Rajiv Kumar Verma

InCl3‐Driven Regioselective Synthesis of Functionalized/Annulated Quinolines: Scope and Limitations

The efficient, regioselective synthesis of functionalized/annulated quinolines was achieved by the coupling of 2-aminoaryl ketones with alkynes/active methylenes/α-oxoketene dithioacetals promoted by InCl(3) in refluxing acetonitrile as well as under solvent-free conditions in excellent yields. This transformation presumably proceeded through the hydroamination-hydroarylation of alkynes, and the Friedländer annulation of active methylene compounds and α-oxoketene dithioacetals with 2-aminoarylketones. In addition, simple reductive and oxidative cyclization of 2-nitrobenzaldehyde and 2-aminobenzylalcohol, respectively, afforded substituted quinolines. Systematic optimization of the reaction parameters allowed us to identify two-component coupling (2CC) conditions that were tolerant of a wide range of functional groups, thereby providing densely functionalized/annulated quinolines. This approach tolerates the synthesis of various bioactive quinoline frameworks from the same 2-aminoarylketones under mild conditions, thus making this strategy highly useful in diversity-oriented synthesis (DOS). The scope and limitations of the alkyne-, activated methylene-, and α-oxoketene dithioacetal components on the reaction were also investigated.

Molecular Docking and in Vitro Antileishmanial Evaluation of Chromene-2-thione Analogues.

Leishmaniases are an epidemic in various countries, and the parasite is developing resistance against available drugs. Thus, development of new drugs against Leishmania is an open area of investigation for synthetic organic chemists. To meet this challenge, a series of chromene-2-thione derivatives have been synthesized and docked into the active site of trypanothione reductase (TryR) enzyme required for redox balance of the parasite. These were screened on promastigote, axenic amastigote, and intracellular amastigote stages of Leishmania donovani and found to show high levels of antileishmanial activity together with minimal toxicity to human peripheral blood mononuclear cells. Compounds 3b and 3k were found to be the most active among the tested compounds. Although the compounds show moderate antileishmanial activity, they identify a chemical space to design and develop drugs based on these chromene-2-thione derivatives against the Leishmania parasite.

4-Dimethylamino pyridine-promoted one-pot three-component regioselective synthesis of highly functionalized 4H-thiopyrans via heteroannulation of β-oxodithioesters.

A highly convergent and regioselective heteroannulation protocol for the synthesis of hitherto unreported highly substituted 2-amino-4-(aryl/alkyl)-5-(aroyl/heteroaroyl)-3-(cyano/carboalkoxy)-6-methylthio-4H-thiopyran derivatives has been developed. This one-pot three-component domino coupling of β-oxodithioesters, aldehydes, and malononitrile/ethyl or methyl cyanoacetate is promoted by 4-dimethylamino pyridine (DMAP) in solvent (dichloromethane (DCM)) as well as under solvent-free conditions. Systematic optimization of reaction parameters identified that the three-component coupling (3CC) protocol is tolerant to a wide array of functionality providing densely functionalized 4H-thiopyrans in excellent yields. The merit of this cascade Knoevenagel condensation/Michael addition/cyclization sequence is highlighted by its high atom-economy, excellent yields, and efficiency of producing three new bonds (two C-C and one C-S) and one stereocenter in a single operation.

InCl3 catalyzed domino route to 2H-chromene-2-ones via [4 + 2] annulation of 2-hydroxyarylaldehydes with α-oxoketene dithioacetal under solvent-free conditions

A facile and efficient synthesis of 3-aroyl/heteroaroyl/ferrocenoyl/alkanoyl-2H-chromen-2-ones has been developed by the cyclocondensation of α-oxoketene dithioacetals and 2-hydroxyarylaldehydes catalyzed by InCl3 under solvent-free conditions. No co-catalyst or activator is needed and MeSH is the only by-product of this protocol. The methodology involves ring annulation of 2-hydroxyarylaldehydes with a variety of α-oxoketene dithioacetals offering rapid entry into differentially substituted chromen-2-ones. The condensation of ferrocene derived α-oxoketene dithioacetal and 2-hydroxyarylaldehyde furnished coumarin installed on a ferrocene platform.

Eco-efficient, regioselective and rapid access to 4,5-disubstituted 1,2,3-thiadiazoles via [3 + 2] cycloaddition of α-enolicdithioesters with tosyl azide under solvent-free conditions

An efficient, sustainable, and regioselective one-pot synthesis of hitherto unreported 4-aroyl/hetaroyl/alkanoyl-5-alkyl/allyl/benzylsulfanyl-1,2,3-thiadiazoles has been achieved by [3 + 2] cycloaddition of α-enolicdithioesters with tosyl azide through cascade 1–2 (S–N) and 3–4 (C–N) bond connections involving Wolff-type heterocyclization. Optimally, the reactions are very fast and completed within 2–15 minutes, when a mixture of α-enolicdithioester and tosyl azide was stirred at 0 °C in the presence of Et3N under solvent-free conditions. Furthermore, no co-catalyst or activator is necessary. The eco-compatibility, mild conditions, excellent yields, easy purification, and avoidance of expensive/toxic reagents are advantages of this protocol to access this medicinally privileged substructure.

Construction of five- and six-membered heterocycles on both Cp rings of the ferrocene moiety of α-oxoketene-S,S-acetal and β-oxodithioester via heteroaromatic annulation

1,1′-Bis(1,1-dimethylsulfanyl-3-oxo-1-propene)ferrocene and 1,1′-Bis(methyl-3-hydroxy-prop-2-ene-dithioate)ferrocene have been shown to be useful three-carbon synthons for the efficient synthesis of hitherto unreported and synthetically demanding Fc-heterocycles. Five-membered (pyrazole, isoxazole, and thiophene) and six-membered (pyrimidine, coumarin, and quinoline) heterocycles have been constructed on both Cp rings of the ferrocene matrix via regioselective heteroaromatic annulation.

Facile One-Pot Synthesis of Novel Tricyclic Dibenzoheterocycles via the Dianion Protocol of Ditopic Ligands

Abstract In our ongoing studies on the synthesis of new heterocyclic ring systems via a dianion intermediate, we herein describe the preparation of novel dibenzoazadioxoninone, dibenzoazadioxoninethione, dibenzoazadioxocine, dibenzoazadioxacycloundecine, dibenzoazadioxacyclododecine, dibenzoaza-2-oxodioxaphosphonine, and dibenzoaza-2-oxo-1,3-thioxaphosphonine in good yields.

Synthesis of New Benzosubstituted Dioxaphosphonines Containing Quinoxaline Subunit

A simple and efficient synthesis of previously unknown benzosubstituted dioxaphosphonines containing a quinoxaline subunit is described. Reasonably good yields of the products, mild reaction conditions, and convenient work-up are the advantages of this method. The procedure does not require any catalyst or activator and can be efficiently achieved via dianion cyclization. All the synthesized compounds have been characterized by satisfactory elemental analyses and spectral (IR, 1H, 13C, 31P NMR, and mass) studies. Supplemental materials are available for this article. Go to the publishers online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.