Metal-free Conditions Research Articles

Carbon nanofiber/taurine-catalyzed synthesis of coumarin and 1,2,4,5-tetra-substituted imidazole derivatives under metal-free conditions

The main subject of this research is the development of a suitable, efficient, and biocompatible carbon nanofiber-based catalytic system for the synthesis of coumarin and 1,2,4,5-tetra-substituted imidazoles. Brønsted acid carbon nanofiber/taurine catalyst was made during three steps: acid treatment, acylation, and then amination. The basic principles and general advantages of the synthesis method are elaborated. The acidity of the prepared nano-catalyst was investigated using the Hammet acidity technique and UV–Vis spectroscopy, and the H0 value for 5 × 10–2 mg/mL of CNF/T in 0.3 mM 4-nitroaniline solution was determined to be 1.47. The structure of the catalyst was successfully characterized using FT-IR, TGA, FESEM, XRD, TEM, EDX, EDS-MAP, BET, and XPS techniques. Here, we report the ability of carbon nanofiber/taurine as a Brønsted acid catalyst for the synthesis of coumarins and 1,2,4,5-tetra-substituted imidazole through a metal-free, cost-effective, and biocompatible multicomponent route. Among the advantages of this protocol are reaction time, excellent efficiency, reusability, and high activity of the catalyst.

Photoredox C(2)-Arylation of Indole- and Tryptophan-Containing Biomolecules.

We introduce a novel and straightforward methodology for photoredox arylation of an indole scaffold using aryldiazonium salts under mild and metal-free conditions. Our approach enables the regioselective and chemoselective introduction of several aryl groups to the C(2) position of indoles and tryptophan, even in competition with other amino acids. This approach extends to the late-stage functionalization of peptides and lysozyme, heralding the unprecedented arylation of tryptophan residues in wild-type proteins and offering broad utility in chemical biology.

Evaluation of a panel of furochromenones as the activator and inhibitor of tyrosinase.

Tyrosinase is a copper-containing enzyme involved in the biosynthesis of melanin pigment. While the excess production of melanin causes hyperpigmentation of human skin, hypopigmentation results in medical conditions like vitiligo. Tyrosinase inhibitors could be used as efficient skin whitening agents and tyrosinase agonists could be used for enhanced melanin synthesis and skin protection from UV exposure. Among a wide range of tyrosinase-regulating compounds, natural and synthetic derivatives of furochromenones, such as 8-methoxypsoralen (8-MOP), are known to both activate and inhibit tyrosinase. We recently reported a synthetic approach to generate a variety of dihydrofuro[3,2-c]chromenones and furo[3,2-c]chromenones in a metal-free condition. In the present study, we investigated these compounds for their potential as antagonists or agonists of tyrosinase. Using fungal tyrosinase-based invitro biochemical assay, we obtained one compound (3k) which could inhibit tyrosinase activity, and the other compound (4f) that stimulated tyrosinase activity. The kinetic studies revealed that compound 3k caused 'mixed' type tyrosinase inhibition and 4f stimulated the catalytic efficiency. Studying the mechanisms of these compounds may provide a basis for the development of new effective tyrosinase inhibitors or activators.

Metal-Free ortho C-H Borylation of Thiobenzamides.

A BBr3-mediated S-directed ortho C-H borylation of thiobenzamides was developed. A variety of ortho-borylated thiobenzamides were obtained in moderate to good yields with a wide functional group tolerance under simple and metal-free conditions. This transformation provided a convenient and practical route to important functionalized thiobenzamides.

Experimental and theoretical investigation of phenylpyridine-based hypercrosslinked polymers for atmospheric CO2 adsorption and fixation under solvent-/metal-free conditions

Several phenylpyridine- and phenyl-based hypercrosslinked polymers (HCPs) were prepared via a one-step Friedel-Crafts polymerization and used as catalysts for the cycloaddition reaction between atmospheric CO2 and epoxides to produce cyclic carbonates. The structural characteristics and catalytic activity of different HCP catalysts were compared, while the recycling performance and universality to various substituted epoxides were investigated. The as-prepared catalysts exhibited regular pore structure and high specific surface area (1133 m2/g). Under the synergistic effect of tetrabutylammonium iodide (TBAI), the optimized TPA-HCP-Py efficiently converted atmospheric CO2 into cyclic carbonates with good to excellent product yields. Furthermore, the TPA-HCP-Py catalyst was easy to recover, and no significant changes were observed after reusing for five times, which demonstrated its excellent recycling performance. The interactions between different active sites and reactants in the TPA-HCP-Py/TBAI catalytic system were investigated by DFT calculation, revealing the catalytic reaction mechanism and providing valuable guidance for developing new multifunctional catalysts.

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

AbstractBrønsted 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, and mild, metal-free reaction conditions. The practicability of the method was demonstrated by a gram-scale reaction and further derivations of the product. Preliminarily studies on a catalytic asymmetric reaction were also undertaken.

Double Regioselective Thermal Azide-Alkyne Cycloaddition of 1,3-Diynes.

A double regioselective cycloaddition reaction of 1,3-diynes with azide is reported to synthesize fully substituted 5-alkynyl-1,2,3-triazoles without any catalyst, metal, or other factor. Computational studies revealed that the 5-alkynyl-1,2,3-triazole derivative is both kinetically and thermodynamically favorable irrespective of the nature of the substituents at the alkyne termini in 1,3-diynes. The simplicity of the reaction, extremely high regioselectivity under metal-free conditions, wide substrate scope, and good to excellent yields might inspire further studies of the cycloaddition of 1,3-diynes in addition to click chemistry.

Synthesis of ω-Chloroalkyl Aryl Ketones via C-C Bond Cleavage of tert-Cycloalkanols with Tetramethylammonium Hypochlorite.

An oxidative C-C bond cleavage of tert-cycloalkanols with tetramethylammonium hypochlorite (TMAOCl) has been developed. TMAOCl is easy to prepare from tetramethylammonium hydroxide, and the combination of TMAOCl and AcOH effectively promoted the C-C bond cleavage in a two-phase system without additional phase-transfer reagents. Unstrained tert-cycloalkanols were transformed into ω-chloroalkyl aryl ketones in moderate to excellent yields under metal-free and mild reaction conditions.

Electrochemical oxidative radical cascade cyclization of dienes and diselenides towards the synthesis of seleno-benzazepines.

Selenium-containing compounds are important scaffolds owing to their value in medicinal chemistry, biochemistry and material chemistry. Herein, we report an electrochemical approach to access seleno-benzazepines through an oxidative radical cascade cyclization of dienes with diselenides under metal-free, external oxidant-free and base-free conditions. In a simple undivided cell, various dienes and diselenides were suitable for this transformation, generating the desired products in up to 84% yields. This method provides a green and convenient route for the synthesis of valuable selenium-containing seven-membered N-heterocycles from simple starting materials.

Salophen-type Organocatalysts for the Cycloaddition of CO2 and Epoxides under Solvent, Halide, and Metal-Free Conditions.

8-Formyl-7-hydroxycoumarin (A) and their derived salophen-type organocatalysts L1, L2, and L3 were used for the synthesis of cyclic carbonates from carbon dioxide (CO2) and epoxides under solvent-, halide-, and metal-free conditions. According to previous optimization tests, L1 and L2 had the best catalytic activity presenting 89 and 92% conversion toward the synthesis of 3-chloropropylene carbonate (2c) using 8 bar CO2, 100 °C at 9 h. Therefore, they were used as organocatalysts to complete the catalytic screening with 11 terminal epoxides (1a-k) exhibiting the highest TOF values of 20 and 22 h-1 using 1c and 1b, respectively. Similarly, they were tested with an internal epoxide, such as cyclohexene oxide (1l) exhibiting 72% conversion, becoming the first salophen organocatalyst to obtain cis-cyclohexane carbonate (2l) in the absence of a cocatalyst. In addition, a reaction mechanism was proposed for the formation of cyclic carbonates based on experimental data and computational techniques; these contributed in establishing a probable role of CO2 pressure along the catalysis and the hydrogen bonds that favor the stabilization of the different intermediates of the reaction.

TFA-Promoted Cascade Sulfonylation/Rearrangement/Cyclization of 1,5-Diynols and Sodium Sulfinates to Construct Sulfonylated Benzo[b]fluorenes.

A novel conversion of 1,5-diynols into sulfonylated benzo[b]fluorenes is reported by a TFA-promoted cascade cyclization with sodium sulfinates under mild conditions. This strategy provides an efficient and practical approach for accessing various sulfonated benzo[b]fluorenes in moderate to excellent yields under metal-free conditions. On the basis of the control experimental results and density functional theory calculations, a possible cascade transformation mechanism consisting of the dehydration of propargylic alcohols, sulfonylation, allenylation, and Schmittel-type cyclization is proposed. It is worth noting that TFA played an important role in this cascade cyclization, which promoted C-SO2R bond cleavage in a propargylic sulfone intermediate to form allenyl sulfones, followed by Schmittel-type cyclization to give the target product.

DMAP-mediated oxidative esterification of α-bromoaryl ketones with alcohols: A facile route to synthesize α-ketoesters

The use of α-bromoacetophenone and alcohols as starting materials provides easy access to a variety of α-ketoesters, which are important building blocks in organic synthesis. Additionally, metal-free conditions make this methodology more cost-effective compared to traditional metal-catalyzed methods. The wide substrate scope of this methodology means that a variety of different a-ketoesters can be obtained in excellent yields, making it a versatile and practical method for organic synthesis.

Pushing Boundaries: What's Next in Metal-Free C-H Functionalization for Sulfenylation?

The synthesis of thioether derivatives has been explored widely due to the potential application of these derivatives in medicinal chemistry, pharmaceutical industry and material chemistry. Within this context, there has been an increasing demand for the environmentally benign construction of C-S bonds via C-H functionalization under metal-free conditions. In the present article, we highlight recent developments in metal-free sulfenylation that have occurred in the past three years. The synthesis of organosulfur compounds via a metal-free approach using a variety of sulfur sources, including thiophenols, disulfides, sulfonyl hydrazides, sulfonyl chlorides, elemental sulfur and sulfinates, is discussed. Non-conventional strategies, which refer to the development of thioether derivatives under visible light and electrochemically mediated conditions, are also discussed. The key advantages of the reviewed methodologies include broad substrate scope and high reaction yields under environmentally benign conditions. This comprehensive review will provide chemists with a synthetic tool that will facilitate further development in this field.

One-Pot Three-Component Reaction for the Synthesis of 3,4-Dihydroquinazolines and Quinazolin-4(3H)-ones.

A highly efficient and straightforward one-pot synthesis of diversely substituted 3,4-dihydroquinazolines and quinazolin-4(3H)-ones has been achieved through a domino three-component assembly reaction of arenediazonium salts, nitriles, and bifunctional aniline derivatives. This new protocol involves three C-N bond formations through the initial formation of N-arylnitrilium intermediates from arenediazonium salts and nitriles, followed by the sequential nucleophilic addition and cyclization reactions with bifunctional anilines, leading to such N-heterocyclic compounds of biological and pharmacological importance. This method offers a simple, expedient, and robust approach with the use of amenable and easily accessible reactants/reagents under metal-free mild conditions, good functional group tolerance, and high efficiency. The synthetic applications were also demonstrated by derivatization of the products obtained from these processes and syntheses of a diverse range of valuable polycyclic N-heterocycles.

A Three-Component Synthesis of Spiropyrrolines.

A rapid synthesis of medicinally important spiropyrrolines has been achieved by the reaction of 1,3-indanediones, benzaldehyde, and (1-azidovinyl)benzene under catalyst- and reagent-free conditions. This is the first report to synthesize diverse spiropyrroline compounds from readily available feedstock materials under metal-free conditions.

Expedient Synthesis of gem-CF2-2H-Thiophenes from Enaminothiones

AbstractAn expedient and easy-to-handle synthetic platform has been established for the constructing of 2H-thiophenes carrying fluorine atoms through [4+1] cyclization of enaminothiones with fluorinated carbene precursors. This simple reaction system is well compatible with a wide range of substrates under completely metal-free conditions. The resulting 2H-thiophenes can undergo further late-stage modifications to yield a wide range of fluorine-substituted heterocycles.

Arenethiolate-Catalyzed 1,5-HAT of Aryl Halides: Synthesis of γ-Spirolactams.

γ-Spirolactam is a privileged building block that is found in a wide range of natural products and bioactive compounds. Herein, we report an arenethiolate-catalyzed 1,5-HAT of aryl halides to obtain γ-spirolactams through a SET reduction/intramolecular 1,5-HAT/cyclization/HAT process. This protocol features metal-free conditions and a broad substrate scope, furnishing the γ-spirolactams in moderate to excellent yields. Notably, aryl bromides, aryl chlorides and even aryl fluorides are well tolerated in this transformation. A mechanism involving arenethiolate as a SET catalyst is proposed based on DFT calculation.

Recyclable ionic liquid-mediated synthesis of quinazolin-4(3H)-ones under metal-free and solvent-free conditions

A metal-free and solvent-free method for the synthesis of quinazolin-4(3H)-ones is proposed by condensation cyclization of 2-aminobenzamides and aldehydes using 1-butyl-3-methylimida-zolium tetrafluoride ([Bmim]BF4) as ionic liquid catalyst. In this reaction, [Bmim]BF4 acts as both a catalyst and a solvent without need for additional catalysts and solvents. This method exhibits favorable functional group tolerance in substrates and affords a series of desired products in moderate to excellent yields. In addition, it is noteworthy that the reaction yield is still as high as 87% after [Bmim]BF4 is recycled at least four times.

Selective Ring-Opening Amination of Isochromans and Tetrahydroisoquinolines.

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.

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.