Cross-dehydrogenative Coupling Research Articles

Cross-Dehydrogenative Couplings to Access C4-Disubstituted Dihydroquinazolines

Cross-Dehydrogenative Couplings to Access C4-Disubstituted Dihydroquinazolines

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.

Two Different Three-Dimensional Uranium-Containing Polymolybdates Based on Zn(II) for the Heterogeneous Catalytic Construction of C-N Bond.

The introduction of transition metal (TM) ions into polyoxometalates (POMs) cannot only bring about interesting structural diversities but also enable changes in properties. However, TM-containing Silverton-type polyoxomolybdates are still lacking in terms of structural diversity and application development. Herein, two Zn(II)-containing Silverton-type {UMo12O42}-based polyoxomolybdates, H1.89Na4.11(H2O)9Zn[UMo12O42]·4.5H2O (Zn-1) and H1.8Na4.2(H2O)12Zn[UMo12O42] (Zn-2) were hydrothermally synthesized, demonstrating a practical strategy to assembly of TM-containing Silverton-type POMs. Zn-1 is proven to be an excellent and recyclable heterogeneous catalyst in cross-dehydrogenation coupling of 1,4-naphthoquinones with amines reactions, and a series of 2-amino-1,4-naphthoquinones with potential medicinal value have been constructed.

Organoselenium-Catalyzed C2,3-Diarylation of N-H Indoles.

An organoselenium-catalyzed C2,3-diarylation of unprotected N-H indoles with electron-rich aromatics has been developed. This one-pot multicomponent tandem cross-dehydrogenation coupling reaction allows for the incorporation of two different aromatic groups to indoles. More importantly, this approach offers significant advantages, including a high atom and step economy, eliminating the need for prepreparation of the reaction substrates, streamlining the synthetic process and enhancing its practicality. Overall, this organoselenium-catalyzed C2,3-diarylation reaction presents an efficient and versatile strategy for the functionalization of indole derivatives.

Oxidative C–N Bond Formation of Isochromans Using an Electronically Tuned Nitroxyl Radical as Catalyst

AbstractThe cross-dehydrogenative coupling between isochromans and nucleophiles using an electronically tuned nitroxyl radical catalyst, which effectively promotes the oxidation of benzylic ethers, has been investigated. Using sulfonamides as a nucleophile, modification of isochromans via oxidative C–N bond formation has been achieved at ambient temperature.

A dual strategy of direct C(sp3)-H sulfonamidation by cross-dehydrogenative coupling and oxidative hydroxylation-condensation

Sulfonamides are an important class of structures, although their construction is a major challenge for the synthetic community. Herein, we report a dual strategy for direct C(sp3)-H sulfonamidation, namely, a combined cross-dehydrogenative coupling and oxidative hydroxylation/condensation. This strategy, catalyzed by n-tetrabutylammonium bromide, reduced oxidant loading to 1.0 equivalent. The reaction was mediated by MgSO4•2H2O, which improved sulfonamide yields. The practicability of this method was highlighted by its broad substrate scope, mildness, site-selectivity, gram-scalability, and capability for late-stage functionalization of drug molecules.

Palladium-Catalyzed Weak Chelation-Assisted Site-Selective C-H Arylation of N-Aryl Pyridones via 2-fold C-H Activation.

Palladium-catalyzed weak chelation-assisted oxidative cross-dehydrogenative coupling of arenes has been accomplished. The use of medicinally important pyridones as the intrinsic directing group, regioselectivity, 2-fold C-H activation, and late-stage modification of bioactive compounds are the important practical features.

Paired electrocatalysis unlocks cross-dehydrogenative coupling of C(sp3)-H bonds using a pentacoordinated cobalt-salen catalyst

Cross-dehydrogenative coupling of C(sp3)-H bonds is an ideal approach for C(sp3)-C(sp3) bond construction. However, conventional approaches mainly rely on a single activation mode by either stoichiometric oxidants or electrochemical oxidation, which would lead to inferior selectivity in the reaction between similar C(sp3)-H bonds. Herein we describe our development of a paired electrocatalysis strategy to access an unconventional selectivity in the cross-dehydrogenative coupling of alcoholic α C(sp3)-H with allylic (or benzylic) C-H bonds, which combines hydrogen evolution reaction catalysis with hydride transfer catalysis. To maximize the synergistic effect of the catalyst combinations, a HER catalyst pentacoordinated Co-salen is disclosed. The catalyst displays a large redox-potential gap (1.98 V) and suitable redox potential. With the optimized catalyst combination, an electrochemical cross-dehydrogenative coupling protocol features unconventional chemoselectivity (C-C vs. C-O coupling), excellent functional group tolerance (84 examples), valuable byproduct (hydrogen), and high regio- and site-selectivity. A plausible reaction mechanism is also proposed to rationalize the experimental observations.

Electrochemical Cross-Coupling between N-(4-Hydroxyphenyl)-sulfonamides and 2-Naphthols: Synthesis of 2,2'-Bis(arenol)s.

We herein present an electrochemical method for the dehydrogenative cross-coupling of N-(4-hydroxyphenyl)-sulfonamides and 2-naphthols. This transformation provides a direct and scalable approach to a wide range of C1-symmetric 2,2'-bis(arenol)s with moderate to high yields under mild conditions. Preliminary attempts with the asymmetric variant of this reaction were also performed with ≤55% ee for the synthesis of 2,2'-bis(arenol)s. Control experiments were conducted to propose a plausible mechanism for the reaction.

Design, Development and Molecular Docking Studies of C-2 Sulfenylated Benzofurans: Potential Interleukin 1-β Antagonist

An environmental friendly methodology for C-2 sulfenylation of benzofurans through dehydrogenative cross-coupling has been developed. Sulfenylation at second position is carried out using commercially available thiols in presence of molecular iodine and DMSO. The reaction accommodates wide spectrum of electronically diverse substituents on thiophenol ring. This process offers diverse advantages, including greener reaction conditions, moderate to good percentage yields, easy workup, no additional metal catalysts requirement and gram scale synthesis. Molecular docking studies is also conducted to substantiate interleukin 1-β antagonist nature of the designed compounds.

Poly(silyl ether)s as Degradable and Sustainable Materials: Synthesis and Applications.

Polymer research is currently focused on sustainable and degradable polymers which are cheap, easy to synthesize, and environmentally friendly. Silicon-based polymers are thermally stable and can be utilized in various applications, such as columns and coatings. Poly(silyl ether)s (PSEs) are an interesting class of silicon-based polymers that are easily hydrolyzed in either acidic or basic conditions due to the presence of the silyl ether Si-O-C bond. Synthetically, these polymers can be formed in several different ways, and the most effective and environmentally friendly synthesis is dehydrogenative cross coupling, where the byproduct is H2 gas. These polymers have a lot of promise in the polymeric materials field due to their sustainability, thermal stability, hydrolytic degradability, and ease of synthesis, with nontoxic byproducts. In this review, we will summarize the synthetic approaches for the PSEs in the recent literature, followed by the properties and applications of these materials. A conclusion and perspective will be provided at the end.

Photocatalyzed Aerobic Cross-Dehydrogenative Coupling of Diarylphosphine Oxides with Alcohols and Phenols.

A photocatalytic cross-dehydrogenative coupling of diarylphosphine oxides with alcohols and phenols has been developed. Using organic dye Rose Bengal as the photocatalyst and air as the oxidant, the reaction proceeded smoothly at room temperature. Both alcohols and phenols were feasible, affording various organophosphinates in high yields. The absence of a halogenating reagent, the absence of a transition-metal catalyst, a green oxidant, and mild conditions make this strategy environmentally benign and sustainable. Mechanistic studies indicated that the reaction is enabled by the cooperation of photoredox catalysis and photosensitization.

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.

Photoredox-Catalyzed Alkene Amination: C(sp2)-H/N-H Radical-Radical Cross Dehydrogenative Coupling.

Direct alkene C-H/N-H cross dehydrogenative coupling is an infrequent, highly challenging transformation. Herein, a photoredox radical-radical cross-coupling reaction between ketene dithioacetal as a persistent alkene radical cation and azole nitrogen center radical (NCR) was developed. This direct alkene amination proceeded through a synergistic photoredox and cobalt catalysis, with only H2 evolution. The reaction showed excellent tolerance and highly regio- and stereospecific manner, expanding the scope of C(sp2)-N construction methods and radical cross-coupling modes.

Heptafluorobutyric Acid Catalyzed Cross-Dehydrogenative Coupling of 7-Aminocoumarins with 1,2,4-Triazines: A Straightforward Pathway to 3-Triazinyl-7-aminocoumarins

AbstractA protocol for C–H/C–H cross-coupling reaction between 7-aminocoumarins and 1,2,4-triazines has been developed. The reaction was carried out under heptafluorobutyric acid catalysis providing products with yield up to 91%. The applicability and scope of the proposed method was demonstrated on 25 compounds containing different substituents both in the triazine ring and at the nitrogen atom of 7-aminocoumarins. The study of the reaction mechanism by EPR and radical trapping suggests that radicals are involved in this transformation.

Dehydrogenative Cross-Coupling of P(O)H and Thiols by a Polyoxomolybdate Photocatalyst

Dehydrogenative Cross-Coupling of P(O)H and Thiols by a Polyoxomolybdate Photocatalyst

Direct esterification of allylic C(sp3)–H via iron nanoparticle–loaded kaolin-catalyzed cross dehydrogenative coupling

ABSTRACT Iron is the most abundant transition metal on Earth. In this study, we have demonstrated an iron nanoparticle–loaded kaolin-catalyzed cross dehydrogenative coupling (CDC) reaction via C(sp3)–H activation. We use CDC of carboxylic acids with cyclohexenes to discuss various reaction parameters such as the amount of catalyst, oxidant, reaction temperature, and time. Under optimized reaction condition, the corresponding allylic ester was obtained with good yield of (85%). Screening of substituted benzoic acids and cyclic and acyclic olefins shows broad catalytic activities. Notably, the catalyst can be easily separated from the reaction mixture via simple centrifugation and remains active over five cycles of reuse.

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.

Cross Dehydrogenative Coupling of SF4-Alkyne with Tetrahydroisoquinolines.

This study introduces a dual-catalytic method for cross-dehydrogenative coupling (CDC) between tetrahydroisoquinolines and Py-SF4-alkyne using visible-light photoredox catalysis. This protocol enables selective C(sp3)-H alkynylation, expanding the synthetic toolkit for SF4-based molecules. Demonstrating efficiency and substrate versatility, this approach opens new avenues in hexacoordinated tetrafluorinated sulfur chemistry and CDC strategies and holds significant promise for drug discovery and materials science.

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.