Transition Metal-free Conditions Research Articles

Difluoroalkylation/1,2-aryl migration of allylic alcohols under transition metal-free conditions

A facile difluoroalkylation and 1,2-aryl migration reaction commencing from allylic alcohols and simple BrCF2COOEt was developed. This metal-free method offers chemists green and efficient access to important difluoro 1,5-dicarbonyl compounds in moderate to good yields with good functional group tolerance. Sodium hydrosulfite was used as a low-toxic, cheap, environmentally friendly, and efficient radical initiator. The feasibility of performing the transformation on a large scale potentially allows the further application of the present method in other fields.

Synthesis and Biological Studies of O3‐Aryl Galactosides as Galectin Inhibitors

Abstractβ‐Galactose derivatives have recently been reported to selectively inhibit galectin‐3, and a library of O3‐arylated galactosides with varying substitution patterns was designed to study such inhibitions further. The O3‐arylated galactosides were synthesized using diaryliodonium salts under mild and transition metal free conditions, providing the target products in moderate to good yields. An O3‐trifluoroethylated galactoside was also synthesized using iodonium salt chemistry. Azido‐substituted products were subsequently transformed into the corresponding triazoles. After deprotection, a selection of galactoside derivatives were evaluated for inhibitory potencies against galectins‐1, 3, 4 N (N‐terminal domain), 4 C (C‐terminal domain), 7, 8 N, 8 C, 9 N, and 9 C and one compound with promising affinity and selectivity for both the N‐ and C‐terminal domain of galectin‐9 was discovered.

Facile and direct halogenation of 1,2,3-triazoles promoted by a KX–oxone system under transition metal free conditions

A convenient and efficient oxidative halogenation of 4-aryl 1,2,3-triazoles is realized at ambient temperature under transition metal free conditions.

Direct C-H aminocarbonylation of N-heteroarenes with isocyanides under transition metal-free conditions.

A C-C bond forming amide synthesis through direct C-H aminocarbonylation of N-heteroarenes with isocyanides was developed. The reaction was mediated by an inorganic persulfate salt under transition metal-free conditions. Mechanistic studies suggested a radical pathway for this reaction without the participation of H2O and O2. This method also showed merits of substrate availability, easy operation and atom economy. It provided an efficient route for straightforward synthesis of N-heteroaryl amides.

Synthesis of vinyl-1,2,3-triazole derivatives under transition metal-free conditions.

Herein, we describe a novel and green route for the direct synthesis of vinyl triazole derivatives with alkynes and triazoles promoted by an inorganic base under transition metal-free conditions. The base shows great catalytic activity for the anti-Markovnikov stereoselective hydroamination of alkynes. Moreover, good yields with excellent functional group tolerance are successfully achieved for a range of substrates, including aryl and heteroaryl groups, terminal alkynes and internal alkynes, and various triazole derivatives. This work presents an advanced concept for the synthesis of alkenyl triazole with a versatile and cost-efficient approach.

Electrochemical strategies for N-cyanation of secondary amines and α C-cyanation of tertiary amines under transition metal-free conditions

Electrochemical N-cyanation of secondary amines and α C-cyanation of tertiary amines have been established under transition metal-free conditions, which provide cyanamides and nitriles with good functional group tolerance from simple systems.

Recent advances in the transition-metal-free synthesis of quinoxalines.

Quinoxalines, also known as benzo[a]pyrazines, constitute an important class of nitrogen-containing heterocyclic compounds as a result of their widespread prevalence in natural products, biologically active synthetic drug candidates, and optoelectronic materials. Owing to their importance and chemists' ever-increasing imagination of new transformations of these products, tremendous efforts have been dedicated to finding more efficient approaches toward the synthesis of quinoxaline rings. The last decades have witnessed a marvellous outburst in modifying organic synthetic methods to create them sustainable for the betterment of our environment. The exploitation of transition-metal-free catalysis in organic synthesis leads to a new frontier to access biologically active heterocycles and provides an alternative method from the perspective of green and sustainable chemistry. Despite notable developments achieved in transition-metal catalyzed synthesis, the high cost involved in the preparation of the catalyst, toxicity, and difficulty in removing it from the final products constitute disadvantageous effects on the atom economy and eco-friendly nature of the transformation. In this review article, we have summarized the recent progress achieved in the synthesis of quinoxalines under transition-metal-free conditions and cover the reports from 2015 to date. This aspect is presented alongside the mechanistic rationalization and limitations of the reaction methodologies. The scopes of future developments are also highlighted.

Transition metal free, green and facile halogenation of ketene dithioacetals using a KX–oxidant system

A facile oxidative halogenation of α-oxo ketene dithioacetals is achieved by using a potassium halide and an oxidant combination under transition metal free conditions at ambient temperature.

Highly chemoselective deoxygenation of N-heterocyclic N-oxides under transition metal-free conditions.

Because their site-selective C-H functionalizations are now considered one of the most useful tools for synthesizing various N-heterocyclic compounds, the highly chemoselective deoxygenation of densely functionalized N-heterocyclic N-oxides has received much attention from the synthetic chemistry community. Here, we provide a protocol for the highly chemoselective deoxygenation of various functionalized N-oxides under visible light-mediated photoredox conditions with Na2-eosin Y as an organophotocatalyst. Mechanistic studies imply that the excited state of the organophotocatalyst is reductively quenched by Hantzsch esters. This operationally simple technique tolerates a wide range of functional groups and allows high-yield, multigram-scale deoxygenation.

BF3·Et2O catalyzed transannulation of pyridotriazoles with isothiocyanates: synthesis of thiazolo[3,4-a]pyridin-3-imines

The synthesis of thiazolo[3,4-a]pyridin-3-imines, through denitrogenative transannulation of pyridotriazoles, under transition metal-free conditions is described.

C-H Electrophilic (phenylsulfonyl)difluoromethylation of (hetero)arenes with a newly designed reagent.

The synthesis of an original electrophilic difluoromethylating reagent was successfully achieved upon a straightforward protocol (3 steps). Like a Swiss army knife, this bench-stable reagent allowed the functionalization of various classes of compounds under mild and transition metal-free conditions. Hence, an efficient and operationally simple tool for the construction of C(sp2)-, C(sp3)- and S-CF2SO2Ph bonds was provided, expanding the chemical space of PhSO2CF2-containing molecules. Late-stage functionalization of bioactive molecules and the synthesis of PhSO2CF2- and HCF2-analogs of Lidocaine were also successfully achieved.

Aqueous Polyethylene Glycols as Green Reaction Media for the Nitration of Aromatic and Heterocyclic Compounds in Presence of Sodium Nitrite Under Transition Metal-Free and Mineral Acid-Free Conditions- A Kinetic Study

Aqueous Polyethylene Glycols as Green Reaction Media for the Nitration of Aromatic and Heterocyclic Compounds in Presence of Sodium Nitrite Under Transition Metal-Free and Mineral Acid-Free Conditions- A Kinetic Study

A metal-free radical cascade reaction of phosphine oxides with 2-aryloxy phenylacetylenes to synthesize diphosphonyl xanthene derivatives.

A radical cascade reaction of 2-aryloxy phenylacetylenes with phosphine oxides promoted by K2S2O8 was developed, which provided diphosphonyl xanthenes as products. This reaction proceeds under transition metal-free and mild conditions with simple operation and good yields. The mechanistic study indicated that phosphine oxide was induced into a phosphonyl radical, and then the following double radical addition/cyclization with 2-aryloxy phenylacetylenes generated bisphosphonyl xanthenes.

Transition-metal-free trifluoromethylthiolation–acylation of arynes by insertion into the C–S bonds

An efficient procedure to access to ortho-SCF3 substituted benzophenones from arynes and trifluoromethylthioesters has been developed under transition-metal free conditions. This difunctionalization process involves the first insertion of arynes into the C–S σ-bonds to achieve vicinal trifluoromethylthiolation-acylation of arenes in one step.

Radical coupling of arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX) reagents to access arylthiodifluoromethylated alkynes

A practical and efficient radical coupling of easily available arylthiodifluoroacetic acids and ethynylbenziodoxolone (EBX) reagents has been reported. Under transition metal-free conditions, aryl-substituted EBXs were converted to the corresponding ArSCF2-substituted alkynes in moderate to good yields, whereas TIPS-EBX underwent silver-catalyzed decarboxylative conditions to deliver the desired coupling products. The synthetic utility of this protocol was demonstrated through the transformation of resulting product to other ArSCF2-substituted alkynes and alkenes.

Transition-Metal-Free Valorization of Biomass-derived Levulinic Acid Derivatives: Synthesis of Curcumene and Xanthorrhizol.

Levulinic acid (LA) is acknowledged one of the most promising biomass-derived platform molecules and can be transformed into various value-added chemicals. Here, we report a new reaction process for the valorization of LA derivatives under transition-metal-free condition. The protocol combined with the conversion of the levulinate to tosylhydrazone and base promoted arylation, acylation, and etherification cross-coupling. Moreover, our method was applied to synthesize three biologically active molecules, rac-curcumene, rac-xanthorrhizol and rac-4,7-dimethyl-l-tetralone. This reaction discloses a new avenue for the high-value utilization of platform molecules.

Vicinal difunctionalization of carbon\u2013carbon double bond for the platform synthesis of trifluoroalkyl amines

Regioselective vicinal diamination of carbon–carbon double bonds with two different amines is a synthetic challenge under transition metal-free conditions, especially for the synthesis of trifluoromethylated amines. However, the synthesis of ethylene diamines and fluorinated amine compounds is demanded, especially in the pharmaceutical sector. Herein, we demonstrate that the controllable double nucleophilic functionalization of an activated alkene synthon, originated from a trifluoropropenyliodonium salt with two distinct nucleophiles, enables the selective synthesis of trifluoromethylated ethylene amines and diamines on broad scale with high efficiency under mild reaction conditions. Considering the chemical nature of the reactants, our synthetic approach brings forth an efficient methodology and provides versatile access to highly fluorinated amines.

Transition Metal-Free Heteroarylation of Quinoxaline: Construction of Heteroaryl-Fused Phenazines by Oxidative Coupling.

A concise method for the construction of heteroaryl-fused phenazines was developed via PIFA-BF3·Et2O-mediated oxidative coupling of di-heteroarylated quinoxalines for the first time. Synthesis of mono- and di-heteroarylation of quinoxaline was performed effectively using only LiTMP reagent under transition metal-free conditions and without the use of halogen-containing starting compounds. In addition, nonsymmetrical di-heteroarylated quinoxalines were synthesized through reheteroarylation of mono-heteroarylated quinoxalines in the same way. Oxidation of the saturated compounds formed after heteroarylation was easily accomplished with iodine. The UV-vis absorption and fluorescence features of some compounds were examined.

Enhanced nonlinear absorption and efficient optical limiting action of a few 1,3,4-oxadiazole-based donor–acceptor systems

Three new π-conjugated donor–acceptor (D–A) systems holding cyanoacrylic acid unit as common acceptor and tunable (10-octyl-7-(5-aryl-1,3,4-oxadiazol-2-yl)-10H-phenothiazines as donor components were synthesized under mild, transition metal-free conditions. Photophysical, electrochemical, optical and thermal properties of the D–A systems were examined. HOMO and LUMO of these D–A systems were mapped on the basis of computational studies. All the three compounds displayed good fluorescence quantum yields. Third order nonlinear optical properties of these compounds were also investigated by Z-scan technique using 532 nm, 7 ns laser pulses and it was found that all the compounds exhibit good reverse saturable absorption behaviour. Optical limiting studies of the compounds reveal their ability to limit intense light with promising limiting threshold values (0.69, 0.91 and 1.18 J/cm2) comparable with many of the benchmark results reported, alluding their potential to act as good optical limiters.

Selective transition metal-free aroylation of diarylmethanes with 2-acyl-imidazolium salts via acyl C–C bond cleavage

A highly chemoselective method is reported for the aroylation of simple diarylmethane derivatives via direct acyl C–C cleavage with 2-acyl-imidazolium salts under transition metal-free conditions. This represents a straightforward way to access a variety of sterically and electronically diverse 1,2,2-triarylethanones, a class of compounds with biological activities and various applications.