Cross-dehydrogenative Coupling Reaction Research Articles

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.

Mechanistic study on the reductive elimination of (aryl)(fluoroaryl)palladium complexes: a key step in regiospecific dehydrogenative cross-coupling.

Cross-dehydrogenative coupling (CDC) reactions have attracted attention as short-step synthetic methods for C-C bond formation. Recently, we have developed CDC reactions between naphthalene and fluorobenzene. Rather than exhibiting general regioselectivity, this reaction proceeds selectively at the β-position of naphthalene. In this study, investigation using model complexes as reaction intermediates revealed that the origin of the unique selectivity is the exclusive occurrence of reductive elimination at the β-position. Detailed studies on the reductive elimination showed that the steric hindrance of the naphthyl group and the electron-withdrawing properties of fluorobenzene determine the position at which the reductive elimination reaction proceeds. These results show that the selectivity of the C-H functionalisation of polycyclic aromatic hydrocarbons (PAHs) is determined not by the C-H cleavage step, but by the subsequent reductive elimination step. The regioselective CDC reaction was adaptable to various PAHs but was less selective for pyrene with extended π-conjugation. In fluorobenzene substrates, the F atoms at the two ortho positions of the C-H moiety are necessary for high selectivity. The substrate ranges are in good agreement with the proposed mechanism, in which the reductive elimination step determines the regioselectivity.

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.

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.

Modular dehydrogenative cross-nucleophile coupling for direct construction of tetrasubstituted carbons

An FeCl3-catalyzed cross-dehydrogenative coupling reaction for the construction of various types of C–Y (Y = C, N, O, S) bonds with air as a green oxidant.

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

Ethanol-assisted grinding effectively facilitated aerobic asymmetric cross-dehydrogenative coupling of glycine esters/amides with ketones/aldehydes, deploying reusable chiral amine/NaCl for rapid synthesis of chiral α-alkyl α-glycine derivatives.

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.

Cu-catalyzed asymmetric regiodivergent electrosynthesis and its application in the enantioselective total synthesis of (-)-fumimycin

Quaternary amino acids are one of the essential building blocks and precursors of medicinally important compounds. Various synthetic strategies towards their synthesis have been reported. On the other hand, developing core-structure-oriented cross-dehydrogenative coupling (CDC) reactions, is a largely unsolved problem. Herein, we describe a copper-catalyzed regiodivergent electrochemical CDC reaction of Schiff bases and commercially available hydroquinones to obtain three classes of chiral quaternary amino acid derivatives for the efficient assembly of complex scaffolds with excellent stereocontrol. The electrochemical anodic oxidation process with slow releasing of quinones serves as an internal syringe pump and provides high levels of reaction efficiency and enantiomeric control. The utility of this strategy is highlighted through the synthetic utility in the asymmetric total synthesis of (-)-fumimycin.

Metal-free photoinduced C(sp3)–H/C(sp3)–H cross-coupling to access α‑tertiary amino acid derivatives

The cross-dehydrogenative coupling (CDC) reaction is the most direct and efficient method for constructing α-tertiary amino acids (ATAAs), which avoids the pre-activation of C(sp3)-H substrates. However, the use of transition metals and harsh reaction conditions are still significant challenges for these reactions that urgently require solutions. This paper presents a mild, metal-free CDC reaction for the construction of ATAAs, which is compatible with various benzyl C-H substrates, functionalized C-H substrates, and alkyl substrates, with good regioselectivity. Notably, our method exhibits excellent functional group tolerance and late-stage applicability. According to mechanistic studies, the one-step synthesized and bench-stable N-alkoxyphtalimide generates a highly electrophilic trifluoro ethoxy radical that serves as a key intermediate in the reaction process and acts as a hydrogen atom transfer reagent. Therefore, our metal-free and additive-free method offers a promising strategy for the synthesis of ATAAs under mild conditions.

Synthesis of 3-sulfenylindole derivatives from 4-hydroxy-2H-chromene-2-thione and indole using oxidative cross-dehydrogenative coupling reaction and anti-proliferative activity study of some of their sulfone derivatives

The synthesis of hitherto unreported 3-sulfenylindole derivatives is achieved from 4-hydroxy-2H-chromene-2-thione (1) and indole (2) by employing an oxidative cross-dehydrogenative coupling reaction using a combination of 10 mol% of molecular iodine and 1 equivalent of TBHP in DMSO at room temperature. Then, the 3-sulfenylindole derivatives 3a, 3b, 3d, 3f, 3 h, and 3 k were converted into their corresponding sulfone derivatives because of lead likeness properties. Subsequently, a target prediction and docking study of six sulfone derivatives (5a-f) was performed, and four sulfones, namely 5a, 5d, 5e, and 5f, were selected for further in-vitro studies. The four sulfones mentioned above exhibited prominent anti-proliferative activity on breast cancer (MCF7) cell lines. In addition, this reaction was exergonic through quantum chemical analysis of the mechanistic steps. The salient features of this reaction are mild reaction conditions, good yields, and broad substrate scope.

Triangulenium Ions: Versatile Organic Photoredox Catalysts for Green-Light-Mediated Reactions

AbstractThe development of tunable organic photoredox catalysts remains important in the field of photoredox catalysis. A highly modular and tunable family of trianguleniums (azadioxatriangulenium, diazaoxatriangulenium, and triazatriangulenium), and the related [4]helicene quinacridinium have been used as organic photoredox catalysts for photoreductions and photooxidations under visible light irradiation (λ = 518–640 nm). A highlight of this family of photoredox catalysts is their readily tunable redox properties, leading to different reactivities. We report their use as photocatalysts for the aerobic oxidative hydroxylation of arylboronic acids and the aerobic cross-dehydrogenative coupling reaction of N-phenyl-1,2,3,5-tetrahydroisoquinoline with nitromethane through reductive quenching. Furthermore, their potential as photoreduction catalysts has been demonstrated through the catalysis of an intermolecular atom-transfer radical addition via oxidative quenching. These transformations serve as benchmarks to highlight that the easily synthesized trianguleniums, congeners of the acridiniums, are versatile organic photoredox catalysts with applications in both photooxidations and photoreductions.