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Herein, we report an atom-economical, one-pot, four-component, diastereoselective double-annulation reaction to construct polyfused pyrroloquinolines. This reaction highlights the cyclization of in situ - formed Povarov adducts with allenoates for the first time.

A mechanochemistry approach is developed for regioselective synthesis of functionalized dihydropyrido[2,3-d]pyrimidines by milling propargylic alcohols and 6-aminouracils with HFIP/p-TsOH. In the case of tert-propargyl alcohols, this [3+3] cascade annulation proceeded through allenylation of uracil followed by a 6-endo trig cyclization. With sec-propargyl alcohols, the reaction furnished the propargylation of uracil. This atom economy ball milling reaction allows access to a broad range of dihydropyrido[2,3-d]pyrimidine derivatives in excellent yields. We demonstrated the gram scale synthesis of 3 g and post-synthetic modifications to effect the cyclization of 5 to 6., (© 2024 Wiley-VCH GmbH.)

A mechanochemical synthesis of 1,2-disubstituted benzimidazoles from donor-acceptor cyclopropyl ketones and 1,2-diaminoarenes under metal-free and solventless conditions is reported. The reaction does not require inert conditions and is promoted by a stoichiometric amount of 1,1,1,3,3,3-hexafluoroisopropanol. This cascade reaction involves ring-opening, cyclization, and retro-Mannich reaction of cyclopropyl ketones with aryl 1,2-diamines. Compared to its solution-phase counterpart, this mechanochemical approach shows fast reactivity (24 vs 1.5 h). Mechanistic investigations by electrospray ionization mass spectrometry helped us to propose the reaction mechanism.

We report here a simple and atom economic cycloisomerization reaction of indole-tethered alkynols for constructing diverse carbazoles using Cu(OTf) 2 /HFIP as the excellent promoter system. The reaction proceeds through a one-pot, domino process of spiro cyclization and 1,2-migration followed by aromatization to deliver carbazoles.

A practically efficient, copper-catalyzed approach for the synthesis of functionally embellished indeno-naphthofurans is developed from 1-(1 H -inden-3-yl)naphthalen-2-ols. This intramolecular cycloetherification proceeds via C(sp 2 )-H oxygenation (C-H bond breaking and C-O bond forming), which enables the atom-economical synthesis of poly fused furans in high yields with large substrate diversity in the open air.

We report here an atom-economical, syn -diastereoselective synthesis of naphtho-fused furo[2,3- b ]furans along with naphthofurans at room temperature using readily available 2-naphthols and 2-oxo aldehydes using an alkaline earth catalyst [Ca(OTf) 2 ]. 2-Oxo aldehydes having both aryl and alkyl substitutions reacted well. A good number of arenols responded to give fused furans, but selected arenols gave only furofurans. Synthetic applications and gram-scale synthesis were also demonstrated to strengthen this strategy.

A unified strategy for the construction of bicyclic furans and pyrroles is developed from tert -propargyl alcohols and α-acyl cyclic ketones using an alkaline earth catalyst under solvent-free conditions. The reaction proceeds via the formation of a β-keto allene intermediate, which upon treatment with a tert -amine underwent thermodynamic enol formation and a subsequent annulation to form bicyclic furans. Interestingly, the same allene forms bicyclic pyrrole with primary amines. The reaction shows excellent atom economy as water is the only byproduct formed in bicyclic furans. The generality of the reaction is well established. Gram-scale synthesis and synthetic applications are demonstrated.

Herein, we report an efficient and practical approach for synthesizing diaryl(het) ketones from R-CO-CHR-Ar through a simultaneous oxidative cleavage of C-C and C-H bonds using KO t Bu. This method enables synthesizing a variety of unsymmetrical and symmetrical (hetero)aryl ketones in excellent yields, which are otherwise difficult to make. Besides, we synthesized natural products using this method.

The target-based discovery of therapeutics against apicoplast, an all-important organelle is an overriding perspective. MEP pathway, an accredited drug target provides an insight into the importance of apicoplast in the survival of the parasite. In this study, we present the rational design strategy employing sustainable catalysis for the synthesis of benzodiazepine (BDZ) conformers followed by their biological evaluation as prospective inhibitors against the potential target of the IPP pathway, 1-deoxy-D-xylulose-5-phosphatereductoisomerase (DXR). The study reported the inhibitory profile of 8c and 6d against the quintessential step of the only drug target in the erythrocytic stages of parasite development. The potential compounds were identified to represent a novel class of inhibitors that serve as the lead molecules to impede the pathway and further affect the survival of the parasite., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

We reveal a direct strategy for the flexible synthesis of C2-aryl/heteroaryl indoles without transition metal catalysts. The synthesis involves a one-pot, four-component reaction of readily available starting materials to offer diversity around the indole moiety with a broad substrate scope and high yields. The reaction proceeds via the Friedel-Crafts C-arylation of C-acylimine formed in situ , followed by N-arylation with aryne, a formal [3+2] cycloaddition, and a subsequent aromatization cascade.

We report here that thioamides can distinguish C-C double bonds and C-C triple bonds chemoselectively when subjected to a reaction with pent-1-en-4-yn-3-ol derivatives in the presence of Ca(OTf) 2 . This protocol offers a fast, efficient, and high-yielding synthesis of functionalized thiazoles. Interestingly, this reaction offers a time-dependent formation of kinetic and thermodynamic products. The products showed stereoselectivity concerning the alkene geometry. Further, we extended this protocol to synthesize oxazoles from propargyl alcohols and ibuprofen (NSAID) was converted into amide and then subjected to oxazole formation with tert -propargyl alcohols., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

A Ca-catalyzed, tetrasubstituted alkenyl-sulfenylation was achieved using readily available aryl/alkyl thiols and easily prepared oxindole-derived propargyl alcohols under solvent-free conditions. The reaction proceeded with hydrogen bonding assisted regioselective α-thiolation and subsequent calcium catalyzed stereoselective alkenylation to yield E -alkenyl thioethers with high diastereoselectivity.

We have developed a one-pot, three-component, and solvent-free reaction for the synthesis of 3-aminofurans using a calcium catalyst. In this cascade reaction, the key intermediate, C,N-diacyliminium ion, is formed in situ from glyoxal and lactam, which further reacted with phenolic nucleophiles to form furan derivatives in good yields with broad substrate diversity. We also present here the preliminary photophysical studies of selected compounds.

Research continues to find a breakthrough for the treatment of Alzheimer's Disease (AD) due to its complicated pathology. Presented herein is a novel series of arydiazoquinoline molecules investigated for their multifunctional properties against the factors contributing to Alzheimer's disease (AD). The inhibitory properties of fourteen closely related aryldiazoquinoline derivatives have been evaluated for their inhibitory effect on Aβ 42 peptide aggregation. Most of these molecules inhibited Aβ 42 fibrillation by 50-80%. Selected molecules were also investigated for their binding behaviour to preformed Aβ 40 aggregates indicating a nanomolar affinity. In addition, these compounds were further investigated as cholinesterase inhibitors. Interestingly, some of the compounds turned out to be moderate in vitro inhibitors for AChE activity with IC 50 values in low micro molar range. The highest anti-AChE activity was shown by compound labelled as 2a with an IC 50 value of 6.2 μM followed by 2b with IC 50 value of 7.0 μM. In order to understand the inhibitory effect, binding of selected molecules to AChE enzyme was studied using molecular docking. In addition, cell toxicity studies using Neuro2a cells were performed to assess their effect on neuronal cell viability which suggests that these molecules possess a non-toxic molecular framework. Overall, the study identifies a family of molecules that show good in vitro anti-Aβ-aggregation properties and moderately inhibit cholinesterase activity., Competing Interests: Authors declare no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Highly robust one-pot, four-component cascade cyclization reaction of α-keto aldehydes, anilines, activated alkynes, and aromatic nucleophiles is developed to synthesize a diverse range of pharmaceutically important penta-substituted pyrroles. The reaction proceeds through the cascade cyclization of acylimines (in situ formed) with activated alkynes and aromatic nucleophiles such as indoles, pyrroles, and naphthols at room temperature under calcium(II) catalysis with high yields and broad substrate diversity.

Calcium-catalyzed highly facile one-pot, A 4 annulation of aldehyde, amine, alkene, and alkyne to form fused 4,5-dihydropyrrolo[1,2- a ]quinolines with exclusive syn diastereoselectivity is reported. This selectivity arises from an inverse electron demand [4+2] aza-Diels-Alder cycloaddition, and the adduct further undergoes a formal [3+2] cyclization with activated alkynes. This diversity-oriented protocol is highly general and furnishes the dihydropyrrolo[1,2- a ]quinoline derivatives with a broad substrate scope in good to excellent yields.

A one-pot, regiospecific synthesis of dihydrofurans bearing a quaternary centre and tetrasubstituted furans is developed from the formal [3 + 2] annulation of tert-propargyl alcohols and 1,3-diketones under Ca(ii)/DBU conditions. The reaction proceeds through the SN2I mechanism to form homoallenyl ketone and a subsequent cycloisomerization to yield novel and new chemical entities of privileged scaffolds.

Herein, we disclose the first report on iodo-cycloisomerization of 1-(indol-3-yl)-1-arylbut-3-yn-2-ols to form 3-iodocarbazoles. The synthesis proceeds through a cascade 5-endo-spirocyclization, followed by selective 1,2-alkyl migration. This method governs the green synthesis principles such as open-flask reaction, AcOEt as the solvent, rt reaction with short time, use of iodine, and broad substrate scope with atom and step economy., Competing Interests: The authors declare no competing financial interest.

Described here is the first report of an unexpected thermal-ring rearrangement (TRR) of benzochromenes to indene derivatives promoted by pTsOH. This cascade ring-rearrangement proceeds through the protonation of benzochromenes by an acid catalyst followed by ring-opening and ring-closure by an intramolecular Friedel-Crafts cyclization to provide a new bicyclic framework, inden-3-yl-naphthols bearing a quaternary center, which also exhibited atropisomerism. Regioselectivity, broad substrate scope, high yields, solvent-free conditions and atom economy are the additional high points of this ring-rearrangement.

A one-pot, sequential Meyer-Schuster (MS) rearrangement of oxindole-derived propargyl alcohols to the corresponding α,β-unsaturated enones and their anti-Michael addition, followed by intramolecular azacyclization is described in a highly regioselective manner using Ca(OTf) 2 as the promoter. Further, we described the one-pot MS rearrangement, followed by C (sp 3 ) -H functionalization of 2-methyl azaarenes at α-carbon of these doubly activated alkenes. Control experiments and computational calculations were performed to propose the reaction mechanism., Competing Interests: The authors declare no competing financial interest.

An amine-triggered facile synthetic approach of anthranilates has been described through benzannulation of readily available chemicals under one-pot solvent-free conditions using Ca(OTf) 2 as the sustainable catalyst. In this regioselective approach, we described a reasonably longer cascade, which proceeds through β-enamino ester formation/Michael addition/intramolecular aldol reaction/elimination/aromatization/oxidative debenzylation/lactonization with a broad substrate scope and high yields. The isolation of intermediates authenticated the mechanism, and the synthetic utility of the products was also demonstrated., Competing Interests: The authors declare no competing financial interest.