Transition Metal-free Approach Research Articles

Transition Metal-free Approach for the Synthesis of 2-substituted Quinazolin-4(3H)-one via Anhydrous Magnesium Perchlorate

Background:A convenient and efficient methodology for the synthesis of quinazolin- 4(3H)-ones from simple and readily available 2-amino benzamides and aromatic aldehydes in ethanol using Magnesium perchlorate are being reported in the present study. Good to excellent isolated yields (68-95%) of the corresponding 2-substituted quinazolinones were obtained under mild reaction conditions with excellent functional group tolerance. The affordability of the catalyst, the wide availability of the starting materials, transition metal free synthesis and the simplicity of the procedure renders the present methodology useful in organic synthesis.Objective:A maneuver methodology developed for the synthesis of quinazolin-4(3H)-ones via using Magnesium perchlorate from 2-amino benzamides and aromatic aldehydes in ethanol.Methods:10% mol anhydrous Magnesium perchlorate in presence of ethanol give to simply rapid formation of Quinazolin-4(3H)-ones from 1 mole of 2-amino benzamides and 1 mole of aromatic aldehydes.Results:Screening results of Anti-leishmanial showed that out of the synthesized series of 12 compounds, compounds 3c, 3d, 3g, 3h and 3i showed significant antileishmanial activities (L. donavani) with IC50 values 8.39, 9.37, 9.43, 7.1 and 8.7 μM.Conclusion:In summary, we have developed convenient synthesis of quinazolin-4(3H)-one, from simple and easily available precursor employing anhydrous Mg(ClO4)2 under green conditions.

Temperature-Controlled Chalcogenation and Chalcogenocyanation of Imidazopyridines in Water under Transition Metal-Free Conditions.

A sustainable and transition metal-free approach for C3 chalcogenation and chalcogenocyanation of imidazopyridines with KXCN (X = S or Se) has been developed under mild conditions. Importantly, this reaction was performed in the presence of catalytic iodine in aqueous medium, which afforded either chalcogenated or chalcogenocyanated imidazopyridines under temperature control. The current protocol featured a broad substrate scope, transition metal-free and organic solvent-free conditions, operational convenience, and gram-scale production.

A transition metal-free approach towards the regioselective synthesis of β-carboline tethered pyrroles and 2,3-dihydro-1H-pyrroles

A transition metal-free one-pot sequential approach has been unfolded for the synthesis of β-carboline tethered pyrroles and 2,3-dihydro-1H-pyrroles by using highly diverse 1-formyl-9H-β-carbolines as a template.

Isatin as a 2-aminobenzaldehyde surrogate: transition metal-free efficient synthesis of 2-(2'-aminophenyl)benzothiazole derivatives.

A transition metal-free, convenient, and efficient practical approach has been devised for the synthesis of substituted 2-(2'-aminophenyl)benzothiazoles via a sulfur insertion strategy using isatin derivatives as 2-aminobenzaldehyde surrogates. KI assisted one-pot operation of isatin, arylamines and elemental sulfur resulted in the formation of a C-N and two C-S bonds and cascade cleavage of the isatin ring resulting in the formation of 2-(2'-aminophenyl)benzothiazoles. The significant features of this strategy are the readily available and inexpensive starting materials, broad substrate scope, sustainable reaction conditions and high yield of products. Importantly, the strategy was found to be appropriate for gram scale synthesis (>10 g) of 2-(2'-aminophenyl)benzothiazole derivatives. Moreover, the excellent photophysical properties (ΦF up to 60%) of 2-(2'-aminophenyl)benzothiazole derivatives provide huge scope in materials science.

A transition metal-free approach to a regioselective total synthesis of the natural product derivative 6-methylellipticine, a potent anticancer agent

A transition metal-free and regioselective total synthesis of 6-methylellipticine, a potent anticancer agent, was developed. This synthetic approach mainly involved two key reactions: a direct amination of multi-functional phenol via an alkylation-Smiles rearrangement protocol, and an intramolecular C–H bond arylation reaction promoted by potassium tert-butoxide. These reactions resulted in the formation of two key intermediates, diarylamine and carbazole derivative, under transition metal-free conditions. The last cyclization afforded the target product 6-methylellipticine.

Synthesis of 3-keto-quinolines from enaminones, anilines and DMSO: Transition metal free one pot cascade

An efficient and transition metal-free approach for the synthesis of functionalized 3-ketoquinolines from readily available anilines, enaminones and DMSO in the presence of K2S2O8 has been conducted. This one pot tandem reaction proceeds through [3+2+1] cycloaddition reaction involving DMSO, enaminones and amines. In this environmental benign approach, DMSO acts as both a one carbon source and the solvent. A broad range of variously substituted amines and enaminones are successfully employed in this one pot tandem process to access a broad range of substituted 3-ketoquinolines.

Self-Condensation of Enaminodiones as a Method for Benzene Ring Construction: Synthesis of Diacyl-Substituted Phenols and Catechols.

A novel transition metal-free approach for the construction of the benzene core has been developed through self-condensation of available enaminodiones. Functionalized acyl-substituted phenols and catechols were obtained in 29-97% yields with high chemoselectivity under mild conditions. This base-promoted formal [4+2] annulation proceeds via cyclohexanone formation and involves the cascade transformation based on double Michael addition and aromatization (retro-Claisen cleavage and amine elimination).

A transition metal-free approach towards synthesis of β-carboline tethered 1,3,4-oxadiazoles via oxidative C–O bond formation

An efficient protocol has been developed for one-pot synthesis of biologically interesting β-carboline substituted 1,3,4-oxadiazoles via an I2-assisted oxidative C–O bond formation strategy.

Improved synthesis of icosahedral carboranes containing exopolyhedral B[sbnd]C and C[sbnd]C bonds

Carboranes are boron-rich molecular clusters possessing electronic characteristics that allow for orthogonal approaches to vertex-selective modifications. We report improved functionalization methods utilizing orthogonal chemistry to achieve efficient substitution at electron-rich B-vertices and electron-poor C-vertices of carborane. Functionalization of B-vertices with alkyl and (hetero)aryl groups using the corresponding Grignard reagents has been improved through the use of a Pd-based precatalyst featuring an electron-rich biaryl phosphine ligand, resulting in reduced reaction times. Importantly, this method is tolerant towards alkyl-based Grignard reagents containing β-hydrogens. Furthermore, a transition metal-free approach to the substitution of carborane C-vertices with (hetero)aryl substrates has been developed under nucleophilic aromatic substitution (SNAr) conditions. The selective substitution of carboranes afforded by these methods holds potential for the rational synthesis of heterofunctionalized boron clusters with substituents on both boron and carbon-based vertices.

Direct Wittig Olefination of Alcohols.

A base-promoted transition metal-free approach to substituted alkenes using alcohols under aerobic conditions using air as the inexpensive and clean oxidant is described. Aldehydes are relatively difficult to handle compared to corresponding alcohols due to their volatility and penchant to polymerize and autoxidize. Wittig ylides are easily oxidized to aldehydes and consequently form homo-olefination products. By the strategy of simultaneously in situ generation of ylides and aldehydes, for the first time, alcohols are directly transferred to olefins with no need of prepreparation of either aldehydes or ylides. Thus, the di/monocontrollable olefination of diols is accomplished. This synthetically practical method has been applied in the gram-scale synthesis of pharmaceuticals, such as DMU-212 and resveratrol from alcohols.

Direct C[sbnd]C coupling of phthalazine-N-oxide with the carboranyl anion – An original approach to C-modification of carboranes

An original transition metal-free approach based on the direct CC coupling of phtalazine-N-oxide with the carboranyl anion has been developed. A series of the novel C-modified closo-carboranes such as 1-(2-oxido-3-acyl-3,4-dihydrophtalazinyl-4-yl)-1,2-dicarba-closo-dodecaboranes and 1-(2-formylbenzyl)-1,2-dicarba-closo-dodecaborane have been obtained. The synthesized boron clusters could be of interest as promising building blocks in design of BNCT delivery agents.

Transition-Metal Free Mechanochemical Approach to Polyyne Substituted Pyrroles.

In this contribution, the synthesis of long chain hexatriynyl- and octatetraynyl-substituted pyrroles in one step from 1-halopolyyne precursors is reported. The products were obtained via a mechanochemical approach by simple grinding of 1-haloalkynes with N-substituted pyrroles and potassium carbonate which played a role of heterogeneous catalyst and this solvent- and transition metal-free approach is unprecedent in the synthesis of new, organic, long chain polyynes. Additionally, an extensive X-ray single crystal study of pyrrole end-capped polyynes is presented. Such compounds are possible substrates for different oligoheterocycles and have a significant application potential such as for instance molecular wires.

ChemInform Abstract: Transition Metal‐Free Generation of the Acceptor/Acceptor‐Carbene via α‐Elimination: Synthesis of Fluoroacetyl Cyclopropanes.

An efficient transition metal-free approach for the generation of acceptor/acceptor-carbene followed by trapping with alkenes to provide fluoroacetyl cyclopropanes has been described. The resulting cyclopropanes could be further converted into the fluoromethyl dihydrofurans or fluorodihydropyrroles through ring-expansion processes.

Transition metal-free N-arylation of secondary amides through iodonium salts as aryne precursors.

By using a diaryliodonium salt as a benzyne precursor, a transition metal-free approach for N-arylation of secondary amides is developed. This novel benzyne precursor, which can be prepared easily by a one step process from an aryl iodide, shows different reactivities with previous benzyne precursors in the N-arylation reaction. Mechanistic studies confirm the involvement of benzyne species (generated in situ from the diaryliodonium salts) as key intermediates.

Transition metal-free generation of the acceptor/acceptor-carbene viaα-elimination: synthesis of fluoroacetyl cyclopropanes.

An efficient transition metal-free approach for the generation of acceptor/acceptor-carbene followed by trapping with alkenes to provide fluoroacetyl cyclopropanes has been described. The resulting cyclopropanes could be further converted into the fluoromethyl dihydrofurans or fluorodihydropyrroles through ring-expansion processes.

ChemInform Abstract: NIS‐Mediated Intramolecular Oxidative α‐Functionalization of Tertiary Amines: Transition Metal‐Free Synthesis of 1,2‐Dihydro‐(4H)‐3,1‐benzoxazin‐4‐one Derivatives.

ChemInformVolume 46, Issue 34 Heterocyclic Compounds ChemInform Abstract: NIS-Mediated Intramolecular Oxidative α-Functionalization of Tertiary Amines: Transition Metal-Free Synthesis of 1,2-Dihydro-(4H)-3,1-benzoxazin-4-one Derivatives. Le Liu, Le Liu Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this authorLiang Du, Liang Du Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this authorDaisy Zhang-Negrerie, Daisy Zhang-Negrerie Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this authorYunfei Du, Yunfei Du Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this author Le Liu, Le Liu Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this authorLiang Du, Liang Du Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this authorDaisy Zhang-Negrerie, Daisy Zhang-Negrerie Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this authorYunfei Du, Yunfei Du Sch. Pharm. Sci. Technol., Tianjin Univ., Tianjin 300072, Peop. Rep. ChinaSearch for more papers by this author First published: 06 August 2015 https://doi.org/10.1002/chin.201534212Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume46, Issue34August, 2015 RelatedInformation

Transition metal-free generation of N-unsubstituted imines from benzyl azides: synthesis of N-unsubstituted homoallylic amines.

An efficient transition metal-free approach for the generation of N-unsubstituted imines from azides followed by trapping with allyl nucleophile to provide N-unsubstituted homoallylic amines has been described. Although catalytic KO(t)Bu in DMSO is sufficient to allow imine generation, stoichiometric KO(t)Bu is essential in THF. Further, an enantio- and diastereoselective synthesis of homoallylic amines from benzyl azide has also been exemplified.

ChemInform Abstract: Base‐Catalyzed Stereoselective Intermolecular Addition of Imidazoles onto Alkynes: An Easy Access to Imidazolyl Enamines.

Abstract An efficient transition metal-free approach for the regio- and stereoselective addition of imidazoles 1a – f onto alkynes 2a – l to provide the Z - and E isomers of imidazolyl enamines 3a – q and 4a – d using catalytic amount of KOH is described. Stereoselectivity of the addition products ( Z and E isomer) was found to be dependent upon time. Competitive experiments show that imidazole is less reactive than pyrrole and more reactive than aniline towards hydroamination.

Stereoselective one-pot synthesis of β-alkylsulfide enol esters. Base-triggered rearrangement under mild conditions.

A stereoselective one-pot procedure was developed to prepare S-substituted (Z)-enol esters through a base-triggered rearrangement. This transition metal-free multicomponent approach can be performed under an air atmosphere at room temperature, tolerates a wide set of chemical functionalities and generally affords high isolated yields. The (Z)-selectivity arises from the [1,4]-S- to O-acyl migration.

Base-catalyzed stereoselective intermolecular addition of imidazoles onto alkynes: an easy access to imidazolyl enamines

An efficient transition metal-free approach for the regio- and stereoselective addition of imidazoles 1a–f onto alkynes 2a–l to provide the Z- and E isomers of imidazolyl enamines 3a–q and 4a–d using catalytic amount of KOH is described. Stereoselectivity of the addition products (Z and E isomer) was found to be dependent upon time. Competitive experiments show that imidazole is less reactive than pyrrole and more reactive than aniline towards hydroamination.