RESUMEN

An efficient method for the asymmetric one-pot synthesis of N-phenyl thioether-tethered tetrasubstituted chiral 4,5-dihydropyrrole-3-carbaldehydes have been developed using readily available benzothiazolium salts and α,ß-unsaturated aldehydes as starting materials in the presence of the chiral organocatalyst (R)-diphenylprolinol trimethylsilyl ether. The protocol afforded various functionally enantioenriched chiral tetrasubstituted 4,5-dihydropyrrole-3-carbaldehydes in high yields, with excellent enantio- and diastereoselectivity (≤90% yield, ≤98% ee, and >20 : 1 d.r.). This asymmetric one-pot reaction starts with the reaction of azomethine ylides with dipolarophiles to yield pyrrolo-thiazine-2-carbaldehydes as intermediates. Subsequently, the electrophile alkyl halide is attacked by the sulfur atom of the intermediate, followed by C-S bond cleavage (ring-opening), which furnishes the desired chiral tetrasubstituted 4,5-dihydropyrroles.

RESUMEN

An efficient approach for the synthesis of chiral pyrrolo[1,2-d][1,4]thiazine-2-carbaldehydes is achieved via formal 1,3-dipolar cycloaddition/rearrangement reactions of benzothiazolium salt and α,ß-unsaturated aldehydes, utilizing an asymmetric organocatalyst. This process results in the formation of fluorescent, highly enantioenriched chiral molecules with three contiguous stereogenic centers, one of which is a chiral quaternary center, with excellent yields and enantio- and diastereoselectivity. A computational study demonstrated the understanding of the reaction mechanism. The synthetic utility of this protocol was successfully employed for gram scale synthesis. Fluorescent and in silico studies showed the application of the present methodology.

RESUMEN

Catalysts play a major role in chemical synthesis, and catalysis is considered to be a green and economic process. Catalysis is dominated by covalent interactions between the catalyst and substrate. The design of non-covalent catalysts came into limelight only recently. Hydrogen bonding (HB) catalysts are well established among non-covalent catalysts, including asymmetric HB catalysts. Though halogen bonding (XB) catalysis and its asymmetric version are gaining admiration, non-covalent chalcogen bonding catalysis (ChB) is in the budding stage. This tutorial review will focus on the recently evolved chalcogen bonding catalysis and emphasis will be given to the chalcogen bonding of chiral molecules. Since successful enantioselective chalcogen bonding catalysis is yet to be reported, this review will focus on the basics of non-covalent bonding catalysis, chalcogen bonding catalysis, chiral chalcogenide synthesis, rigidification of transition states by ChB, stabilization of cations by chiral chalcogens, details of unsuccessful asymmetric chalcogen bonding catalysis, enantioseparation of racemic molecules using ChB, and the existence of ChB in chiral biomolecules.

RESUMEN

An efficient, commercially available, and reusable copper-oxide nanoparticle (CuO-NPs) and (R)-(-)-DTBM SEGPHOS catalyzed chemo- and enantioselective reduction of α-keto amides to α-hydroxy amides has been developed. The scope of the reaction has been studied with various α-keto amides containing electron-donating and electron-withdrawing groups affording the enantiomerically enriched α-hydroxy amides in good yields with excellent enantioselectivity. The CuO-NPs catalyst has been recovered and reused up to four catalytic cycles without any significant change in particle size, reactivity, and enantioselectivity.

RESUMEN

Stereoselective, one-pot synthesis of 3-arylidene-2-oxindoles has been accomplished via Heck-like carbocyclization/nucleophilic addition of N-(2-iodophenyl)-N-methyl-3-phenylpropiolamide, phenylacetylene, and secondary amine using binaphthyl stabilized palladium nanoparticles (Pd-BNP) as a reusable catalyst. Less reactive aryl bromides generally provided a similar yield of 3-arylidene-2-oxindoles compared with more reactive aryl iodides. The Pd-BNP nanocatalyst has been recovered and recycled for five catalytic cycles with only an insignificant reduction in particle size, reactivity, and reaction yield.

RESUMEN

An efficient method for transition metal-free halogen bond-assisted regioselective C-H arylation of 2-phenylimidazo-[1,2-a]pyridines under visible-light condition has been developed. The halogen bond between an aryl halide and base KOtBu initiates an electron transfer process and generates an aryl radical, which catalyzes its coupling with 2-phenylimidazo-[1,2-a]pyridines to give arylated products in good yield. Several control experiments, density functional theory calculations, and ultraviolet-visible analysis indicate the presence of a halogen bond between an aryl halide and KOtBu. This methodology has been successfully utilized to synthesize antileishmanial agents.

RESUMEN

An efficient method for synthesizing thioaurones has been developed using xanthate as an odorless sulfur surrogate. This reaction's key success lies in the use of iodine as a reagent, which promotes the α-iodination followed by cyclization of saturated ketones. This methodology has also been demonstrated with less reactive 2'-bromochalcones in good yield. Synthesis of the red isomer of indigo, i.e. a thia-analog of indirubin, was also achieved.

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RESUMEN

An iodine-catalyzed denitrative C-S cross-coupling reaction has been developed to attain thiochromanones from 2'-nitrochalcones and xanthate. The strategy was extended for a three-component synthesis of thiochromenes via intermolecular C-S cross-coupling followed by aldol reaction. The reaction proceeds via activation of the keto group of chalcone through a halogen bond complex with iodine/denitrative C-S bond formation with xanthate/sulfa-Michael addition to chalcones. The methodology was also demonstrated for chemoselective reduction of chalcones. The protocol was also employed to synthesize biologically important 3'-hydroxythioflavone and thiochromenones.

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RESUMEN

The development of direct and controlled oxidation of C(sp3)-H bonds is of great importance. Herein, an iodine-catalyzed controlled oxidation of (aryl)(heteroaryl)methanes to (aryl)(heteroaryl)methanols is disclosed under metal-free reaction conditions. A catalytic system comprised of iodine/silyl chloride with HI as an additive in the presence of dimethyl sulfoxide selectively oxidizes the C(sp3)-H bonds without being overoxidized to corresponding ketones. Therapeutically important aryl heteroaryl methanol derivatives were obtained in good yields. The preliminary mechanistic investigation proves that the primary source of oxygen is DMSO.

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RESUMEN

An efficacious and mild KOtBu-promoted intramolecular C-S cross-coupling of ortho-iodothioanilides in conjunction with a catalytic quantity of phenanthroline as an additive has been described for the convenient synthesis of 2-substituted benzothiazoles. The methodology is suitable for attaining a wide variety of 2-alkyl- and 2-aryl-substituted benzothiazoles. Single-crystal XRD, DFT calculations, NMR, and UV studies suggest that halogen bonds between the units of ortho-iodothioanilides may assist in the electron transfer process.

RESUMEN

The Cu-catalyzed domino synthesis of multi-substituted benzo[b]thiophene through radical cyclization of 2-iodophenyl ketones was developed using xanthate as a sulfur surrogate. This method was extended to obtain tetracyclic Lupinalbin analogues through double C-S/C-O bond formation by changing the substituents. The products were converted to a HTI photoswitch, benzothiophene-fused flavone.

RESUMEN

An efficient visible light mediated photocatalyst free C-S cross-coupling reaction has been developed for the synthesis of thiochromane derivatives through photoinduced electron transfer (PET). This methodology was further utilized for the synthesis of thiochroman-4-ol through intermolecular three-component cross-coupling reaction. The reaction proceeds via C-S bond formation through EDA complex/thioester cleavage/inter-or intramolecular sulfa-Michael addition followed by aldol reaction sequence. The EDA complex formation between aryl iodides and xanthate has been substantiated using spectroscopic experiments and DFT calculations.

RESUMEN

Sulfur-containing compounds are present in a wide range of biologically important natural products, drugs, catalysts, and ligands and they have wide applications in material chemistry. Transition metal-catalyzed C-S bond-forming reactions have successfully overcome the obstacles associated with traditional organosulfur compound syntheses such as stoichiometric use of metal-catalysts, catalyst-poisoning and harsh reaction conditions. One of the key demands in metal-catalyzed C-S bond-forming reactions is the use of an appropriate sulfur source due to its odor and availability. The unpleasant odor of many organic sulfur sources might be one of the reasons for the metal-catalyzed C-S bond-forming reactions being less explored compared to other metal-catalyzed C-heteroatom bond-forming reactions. Hence, employing an appropriate sulfur surrogate in the synthesis of organosulfur compounds in metal-catalyzed reactions is still of prime interest for chemists. This review explores the recent advances in C-S bond formation using transition metal-catalyzed cross-coupling reactions and C-H bond functionalization using diverse and commercially available sulfur surrogates. Based on the different transition metal-catalysts, this review has been divided into three major classes namely (1) palladium-catalyzed C-S bond formation, (2) copper-catalyzed C-S bond formation, and (3) other metal-catalyzed C-S bond formation. This review is further arranged based on the different sulfur surrogates. Also, this review provides an insight into the growing opportunities in the construction of complex organosulfur scaffolds covering natural product synthesis and functional materials.

RESUMEN

An efficient protocol for the synthesis of thioether directly from heteroarenes has been developed in the presence of visible light in a one-pot manner at room temperature. This method involves two sequential reactions in a single pot where the formation of the iodinated heteroarene is followed by a transition-metal-free C-S coupling reaction. A wide range of heteroarene and thiol partners (including aliphatic thiols) have been used for the synthesis of thioethers. NMR studies and DFT calculations revealed the presence of a halogen bond between the thiolate anion (halogen bond acceptor) and iodoheteroarene (halogen bond donor). This halogen bonded complex on photoexcitation facilitates the electron transfer from the thiolate anion to the iodoheteroarene at room temperature.

RESUMEN

The binaphthyl stabilized palladium nanoparticles (Pd-BNP) catalyzed single-step, stereoselective domino synthesis of symmetrically and unsymmetrically all-carbon tetrasubstituted olefin containing oxindoles from readily accessible anilides has been developed. The Pd-BNP catalyst showed a wide range of functional group tolerance that enabled building a library of heteroaromatics. This reusable Pd catalyst reflected its utility in the synthesis of biologically important AMP-activated protein kinase deprived of any metal Pd contamination. The nanocatalyst was easily recovered and reused five times without any appreciable loss in particle size or catalytic activity.

RESUMEN

An efficient domino process is developed for the synthesis of diversely substituted 2,3-dihydrobenzo[b]thiophenes from 2-iodoketones using a Cu-catalyst and easily available xanthate as a sulfur surrogate in good yields. This domino method has been expanded for the synthesis of 2-acylbenzo[b]thiophenes using in situ generated iodine (I2) from by-product KI in high yields. Treatment of xanthate with the copper(ii)-catalyst reduced it to a Cu(i)-catalyst, which initiates the catalytic cycle. A possible mechanism has been proposed based on the results from XPS-analysis, an iodine color test and several other control experiments.

RESUMEN

A copper catalyzed three-component synthesis of π-conjugated tetracyclic thiochromeno-quinolinone and thiochromeno-thioflavone was established via oxidative double hetero Michael addition using in situ generated nucleophiles. Xanthate plays a dual role as an odourless sulfur source and a chemoselective reducing agent. The in situ formed iodine plays a crucial role in the oxidation step.

RESUMEN

The application of stabilized iodonium ions in organic synthesis remains largely unexplored. Herein, a metal-free domino synthesis of Z-selective α,ß-diphenylthio enones is developed from easily available benzylic secondary alcohols employing thiophenol-stabilized iodonium ion as a catalyst. This methodology was further extended to five-membered and six-membered cyclic secondary alcohols. The UV-vis experiments suggest the formation of thiol-coordinated iodine(I) intermediates. Several control experiments establish that the reaction proceeds via the oxidation of alcohol to ketone, α-thiolation of ketones followed by α,ß-unsaturation, and finally the ß-thiolation of α,ß-unsaturated ketones to generate bis-vinyl sulfides. The in situ-generated stabilized iodonium ion is highly efficient to catalyze multiple functional group transformations in a domino manner.

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RESUMEN

A single-step, stereoselective protocol for the synthesis of unsymmetrically substituted (E)-3-allylideneoxindole and (E)-3-allylidenebenzofuran from readily accessible starting materials using palladium binaphthyl nanoparticles (Pd-BNPs) has been developed. Pd-BNP showing a wide range of functional group tolerance and an immense array of substrate scope have been explored with the successful synthesis of the drug molecule "tubulin polymerization inhibitor" free from trace metal impurities. The model reaction is extended to a gram-scale synthesis, and one of the products is utilized for derivatization. The Pd-BNP has been recycled up to 5 catalytic cycles without any loss in reaction yields and particle size of nanoparticles.

RESUMEN

An efficient and mild protocol has been developed for the synthesis of 2-substituted benzothiazole under solvent- and metal-free conditions using CBr4 as the catalyst. This process involves the activation of a thioamide through halogen bond formation between the sulphur atom of the thioamide and bromine atom of the CBr4 molecule. The presence of halogen-bonding interaction between N-methylthioamides and tetrabromomethane has been demonstrated with several control experiments, spectroscopic analysis and density functional theory (DFT). This methodology has a wide substrate scope for the synthesis of both 2-alkyl and 2-aryl substituted benzothiazoles.