Effect of substitution on the intramolecular 1,3-dipolar cycloaddition of alkene tethered münchnones

A sequence of chemoselective activation of N-acylaminoacids, münchnone generation, intramolecular 1,3-dipolar cycloaddition, and ring opening efficiently generated functionalized polycyclic structures such as cyclopenta[b]pyrroles or zwitterionic bicyclo[4.3.0]nonane or bicyclo[3.3.0]octanes in one operation is given. These zwitterionic species were isolated for the first time and were subsequently reduced to bicyclic aminoalcohols. The effect of the substitution of both the dipolarophile and the münchnone on the intramolecular cycloaddition outcome was examined. It was found that either nonactivated or electron-poor alkenes can react with the münchnone if these alkenes are tethered at position 4 on the münchnone (2, R2 = alkene tether), whereas only an electron-poor alkene at position 2 (2, R3 = alkene tether) could undergo successful cycloaddition. Also, münchnones substituted at position 2 with a phenyl (2, R3 = Ph) showed a dramatic increase in reactivity, whereas a phenyl at position 4 (2, R2 = Ph) had a very limited effect.     

Diastereoselective catalyst-free construction of isoxazolidine-cis-fused phospha dihydrocoumarins via an intramolecular Nitrone–Vinylphosphonate dipolar cycloaddition

An efficient stereoselective method towards the construction of isoxazolidine-cis-fused phosphadihydrocoumarins frameworks involving an intermolecular 1,3-dipolar nitrone cycloaddition reaction utilizing O-vinylphosphonylated salicylaldehydes and N-substituted hydroxylamines in situ formation of Nitrone–Vinylphosphonate bifunctional intermediates under catalyst free condition have been described.     

Synthesis of N-substituted imidazo[4,5-e]benzo[1,2-c;3,4-c’]difuroxans

N-Substituted imidazo[4,5-e]benzo[1,2-c;3,4-c’]difuroxans were synthesized by phase-transfer catalyzed alkylation of imidazo[4,5-e]benzo[1,2-c;3,4-c’]difuroxan salts with various alkylating agents. Acid hydrolysis of N-(ethoxycarbonylmethyl)imidazo[4,5-e]benzo-[1,2-c;3,4-c’]difuroxans gives the corresponding carboxylic acids. Structures of the synthesized compounds were confirmed by NMR spectroscopy, high resolution mass spectrometry, IR spectroscopy, and elemental anslysis.

     

Towards a synthesis of (±)modhephene via cascade rearrangement: Synthesis and rearrangement of dispiro[3.0.4.2]undecanes to [3.3.3]propellanes

The dispiro [3.0.4.2] undecanes 2 and 6 undergo cascade rearrangements yielding the [3.3.3]propellanes 3 and 7, respectively. The rearrangement of 6 proceeds regiospecifically and renders 9 a promising candidate for a direct conversion to (±)modhephene 10.     

Synthesis of N-heterocycles via [4 + 3] cycloaddition of azomethine imine

Di, tri and tetra-nitrogen containing 7-membered heterocycles are the key building blocks for natural and medicinally active compounds. They are using as antidepressants, antiulcer, antibiotics, antiemetic and also used as herbicides and insecticides. These building blocks can be synthesized easily from [4 + 3] cycloadditon reaction of azomethine imine with the other suitable reacting partner. Research on this area is very much important as this area is not much explored till now. Hence, the synthetic literature survey towards the di-nitrogen containing heterocycles is paramount importance. Herein, we report numerous synthetic routes (metal catalyzed, metal free, asymmetric) of di-nitrogen containing 7-membered heterocycle through [4 + 3] cycloadditon reaction of the last 10 years (2011-2019).     

New Approach to Synthesis of Tetrahydroisoquino[2,1-c] [1,3]benzodiazepine

A concise and efficient synthesis of the new compounds tetrahydroisoquino [2,1-c] [1,3]benzodiazepine 5 and 7 is reported.     

One-pot synthesis of pyrrolo[1,2-a]quinoxaline and pyrrolo[1,2-a]pyrazine derivatives via the three-component reaction of 1,2-diamines,ethyl pyruvate and α-bromo ketones

A simple synthetic protocol has been developed involving the three-component reaction between 1,2-diamines, ethyl pyruvate and a-bromo ketones in the presence of Fe Cl3 as a catalyst. A number of pyrrolo[1,2-a]quinoxaline and pyrrolo[1,2-a]pyrazine derivatives were synthesized in excellent yields using this protocol.     

Synthesis,photophysical and antioxidant properties of pyrrolo[3,2-c]carbazole and dipyrrolo[3,2-c:2′,3′-g]carbazole compounds

Research on Chemical Intermediates - The synthesis of (6-ethyl-1,6-dihydropyrrolo[3,2-c]carbazol-2-yl)methanol 5 and...     

Synthesis of bicyclo[3.1.0]hexanones via 1,3-dipolar cycloaddition of diazoalkanes to homochiral α-sulfinyl-2-cyclopentenones

The reactions of diazomethane, diazoethane, and (trimethylsilyl)diazomethane with (S)-2-p-tolylsulfinylcyclopent-2-en-1-one have been studied. The sulfinyl group increases the reactivity and controls the π-facial and endo/exo selectivities. The π-facial selectivity can be inverted in the presence of Yb(OTf)₃, which makes possible the stereodivergent synthesis of both diastereoisomeric pyrazolines. Completely stereoselective denitrogenation of optically pure pyrazolines into cyclopropanes was achieved under substoichiometric Yb(OTf)₃ catalysis.     

Intramolecular Ullmann-type C−N coupling for the synthesis of substituted benzo[4,5]imidazo[1,2-a]pyrrolo[3,4-c]pyridines

An efficient CuI catalyzed intramolecular Ullmann-type C−N coupling reaction is described here. Newly substituted 1H-benzo[4,5]imidazo[1,2-a]pyrrolo[3,4-c]pyridine-1,3,5(2H, 11H)-trione has been easily synthesized from ortho halogenated N-substituted pyrrolo[3,4-c]pyridine-1,3,6(5H)-triones in presence of CuI catalyst and K₂CO₃ base without any ligand. This procedure is based on intramolecular Ullmann-type reaction and provides a proficient method of making fused tetracyclic heterocycles.     

Synthesis of 11H-Indeno[1,2-b]quinolines via the Friedliinder Reaction

The nine new 11H-indeno[1,2-b]quinolines were synthesized in high yield with sodium ethoxide as a catalyst via the Friedlander condensation reaction, The possible reaction mechanism was proposed.     

Synthesis of Angular [1,2,5]Oxadiazolo[3,4-b]pyrazino-[1′,2′ : 1,2]pyrrolo[2,3-e][1,4]diazepine by Stepwise Reaction of Pyrrolo[1,2-a]pyrazinetrione with 3,4-Diaminofurazan

Russian Journal of Organic Chemistry - Diaminofurazan reacted with 8-benzoyl-2-phenyl-3,4-dihydropyrrolo[1,2-a]pyrazine-1,6,7(2H)- trione to give addition product of the amino group to the double...     

Catalytic asymmetric dipolar cycloadditions of indolyl delocalized metal-allyl species for the enantioselective synthesis of cyclopenta[b]indoles and pyrrolo[1,2-α]indoles

The development of novel synthons and efficient methods to synthesize chiral polycyclic indoles has been a hot topic in organic synthesis and medicinal chemistry owing to their broad applications in medicines,pesticides,and other functional molecules.Here,we disclosed novel indolyl substituted metal-allyl zwitterionic intermediates through the decarboxylation of conveniently available vinyl indoloxazolidones,which could be regarded as two types of dipolar species through the anionic delocalization.The palladium-π-allyl species tended to serve as an all-carbon 1,3-dipole in the asymmetric[3+2]cycloaddition with electrondeficient alkenes,which furnished polysubstituted cyclopenta[b]indoles with high regio-and stereoselectivities.Meanwhile,the iridium-π-allyl species was recognized as an aza-1,3-dipole in asymmetric[3+2]cycloaddition with in situ generated C1 ammonium enolates,affording pyrrolo[1,2-α]indoles with high diastereo-and enantioselectivities.In addition,the dipolar cycloadditions could be easily scaled-up and several synthetic transformations of the cycloadducts were demonstrated for the rapid synthesis of diverse chiral polycyclic indoles.     

Synthesis of novel [1,2,3]triazolo[4′,5′:3,4]pyrrolo[1,2-a]thieno[2,3-d] pyrimidines: Potent EGFR targeting anti-breast cancer agents

In this study, we designed and synthesized several novel fused [1,2,3]triazolo [4′,5′:3,4]pyrrolo[1,2-a]thieno[2,3-d]pyrimidine derivatives using in a single [3 + 2] reaction cycloaddition reaction of 3-(3-iodoprop-2-yn-1-yl)thieno[2,3-d]pyrimidin-4(3H)-one ( 4 ) followed by C-C bond coupling with various aryl azides in a PEG-400 medium. All of the newly synthesized compounds were evaluated in vitro for EGFR kinase inhibitory action as well as anti-breast cancer activity against MDA-MB-231 and MCF-7 breast cancer cell lines. When compared to the reference molecule, erlotinib, the majority of the compounds demonstrated adequate efficacy. The most promising compounds, 5g and 5i , demonstrated excellent anticancer activity against both cancer cell lines, with IC₅₀ values ranging from 04.17 ± 0.55 to 8.65 ± 0.89 μM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC₅₀ = 0.467 ± 0.063 and 0.412 ± 0.081 μM). The in silico studies of five potent compounds 5f , 5g , 5h , 5i , and 5k were also carried out to identify the interactions against the EGFR receptor and found that the energy calculations were covenant with the obtained IC₅₀ values.     

Synthesis of two-dimensional π-conjugated polymers pendent with benzothiadiazole and naphtho[1,2-c:5,6-c]bis[1,2,5]thiadiazole moieties for polymer solar cells

Four new 2D donor–acceptor conjugated polymers were designed and synthesized.These new polymers comprised fluorenealt-triphenylamine or carbazole-alt-triphenylamine as the backbones,and pendants with 2,1,3-benzothiadiazole(BT)or naphtho[1,2-c:5,6-c]bis[1,2,5]thiadiazole(NT)in a triphenylamine unit as the side groups.By changing the acceptor BT for a stronger electron-withdrawing unit of NT moiety in the side chain,the energy levels,absorption spectra,band gaps,and charge-transport abilities of the resultant polymers could be effectively tuned.Bulk heterojunction solar cells with these polymers as the electron donors and(6,6)-phenyl-C71-butyric acid methyl ester as the electron acceptor exhibited high open-circuit voltage(more than 0.8 e V).The power conversion efficiency can be improved from 1.37%to 3.52%by replacing the BT with an NT moiety,which indicates that introducing NT as the side-chain building block can be an effective strategy to construct efficient 2D conjugated polymers for PSCs.     

Synthesis of 11H-Indeno[1,2-b]quinolines via the Friedlnder Reaction

The quinoline nucleus occurs in several natural compounds (cincona alkaloids) andpharmacologically active substances displaying a broad range of biological activity1.The biological activity of quinoline compounds has been found to possess antiasthmatic,an…     

Asymmetric [4+2] cycloaddition of azlactones with dipolar copper–allenylidene intermediates for chiral 3,4-dhydroquinolin-2-one derivatives

In this paper, a pybox-copper catalyzed enantioselective decarboxylative [4+2] cycloaddition reaction of ethynyl benzoxazinanones with azlactones has been developed, which provides optically active 3,4-dihydroquinolin-2-ones in high yields with good enantioselectivities and diastereoselectivities. In this transformation, the chiral dipolar copper–allenylidene intermediates are kinetically generated via decarboxylative ethynyl benzoxazinanones, followed by the attack of the enolate azlactones to form enantiomerically enriched 3,4-dihydroquinolin-2-one structures.