Synthesis of Highly π-Extended Dihydrobenzo[a]indenocarbazole Scaffolds via Tandem Benzannulation and Friedel-Crafts Reaction of 2-Alkynylanilines and 2-Alkynylbenzaldehydes Promoted by Lewis Acid.

A novel and efficient tandem protocol for the swift synthesis of dihydrobenzo[a]indenocarbazole frameworks from 2-alkynylanilines and 2-alkynylbenzaldehydes via BF3·OEt2-facilitated benzannulation and Friedel-Crafts reaction has been described. This innovative approach accommodates a wide array of functional groups, offering a myriad of diversified carbazole products. Later, postsynthetic modification leads to its C(sp3)-H hydroxylation. Furthermore, the photophysical properties of some selected synthesized moieties have been meticulously investigated, promising exciting avenues for further exploration.

A Lewis Acid-Catalyzed Cascade Synthesis of Fused N-Heterocycles from 2-Alkynylanilines and 2-Formylbenzonitriles: Unveiling Iminoisoindoloindolone and Its Derivatives.

We herein reveal a streamlined synthesis of structurally fused 6-iminoisoindoloindolones via a meticulously orchestrated cascade reaction. This process seamlessly intertwines 2-alkynylaniline and 2-formylbenzonitrile under the catalytic influence of TMSOTf, giving rise to these compounds in remarkable yields that stand as a testament to the efficiency of our approach. Moreover, the versatility of this synthetic strategy extends far beyond mere synthesis, offering a gateway to the creation of both isoindoloindolone and unprecedented diphenylbenzopyrrolizinoisoquinolinone derivatives, thereby opening new horizons in the realm of chemical innovation. Furthermore, the strategic elegance of this synthetic methodology is underscored by its potential for scale-up production and applicability across diverse chemical contexts.

Nitrile stabilized synthesis of pyrrolidine and piperidine derivatives via tandem alkynyl aza-Prins-Ritter reactions.

An efficient methodology for the synthesis of N-(pyrrolidine-3-ylidenemethyl)acetamides mediated by triflic acid in good yields with separable Z/E isomers within a short reaction time has been demonstrated. The reaction involves the initial formation of the pyrrolidin-3-ylidenemethylium carbocation via the Prins cyclization reaction followed by the Ritter reaction to produce N-(pyrrolidine-3-ylidenemethyl)acetamides. This methodology is also used for the synthesis of their piperidine derivatives.

Stereoselective synthesis of gem-dihalopiperidines via the halo-aza-Prins cyclization reaction: access to piperidin-4-ones and pyridines.

An efficient methodology for the synthesis of 4,4-dihalopiperidine derivatives in excellent yields has been developed using N-(3-halobut-3-en-1-yl)-4-methylbenzenesulfonamide and an aldehyde catalyzed by In(OTf)3. The reaction involves an initial formation of a six-membered carbocation via the aza-Prins cyclization reaction followed by a nucleophilic attack by a halide ion to give 4,4-dihalopiperidine. The dihalopiperidine is converted to tetrahydropiperidinone using Ac2O/Et3N in DCM/H2O (1 : 1). It is also utilized for the synthesis of pyridine scaffolds by treatment with DBU. Furthermore, the dihalopiperidine is transformed to its enol ether derivatives using KOH in alcohol.

Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydropyranones via Prins Cyclization of 3-Bromobut-3-en-1-ols and Aldehydes.

Tetrahydropyranones are synthesized from 3-bromobut-3-en-1-ols and aldehydes in good yields with excellent diastereoselectivity at -35 °C. The reaction involves an initial formation of a most stable six-membered chairlike tetrahydropyranyl carbocation followed by nucleophilic attack of the hydroxyl group and subsequent elimination of HBr to give tetrahydropyranone. The carbonyl moiety of the tetrahydropyranone is converted to enol ether and esters using Wittig reaction. It is also transformed into 4-hydroxy-2,6-disubstituted tetrahydropyran with 2,4- and 4,6-cis configuration by lithium aluminum hydride in up to 96% diastereoselectivity. Furthermore, the methodology is extended toward the synthesis of novel anticancer aminoguanidine compounds.

Regio- and Chemoselective Synthesis of 3-(Dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines via Tandem Alkynyl Prins- and Intramolecular Oxycyclization Reactions.

A metal-free Lewis acid-initiated protocol for the synthesis of highly substituted 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines from 2-(4-hydroxybut-1-yn-1-yl)benzamides and aldehydes has been demonstrated. The reaction involves the initial formation of dihydrofuranylidene carbocation via a Prins cyclization reaction using BF3·OEt2, followed by intramolecular cyclization to produce 3-(dihydrofuran-3(2H)-ylidene)isobenzofuran-1(3H)-imines up to E/Z = 6:1 with moderate to good yields. The methodology can also be used for the synthesis of 3-(dihydro-2H-pyran-3(4H)-ylidene)-isobenzofuran-1(3H)-imines. The strategy leads to the formation of two C-O bonds and one C-C bond with two different heterocycles connected by a tetra-substituted double bond. Post synthetic application of the reaction was extended for the synthesis of furanylidene isobenzofuranones in excellent yields.

Base-Promoted [4 + 2] Annulation Reaction of In Situ-Generated Azadienes from N-Propargylamines with Active Methylene Compounds: Access to Highly Functionalized 2-Pyridones.

A facile and efficient synthesis of structurally diversified 2-pyridones is demonstrated using the [4 + 2] annulation of in situ generated azadienes from N-propargylamines and active methylene compounds. The reaction is promoted by an inorganic base giving moderate to good yields. The developed methodology is applicable for the direct and formal synthesis of various bioactive molecules. The synthetic utility of the protocol was also illustrated by late-stage functionalization of the products.

Synthesis of 1,2,3-triazole-fused N-heterocycles from N-alkynyl hydroxyisoindolinones and sodium azide via the Huisgen reaction.

An efficient methodology for the synthesis of dihydro[1,2,3]triazolo-pyrimidoisoindolones and dihydro[1,2,3]triazolo-diazepinoisoindolones has been developed using the Huisgen reaction from sodium azide and alkyne substituted amido alcohols in moderate to good yields. The reaction involves the in situ generation of the N-acyliminium ion intermediate, which undergoes a nucleophilic attack by the azide ion, followed by a [3 + 2]-intramolecular azide-alkyne cycloaddition reaction. Importantly, the reaction proceeds without the involvement of any transition metal catalyst. This methodology can be further utilized for the synthesis of dihydro[1,2,3]triazolo-pyrimidoisoindolthiones via thionation of amides.

Synthesis of Spiro[furan-2,1'-isoindolin]-3'-ones from 2-(4-Hydroxybut-1-yn-1-yl)benzonitriles and Aryl Aldehydes under the Action of Triflic Acid.

The synthesis of spiro[furan-2,1'-isoindolin]-3'-ones from 2-(4-hydroxybut-1-yn-1-yl)benzonitriles and aryl aldehydes is demonstrated. It involves the initial formation of dihydrofuranylideneisoindolinone via intramolecular sequential Prins and Ritter reactions, followed by the ring opening of the furanyl moiety to generate N-acyliminium ions and alcohols for the final cyclization reaction, and the spiro-cyclic compounds are produced in moderate to good yields. It is a one-pot, three-component reaction in which one new quaternary carbon, two five-membered rings, one C-N bond, two C-O bonds, and one C-C bond are formed. The reaction is carried out with a Brønsted acid from 0 °C to room temperature within a short period of time.

Synthesis of Thiazole-2(3H)-ones via [3,3]-Sigmatropic Rearrangement/5-exo-dig Cyclization of N-Propargylamines.

An efficient methodology has been developed for the synthesis of both di- and trisubstituted thiazol-2(3H)-ones from N-propargylamines and silver(I) trifluoromethanethiolate (AgSCF3) in good yields. The reaction proceeds via [3,3]-sigmatropic rearrangement/5-exo-dig cyclization of N-propargylamines. The starting material can be easily prepared from the A3-coupling reaction of amines, aldehydes, and alkynes. The methodology can be extended for the synthesis of thiozole-2(3H)-thione derivatives, and photophysical properties have been studied for some synthesized compounds.

K2S2O8-Mediated Synthesis of Highly Functionalized Pyrroles via Oxidative Self-Dimerization of N-Propargylamines.

An efficient methodology has been developed for the synthesis of tetra- and pentasubstituted pyrroles via oxidative self-dimerization of N-propargylamines catalyzed by silver benzoate in the presence of K2S2O8 in good yields. The protocol provides a simple route for the synthesis of both tetra- and pentasubstituted pyrroles with two carbonyl groups in the side chain. The methodology can be extended toward the synthesis of pyrrolo[3,4-d]pyridazine.

Synthesis of dibenzocyclohepta[1,2-a]naphthalene derivatives from phenylacetaldehyde and alkynyl benzyl alcohols via sequential electrophilic addition and double Friedel-Crafts reactions.

A simple methodology has been developed for the synthesis of substituted 9H-dibenzo[3,4:6,7]-cyclohepta[1,2-a]naphthalenes from phenylacetaldehydes and ortho-alkynyl benzyl alcohols in the presence of a Lewis acid in moderate to good yields within a short reaction time. Interestingly, the reaction proceeds through a highly regioselective electrophilic addition followed by double Friedel-Crafts reaction to form uncommon dibenzo-fused seven-membered carbocycles.

In(OTf)3-Catalyzed One-Pot Tandem Mannich and Conia-Ene Cyclization Reaction of N-Propargyl Amido Alcohols with 1,3-Dicarbonyl Compounds: An Approach To Construct Tetrahydro-1H-pyrrolo[2,1-a]isoindolone-1,1-dicarboxylate and Its Application.

A one-pot tandem reaction has been developed for the synthesis of substituted tetrahydropyrroloisoindolone via Mannich reaction of N-propargyl amido alcohols with 1,3-dicarbonyl compounds followed by Conia-ene cyclization reaction in moderate to good yields catalyzed by indium(III)triflate [In(OTf)3]. The reaction is highly regioselective with an exo-cyclic double bond in the pyrrolidine ring. The substituted tetrahydropyrroloisoindolone can be converted to 5H-pyrrolo[2,1-a]isoindol-5-one via decarboxylative aromatization reaction.

Stereoselective synthesis of hexahydrofuro[3,4-b]furan-4-ol and its dimer via tandem Prins and pinacol rearrangement.

A novel synthetic route for the cyclization of ((4S,5R)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)methanol with aldehydes to give hexahydrofuro[3,4-b]furan-4-ol and its dimer was developed. A variety of substituted furanol (up to 86%) and its bis-derivatives were obtained in good yields (up to 66%) with excellent diastereo- and enantio-selectivity mediated by borontrifluoride etherate. The dimer was conveniently converted into its corresponding monomer using aqueous zinc(ii) chloride in THF in quantitative yields.

Synthesis and Evaluation of Methyl 4-(7-Hydroxy-4,4,8-Trimethyl-3-Oxabicyclo[3.3.1]Nonan-2-yl)Benzoate as an Antileishmanial Agent and Its Synergistic Effect with Miltefosine.

In our interest in oxabicyclic compounds as potent antileishmanial agents, the present work deals with the chemical synthesis of a new oxabicyclic derivative, methyl 4-(7-hydroxy-4,4,8-trimethyl-3-oxabicyclo[3.3.1]nonan-2-yl)benzoate (PS-207). This oxabicyclic derivative showed a good antileishmanial effect on the parasite, on both the promastigote and the amastigote. The mode of parasitic death from PS-207 seemed to be apoptosis-like. Interestingly, the combination of PS-207 with a low dose of miltefosine showed a synergistic effect against the parasite.

Stereoselective Synthesis of Pyrroloisoindolone and Pyridoisoindolone via aza-Prins Cyclization of Endocyclic N-Acyliminium Ions.

A simple methodology has been developed for the synthesis of substituted pyrroloisoindolone and pyridoisoindolone via aza-Prins cyclization of endocyclic N-acyliminium ions, which are derived from the triflic acid treatment of regioselectively reduced N-homopropargyl imides in excellent yields. The reaction is highly diastereoselective, and only one diastereoisomer is formed during the reaction. The methodology can be utilized for the synthesis of pyrimidoisoindole.

Regio- and Diastereoselective Synthesis of Dihydropyrans and Pyranopyrans via Oxonium-Ene Reaction of ß-Allenols and Aldehydes.

Bismuth trifluoromethanesulfonate can be efficiently used for the preparation of dihydropyrans from ß-allenols and aldehydes by oxonium-ene reaction in good yields. The reaction is highly regioselective. On the other hand, the same reaction with trimethylsilyl trifluoromethanesulfonate at -45 °C affords the hexahydropyrano[4,3- b]pyran skeleton in moderate yields.

Ene cyclization reaction in heterocycle synthesis.

The ene cyclization has evolved to become an indispensable tool for the synthesis of various ring size heterocyclic compounds. In the past and recent years, many exciting reports have demonstrated the broad scope and synthetic utility of ene cyclization and the versatility of oxonium ion, iminium ion and thionium ion intermediates. Moreover, the ease of regio- and stereoselectivity of ene cyclization has led to the development of new types of heterocyclic compounds. This article aims at reviewing the utilities of ene cyclization reactions for the synthesis of various ring sizes of oxygen, nitrogen and sulfur heterocycles. It also covers some applications in natural product synthesis. The mechanism of the reactions is discussed wherever necessary. The review article covers the time period from 1986 to 2017.

Diastereoselective Synthesis of Substituted Morpholines from N-Tethered Alkenols: Total Synthesis of (±)-Chelonin A.

Intramolecular cyclization of nitrogen tethered alkenols catalyzed by palladium chloride leads to substituted morpholines in good yields. The methodology was used for the total synthesis of (±)-chelonin A.

Synthesis of Tetrahydro-1H-indeno[1,2-b]pyridine via Cascade Cyclization and Friedel-Crafts Reaction.

A convenient protocol has been established for the synthesis of 1-tosyl-2,3,4,5-tetrahydro-1H-indeno[1,2-b]pyridine via cascade cyclization and Friedel-Crafts reaction of 4-methyl-N-(pent-4-yn-1-yl)benzenesulfonamides and aldehydes in good yields. The methodology has been used for the total synthesis of the antidepressant agent (±)-5-phenyl-2,3,4,4a,5,9b-hexahydro-1H-indeno[1,2-b]pyridine.