Metal-free Reaction Research Articles

Brønsted Acid-Catalyzed Intramolecular Allylic Substitution Reaction of Allylic Alcohols: A Facile Synthesis of 2-Vinylchromans

Brønsted acid-catalyzed intramolecular allylic substitution reaction of secondary and tertiary allylic alcohols has been developed. A variety of 2-vinylchromans were efficiently prepared in moderate to excellent yields. The given method features wide substrate scope, operational simplicity, metal-free, and mild reaction conditions. The practicability of the method was demonstrated by the gram-scale reaction and further derivations of the product. Catalytic asymmetric reaction was preliminarily studied.

Photobleachable coumarin-thioester derivatives with low cytotoxicity as visible-light photoinitiators for free radical and cationic photopolymerization

The development of photoinitiators is suffering from deep color, low solubility, and biotoxicity caused by the introduction of large-conjugated structures, also the complex synthetic procedures constrain the application of photoinitiators. To overcome this issue, nine kinds of coumarin thioester photoinitiators (CTEs) have been delicately designed and synthesized through a simple, metal-free two-step reaction. CTEs with excellent light absorption properties in the visible light range can be used not only as a type I photoinitiator but also as a type II photoinitiator, and sensitizer in the cationic photoinitiating system. CTEs effectively initiate the photopolymerization of tripropylene glycol diacrylate (TPGDA) under the irradiation of 405 nm LED, and the double bond conversions are similar to or better than those of commercial photoinitiators. Also, the cationic photopolymerization of bisphenol A diglycidyl ether (BADGE) is successfully initiated by CTEs/IOD systems. Notably, the epoxy group conversion initiated by 6O-CTE/IOD reaches 72.1 %, surpassing that of the commercial photoinitiating system. The photoinitiating mechanism of CTEs is proposed and supported by theoretical calculations. Furthermore, the bond cleavage abilities of CS bonds endow CTEs with photobleaching properties. The colorless cured film initiated by 6O-CTE was obtained under only 15 s irradiation, indicating their application prospects of CTEs in colorless photopolymerization. More importantly, the cytotoxicity of CTEs is much lower than that of commercial photoinitiator TPO. This work provides new insight into the design of biocompatible photoinitiators with a photobleaching property for LED photopolymerization.

Facile metal-free synthesis of thiazolo[5,4-d]thiazole-containing conjugated polymers for thin-film electronics

Herein, we report the facile metal-free polycondensation reaction between dicarbonyl derivative and dithioxamide for the synthesis of thiazolo[5,4-d]thiazole-based semiconductor polymer. We showed that the polymers obtained by classical Suzuki or Stille reactions and proposed metal-free polycondensation possess similar optoelectronic and physicochemical characteristics. Their application as hole-transport layers in perovskite solar cells (PSCs) showed that the polymer obtained by an alternative method provides comparable or even slightly higher performance of devices. These results illustrate availability of organic semiconductor materials via alternative green and sustainable polycondensation reaction for the state-of-the-art photovoltaic technologies.

HFIP-promoted synthesis of imidazo [1,2-a]pyridines containing CF3-substituted tertiary alcohols at room temperature

Herein, we introduce a facile and efficient method for the synthesis of imidazo [1,2-a]pyridines containing CF3-substituted tertiary alcohol moieties using trifluoropyruvates as synthons under metal-free reaction conditions. The reaction promoted by the HFIP proceeds well at room temperature, displaying good to satisfactory yields and high functional group tolerance. Some advantages of the protocol are mild reaction conditions, simple operation and ready scalability.

Acid-Mediated Domino Cyclization of ortho-Formyl Cinnamate Esters: Synthesis of Substituted Indene/Indane Esters and Indeno[a]indenones.

A Bro̷nsted acid-driven protocol to access substituted monoarylindene esters, biarylindane esters, and indeno[a]indenones from simple ortho-formylcinnamate esters and external arenes has been revealed. Remarkably, this single-pot process enabled the construction of two, three, and four new C-C bonds in building monoarylindene esters, biarylindane esters, and indeno[a]indenones, respectively, under metal-free and mild reaction parameters via triggering the inactive cinnamate ester moiety. In addition, the present strategy is investigated with widespread substrate scope.

Introducing Carborane Clusters into Crystalline Frameworks via Thiol-Yne Click Chemistry for Energetic Materials.

Crystalline frameworks represent a cutting-edge frontier in material science, and recently, there has been a surge of interest in energetic crystalline frameworks. However, the well-established porosity often leads to diminished output energy, necessitating a novel approach for performance enhancement. Thiol-yne coupling, a versatile metal-free click reaction, has been underutilized in crystalline frameworks. As a proof of concept, we herein demonstrate the potential of this approach by introducing the energy-rich, size-matched, and reductive 1,2-dicarbadodecaborane-1-thiol (CB-SH) into an acetylene-functionalized framework, Zn(AIm)2, via thiol-yne click reaction. This innovative decoration strategy resulted in a remarkable 46.6 % increase in energy density, a six-fold reduction in ignition delay time (4 ms) with red fuming nitric acid as the oxidizer, and impressive enhancement of stability. Density functional theory calculations were employed to elucidate the mechanism by which CB-SH promotes hypergolic ignition. The thiol-yne click modification strategy presented here permits engineering of crystalline frameworks for the design of advanced energetic materials.

Rapid Synthesis of 3-Methyleneisoindolin-1-ones via Metal-Free Tandem Reactions of Ester-Functionalized Aziridines.

We have disclosed a novel metal-free tandem cyclization reaction for the synthesis of 3-methyleneisoindolin-1-ones starting from ester-functionalized aziridines. This strategy can be effectively promoted by DBU and carboxylic acids. Mechanistically, it involves sequential ring opening of aziridines with carboxylic acids, lactamization, and elimination of carboxylic acids.

Potassium persulfate-glucose mediated synthesis of 3,3′-Bis(indolyl)methanes from arylacetic acid and indoles in water

An efficient and eco-friendly method has been developed for the preparation of 3,3′-bis(indolyl)methanes from indoles and aryl acetic acid is reported. The in-situ conversion of aryl acetic acid to their corresponding carbonyl compounds, and subsequent condensation with indoles was prompted by K2S2O8 in presence of glucose in water. The metal-free reaction with room temperature conditions, and wide substrate scope with good functional group tolerance are the salient features of the developed methodology.

Photosensitized 1,2-Difunctionalization of Alkenes to Access β-Amino Sulfonamides.

A metal-free photosensitized 1,2-imino-sulfamoylation of olefins by employing a tailor-made sulfamoyl carbamate as the difunctionalization reagent has been established. This protocol exhibits versatility across a broad substrate scope, including aryl and aliphatic alkenes, leading to the synthesis of diverse β-imino sulfonamides in moderate to good yields. This method is characterized by its metal-free reaction system, mild reaction conditions, excellent regioselectivity, and high atom economy, serving as a promising platform for the preparation of β-amino sulfonamide-containing molecules, particularly in the context of drug discovery.

Asymmetric Brominative Dearomatization of 2-Naphthols Using a Cinchona Alkaloid-Based Organocatalyst.

A cinchona alkaloid-based organocatalyst enables asymmetric brominative dearomatization of 2-naphthols, providing the corresponding bromonaphthalenones with high enantioselectivities. The first metal-free reaction can accommodate a variety of functional groups and give useful frameworks bearing a Br-containing tetrasubstituted stereogenic center.

Regio- and Stereoselective Synthesis of 3-Selenylazaflavanones and 3-Selenylflavanones via Electrochemically Facilitated Selenylation Cascade.

Herein, an oxidant- and metal-free electrochemical selenylation reaction of chalcones with diselenides for the synthesis of 3-selenylazaflavanones and 3-selenylflavanones at room temperature was reported. The method proceeded under mild conditions, exhibited a broad substrate scope, and provided the selenylated products in moderate to excellent yields with high regio- and stereoselectivity. The reaction could also be readily scaled up with high efficiency. Detailed mechanistic studies through control experiments disclosed that a selenium-based radical might participate in this electrochemical transformation.

Acid-Promoted Domino Access to Substituted Benzo[b]carbazoles.

Herein, a straightforward Bro̷nsted acids-promoted domino pathway to build substituted benzo[b]carbazoles has been described from easily accessible ortho-formyl (or ortho-acyl) cinnamate esters and indoles. Noticeably, the protocol was amenable to protecting group-free indoles. Notably, this methodology is based on a single-pot regioselective construction of two new C-C bonds and aromatization sequences under mild and metal-free reaction conditions. The mechanistic studies suggested the initial formation of bis-indole substituted intermediate via a dual aromatic substitution with two indole molecules at the carbonyl carbon of ortho-formyl (or ortho-acyl) cinnamate ester followed by intramolecular cyclization and aromatization with exclusion of a second indole molecule. Besides, the efficacy of this approach was also illustrated by scale-up and derivatization reactions, including the photophysical properties study.

An Efficient Access to Heteroaryl/Aryl-Annulated Pyridine Derivatives and a Study of Their Mosquito Larvicidal Activity Against Dengue Vector

AbstractWe report a convergent synthesis of heteroaryl/aryl-annulated pyridine and quinoline derivatives by a metal-free Povarov reaction. para-Toluene sulfonic acid was used as the catalyst in this reaction, which produced the products in good yields from the corresponding aromatic amines and ethyl vinyl ether. A pyridocoumarin and a pyridopyrimidine product were evaluated for their mosquito larvicidal activity against the third instar larvae of the dengue vector mosquito Aedes aegypti. Examination of morphological changes in the larvae showed damage to the target body part after treatment with both the pyridocoumarin and pyridopyrimidine products at the LC50 concentrations.

Exploring Efficient Dual-Phase Emissive Fluorophores with High Mobility by Integrating a Rigid Donor and Flexible Acceptor.

Developing luminogens with a high emission efficiency in both single-molecule and aggregate states, as well as high mobility, shows promise for advancing the iteration and update of organic optoelectronic materials. However, achieving a delicate balance between the plane configuration of luminophores and the strong exciton interactions of aggregates is a formidable task from the molecular design perspective. This dilemma was overcome by integrating a rigid donor and flexible acceptor to establish donor-acceptor (D-A) type emitters. The π-conjugate-extended donor ensures the substantial planarity of these molecules, allowing strong emission in solution with photoluminescence quantum yield values of 86% and 75%. Furthermore, the restricted molecular motion of the aggregation-induced emission moiety and the formation of J-aggregates reduce the quenching effect, leading to a high emissive efficiency of 85% and 91% in the aggregate state. The mildly distorted D-A geometry builds moderate electrostatic interaction, resulting in high mobility with μM,h of 7.12 × 10-5 and 3.27 × 10-4 cm2/V s. Additionally, an improved synthesized procedure for terminal E-configured acrylonitrile with metal-free and concise reaction conditions is presented. The successful application of the synthesized compounds in organic light-emitting diode devices demonstrates the practicability of the molecular design strategy with connecting a rigid donor and flexible acceptor.

Metal-Free N-Formylation of Amines Using Carbohydrates as C1 Synthon via C–C Bond Cleavage

AbstractFormamide group is an important part of many drug molecules, and herein a process for N-formylation of amines using carbohydrates as the C1 synthon under oxidative metal-free reaction conditions has been reported for the first time. Literature syntheses of formamides uses toxic, moisture sensitive and costly reagents under harsh reaction conditions. Our metal-free formylation is a facile, economical, and an efficient process of broad substrate scope that has led to the synthesis of thirty-three N-formylated compounds in excellent isolated yields.

Benzyl Deuteriodifluoromethyl Sulfoxide: An Easily Accessible and Stable Reagent for Direct Deuterodifluoromethylthiolation.

A new, stable and scalable reagent based on a sulfoxide skeleton for direct deuteriodifluoromethylthiolation has been developed. The reagent displays excellent reactivities toward Tf2O promoted C-H deuteriodifluoromethylthiolation of electron-rich arenes, indoles, alkenes, and intramolecular lactonization of 2-alkynylbenzoates. Moreover, high deuteration rates and good to excellent yields were achieved under metal-free reaction conditions. As a result, a wide range of deuteriodifluoromethylthilolated compounds were prepared, enabling further applications in drug discovery.

How important is the Metal-free Catalytic Knoevenagel Reaction in Medicinal Chemistry? An Updated Review.

The Knoevenagel condensation is a powerful and primary step for the development of carbon-carbon bond transformations. These condensations offer versatile products/intermediates for diverse uses in polymers, cosmetics, chemical industries, and medicinal chemistry. Various homogenous and heterogenous catalysts have been found to promote the Knoevenagel condensation reaction, both environmentally and economically. Due to their attractive use in the production of pharmaceutical drugs, they are proven to be the main force that drives the synthesis involving numerous multi-component and multistep reactions. The present study, therefore, aims to summarise reported Knoevenagel condensation reactions using metal-free catalysts resulting in pharmaceutically useful compounds with anti-cancer, anti-tumor, anti-oxidant, anti-malarial, anti-diabetic, and anti-bacterial activities. By considering factors like their structure-activity relationships (SARs), the reaction conditions, and the steps involved, as well as the advantages and limitations of the particular approach, we also provide a general framework and direction in order to achieve superior characteristics of the catalyst.

Thiol-Ene Click Reaction in Constructing Liquid Separation Membranes for Water Treatment.

In the evolving landscape of water treatment, membrane technology has ascended to an instrumental role, underscored by its unmatched efficacy and ubiquity. Diverse synthesis and modification techniques are employed to fabricate state-of-the-art liquid separation membranes. Click reactions, distinguished by their rapid kinetics, minimal byproduct generation, and simple reaction condition, emerge as a potent paradigm for devising eco-functional materials. While the metal-free thiol-ene click reaction is acknowledged as a viable approach for membrane material innovation, a systematic elucidation of its applicability in liquid separation membrane development remains conspicuously absent. This review elucidates the pre-functionalization strategies of substrate materials tailored for thiol-ene reactions, notably highlighting thiolation and introducing unsaturated moieties. The consequential implications of thiol-ene reactions on membrane properties-including trade-off effect, surface wettability, and antifouling property-are discussed. The application of thiol-ene reaction in fabricating various liquid separation membranes for different water treatment processes, including wastewater treatment, oil/water separation, and ion separation, are reviewed. Finally, the prospects of thiol-ene reaction in designing novel liquid separation membrane, including pre-functionalization, products prediction, and solute-solute separation membrane, are proposed. This review endeavors to furnish invaluable insights, paving the way for expanding the horizons of thiol-ene reaction application in liquid separation membrane fabrication.

Recent Advances in the Synthesis of Peptidomimetics via Ugi Reactions.

Peptidomimetics have been extensively explored in many area due to their ability to improve pharmacological qualities and interesting biological activities. Cycles could be incorporated in peptides to reduce their flexibility, often enhancing the affinity for a certain receptor. Many efforts have been made to synthesize various peptidomimetics. Among them, the Ugi reaction is a popular way for the synthesis of peptidomimetics because it provides peptide-like products. The Ugi reaction consists of the condensation of an aldehyde or ketone, a carboxylic acid, an amine, and an isocyanide usually giving a linear peptidomimetic. In order to obtain other linear, cyclic or polycyclic peptidomimetics, the acyclic products have to undergo additional transformations or cyclizations. This review covers the years from 2018-2023, regarding the synthesis of linear, cyclic and polycyclic peptidomimetics, employing Ugi reactions eventually followed by post-Ugi transformations. Organo-catalyzed reactions, base-promoted reactions, and metal-free reactions toward peptidomimetics are highlighted.

Unraveling the potential of backbone modifications in iron(II) NHC complexes for olefin aziridination and imination

A model catalysis reaction for a C2 + N1 type aziridination and imination of p-tolyl azide with cis-cyclooctene in toluene is reported. Applying 10 equivalents related to the azide, cis-cyclooctene is consumed within 24 h. A reaction temperature of 90 °C is chosen for solubility and activity reasons. A variety of Fe(II) N-heterocyclic carbene (NHC) complexes (1–5) are tested as additives. All show promising formation of aziridine and its imine isomer in the benchmark reaction. However, similar activities are also achieved by a metal-free control reaction together with a similar product distribution of A (aziridine), B (imine) and C (aziridine). The metal compounds cannot be considered as catalysts, but they do indeed influence the isomeric distribution of the reaction. To contextualize the conceivable product isomers, density functional theory calculations were performed (B3LYP/6–31G(d,p)) to determine the minimum ground state energies. As expected, these are nearly identical. However, the backbone modification of the open-chain NHC ligated iron(II) complex (5) allows switching of the predominant reaction, favoring imine (B) as main product.