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Selective hydroboration of C-C single bonds presents a fundamental challenge in the chemical industry. Previously, only catalytic systems utilizing precious metals Ir and Rh, in conjunction with N- and P- ligands, could achieve this, ensuring bond cleavage and selectivity. In sharp contrast, we discovered an unprecedented and general transition-metal-free system for the hydroboration of C-C single bonds. This methodology is transition-metal and ligand-free and surpasses the transition-metal systems regarding chemo- and regioselectivities, substrate versatility, or yields. In addition, our system tolerates various functional groups such as Ar-X (X = halides), heterocyclic rings, ketones, esters, amides, nitro, nitriles, and C=C double bonds, which are typically susceptible to hydroboration in the presence of transition metals. As a result, a diverse range of γ-boronated amines with varied structures and functions has been readily obtained. Experimental mechanistic studies, density functional theory (DFT), and intrinsic bond orbital (IBO) calculations unveiled a hydroborane-promoted C-C bond cleavage and hydride-shift reaction pathway. The carbonyl group of the amide suppresses dehydrogenation between the free N-H and hydroborane. The lone pair on the nitrogen of the amide facilitates the cleavage of C-C bonds in cyclopropanes.

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Alcohols are common alkylating agents and starting materials alternative to harmful alkyl halides. In this study, a simple, benign and efficient pathway was developed to synthesize 1,3-diphenylpropan-1-ols via the ß-alkylation of 1-phenylethanol with benzyl alcohols. Unlike conventional borrowing hydrogen processes in which alcohols were activated by transition-metal catalyzed dehydrogenation, in this work, t-BuONa was suggested to be a dual-role reagent, namely, both base and radical initiator, for the radical coupling of aromatic alcohols. The cross-coupling reaction readily proceeded under transition metal-free conditions and an inert atmosphere, affording 1,3-diphenylpropan-1-ol with an excellent yield. A good functional group tolerance in benzyl alcohols was observed, leading to the production of various phenyl-substituted propan-1-ol derivatives in moderate-to-good yields. The mechanistic studies proposed that the reaction could involve the formation of reactive radical anions by base-mediated deprotonation and single electron transfer.

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Olefins play an essential role in synthetic chemistry, serving not only as important synthons but also as key functional groups in numerous bio-active molecules. Consequently, there has been considerable interest in the development of more powerful methods for olefins. While the Wittig reaction stands as a prominent choice for olefin synthesis due to its simplicity and the ready availability of raw materials, its limitation lies in the challenge of controlling cis-trans selectivity, hampering its broader application. In this study, a novel Boron-Wittig reaction has been developed utilizing gem-bis(boryl)alkanes and aldehydes as starting materials. This method enables creating favourable intermediates, which possess less steric hindrance, and leading to trans-olefins via intramolecular O-B bonds elimination. Notably, synthesis studies have validated its good efficacy in modifying bioactive molecules and synthesizing drug molecules with great trans-selectivity. Furthermore, the reaction mechanism was elucidated based on intermediate trapping experiments, isotope labelling studies, and kinetic analyses.

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The beginning of photochemical reactions revolutionized synthetic chemistry through sustainable practices. This review explores cutting-edge developments in leveraging light-induced processes for generating cascaded C-C and C-hetero bonds without catalysts. Significantly, catalyst-free photoinduced methodologies have garnered considerable attention, especially in the creation of varied heterocyclic frameworks for drug design and the synthesis of natural products. The article delves into underlying mechanisms, addresses limitations, and evaluates various methodologies, emphasizing the potential of photocatalyst and transition metal-free photochemical reactions to enhance sustainability. Divided into two sections, it covers recent strides in C-C and C-heteroatom and multiple C-heteroatom bond formation reactions.

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Catalytic cross-coupling between aryl halides and alkynes is considered an extremely important organic transformation (popularly known as the Sonogashira coupling) and it requires a transition metal-based catalyst. Accomplishing such transformation without any transition metal-based catalyst in the absence of any external stimuli such as heat, photoexcitation or cathodic current is highly challenging. This work reports transition-metal-free cross-coupling between aryl halides and alkynes synthesizing a rich library of internal alkynes without any external stimuli. A chemically double-reduced phenalenyl (PLY)-based molecule with the super-reducing property was employed for single electron transfer to activate aryl halides generating reactive aryl radicals, which subsequently react with alkyne. This protocol covers not only various types of aryl, heteroaryl and polyaryl halides but also applies to a large variety of aromatic alkynes at room temperature. With a versatile substrate scope successfully tested on more than 75 entries, this radical-mediated pathway has been explained by several control experiments. All the key reactive intermediates have been characterized with spectroscopic evidence. Detailed DFT calculations have been instrumental in portraying the mechanistic pathway. Furthermore, we have successfully extended this transition-metal-free catalytic strategy for the first time towards solvent-free cross-coupling between solid aryl halide and alkyne substrates.

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The molecular structure-editing through selective C-C bond cleavage allows for the precise modification of molecular structures and opens up new possibilities in chemical synthesis. By strategically cleaving C-C bonds and editing the molecular structure, more efficient and versatile pathways for the synthesis of complex compounds could be designed, which brings significant implications for drug development and materials science. o-Aminophenethyl alcohols and amines are the essential key motifs in bioactive and functional material molecules. The traditional synthesis of these compounds usually requires multiple steps which could generate inseparable isomers and induce low efficiencies. By leveraging a molecular editing strategy, we herein reported a selective ring-opening amination of isochromans and tetrahydroisoquinolines for the efficient synthesis of o-aminophenethyl alcohols and amines. This innovative chemistry allows for the precise cleavage of C-C bonds under mild transition metal-free conditions. Notably, further synthetic application demonstrated that our method could provide an efficient approach to essential components of diverse bioactive molecules.

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Conjugated polymers with strong absorption in the second near-infrared (NIR-II) window have multiple applications. However, the development of new type of NIR-II conjugated polymers via facile and green methods remains challenging. Herein, this work reports a mild and convenient transition-metal-free method to synthesize near-infrared absorbing quinoidal conjugated polymers containing para-azaquinodimethane (AQM) moieties. The AQM quinoidal conjugated polymers with unique molecular structures and tunable optoelectronic properties can be synthesized by combining the Knoevenagel polycondensation of aromatic dialdehyde monomers with commercially available 1,4-diacetyl-2,5-piperazinedione and the following alkylation reaction. The resultant polymer PQ-DPP shows remarkable NIR-II absorption with a narrow band gap of about 1.08 eV. PQ-DPP nanoparticles exhibit high photothermal conversion efficiency of up to 48% under 1064 nm laser irradiation (1 W cm-2) endowing this polymer with potential in bio-related applications.

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Transition-mental-free multi-component hydroxysulfenylation of styrenes with NH4 SCN and water to from ß-hydroxysulfides is established. The reaction mechanism proceeded via a domino reaction after a radical addition to 2-phenylimidazo[1,2-a]pyridines. This approach features a wide substrate scope and functional group compatibility, providing 34 compounds in acceptable yields.

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A series of benzofuran and benzo[b]thiophen derivatives was synthesized via a transition-metal-free one-pot process at room temperature. This one-pot protocol enables the synthesis of compounds with high reaction efficiency, mild conditions, simple methods, and a wide-ranging substrate scope. Regioselective five-membered heterocycles were constructed in good-to-excellent yields.

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An iodine-mediated one-pot synthesis of pyrrolo/indolo [1,2-a]quinoxalines and quinazolin-4-one via utilizing epoxides as alkyl precursors under metal-free conditions has been described. Both 1-(2-aminophenyl)-pyrrole and 2-aminobenzamide could be applied to this protocol. A total of 33 desired products were obtained with moderate to good yields. This methodology was suitable for wide-scale preparation and the obtained products could be further modified into promising pharmaceutically active reagents.

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A simple and efficient method for the synthesis of diarylmethyl-functionalized anilines through the hexafluoroisopropanol (HFIP)-mediated regioselective 1,6-hydroarylation reaction of para-quinone methides (p-QMs) with anilines under catalyst- and additive-free conditions is reported. Various kinds of p-QMs and amines (e. g. primary, secondary and tertiary amines) are well tolerated in this transformation without the pre-protection of amino group, and the corresponding products could be generated with good to excellent yields and satisfactory regioselectivity under the optimized reaction conditions. In addition to adaptable amine compounds, indoles and their derivatives are also compatible with this reaction system. This transformation can be easily extended to a gram scale-synthesis level to synthesize the target product. Furthermore, it is worth noting that some complex small aniline molecules with biological activity can be selectively modified using this method. The possible reaction mechanism is proposed through the step-by-step control experiments and DFT calculations, showing that the key process for achieving the regioselective 1,6-hydroarylation of p-QMs is the hydrogen bonding effect of HFIP to substrates.

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The increasing global warming concerns have propelled a surge in the demand for sustainable energy sources within the domain of synthetic organic chemistry. A particularly prominent area of research has been the development of mild synthetic strategies for generating heterocyclic compounds. Heterocyclic compounds containing boron have notably risen to prominence as pivotal reagents in a myriad of organic transformations, showcasing their wide-ranging applicability. This comprehensive review is aimed at collecting the literature pertaining to borylation reactions induced by light, specifically focusing on photocatalyst-free and transition metal-free methodologies. The central emphasis is on delving into selective mechanistic investigations. The amalgamation and analysis of these research insights elucidate the substantial potential inherent in eco-friendly approaches for synthesizing heterocyclic compounds, thus propelling the landscape of sustainable organic chemistry.

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Organic thioethers play an important role in the discovery of drugs and natural products. However, the green synthesis of organic sulfide compounds remains a challenging task. The convenient and efficient synthesis of 5-alkoxy-3-halo-4-methylthio-2(5H)-furanones from DMSO is performed via the mediation of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH), affording a facile route for the sulfur-functionalization of 3,4-dihalo-2(5H)-furanones under transition metal-free conditions. This new approach has demonstrated the functionalization of non-aromatic Csp2-X-type halides with unique structures containing C-X, C-O, C=O and C=C bonds. Compared with traditional synthesis methods using transition metal catalysts with ligands, this reaction has many advantages, such as the lower temperature, the shorter reaction time, the wide substrate range and good functional group tolerance. Notably, DMSO plays multiple roles, and is simultaneously used as an odorless methylthiolating reagent and safe solvent.

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Herein we report the synthesis of transition-metal-free potassium borophosphate glasses and their application as bactericidal and bacteriostatic material. The antimicrobial activity was achieved through a simple change in the molar ratio of boron and phosphorus atoms, making borophosphate glass soluble in water. The glasses were analyzed by X-ray powder diffraction, Raman spectroscopy, laser-induced breakdown spectroscopy, and water absorption. The addition of a boron compound is required to obtain potassium-based phosphate glasses. Moreover, the change in the phosphorus and boron molar ratio (P/B), 2, 1 or 0.5 affects the glass solubilization in water, which increases with the phosphorus content. The glass materials were submitted to tests of biological activity against the bacteria Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. These water-soluble borophosphate glasses were employed in the development of hydrogel formulations using Carbopol®. Phosphorous-rich samples at a concentration of 15 % (w/w) in hydrogel showed better antimicrobial activity against S. aureus and E. coli, when compared to other samples, including commercial alcohol hand sanitizer gel, with an average size of the inhibition halo of 24.02±1.43 and 19.24±1.63mm, respectively.

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3-Azabicyclo[3.1.0]hexanes are an important class of nitrogen-containing heterocycles that have been found to be key structural features in a wide range of biologically active natural products, drugs, and agrochemicals. As a cutting-edge area, the synthesis of these derivatives has made spectacular progress in recent decades, with various transition-metal-catalyzed and transition-metal-free catalytic systems being developed. In this review, we provide an overview of recent advances in the efficient methods for the synthesis of 3-azabicyclo[3.1.0]hexane derivatives since 2010, emphasizing the scope of substrates and synthesis' applications, as well as the mechanisms of these reactions.

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Quinazolines are a privileged class of nitrogen-containing heterocycles, widely present in a variety of natural products and synthetic chemicals with a broad spectrum of biological and medicinal activities. Owing to their pharmaceutical applications and promising biological value, a variety of synthetic methodologies have been reported for these scaffolds. From the perspective of green and sustainable chemistry, transition-metal-free synthesis provides an alternative method for accessing several biologically active heterocycles. In this review, we summarize the recent progress achieved in the transition-metal-free synthesis of quinazolines and we cover the literature from 2015 to 2022. This aspect is present alongside the advantages, limitations, mechanistic rationalization, and future perspectives associated with the synthetic methodologies.

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An environmentally friendly oxidation system has proposed for the practical and scalable production of value-added 2,5-furandicarboxylic acid from 1 kg of 5-hydroxymethylfurfural. The system is composed of a simple base, oxygen, and a green solvent, thereby providing a sustainable and economical approach to organic synthesis. To gain insight into the mechanism of this oxidation process, NMR spectroscopic analysis and kinetic study are used for the mechanistic investigation of this environmentally friendly oxidation process.

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The development of aryl alkyl sulfides as dichotomous electrophiles for site-selective silylation via C-S bond cleavage has been achieved. Iron-catalyzed selective cleavage of C(aryl)-S bonds can occur in the presence of ß-diketimine ligands, and the cleavage of C(alkyl)-S bonds can be achieved by t-BuONa without the use of transition metals, resulting in the corresponding silylated products in moderate to excellent yields. Mechanistic studies suggest that Fe-Si species may undergo metathesis reactions during the cleavage of C(aryl)-S bonds, while silyl radicals are involved during the cleavage of C(alkyl)-S bonds.

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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.

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The synthesis of imines denotes a cornerstone in organic chemistry. The use of alcohols as renewable substituents for carbonyl-functionality represents an attractive opportunity. Consequently, carbonyl moieties can be in situ generated from alcohols upon transition-metal catalysis under inert atmosphere. Alternatively, bases can be utilized under aerobic conditions. In this context, we report the synthesis of imines from benzyl alcohols and anilines, promoted by KOt Bu under aerobic conditions at room temperature, in the absence of any transition-metal catalyst. A detailed investigation of the radical mechanism of the underlying reaction is presented. This reveals a complex reaction network fully supporting the experimental findings.