years, direct functionalization of C-H bonds has been used to synthesize organic optoelectronic materials. Representative reactions include direct arylation reactions (C-H/C-X couplings, with X being halogen or pseudo-halogen) and cross-dehydrogenative coupling (C-H/C-H cross-coupling) reactions. Although these reactions are convenient for short-step synthesis, they require regioselectivity in the C-H bonds and suppression of undesired homo-coupling side reactions. This review introduces examples of the synthesis of organic optoelectronic materials using two types of direct C-H functionalization reactions. In addition, we summarize our recent activities in the development of direct C-H functionalization reactions using fluorobenzenes as substrates. This review covers the reaction mechanism and material properties of the resulting products.