Transition Metal-free Conditions Research Articles

Electrochemically Driven Denitrative Cyanation of Nitroarenes.

A practical denitrative cyanation of feedstock nitroarenes under mild and transition metal-free reaction conditions has been developed. The key to success lies in the use of electrochemically driven, inexpensive ionic liquid N-methylimidazolium p-toluenesulfonate-promoted selective cathode reduction of nitroarenes to anilines, followed by diazoation, cathode reduction to form the aryl radical, and the essential radical cyanation process in one pot. Our protocol shows broad functional group tolerance and can be applied for the modification of bioactive targets.

Cross-Electrophile Couplings of Benzyl Sulfonium Salts with Thiosulfonates via C-S Bond Activation.

A zinc-mediated cross-electrophile coupling of benzyl sulfonium salts with thiosulfonates via C-S bond cleavage was achieved. The reductive thiolation proceeded well under transition metal-free conditions to afford the desired benzyl sulfides in good yields, exhibiting both broad substrate scope and good functionality tolerance. In addition, the reaction could be applied to the use of selenosulfonate as an effective selenylation agent and be subjected to scale-up synthesis.

Transition metal-free efficient synthesis of bis(indolyl)propynes (BIPs).

A transition metal-free approach has been devised for the synthesis of a variety of bis(indolyl)propyne (BIP) derivatives. The strategy involves an iodine-catalyzed cascade condensation of α,β-unsaturated acetylenic aldehydes with diversely substituted indoles. The strategy was applicable to gram scale synthesis and a library of 50 molecules, which were afforded in good to excellent yields (up to 96%), was developed. The salient features of the reaction involve the synthesis of indole based privileged scaffolds in a short reaction time under transition metal-free conditions, with a wide substrate scope and excellent yields under ambient conditions.

Green Synthesis of Diphenyl-Substituted Alcohols Via Radical Coupling of Aromatic Alcohols Under Transition-Metal-Free Conditions.

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 β-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.

General Defluoroalkylation of Trifluoromethylarenes with Both Electron-Donating and -Withdrawing Alkenes.

The incorporation of gem-difluoromethylene units into organic molecules remains a formidable challenge. Conventional methodologies for constructing aryldifluoromethyl derivatives relied on the use of high-functional fluorinating regents under harsh conditions. Herein, we report general and efficient photoredox catalytic systems for defluoroalkylation of readily available trifluoromethylarenes through selective C-F cleavage to deliver gem-difluoromethyl radicals which proceed through reductive addition to both electron-donating and withdrawing alkenes under transition-metal free conditions. Mechanistic studies reveal that thiol serves as both photocatalyst and HAT reagent under visible light irradiation. This synergistic photocatalysis and HAT catalysis protocol exhibits ample and salient features such as high chemo- and regioselectivity, broad substrate scope, amenable gram-scale synthesis and late-stage modification of bioactive molecules.

Synthesis of Spirocyclic-1,3-indandione Containing-Cyclopentenones and -Benzotropones.

Synthesis of functionalized 1,3-indandiones containing-cyclopentenones and -benzotropones has been achieved by the reaction of 1,5-diphenylpenta-1,4-diyn-3-ones with 1,3-indandiones, bindone respectively. The developed method involves Michael-anti-Michael addition cascade reactions under transition-metal-free conditions. This is the first report to synthesise diverse benzotropone fused with 1,3-indandiones under transition metal-free conditions from bindone.

One-Pot Tandem/Spirocyclization Reaction: Synthesis of Spiro[pyridine-thiazolidine] Ring Derivatives.

An efficient one-pot, three-component approach was devised to synthesize spiro[pyridine-thiazolidine] ring skeletons using thiazole salts, aldehydes, and enaminones. This method allows the assembly of structurally diverse spiroazepines through [3 + 1 + 2] tandem/spirocyclization reactions. This spirocyclization reaction offers several advantages, including transition metal-free conditions, high chemoselectivity, and the ability to construct structurally novel polycyclic compounds.

Light-Driven Intramolecular Cyclopropanation of Alkene-Tethered N-Tosylhydrazones: Synthesis of Fused-Cyclopropane γ-Lactones.

Fused-cyclopropane ring-containing γ-lactone compounds are versatile building blocks in many fields, including the synthesis of biologically active compounds. Here, we report the light-driven intramolecular cyclopropanation of alkene-tethered N-tosylhydrazones in the presence of Cs2CO3 and visible light. We have synthesized various electronically and sterically substituted and heterocyclic-containing fused-(spiro)cyclopropane γ-lactone compounds in good yields under transition metal-free conditions using a radical-free approach. In addition, the one-pot synthesis of fused-cyclopropane γ-lactones from α-ketoesters and their synthetic utility are also presented.

Photoinduced Asymmetric Formal Siloxycarbene Insertion into sp3 C-H Bonds Enabled by Chiral Phosphoric Acid.

We disclosed herein an enantioselective formal siloxycarbene insertion reaction enabled by chiral phosphoric acid and blue LED irradiation. This is the first time the asymmetric siloxycarbene insertion into an sp3 C-H bond under transition-metal free conditions has been realized. The reaction features good isolated yields (up to 92%), high enantioselectivity (up to 99:1 er), mild reaction conditions, and good compatibility. Moreover, this method also provides a green and efficient method to construct a chiral quaternary carbon center.

Arylation of Diethyl Acetamidomalonate with Diaryliodonium Salts En Route to α-Arylglycines.

Diethyl acetamidomalonate (DEAM) has been widely used for the synthesis of α-amino acids via C-alkylation under basic conditions followed by hydrolysis/decarboxylation. In contrast, the C-arylation of this reagent remains undeveloped. Herein, we report a novel strategy for the synthesis of racemic α-arylglycines based on the selective arylation of DEAM with diaryliodonium salts under mild, transition metal-free conditions. The reaction features good functional group tolerance and easy scalability and is applicable to the chemoselective C-H-modification of arenes including approved drugs, thus enabling a straightforward approach to complex α-arylglycines that would be challenging to make otherwise.

Photo-induced oxidative esterification via aldehyde and alkyl halides using dimethyl carbonate as green solvent

For a practical and environmentally benign strategy, we have devised an innovative approach for esterification in green dimethyl carbonate (DMC). Moreover, we employed a compatible system comprising abundantly available aldehydes and halides catalyzed using simple and commercial eosin Y under photocatalytic conditions. This strategy offers merits such as readily accessible feedstocks, remarkable functional tolerance and transition metal–free conditions, which allows to access wide scope of substrates with 34 examples and up to 93 % yield. Notably, cinnamaldehyde and 3-phenylpropiolaldehyde could accomplish this transformation while preserving CC unsaturated bonds. The density functional theory calculations (DFT) reveal that this transformation might undergo photoexcitation of the aldehyde to produce an acyl radical, which could further oxidatively esterify with halides to generate corresponding esters.

Borane-Catalyzed Coupling of Diazooxindoles and Difluoroenoxysilanes to Tetrasubstituted Monofluoroalkenes.

A highly stereoselective coupling reaction of diazooxindoles with difluoroenoxysilanes catalyzed by Lewis acidic boranes has been developed. The reaction proceeded at ambient temperature under transition metal-free conditions with wide functional group tolerance. By using this simple procedure, a series of tetrasubstituted monofluoroalkenes can be accessed in good yield with high selectivity.

Acid‐Mediated Condensation of 2‐Aminoaryl Cyclopropyl Ketones with Aldehydes for the Synthesis of 2,3‐Dihydrofuro[3,2‐c]quinolines

AbstractA method for the synthesis of 2,3‐dihydrofuro[3,2‐c]quinolines via TfOH or TMSOTf mediated condensation of 2‐aminoaryl cyclopropyl ketones with aldehydes has been developed. The reaction proceeds under transition metal or halogen free conditions, giving access to the target molecules in 27–90% isolated yields. Mechanistic study indicates that the reaction sequence involves imine formation, intramolecular Mannich condensation, Cloke‐Wilson rearrangement, and auto‐oxidation.

Insight into the MOtBu (M=Na, K)-Mediated Dehydrogenation of Dimethylamine-Borane and Transfer Hydrogenation of Nitriles to Primary Amines.

Selective synthesis of primary amines from nitriles is challenging in synthetic chemistry due to the possible en-route generation of various amines and imines. Herein, we report a practical and operationally simple MOtBu-mediated (M=Na, K) transfer hydrogenation of nitriles to the corresponding primary amines with a relatively unexplored sacrificial hydrogen source (dimethylamine borane). The strategy encompasses a broad substrate scope under transition metal-free conditions and does not require any solvent. The mechanistic investigation was performed with the aid of control experiments and spectroscopic studies. The GC analysis of the reaction mixture exhibited the evolution of the H2 gas. Additionally, detailed computational calculations were undertaken to shed light on the possible intermediates and transition states involved during the present protocol.

A four-component protocol for tandem C–S and C–C bond formation to access thienopyrrolediones under transition-metal free conditions

A mild and simple multicomponent procedure has been established for the preparation of substituted thienopyrrolediones. The advantages of this strategy include the use of a cheap, stable and smell-free in nature sulfur source, readily available raw materials, wide substrate scope, easily-handled protocol and a simple metal free procedure.

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.

Microwave assisted biomass derived carbon aerogel for highly efficient oxytetracycline hydrochloride degradation: Singlet oxygen mechanism and C vacancies accelerated electron transfer

With plant biomass α-cellulose and sodium lignosulfonate as starting materials, biochar aerogel catalysts were prepared with facile microwave assisted pyrolysis in 5 min; and the as-prepared biochars were utilized for efficient peroxymonosulfate (PMS) activation and oxytetracycline hydrochloride (OTC) degradation under transition metal free conditions. It was found that microwave treatment and sodium lignosulfonate were beneficial for thiophene S introduction, C = O groups and C vacancies enrichment, as well as specific surface area increase. The optimal α-cellulose and sodium lignosulfonate derived metal free biochar aerogel catalyst C3S2 displayed excellent ability to promote PMS activation for 99.9 % OTC degradation during 15 min with rate constant up to 0.818 min−1. Through correlation analysis, quenching tests as well as EPR characterization, C = O groups and thiophene S were considered as main sites for PMS activation to produce nonradicals singlet oxygen (1O2) in OTC degradation. Meanwhile, C vacancies enrichment further improved the pollutants degradation by means of electron transfer acceleration. This research demonstrated new insight in metal-free biochar catalyst design for highly efficient contaminants degradation with 1O2 pathway.

Transition metal-free tunable synthesis of 3-(trifluoromethylthio) and 3-trifluoromethylsulfinyl chromones via domino C[sbnd]H functionalization and chromone annulation of enaminones

The new reactions between o-hydroxyphenyl enaminones and Langlois reagent (CF3SO2Na) for the tunable synthesis of 3-(trifluoromethylthio) chromones and 3-trifluoromethylsulfinyl chromones are reported herein. Both type of reactions proceed under transition metal-free conditions. In addition, the conditions for the synthesis of 3-trifluoromethylsulfinyl chromones have also been found to be applicable for the synthesis of 3-alkyl/arylsulfinyl chromones.

Electrochemical bromination of electron-rich compounds employing LiBr as a “Br” source

A direct electrochemical-mediated CH bromination strategy of electron-rich compound is established using LiBr as a “Br” source under transition metal-free and oxidant-free catalysis condition. This method is performed in a green and sustainable system. A wide range of electron-rich compounds were found to be compatible, providing the corresponding products with moderate yields.

Deboronative Selenylation, Bromination, or Hydroxylation of Organic Boronic Acids Facilitated by Tetrabutylammonium Tribromide under Transition Metal-Free Conditions

Deboronative Selenylation, Bromination, or Hydroxylation of Organic Boronic Acids Facilitated by Tetrabutylammonium Tribromide under Transition Metal-Free Conditions