Electrosynthetic C−O Bond Activation in Alcohols and Alcohol Derivatives

Alcohols and their derivatives are ubiquitous and versatile motifs in organic synthesis. Deoxygenative transformations of these compounds are often challenging due to the thermodynamic penalty associated with the cleavage of the C−O bond. However, electrochemically driven redox events have been shown to facilitate the C−O bond cleavage in alcohols and their derivatives either through direct electron transfer or through the use of electron transfer mediators and electroactive catalysts. Herein, a comprehensive overview of preparative electrochemically mediated protocols for C−O bond activation and functionalization is detailed, including direct and indirect electrosynthetic methods, as well as photoelectrochemical strategies.     

Direct Light-Enabled Access to α-Boryl Radicals: Application in the Stereodivergent Synthesis of Allyl Boronic Esters**

Operationally simple strategies to assemble boron containing organic frameworks are highly enabling in organic synthesis. While conventional retrosynthetic logic has engendered many platforms focusing on the direct formation of C−B bonds, α-boryl radicals have recently reemerged as versatile open-shell alternatives to access organoborons via adjacent C−C bond formation. Direct light-enabled α-activation is currently contingent on photo- or transition metal-catalysis activation to efficiently generate radical species. Here, we disclose a facile activation of α-halo boronic esters using only visible light and a simple Lewis base to enable homolytic scission. Intermolecular addition to styrenes facilitates the rapid construction of highly versatile E-allylic boronic esters. The simplicity of activation permits the strategic merger of this construct with selective energy transfer catalysis to enable the complimentary stereodivergent synthesis of Z-allylic boronic esters.     

Frontispiece: Photocatalytic Terminal C−C Coupling Reaction Inside Water Soluble Nanocages

Developing methods that activate C−H bonds directly with high selectivity for C−C bond formation in complex organic synthesis has been a major chemistry challenge. Recently it has been shown that photoactivation of weakly polarized C−H bonds can be carried out inside a cationic water-soluble nanocage with visible light-mediated host-guest charge transfer (CT) chemistry. Using this novel photoredox activation paradigm, here we demonstrate C−C bond formation to photo-generate 1,3-diynes at room temperature in water from terminal aromatic alkynes for the first time. The formation of cavity-confined alkyne radical cation and the proton-removed neutral radical species highlight the unique C−C coupling step driven by supramolecular preorganization.     

Recent Advances in Carbon-Nitrogen/Carbon-Oxygen Bond Formation Under Transition-Metal-Free Conditions

Carbon-heteroatom bond formation under transition-metal free conditions provides a powerful synthetic alternative for the efficient synthesis of valuable molecules. In particular, C−N and C−O bonds are two important types of carbon-heteroatom bonds. Thus, continuous efforts have been deployed to develop novel C−N/C−O bond formation methodologies involving various catalysts or promoters under TM-free conditions, which enables the synthesis of various functional molecules comprising C−N/C−O bonds in a facile and sustainable manner. Considering the significance of C−N/C−O bond construction in organic synthesis and materials science, this review aims to comprehensively present selected examples on the construction of C−N (including amination and amidation) and C−O (including etherification and hydroxylation) bonds without transition metals. Besides, the involved promoters/catalysts, substrate scope, potential application and possible reaction mechanisms are also systematically discussed.     

Palladium-Catalyzed C−H Bond Arylation of Cyclometalated Difluorinated 2-Arylisoquinolinyl Iridium(III) Complexes

The utility of C−H bond functionalization of metalated ligands for the elaboration of aryl-functionalized difluorinated-1-arylisoquinolinyl Ir(III) complexes has been explored. Bis[(3,5-difluorophenyl)isoquinolinyl](2,2,6,6-tetramethyl-3,5-heptanedionato) iridium(III) undergoes Pd-catalyzed C−H bond arylation with aryl bromides. The reaction regioselectively occurred at the C−H bond flanked by the two fluorine atoms of the difluoroaryl unit, and on both cyclometalated ligands. This post-functionalization gives a straightforward access to modified complexes in only one manipulation and allows to introduce thermally sensitive functional groups, such as trifluoromethyl, nitrile, benzoyl, or ester. The X-ray crystallography, photophysical, and electrochemical properties of the diarylated complexes were investigated. Whatever the nature of the incorporated substituted aryl groups is, all obtained complexes emit red phosphorescence (622–632 nm) with similar lifetimes (1.9–2 μs).     

Increasing Chemical Diversity of B2N2 Anthracene Derivatives by Introducing Continuous Multiple Boron-Nitrogen Units

Increasing the chemical diversity of organic semiconductors is essential to develop efficient electronic devices. In particular, the replacement of carbon-carbon (C−C) bonds with isoelectronic boron-nitrogen (B−N) bonds allows precise modulation of the electronic properties of semiconductors without significant structural changes. Although some researchers have reported the preparation of B₂N₂ anthracene derivatives with two B−N bonds, no compounds with continuous multiple BN units have been prepared yet. Herein, we report the synthesis and characterization of a B₂N₂ anthracene derivative with a BNBN unit formed by converting the BOBN unit at the zigzag edge. Compared to the all-carbon analogue 2-phenylanthracene, BNBN anthracene exhibits significant variations in the C−C bond length and a larger highest occupied molecular orbital–lowest unoccupied molecular orbital energy gap. The experimentally determined bond lengths and electronic properties of BNBN anthracene are confirmed through theoretical calculations. The BOBN anthracene organic light-emitting diode, used as a blue host, exhibits a low driving voltage. The findings of this study may facilitate the development of larger acenes with multiple BN units and potential applications in organic electronics.     

Porous Organic Phenanthroline-Based Polymer as an Efficient Transition-Metal-Free Heterogeneous Catalyst for Direct Aromatic C−H Activation

Direct C−H bond transformation has been regarded as one of the most important areas in organic synthesis in both academia and industry. However, the heterogeneous transition-metal-free catalysis of direct C−H bond transformation has remained a contemporary challenge. To tackle this challenge, we designed and constructed a porous phenanthroline-based polymer (namely POP-Phen) via free radical polymerization of vinyl-functionalized phenanthroline monomers. POP-Phen shows excellent catalytic performances in transition-metal-free catalyzed C−H arylation, even better than those of the corresponding homogeneous catalyst, which is mainly attributed to the high density of catalytically active sites in the heterogeneous catalyst. Kinetic isotope experiments and spectral characterizations demonstrate the electron-transfer between the heterogeneous catalyst and the base (t-BuOK), a key step for C−H activation. We believe that this porous organic phenanthroline polymer could open a new door for the design of novel heterogeneous transition-metal-free catalysts for direct C−H activation.     

Rapid Charge Transfer Enabled by Noncovalent Interaction through Guest Insertion in Supercapacitors based on Covalent Organic Frameworks

Covalent organic frameworks (COFs) have been proposed for electrochemical energy storage, although the poor conductivity resulted from covalent bonds limits their practical performance. Here, we propose to introduce noncovalent bonds in COFs through a molecular insertion strategy for improving the conductivity of the COFs as supercapacitor. The synthesized COFs (MI−COFs) establish equilibriums between covalent bonds and noncovalent bonds, which construct a continuous charge transfer channel to enhance the conductivity. The rapid charge transfer rate enables the COFs to activate the redox sites, bringing about excellent electrochemical energy storage behavior. The results show that the MI−COFs exhibit much better performance in specific capacitance and capacity retention rate than those of most COFs-based supercapacitors. Moreover, through simply altering inserted guests, the mode and strength of noncovalent bond can be adjusted to obtain different energy storage characteristics. The introduction of noncovalent bonds is an effective and flexible way to enhance and regulate the properties of COFs, providing a valuable direction for the development of novel COFs-based energy storage materials.     

Synthesis of Conjugated Polymers via Transition Metal Catalysed C−H Bond Activation

Transition metal catalysed C−H bond activation chemistry has emerged as an exciting and promising approach in organic synthesis. This allows us to synthesize a wider range of functional molecules and conjugated polymers in a more convenient and more atom economical way. The formation of C−C bonds in the construction of pi-conjugated systems, particularly for conjugated polymers, has benefited much from the advances in C−H bond activation chemistry. Compared to conventional transition-metal catalysed cross-coupling polymerization such as Suzuki and Stille cross-coupling, pre-functionalization of aromatic monomers, such as halogenation, borylation and stannylation, is no longer required for direct arylation polymerization (DArP), which involve C−H/C−X cross-coupling, and oxidative direct arylation polymerization (Ox-DArP), which involves C−H/C−H cross-coupling protocols driven by the activation of monomers’ C(sp²)−H bonds. Furthermore, poly(annulation) via C−H bond activation chemistry leads to the formation of unique pi-conjugated moieties as part of the polymeric backbone. This review thus summarises advances to date in the synthesis of conjugated polymers utilizing transition metal catalysed C−H bond activation chemistry. A variety of conjugated polymers via DArP including poly(thiophene), thieno[3,4-c]pyrrole-4,6-dione)-containing, fluorenyl-containing, benzothiadiazole-containing and diketopyrrolopyrrole-containing copolymers, were summarized. Conjugated polymers obtained through Ox-DArP were outlined and compared. Furthermore, poly(annulation) using transition metal catalysed C−H bond activation chemistry was also reviewed. In the last part of this review, difficulties and perspective to make use of transition metal catalysed C−H activation polymerization to prepare conjugated polymers were discussed and commented.     

Advances in Electrochemical Decarboxylative Transformation Reactions

Owing to their non-toxic, stable, inexpensive properties, carboxylic acids are considered as environmentally benign alternatives as coupling partners in various organic transformations. Electrochemical mediated decarboxylation of carboxylic acid has emerged as a new and efficient methodology for the construction of carbon-carbon or carbon-heteroatom bonds. Compared with transition-metal catalysis and photoredox catalysis, electro-organic decarboxylative transformations are considered as a green and sustainable protocol due to the absence of chemical oxidants and strong bases. Further, it exhibits good tolerance with various functional groups. In this Minireview, we summarize the recent advances and discoveries on the electrochemical decarboxylative transformations on C−C and C−heteroatoms bond formations.     

Transient and Recyclable Halogenation Coupling (TRHC) for Isoflavonoid Synthesis with Site-Selective Arylation

A transient and recyclable C−H iodination has been designed for the synthesis of isoflavonoids through the domino reactions of o-hydroxyphenyl enaminones and aryl boronic acids in the presence of catalytic KI and Pd catalyst. Instead of the conventional cross-coupling strategy employing pre-halogenated substrates, this method transforms raw C−H bond by means of a transient C−H halogenation to smoothly relay the subsequent C-arylation. Consequently, such a method avoids the pre-functionalization for C−halogen bond installation as well as the generation of stoichiometric halogen-containing waste following the cross-coupled product, disclosing an intriguing new coupling protocol to forge the C−C bond in the virgin area between classical C−X (X=halogen) bond cross coupling and the C−H activation.     

Photocatalytic Reductive Radical-Polar Crossover for a Base-Free Corey–Seebach Reaction

A metal-free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey–Seebach reaction. The presented method operates under mild redox-neutral and base-free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo- and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C−H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α-hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical–radical homocoupling and deuterium labeling studies as well as by calculated redox-potentials and bond strengths.     

Inside Back Cover: Effective Activation of Strong C−Cl Bonds for Highly Selective Photosynthesis of Bibenzyl via Homo-Coupling (Angew. Chem. Int. Ed. 43/2023)

Carbon-carbon (C−C) coupling of organic halides has been successfully achieved in homogeneous catalysis, while the limitation, e.g., the dependence on rare noble metals, complexity of the metal-ligand catalylst and the poor catalyst stability and recyclability, needs to be tackled for a green process. The past few years have witnessed heterogeneous photocatalysis as a green and novel method for organic synthesis processes. However, the study on C−C coupling of chloride substrates is rare due to the extremely high bond energy of C−Cl bond (327 kJ mol⁻¹). Here, we report a robust heterogeneous photocatalyst (Cu/ZnO) to drive the homo-coupling of benzyl chloride with high efficiency, which achieves an unprecedented high selectivity of bibenzyl (93 %) and yield rate of 92 % at room temperature. Moreover, this photocatalytic process has been validated for C−C coupling of 10 benzylic chlorides all with high yields. In addition, the excellent stability has been observed for 8 cycles of reactions. With detailed characterization and DFT calculation, the high selectivity is attributed to the enhanced adsorption of reactants, stabilization of intermediates (benzyl radicals) for the selective coupling by the Cu loading and the moderate oxidation ability of the ZnO support, besides the promoted charge separation and transfer by Cu species.     

Metal–Organic Framework (MOF)-Based Materials as Heterogeneous Catalysts for C−H Bond Activation

Converting light hydrocarbons such as methane, ethane, propane, and cyclohexane into value-added chemicals and fuel products by means of direct C−H functionalization is an attractive method in the petrochemical industry. As they emerge as a relatively new class of porous solid materials, metal–organic frameworks (MOFs) are appealing as single-site heterogeneous catalysts or catalytic supports for C−H bond activation. In contrast to the traditional microporous and mesoporous materials, MOFs feature high porosity, functional tunability, and molecular-level characterization for the study of structure–property relationships. These virtues make MOFs ideal platforms to develop catalysts for C−H activation with high catalytic activity, selectivity, and recyclability under relatively mild reaction conditions. This review highlights the research aimed at the implementation of MOFs as single-site heterogeneous catalysts for C−H bond activation. It provides insight into the rational design and synthesis of three types of stable MOF catalysts for C−H bond activation, that is, i) metal nodes as catalytic sites, ii) the incorporation of catalytic sites into organic struts, and iii) the incorporation of catalytically active guest species into pores of MOFs. Here, the rational design and synthesis of MOF catalysts that lead to the distinct catalytic property for C−H bond activation are discussed along with the post-synthesis of MOFs, intriguing functions with MOF catalysts, and microenvironments that lead to the distinct catalytic properties of MOF catalysts.     

Cooperative Light-Activated Iodine and Photoredox Catalysis for the Amination of C −H Bonds

An unprecedented method that makes use of the cooperative interplay between molecular iodine and photoredox catalysis has been developed for dual light-activated intramolecular benzylic C−H amination. Iodine serves as the catalyst for the formation of a new C−N bond by activating a remote C −H bond (1,5-HAT process) under visible-light irradiation while the organic photoredox catalyst TPT effects the reoxidation of the molecular iodine catalyst. To explain the compatibility of the two involved photochemical steps, the key N−I bond activation was elucidated by computational methods. The new cooperative catalysis has important implications for the combination of non-metallic main-group catalysis with photocatalysis.     

Hydrogen Bond Networks Stabilized High-Capacity Organic Cathode for Lithium-Ion Batteries

High-capacity small organic materials are plagued by their high solubility. Here we proposed constructing hydrogen bond networks (HBN) via intermolecular hydrogen bonds to suppress the solubility of active material. The illustrated 2, 7- diamino-4, 5, 9, 10-tetraone (PTO-NH₂) molecule with intermolecular hydrogen (H) bond between O in −C=O and H in −NH₂, which make PTO-NH₂ presents transverse two-dimensional extension and longitudinal π–π stacking structure. In situ Fourier transform infrared spectroscopy (FTIR) has tracked the reversible evolution of H-bonds, further confirming the existence of HBN structure can stabilize the intermediate 2-electron reaction state. Therefore, PTO-NH₂ with HBN structure has higher active site utilization (95 %), better cycle stability and rate performance. This study uncovers the H-bond effect and evolution during the electrochemical process and provides a strategy for materials design.     

Diaryl Dihydrophenazine-Based Porous Organic Polymers Enhance Synergistic Catalysis in Visible-Light-Driven Organic Transformations

Porous organic polymers (POPs) have emerged as a novel class of porous materials that are synthesized by the polymerization of various organic monomers with different geometries and topologies. The molecular tunability of organic building blocks allows the incorporation of functional units for photocatalytic organic transformations. Here, we report the synthesis of two POP-based photocatalysts via homopolymerization of vinyl-functionalized diaryl dihydrophenazine (DADHP) monomer ( POP1 ) and copolymerization of vinyl-functionalized DADHP and 2,2′-bipyridine monomers ( POP2 ). The fluorescence lifetimes of DADHP units in the POPs significantly increased, resulting in enhanced photocatalytic performances over homogeneous controls. POP1 is highly effective in catalysing visible-light-driven C−N bond forming cross-coupling reactions. Upon coordination with Ni²⁺ ions, POP2-Ni shows strong synergy between photocatalytic and Ni catalytic cycles due to the confinement effect within the POP framework, leading to high efficiency in energy, electron, and organic radical transfer. POP2-Ni displays excellent activity in catalysing C−P bond forming reactions between diarylphosphine oxides and aryl iodides. They increased the photocatalytic activities by more than 30-fold in C−N and C−P cross-coupling reactions. These POP catalysts were readily recovered via centrifugal separation and reused in six catalytic cycles without loss of activities. Thus, photosensitizer-based POPs provide a promising platform for heterogeneous photocatalytic organic transformations.     

Cross- and Multi-Coupling Reactions Using Monofluoroalkanes

Carbon-fluorine bonds are stable and have demonstrated sluggishness against various chemical manipulations. However, selective transformations of C−F bonds can be achieved by developing appropriate conditions as useful synthetic methods in organic chemistry. This review focuses on C−C bond formation at monofluorinated sp³-hybridized carbons via C−F bond cleavage, including cross-coupling and multi-component coupling reactions. The C−F bond cleavage mechanisms on the sp³-hybridized carbon centers can be primarily categorized into three types: Lewis acids promoted F atom elimination to generate carbocation intermediates; nucleophilic substitution with metal or carbon nucleophiles supported by the activation of C−F bonds by coordination of Lewis acids; and the cleavage of C−F bonds via a single electron transfer. The characteristic features of alkyl fluorides, in comparison with other (pseudo)halides as promising electrophilic coupling counterparts, are also discussed.