Cross-dehydrogenative Coupling Research Articles

Dual Ce@g-C3N4-Photoredox/Chlorine Catalysis: Cross-Dehydrogenative Coupling of N-Heteroarenes and Alkanes/Ethers with H2 Evolution.

With Ce@g-C3N4 as a heterogeneous semiconductor photocatalyst, nBu4NCl as both a redox catalyst and a hydrogen atom transfer catalyst, the first example of semiheterogeneous photocatalytic cross-dehydrogenative coupling of N-heteroarenes and alkanes/ethers with H2 evolution was developed. Both a diverse array of high-value alkylated N-heteroarenes and clean H2 can be efficiently coproduced under sacrificial reagent- and chemical oxidant/reductant-free conditions. Combining both the reversible Ce4+/Ce3+ redox pair and the reversible Cl̅/Cl ̇ redox pair can considerably improve the photocatalytic efficiency.

Iron-Catalyzed Cross-Dehydrogenative Coupling of para-Quinone Methides with Formamides: In Situ Activation of C(sp2)-H Bonds.

A novel and straightforward method for the iron-catalyzed regioselective cross-dehydrogenative coupling of para-quinone methides (p-QMs) with formamides has been developed, facilitated by the in situ activation of the C(sp2)-H bonds of the formyl and alkenyl substituents via a radical strategy. This method does not require the preactivation of the substrates, and it can accommodate a wide range of p-QMs and formamides under the optimized reaction conditions, resulting in the formation of the expected C-7 acetamides-functionalized para-quinone methides with moderate to good yields. The control experiments revealed that the reaction follows the fundamental equation of second-order kinetics. Additionally, an exploration of the Hammett effect was undertaken to elucidate the impact of the substituents for the reaction. In combination with the DFT calculation, a plausible reaction mechanism was proposed through meticulously controlled experiments.

Copper-Catalyzed Aerobic Cross-Dehydrogenation Coupling of Indoles for Synthesis of 2,3'-Bisindoles.

2,3'-Bisindoles with C-C linkages have attracted interest in medicinal chemistry, yet their synthesis is intricate with many steps. Notably, direct C-H/C-H cross-coupling of non-directed heteroaromatics remains challenging, often requiring precious metals and oxidants to enhance coupling efficiency. Herein, we present a copper-catalyzed C-H/C-H cross-coupling method for N-substituted indoles without directing groups, facilitated by molecular oxygen under gentle conditions. It showed reasonable functional group compatibility and provided one-pot access to a variety of 2,3'-bisindoles derivatives in moderate to good yields.

Covalent Organic Framework (COF) Based Catalysts for Photocatalytic Cross‐Dehydrogenative Coupling Reactions

Covalent organic frameworks (COFs) are robust, porous materials with well‐defined structures that have been employed for gas separation, photoluminescence, sensing, energy storage, and heterogeneous catalysis. This review summarizes recent progress in the use of COFs as a versatile platform for heterogeneous photocatalytic cross‐dehydrogenative coupling (CDC) reactions, which are an efficient and clean methodology for the formation of C‐C or C‐P bonds. We review the synthesis of these photocatalytic COFs, correlating their catalytic performance with their structures and photoelectric properties.

Heterogeneous visible-light photoredox catalysis with NiCl2@g-C3N4 for induced C(sp2)-H/N[sbnd]H cross-dehydrogenative coupling

A novel photoactive NiCl2@g-C3N4 catalyst system, which effectively drives C(sp2)-H/NH bond formation between quinolin-2(1H)-ones, primary and secondary aliphatic amines under blue light irradiation. The NiCl2@g-C3N4 composite with a NiCl2 loading of 0.7wt% had the highest photoactivity, and the calculated band gap energy value is 2.56 eV The nickel ion could act as an electron acceptor enhancing carrier separation and transfer efficiency, greatly enhanced the photoreaction efficiency of g-C3N4. Preliminary mechanistic studies indicate upon visible light irradiation, the photo-generated electrons and holes act as oxidants, thereby generating amine radicals in the absence of external chemical oxidants. This provides a straightforward and efficient approach for directly 3-aminating quinoxalines-2(1H)-ones. Moreover, the heterogeneous catalyst can be recycled at least six times without significant activity loss.

Open frame-like Co-Fe oxides superstructures for highly efficient cross-dehydrogenative coupling reaction of N-phenyltetrahydroisoquinoline under mild conditions

An open frame-like Co-Fe oxides catalyst has been successfully prepared using a time-controlled strategy. Benefiting from the unique open frame-like superstructure and synergistic bimetallic composition, this novel catalyst exhibits excellent catalytic activity (up to 91 % isolated yield) and substrate suitability for Cross-Dehydrogenative Coupling reaction (CDC) of N-phenyltetrahydroisoquinolines and nitroalkanes using oxygen as the oxidant under mild reaction conditions. And after several runs, the reused catalyst still maintains great stability. This may attributed to the interaction between Fe and Co. In addition, through the radical trapping experiments, we found that O2·− species play an important role in the cross-dehydrogenative coupling reaction.

Synthesis of α-Carbonyl-α'-sulfenyl Sulfoxonium Ylides in Water at Room Temperature.

An efficient synthesis of α-carbonyl-α'-sulfenyl sulfoxonium ylides through a KIO3-promoted cross-dehydrogenative coupling reaction of aryl thiols and α-carbonyl sulfoxonium ylides in an aqueous medium at room temperature has been described. The α-carbonyl sulfoxonium ylides and aryl thiols adorned with various functional groups were well-tolerated and afforded moderate to high yields of α-carbonyl-α'-sulfenyl sulfoxonium ylide derivatives. Finally, by converting synthesized ylide 3a into other valuable compounds, we demonstrated the practicality of this synthetic method.

RhRu Bimetallic Cluster Catalysts for Dehydrogenative Cross-Coupling of Arenes and Carboxylic Acids

RhRu Bimetallic Cluster Catalysts for Dehydrogenative Cross-Coupling of Arenes and Carboxylic Acids

Photoelectrocatalytic [4+2] Annulation for S-Heterocycle Assembly Enabled by Proton-Coupled Electron Transfer (PCET).

Cross-dehydrogenative couplings (CDC) present an efficient strategy for the assembly of biorelevant heterocycles, but are thus far largely limited to toxic transition metals and rather harsh reaction conditions. In sharp contrast, we, herein report on a mild photoelectrocatalyzed CDC-[4+2] annulation enabling the synthesis of functionalized isothiochromenes enabled by a proton-coupled electron transfer (PCET) strategy. The transformative photoelectrocatalysis obviated toxic transition-metal, high reaction temperatures, and stoichiometric chemical redox reagents. This approach was characterized by exceedingly mild conditions, ample substrate scope, and a commercially available catalyst. Gram-scale reactions and a telescoped synthesis route reflected the unique potential in the green synthesis of important S-heterocycles.

NHC-Catalyzed Umpolung Driven Intramolecular Cyclizations for the Generation of 3,4-Cycloheptanone Annulated Tetracyclic Indole Derivatives.

In this Letter, we disclose the development and exploitation of umpolung reactivity of N-heterocyclic carbene (NHC) organocatalysts in generating tetracyclic indole derivatives with the introduction of a cycloheptane ring forming event. The NHC-catalyzed intramolecular vinylogous Stetter, Stetter, benzoin, and formal cross-dehydrogenative coupling transformations have been executed, enabling the construction of 3,4-cycloheptannulated indole derivatives in good to excellent yields. The developed protocols utilize an inexpensive catalyst and feature operational simplicity, atom economy, gram-scale syntheses, and postsynthetic availability.

Photoinduced HCl-Mediated Cross-Dehydrogenative Coupling of Quinolines with Alcohols and Ethers.

Via light irradiation, cross-dehydrogenative coupling of quinolines with alcohols and ethers was achieved under mild conditions. A stoichiometric amount of HCl and room temperature were necessary to promote the reaction. A green Minisci-type cross-dehydrogenative coupling reaction was performed without an oxidant or a transition-metal catalyst.

RuII-Catalyzed C-H Activated Diverse Cyclization with Transformation of Substrate-DG to Functional Groups: Synthesis of Functionalized Indoles and Indenones.

We present an elegant and efficient method for Ru(II)-catalyzed C-H activation, followed by a diverse range of intermolecular cross-dehydrogenative coupling reactions. This process is facilitated by an intrinsic directing group (DG) and includes the in situ transformation of the DG into common and useful functional groups. Notably, this method avoids the installation and deinstallation of the directing group. Our approach enables the selective functionalization of benzimidate, coupled with the cyclization of o-alkynyl-aniline, resulting in the high-yield synthesis of diverse compounds such as indoles, and indenones. The sequential formation of C-N, C-C, and C-O bonds, followed by hydrolysis, underscores the versatile in situ transformation of the directing group. This work not only broadens the synthetic toolbox for constructing complex heterocyclic structures but also highlights the potential for sustainable and selective synthesis of valuable compounds.

A Telescoped Photo-/Organo-Catalyzed Cross Dehydrogenative Coupling (CDC) between Glycine Derivatives and Ketones to Afford Nonproteinogenic Amino Acids (NPAAs) Enabled by Heterogeneous Continuous Flow Catalysis

A Telescoped Photo-/Organo-Catalyzed Cross Dehydrogenative Coupling (CDC) between Glycine Derivatives and Ketones to Afford Nonproteinogenic Amino Acids (NPAAs) Enabled by Heterogeneous Continuous Flow Catalysis

Anchoring Catalytic Metal Nodes within a Single-Crystalline Pyrazolate Metal-Organic Framework for Efficient Heterogeneous Catalysis.

The synthesis of single-crystalline and robust pyrazolate metal-organic frameworks (Pz-MOFs) capable of facilitating challenging organic transformations is fundamentally significant in catalysis. Here we demonstrate a metal-node-based catalytic site anchoring strategy by synthesizing a single-crystalline and robust Pz-MOF (PCN-1004). PCN-1004 features one-dimensional (1D) copper-Pz chains interconnected by well-organized ligands, forming a porous three-dimensional (3D) network with two types of 1D open channels. Notably, PCN-1004 displays exceptional stability in aqueous solutions across a broad pH range (1 to 14), attributed to the robust copper-Pz coordination bonds. Significantly, PCN-1004 functions as an outstanding catalyst in cross dehydrogenative coupling reactions for constructing C-O/C-S bonds, even in the absence of directing groups, achieving yields of up to ~99%, with long cycle lives and high substrate compatibility. PCN-1004 outperforms all previously reported porphyrin-based homogeneous and heterogeneous catalysts. Control experiments and computations elucidate the pivotal catalytic role of the copper-Pz chains and reveal a free radical pathway for the reaction. This work not only demonstrates the successful implementation of a metal-node-based catalytic site anchoring strategy for the efficient catalysis of challenging organic transformations but also highlights the synergistic effect of a robust framework, 1D open channels, and active sites in enhancing catalytic efficiency within MOFs.

Anchoring Catalytic Metal Nodes within a Single‐Crystalline Pyrazolate Metal‐Organic Framework for Efficient Heterogeneous Catalysis

The synthesis of single‐crystalline and robust pyrazolate metal‐organic frameworks (Pz‐MOFs) capable of facilitating challenging organic transformations is fundamentally significant in catalysis. Here we demonstrate a metal‐node‐based catalytic site anchoring strategy by synthesizing a single‐crystalline and robust Pz‐MOF (PCN‐1004). PCN‐1004 features one‐dimensional (1D) copper‐Pz chains interconnected by well‐organized ligands, forming a porous three‐dimensional (3D) network with two types of 1D open channels. Notably, PCN‐1004 displays exceptional stability in aqueous solutions across a broad pH range (1 to 14), attributed to the robust copper‐Pz coordination bonds. Significantly, PCN‐1004 functions as an outstanding catalyst in cross dehydrogenative coupling reactions for constructing C‐O/C‐S bonds, even in the absence of directing groups, achieving yields of up to ~99%, with long cycle lives and high substrate compatibility. PCN‐1004 outperforms all previously reported porphyrin‐based homogeneous and heterogeneous catalysts. Control experiments and computations elucidate the pivotal catalytic role of the copper‐Pz chains and reveal a free radical pathway for the reaction. This work not only demonstrates the successful implementation of a metal‐node‐based catalytic site anchoring strategy for the efficient catalysis of challenging organic transformations but also highlights the synergistic effect of a robust framework, 1D open channels, and active sites in enhancing catalytic efficiency within MOFs.

Hollow CoFe Oxide Prisms for Cross-Dehydrogenative Coupling Reactions of 1,2,3,4-Tetrahydroisoquinolines under Mild Conditions.

A three-dimensional hollow CoFe oxide prism catalyst was successfully prepared via a self-template strategy. This bimetallic oxide catalyst demonstrated excellent catalytic activity in cross-dehydrogenative coupling reactions of 1,2,3,4-tetrahydroisoquinolines under mild conditions compared to its monometallic oxide counterparts. A preliminary mechanistic investigation showed the involvement of reactive oxygen species, produced from molecular O2 by the active bimetallic oxide catalyst in the catalytic cycle.

An environment-friendly phosphotungstic acid catalyzed cross-dehydrogenative coupling reaction to synthesize 9-substituted-9H-xanthenes with photoelectrochemical performance

An environment-friendly phosphotungstic acid catalyzed cross-dehydrogenative coupling reaction for the synthesis of 9-substituted-9H-xanthenes under oxygen and solvent-free conditions have been developed. The economic and practical reaction exhibited good substrate applicability tolerance, various 9-substituted-9H-xanthenes were synthesized in moderate to excellent yields by tuning the ratio of xanthenes and ketones (22 examples, up to 99% yield). By testing the photoelectrochemical performance, some of the xanthene derivatives (10c, 12c, 13c and 2d) showed stable photocurrent value, especially 2d had better cathode photocurrent value and application potential.

Investigation of heavy atom effects and pH sensitivity on the photocatalytic cross-dehydrogenative coupling reaction of halogenated fluorescein dyes

Fluorescein halogenated dyes are excellent photocatalysts for cross-dehydrogenation-coupled (CDC) reaction. In this paper, seven different halo-fluorescein dyes were selected to investigate the influence of heavy halogen atoms and proton concentrations on halo-fluoresceins for photocatalytic CDC reaction. The results showed that the heavy atoms directly affected intersystem crossing (ISC), which could act as a gatekeeper in the photoredox cycle and also affect photoinduced electron transfer (PET) process. Thus, the photocatalytic performance clearly increased in the following order: fluorescein FL (0.11 mol L−1•h−1)＜dibromo-fluorescein FL-2Br (0.19 mol L−1•h−1)＜diiodo-fluorescein FL-2I (0.29 mol L−1•h−1)＜tetrabromo-fluorescein FL-4Br (0.375 mol L−1•h−1)＜tetrabromo-tetrachloro-fluorescein FL-4Br–4Cl (0.53 mol L−1•h−1)＜tetraiodo-fluorescein FL-4I (0.58 mol L−1•h−1)＜ tetraiodo-tetrachloro-fluorescein FL-4I–4Cl (0.74 mol L−1•h−1). Furthermore, the visible light absorption of halogenated fluorescein dyes varied significantly with pH, thereby affecting their photocatalytic activity of CDC reaction. The dianionic FL-4I–4Cl could fully absorb light energy and exhibit excellent photocatalytic performance under mildly alkaline conditions (pH = 8), achieving a CDC reaction conversion rate of 99.92 %, which was 2.6 times higher than that of the lactone form of FL-4I–4Cl under acidic conditions (pH = 2).

Electrosynthesis of Highly Functionalized Quinolines through Radical Annulation-Polar Addition Cascade.

Synthesis of diversely functionalized quinoline-2-carboxylates is illustrated through electrochemical cross-dehydrogenative coupling between N-aryl glycinates and methylenecyclopropanes. An extensive range of distinct functionalities is well-compatible under these transition-metal- and oxidant-free mild electrochemical conditions, contributing to a broad substrate scope and practical applicability. Cyclic voltammetric measurements and control experiments suggested a formal [4 + 2] cycloaddition involving radical intermediates, followed by a cyclopropyl ring opening through nucleophilic polar addition, consecutively fabricating C-C and C-N bonds.

TBHP Promotes Cross-Dehydrogenative Coupling of SF4 Alkynes with Tetrahydroisoquinolines under Copper Catalysis.

We present a viable approach for the cross-dehydrogenative coupling of Het-SF4-alkynes with tetrahydroisoquinolines under oxidative conditions, using TBHP and copper catalysts. These newly developed conditions boast enhanced yields and a more extensive range of substrates, demonstrating tolerance to various functional groups and addressing the limitations of earlier reports. Consequently, this method should increase opportunities for the exploration of SF4-containing compounds and their potential applications in drug discovery, materials science, and as alternatives to PFAS.