Transition Metal-free Conditions Research Articles

Efficient one-pot synthesis of dan-substituted organo- and silyl-boron compounds.

Direct, transition metal-free B(dan)-installation into organic frameworks has been developed. Heteroaryl-H bonds were transformable into the respective heteroaryl-B(dan) bonds through deprotonation. The resulting heteroaryl-B(dan) compounds, which are otherwise difficult to access, can undergo the direct Suzuki-Miyaura coupling. The method was demonstrated to apply to a silicon nucleophile, giving Lewis acidity-diminished stable silyl-B(dan) and -B(aam) in one pot.

Expedient (3+3)-annulation of in situ generated azaoxyallyl cations with diaziridines.

Efficient annulation of in situ formed azaoxyallyl cations using a base has been accomplished with diaziridines to provide 1,2,4-triazines at room temperature. The substrate scope, scale up, functional group tolerance and transition-metal free reaction conditions are the important practical features.

Electrochemical selenium-catalyzed para-amination of N-aryloxyamides: access to polysubstituted aminophenols.

Aminophenols are a class of important compounds with various pharmacological activities such as anticancer, anti-inflammatory, antimalarial, and antibacterial activities. Herein, we introduce a mild and efficient electrochemical selenium-catalyzed strategy to synthesize polysubstituted aminophenols. High atom efficiency and transition metal-free and oxidant-free conditions are the striking features of this protocol. By merging electrochemical and organoselenium-catalyzed processes, the intramolecular rearrangement of N-aryloxyamides produces para-amination products at room temperature in a simple undivided cell.

Synthesis of flavones via the Stork-Danheiser reaction.

A new method to access flavones in a convergent fashion has been developed, based on the Stork-Danheiser reaction. By this method, 4-methoxy coumarins are allowed to react with organolithium at low temperatures (-78 °C to -40 °C) and then acidic workup gives the desired flavones in 18-86% yields. This method features transition metal-free conditions, readily available starting materials, and simple operation. It is particularly efficient when rapid generation of B ring flavone derivatives is desired.

Synthesis of functionalized tetrahydrodibenzo[b,g][1,8]naphthyridin-1(2H)-ones through base-promoted annulation of quinoline-derived dipolarophiles and cyclic enaminones.

An eco-friendly and metal-free method for the synthesis of tetrahydrodibenzo[b,g][1,8]naphthyridin-1(2H)-ones was established. Quinoline-derived dipolarophiles and cyclic enaminones as starting materials undergo a 1,4-Michael addition/SNAr tandem annulation reaction affording the target products. This approach features transition metal-free conditions, good functional group tolerance and operational simplicity.

Photochemical oxidation of alcohols to ketones or aldehydes using DMSO as an oxidant without activated agent

We report visible light mediated oxidation of alcohols to ketones or aldehydes catalyzed by anthraquinone under irradiation at 430–440 nm at room temperature, using DMSO as an oxidant without activated agent. Key parameters, including irradiating wave-length, reaction medium and photocatalyst, are investigated. According this procedure, a variety of alcohols are oxidized to the corresponding ketones or aldehydes in satisfactory yields. This protocol features transition metal free and mild reaction conditions.

Light-driven Radical-polar Crossover Catalysis Enabling Decarboxylative Fluorination of Redox Active Esters

This manuscript represents an organophotoredox-catalyzed decarboxylative fluorination of alkyl redox active esters with triethylamine trihydrofluoride. The reaction proceeds through a radical-polar crossover mechanism to generate a carbocation equivalent under non-acidic and transition metal free conditions. This protocol allows delivery of various tertiary alkyl and benzyl fluorides in an environmentally benign manner.

Light-driven radical-polar crossover catalysis for cross-coupling with organosilanes

In this communication, we report a visible light-mediated organophotoredox catalysis enabling the cross-coupling between aliphatic carboxylic acid-derived redox active esters and organosilanes. In this protocol, a carbocation equivalent generated from the redox active ester by radical-polar crossover process could react with an organosilane reagent. This protocol allows to forge C(sp3)–C(sp3), C(sp3)–C(sp2) and C(sp3)–C(sp) bonds under transition-metal free and mild reaction conditions. The privileged feature of radical-mediated process was demonstrated as radical-relay type dicarbofunctionalization of styrene derivatives using organosilanes and aliphatic redox active esters.

Trifluoromethylsulfonyl pyridinium salt for trifluoromethythiolation of indoles

The trifluoromethylsulfonyl pyridinium salt (TFSP) was used as a CF3S source for the trifluoromethylthiolation of indole derivatives. It is proposed that TFSP is reduced in the presence of diethyl phosphite and NaCl. The protocol features a facile access to the CF3S source, and high efficiency and transition-metal free conditions for trifluoromethylthiolation.

Aryldiazonium salts can serve as nitrogen-based Lewis acid catalysts and their applications in the formation of photoactive charge transfer complexes

We report the Lewis acid catalysis of aryldiazonium salts, and their Lewis acidity applications in photogeneration of aryl radicals under additive-, photocatalyst- and transition metal-free conditions. In this visible light-mediated transformation, the Lewis acidic character of aryldiazonium salts enables access to the photoactive charge transfer complex with dichalcogenides. The usefulness and versatility of this new protocol are demonstrated through the chalcogenation of a variety of aryldiazonium salts.

Metal-Free Aminocarbonylation of p-Quinone Methides with Isocyanides: Synthesis of Sterically Hindered α-Arylated Acetamides.

The synthesis of sterically hindered α-arylated acetamides generally requires a multistep reaction sequence and is also difficult to access due to steric constraints. This protocol allows the synthesis of sterically hindered α-arylated acetamides in moderate to high yields via 1,6-addition of isocyanides to p-quinone methides in the presence of BF3 .OEt2 . The present transformation features transition metal-free conditions, avoiding the use of toxic carbon monoxide, broad substrate scope, mild reaction conditions, and operational simplicity.

Benzylic C[sbnd]H heteroarylation of 4-Methylphenols with 2H-Indazoles

A simple benzylic CH heteroarylation of 4-methylphenols was developed via the K2S2O8-promoted C(sp3)−H and C(sp2)−H bonds cross-dehydrogenative coupling with 2H-indazoles under transition-metal free conditions. A variety of 4-((2H-indazol-3-yl)methyl)phenols were obtained in moderate to good yields. Mechanistic investigation indicated that the reactions probably proceed through a radical pathway.

Explaining Regiodivergent Vinylations with Vinylbenziodoxolones.

Vinylbenziodoxolones have recently been identified as efficient hypervalent iodine(III) reagents for electrophilic vinylations under transition metal‐free conditions. Their unique reactivity allows synthesis of either internal or terminal alkenes, depending on the nucleophile class. This paper constitutes the first mechanistic investigation of VBX vinylations, and makes use of NMR studies, deuterium labelling and computations to rationalize the observed regio‐ and stereochemical outcome. Internal alkene formation in S‐vinylation was found to proceed through the ligand coupling mechanism typical of diaryliodonium salts, whereas terminal alkene formation in P‐vinylations took place via a phosphinous acid‐coordinated VBX complex, which underwent concerted deprotonation and Michael‐type addition. Subsequent base‐assisted protonation and E2 elimination delivered the terminal alkene. The findings can be used to predict the regioselectivity in vinylations of other nucleophile classes.

A Four-Component Reaction for the Synthesis of Thienopyrrolediones under Transition Metal Free Conditions

A three-starting-material four-component reaction strategy is described to construct thienopyrrolediones (TPDs) from the simplest raw materials, elemental sulfur, aldehydes, and β-ketoamides, under transition metal free conditions. Compared with traditional multistep reaction sequences, this process is simple, efficient, environmentally friendly, and atom-economic and has laid the foundation for further development of an easily synthesized TPD unit.

Base-promoted cascade radical difluoroalkylation/cyclization of acrylamides for the synthesis of CF2-containing oxindoles and isoquinoline-1,3-diones

A base-promoted cascade radical difluoroalkylation/cyclization of acrylamides with ICF2COOEt to synthesize CF2-containing oxindoles and isoquinoline-1,3-diones in moderate to excellent yields was developed under transition metal-free and catalyst-free conditions. This reaction tolerated a variety of functional groups and provided an alternative and mild method for the preparation of difluoroester-substituted five- and six-membered nitrogen-containing heterocyclic products.

Recent Advancements in Development of Radical Silylation Reactions

Abstract: Transition metal-free radical hydrosilylation of alkynes and factionalized alkenes to vinylsilanes, organosilanes from alkenes, radical silylative cyclizations for sila heterocycles, aromatic dehydrogenative radical silylation, sila-amino acids, silyl hydroperoxides by using transition metal-free reaction conditions such as peroxides, photocatalyst, hydrogen atom transfer catalyst, radical initiators have become one of the most important and useful methodologies for the construction of C-Si bonds for their synthetic applications. In order to demonstrate the growth in this area, this review highlights the last twenty years of success in the fields of silylation of aromatics, silylative cyclizations of sila heterocycles, synthesis of vinylsilanes by hydrosilylation of alkynes, and functionalized alkenes, organosilanes from alkenes and dehydrogenative approaches for vinylsilanes involving radical mechanisms. We believe that summarizing these methods would be very useful for the chemists who are interested in the synthesis of organosilicon compounds for drug discovery or the development of silicon-based materials for industrial applications.

Nucleophilic Dearomatization Strategy to Synthesize Disubstituted 3-Isoquinolinones under Transition Metal-Free Conditions.

Herein, a one-pot protocol for constructing the disubstituted isoquinolinone derivatives via the three-component reactions of 3-haloisoquinolines, alkyl halides, and indoles under transition-metal-free conditions is described. The reaction realized the trifunctionalization of isoquinoline via a dearomatization strategy, which displayed high chemical selectivity, excellent functional group tolerance, and a wide range of substrates, and is environmentally friendly. The three-component coupling involves the construction of new C-N, C═O, and C-C bonds in one step.

A Method to Access Highly Functionalized Dibenzobicyclo[3.2.1]octadienones: Application to the Construction of the 6/6/5/6/6 Carbon Skeleton of Rubialatin A.

The dibenzobicyclo[3.2.1]octadienone scaffold, which has been found in naphthocyclinones, engelharquinones, rubialatin A, etc., has been synthesized under mild transition metal-free conditions by aryne insertion reaction with 2-keto-1,3-indandiones. The application of this methodology has been demonstrated for the synthesis of the 6/6/5/6/6 scaffold of rubialatin A. 1H NMR experimental studies confirm that the reaction proceeds through the formation of benzocyclobutane followed by a 7-member carbocycle ring.

Aryldiazonium Salts and DABSO: A Versatile Combination for Three-Component Sulfonylative Cross-Coupling Reactions.

A combination of aryldiazonium salts and DABSO provides a unique opportunity for sulfonylative multicomponent cross-coupling reactions. Here, a copper-catalyzed three-component cross-coupling of aryldiazonium salts, DABSO with arylboronic acids to obtain medicinally relevant unsymmetrical diarylsulfones is disclosed. Interestingly, a catalyst-free approach for the synthesis of arylvinylsulfones from the corresponding vinyl boronic acids or vinyl halides is explored under basic condition. Tethered aryldiazonium salts provided the corresponding annulated alkylvinylsulfones via alkene difunctionalization under the same transition metal-free condition. Mechanistically, these multicomponent reactions proceed through a single electron pathway by the formation of arylsulfonyl radical as a key intermediate.

Synthesis of benzisothiazoles by a three-component reaction using elemental sulfur and ammonium as heteroatom components under transition metal-free conditions

A strategy for the synthesis of benzisothiazoles by a three-component reaction was developed using elemental sulfur and ammonium as heteroatom components under transition metal-free conditions. The reaction is preferably based on pyridine or quinoline ring substrate, and good to excellent yields can be obtained. Notably, this reaction has been applied to the gram-scale synthesis of bioactive molecules.