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In this work, we report the synthesis of three series of 3,5-disubstituted isoxazoles (4a-d , 5a-d and 6a-d), as analogues of the clinically important drug baclofen. The isoxazole ring systems were assembled through the key copper-catalyzed 1,3-dipolar cycloaddition reaction between a nitrile oxide (generated in situ from nitro compounds) and an alkyne. An X-ray crystallography study shows that the 1,3-dipolar cycloaddition reactions proceeded with very high regioselectively, leading exclusively to the formation of the 3,5-disubstituted regio isomers. Additionally, it was possible to obtain these compounds in enantiomerically pure form using SuperQuat-type chiral auxiliary. As suggested by our QSAR analysis and docking studies, these analogues have the potential to be biologically active as GABA B receptor modulators. Finally, the absorption, distribution, properties of metabolism and excretion (ADME) of the synthesized molecules was also determined by a computational approach. From this work we obtained five molecules ((S)- 4d , (S)- 5b , (S)- 6b , (S)- 6c and (S)- 6d) as potential GABA B receptor agonists. [Display omitted] [ABSTRACT FROM AUTHOR]

An oxidant-free, microwave-promoted tandem 1,3-dipolar cycloaddition and dehydrogenation oxidation is achieved under environmentally friendly conditions, delivering novel fused pyrrolidinyl-spirooxindoles in good to excellent yields. This work provides powerful means to expand the structural diversity of pyrrolidinyl-spirooxindole as a promising scaffold for novel drug discovery. [Display omitted] • A facile, efficient and green tandem 1,3-dipolar cycloaddition and dehydrogenation reaction is described. • New fused pyrrolidinyl-spirooxindoles were synthesized in good yields. • This protocol could serve as an efficient pathway to construct this novel pyrrolidinyl-spirooxindoles ring systems. • A plausible mechanism is proposed based on control experimental results. • This work provides powerful means to expand the structural diversity of pyrrolidinyl-spirooxindole as a promising scaffold for novel drug discovery. [ABSTRACT FROM AUTHOR]

Owing to the biological importance of 1,2,3-triazoles and benzoxazine-3(4H)-ones scaffolds, we have attempted to design and synthesize novel 1,2,3-traizoles linked to benzoxazin-3-one moiety. Indeed, a novel series of 1,4-disubstituted 1,2,3-triazoles containing 2H-1,4-benzoxazin- 3-(4H)-one were synthesized. The 1,2,3-triazoles were obtained in high yields by a double copper-catalyzed azide-alkyne click chemistry reaction between azides and corresponding propargylated benzoxazin-3-ones. These compounds incorporate both the 2H-benzo[b] (Rao et al., 2019; Fringuelli et al., 2009) [1,4]oxazin-3-one motif and two 1,2,3-triazole heterocycles. The synthesized molecules were characterized by spectroscopic techniques such 1H NMR, 13C NMR, FT-IR and elemental analysis. [Display omitted] • Developed a synthetic route for new 2H-benzo[b] [1,4]oxazin-3-one derivatives. • Utilized click chemistry to incorporate 1,2,3-triazole moieties. • Demonstrated efficient and regioselective formation of 1,2,3-triazoles. • High yield and purity of the synthesized compounds. • Comprehensive characterization of the new derivatives using NMR, IR, and elemental analysis. [ABSTRACT FROM AUTHOR]

The 1,3-dipolar cycloaddition of 3-nitro-2(1 H)-quinolones with azomethine ylides derived from sarcosine or thiazolidine-4-carboxylic acid and various 1 H -indole-2,3-diones (isatins) have been investigated. The structure and stereochemistry of the formed cycloadducts were studied in detail by X-ray diffraction and NMR spectroscopy methods. [Display omitted] [ABSTRACT FROM AUTHOR]

A diastereoselective 1,3-dipolar cycloaddition of azomethine ylides generated from acenaphthylene-1,2-dione (or aceantrylene-1,2-dione) and amino acids with 1,2-diphenylcyclopropenes has been developed. As a result, cyclopropa[ a ]pyrrolizidines and 3-azabicyclo[3.1.0]hexanes spiro-fused to acenaphthylen-1(2 H)-one and aceanthrylen-1(2 H)-one fragments were obtained for the first time. Based on DFT calculations at M11/cc-pVDZ level of theory, a concerted mechanism of cycloaddition was proposed to explain the observed diastereoselectivity. The cytotoxic activity of newly synthesized compounds against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines was evaluated in vitro by MTS-assay. [Display omitted] [ABSTRACT FROM AUTHOR]

An I 2 /CuI-promoted multi-component reaction from pyridines, aryl methyl ketones and electron deficient acrylates has been accomplished in a "one-pot" manner, which provides a straightforward and efficient access to C-3 acylated indolizines. The key intermediate of N -ylides is hypothesized to be generated in situ from pyridines and (hetero)aryl methyl ketones in the presence of iodine. This method has been applied in the synthesis of two molecules with anticonvulsant and anti-inflammatory activities. Image 1 [ABSTRACT FROM AUTHOR]

Abstract The asymmetric access to unreported trans 4-quinolinoxy oxaproline precursors is investigated here in a comparative way by 1,3-dipolar cycloaddition of vinyloxy quinolines with chiral α-alkoxycarbonyl aldonitrones and chiral cyclic surrogates. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

An analysis of the literature over the past 10 years shows that there is a trend towards simplification of the synthetic procedures, usage of readily available and unexpensive materials, and concern for the safety of the experimental chemist. The use of calcium carbide as a solid acetylene analogue fits this trend perfectly. By replacing gaseous acetylene with calcium carbide, a complex of problems associated with working with gases can be solved at once. Due to this, the chemistry of calcium carbide is rapidly developing, opening up new possibilities of acetylene chemistry. This review highlights recent advances in carbide chemistry demonstrating its advantages in the construction of heterocycles. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract Two types of bicyclic N -cyclopropyl glycine ester derivatives have been prepared and put under scrutiny as possible precursors of azomethine ylides. The results demonstrate that they can indeed participate in 1,3-dipolar cycloaddition reactions with dipolarophiles, as illustrated in the cases of phenyl vinyl sulfone, N -phenylmaleimide, diethyl fumarate and diethyl maleate. The relative configurations of the major diastereoisomers produced are consistent with the predicted generation of azomethine ylide species, reacting in concerted cycloaddition processes. This unprecedented way of generating such 1,3-dipoles provides access to functionalised pyrrolizidine and pyrrolidine derivatives, that would be difficult to make directly by more classic methods. It was also found that using phenyl vinyl sulfone or N -phenylmaleimide as the dipolarophile reactant, a domino nucleophilic conjugate addition/1,3-dipolar cycloaddition process may operate competitively. Graphical abstract Image 1 [ABSTRACT FROM AUTHOR]

The application of nitrous oxide as an alternative oxidant provides new opportunities for selective oxidation of olefins. Here, we studied for the first time the thermal oxidation of isobutene with N 2 O in the liquid phase. The study revealed that the oxidation proceeds via 1,3-dipolar cycloaddition of N 2 O to the C C bond by two routes forming unstable 4,5-dihydro-[1,2,3]-oxadiazole intermediates. The main route (the contribution of 91%) includes the addition of the N 2 O oxygen to the second carbon atom in olefin. In this case, the oxadiazole decomposes with the C C bond cleavage yielding acetone, methylene (:CH 2 ), and N 2 . The methylene then readily reacts with isobutene and benzene (solvent). The minor route involves the addition of the N 2 O oxygen to the first carbon atom and the oxadiazole decomposition with a hydrogen shift leading to isobutanal and N 2 . The main distinctive feature of the studied reaction is the formation of methylene in high yield. [ABSTRACT FROM AUTHOR]

An organic base-catalyzed 1,3-dipolar cycloaddition between 2-alkenylindolenines and azomethine ylides derived from isatins and benzylamines was successfully developed to assemble indolenine-substituted spiro [pyrrolidine-2,3′-oxindole] ring systems. Generally, good regioselectivities (up to 14:1 rr ) and high yields (up to 91%) were obtained under mild conditions. [ABSTRACT FROM AUTHOR]

Four histrionicotoxin analogues were prepared in an efficient manner utilizing a nitrone dipolar cycloaddition reaction as the key step in forming tricyclic intermediate 13 . The nitrile in intermediate 13 was reduced with DIBAL to an aldehyde which then underwent Z -selective Wittig reactions to produce intermediates containing the Z -alkene side-chain. Hydrogenation of the Z -alkenes produced saturated histrionicotoxin analogues whereas reduction with SmI 2 afforded the unsaturated histrionicotoxin analogues. The histrionicotoxin analogues were shown to be potent non-competitive antagonists of the α4β2 and α7 nAChR's with the most potent analogue 3 displaying IC 50 's of 0.10 μM and 0.45 μM against the α4β2 and α7 nAChR's, respectively. The unsaturated analogues 15 and 18 displayed Hill slope ( n H ) of approximately 1 whilst the saturated analogues 16 and 3 had a n H of approximately 0.5, which may indicate that the saturated analogues are binding to more than one binding site. [ABSTRACT FROM AUTHOR]

π-Deficient ethynyl hetarenes were used as dipolarophiles in a 1,3-dipolar cycloaddition reaction with azomethine imines (2-arylidene-5-oxopyrazolidin-2-ium-1-ides). Both CuI-catalyzed and catalyst-free thermally induced reactions proceeded with high regioselectivity providing 6-hetaryl-5-aryl-2,3-dihydropyrazolo[1,2- a ]pyrazol-1(5 H )-ones in moderate to excellent yields. The ethynyl hetarenes (pyridines, pyrazines, quinoxalines, pteridines and pyrimido[4,5- c ]pyridazines) with ortho -methyl, ortho -cyano and ortho -alkynyl substituents were applicable to this reaction. 1,3-Dipolar cycloaddition reactions of alkynyl hetarenes with azomethine imines or other 1,3-dipole reagents can be considered as an alternative synthetic approach to heterobiaryls. [ABSTRACT FROM AUTHOR]

An efficient method of synthesizing bicyclic fused [1,2,4]oxadiazolo[4,5- c ]pyrimidine-5,7(6 H )-dione derivatives was developed through a [3 + 2] cycloaddition of uracil derivatives and nitrile oxides. In the one step reaction, C N and C O bonds were constructed, the target compounds were efficiently obtained in good yields. The method represents a valuable way to obtain highly functional fused bicyclic heterocycle derivatives in a simple, rapid and practical manner. The method fusing bicyclic heterocycles can be applied for modification of uracil analogues that may have potential biological activities. [ABSTRACT FROM AUTHOR]

A highly efficient procedure for the construction of indeno[1,2- b ]pyrroles bearing bistriazole unit from hydrazonoyl chlorides and oxa-aza[3.3.3]propellanes in EtOH in the presence of Et 3 N is reported. The reaction is supposed to proceed through a 1,3-dipolar cycloaddition reaction and ring opening process. Two new cycles and four new C N bonds are formed in this transformation. The reaction scope was explored with different substituents on both substrates. [ABSTRACT FROM AUTHOR]

In this manuscript, we are reporting an efficient protocol for the construction of highly functionalized N, O-heterocyclic derivatives such as 1,2,4-oxadiazine and 1,4,2-dioxazine-6-carboxylate derivatives via a 1,3-dipolar (3 + 3) cycloaddition between nitrile oxide and unprotected α -diazo esters in the presence of 2 mol% Cu(OTf) 2 catalyst. The expected N, O-heterocycles were obtained in excellent yields. These N, O-heterocycles are known to exhibit insecticidal and acaricidal properties. [ABSTRACT FROM AUTHOR]

The spiroisoxazolidinyl-benzoisothiazoline derivatives were synthesized through a highly diastereoselective 1,3-dipolar cycloaddition of benzoisothiazole-2,2-dioxide-3-ylidenes with nitrones. The regiochemistry of cycloaddition was assigned on the 1 H NMR chemical shift of methane-H in 3 and 5 . The relative stereochemistry of cycloadducts was determined from the single-crystal X-ray crystallography. [ABSTRACT FROM AUTHOR]

An advanced intermediate in the synthesis of the racemic Neuraminidase inhibitor Peramivir was synthesised in a new and versatile manner starting from a stereoselective 1,3-dipolar cycloaddition reaction between the nitrile oxide deriving from 2-ethylbutanal and the commercially available and inexpensive bicyclo[2.2.1]hepta-2,5-diene. The reaction mainly afforded the exo -isoxazolino-norbornene derivative from which the oxidative cleavage of the carbon carbon double bond followed by subsequent dehydration led to the corresponding anhydride intermediate. Amines and alcohols were used as nucleophiles for opening the anhydride, with amines providing the better results. Both the monoester–monoacid and the monoester–monoamide were transformed into the monoester–monoamino intermediate from which the synthesis continued using previously published methods. In the best protocol, the total yield of this key intermediate was increased up to 17% from bicyclo[2.2.1]hepta-2,5-diene. [ABSTRACT FROM AUTHOR]

Reactions of 3,3,3-trihalogen-1-nitropropenes with N -alkyl-α-amino acids (sarcosine, proline) and isatins proceed regio- and diastereoselectively to give a wide range of trihalomethylated spiro[indoline-3,2′-pyrrolidin]-2-ones and spiro[indoline-3,3′-pyrrolizin]-2-ones in good yields as a result of a 1,3-dipolar cycloaddition of the intermediate stabilised azomethine ylide at the double bond of the nitroalkenes. [ABSTRACT FROM AUTHOR]

Highly regio- and diastereoselective syntheses of a new set of functionalized pyrrolidines, spiro-pyrrolidine/pyrrolizidine oxindoles, spiroacenaphthylenolyl-pyrrolidines/pyrrolizidines and spiro-1,3-indandionolyl-pyrrolidines/pyrrolizidines appended with various aryl- and heteroaryl moieties via the azomethine ylide cycloaddition reaction are reported. The Ag-catalyzed [3+2] cycloaddition of azomethine ylides derived from N -benzylideneiminoglycinates with various arylidene/heteroarylidenemalononitriles gave C-3,C-5-aryl/heteroaryl substituted C-4,C-4-dicyanopyrrolidine-2-carboxylate scaffolds with good regio- and diastereoselectivity. Further, the [3+2] cycloaddition of azomethine ylides derived from the decarboxylative reactions of different 1,2-dicarbonyls and α-amino acids with the indole/pyrrole-based dipolarophiles were investigated. In the context of enriching the library of functionalized spiropyrrolidine- and spiropyrrolizidine scaffolds, these reactions have led to the assembling of various spiro-pyrrolidine/pyrrolizidine oxindoles, spiroacenaphthylenolyl-pyrrolidines/pyrrolizidines and spiro-1,3-indandionolyl-pyrrolidines/pyrrolizidines appended with the indolyl- and pyrrolyl moieties at the C-3 position of the spiro-pyrrolidine/pyrrolizidine rings. The stereochemistry of the cycloadducts was assigned based on the single crystal X-ray structures of representative major diastereomers 8c , 8d , 9b , 9c , 17a , 17b , 17c , 18a , 18e and 19a obtained from the azomethine ylide cycloaddition reactions. [ABSTRACT FROM AUTHOR]

A FeCl 3 ·6H 2 O-mediated reaction of [60]fullerene with amidoximes for the preparation of fulleroimidazolines has been presented. This reaction shows a wide substrate scope, and the products obtained from alkyl-substituted amidoximes are first disclosed. In addition, a possible mechanism is proposed. [ABSTRACT FROM AUTHOR]

For the first time, π-deficient alkynyl hetarenes were used as dipolarophiles in a 1,3-dipolar cycloaddition reaction with in situ generated azinium ylides. A three-component reaction of pyridine or isoquinoline, ethyl chloroacetate and alkynyl hetarene (pyrazine, quinoxaline, uracil, or lumazine derivative) in the presence of a base gave the corresponding indolizine or pyrrolo[2,1- a ]isoquinoline based heterobiaryl in good yields. The reactions proceeded with high regioselectivity; in all cases the most electron-deficient carbon atom of the C C bond of the starting alkynyl hetarene adds to the side-chain carbon of the azinium ylide. 1,3-Dipolar cycloaddition reactions of alkynyl hetarenes with azinium ylides or other 1,3-dipole reagents can be considered as an alternative synthetic approach to heterobiaryls. [ABSTRACT FROM AUTHOR]

Regio- and stereoselective 1,3-dipolar cycloadditions of C -(3-indolyl)- N -phenylnitrone ( 2 ) with variedly substituted dipolarophiles were carried out to obtain syn - C4 and C5 substituted indolyl-isoxazolidines 6a–c and 7a–f , respectively. Reduction of obtained isoxazolidines, by employing various reducing agents, causes cleavage of the N–O bond, which is accompanied by concomitant cleavage of C–N bond leading to the formation of a library of novel indole based natural product analogs and precursors. [ABSTRACT FROM AUTHOR]

A series of new dispiro pyrrolidines were regioselectively synthesised via [3 + 2]-cycloaddition reactions of 3,5-bis(arylidene)-1-phenylethyl-4-piperidones with azomethine ylides generated in situ from N -methylglycine and appropriate isatin derivatives. The structures of the synthesised compounds were characterized by NMR, FT-IR and MS. These compounds were assayed in vitro for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using Ellman's assay. The results demonstrate better inhibitory activity against butyrylcholinesterase as compared to acetylcholinesterase. Compound 7b exhibits potential as a new BChE inhibitor, with an IC 50 of 12.78 ± 1.52 μM. A kinetic study suggests 7b as a mixed-mode inhibitor, where the active molecule can bind to the active or allosteric sites of the enzyme. An in silico study was performed using AutoDock Vina to identify the binding energy and conformation of 7b with the crystal structure of BChE complexed with Thioflavin T (PDB ID: 6ESY) and the crystal structure of human AChE complexed with dihydrotanshinone 1 (PDB ID: 4M0E). The results indicate better binding properties of 7b compared with the standard inhibitor Thioflavin T, with calculated binding energies of −13.9 and −9.7 kcal mol-1 for BChE and AChE, respectively. [Display omitted] • A new series of dispiro pyrrolidines were synthesised and characterized. • Compound 7a-d and 8a-d were evaluated for in vitro α-amylase and α-glucosidase inhibitory activity. • Compound 7b was found good BChE inhibitor with IC 50 of 12.78 ± 1.52 μM compared to acetylcholinesterase. • Kinetic studies suggested compound 7b represented as a mixed a mixed-mode inhibitor, where the active molecule can bind to the active or allosteric sites of the enzyme. • In silico study for 7b show better binding properties compared with the standard inhibitor Thioflavin T. [ABSTRACT FROM AUTHOR]

1,3-Dipolar cycloaddition reaction of sydnone- N -ylides, as model bis(1,3-dipoles), with acetylenic dipolarophiles in 1,2-epoxybutane under reflux gave exclusively pyrroloazines containing a sydnone moiety that resulted by preferred reaction of the N -ylide 1,3-dipole with the acetylenic dipolarophiles. The assembled sydnone-ylide hybrid structures were generated in situ from N -heteroaromatic bromides. The structure of the new compounds was assigned by IR and NMR spectroscopy and confirmed by X-ray analysis for a representative compound. [ABSTRACT FROM AUTHOR]

1,3-Dipolar cycloadditions of nitrones with pentafluorosulfanyl-substituted acrylic ester and amides afforded new trisubstituted pentafluorosulfanylated isoxazolidines in moderate yields as 4-SF 5 -regioisomers. Theoretical calculations were carried out and the regioselectivity could be explained by the fact that the 5-SF 5 -regioisomer probably undertook a spontaneous degradation in the reaction medium via the loss of pentafluorosulfanyl anion. Diastereoselectivity of the 1,3-dipolar cycloadditions was also assessed according to NMR and X-ray diffraction analysis. [ABSTRACT FROM AUTHOR]

We have demonstrated that chiral 1-(1,3-dithian-2-yl)prop-2-en-1-ols as new scaffolds, obtained by enzyme-catalyzed kinetic resolution, undergo Suzuki-Miyaura cross-couplings and hydroformylation smoothly. Also, we have found that a 1,3-dithianyl group of the products can be removed without any erosion of the enantiopurity under mild conditions. A new access to a variety of enantiopure α-hydroxyaldehydes with ensured absolute configuration is described. [ABSTRACT FROM AUTHOR]

A concise stereocontrolled total synthesis of (−)-rhazinilam was achieved by the regioselective 1,3-dipolar cycloaddition of a fully elaborated optically active münchnone intermediate prepared from d -aspartic acid dimethyl ester. The regiochemistry of the 1,3-dipolar cycloaddition of münchnone intermediate to various arylacetylenes was also investigated. [ABSTRACT FROM AUTHOR]

An efficient method for the synthesis of functionalized phosphonopyrazolines has been developed. The procedure involved the microwave-assisted cycloaddition of diisopropyl diazomethylphosphonate to dipolarophiles, such as α,β-unsaturated-nitriles and -esters, performed in neat conditions. By oxidative aromatization the phosphonopyrazolines, thus obtained, were converted into the corresponding phosphonopyazoles. Alternatively, phosphonopyazoles could be obtained by a one-pot, two step procedure directly from dipolarophiles, thus avoiding the isolation of the intermediate pyrazolines. Full spectroscopic characterization of the compounds has been also reported. [ABSTRACT FROM AUTHOR]

The new spirocyclic compounds, spiropyrrolidinyl-benzoisothiazoline derivatives were synthesized by the 1,3-dipolar cycloaddition of benzoisothiazole-2,2-dioxide-3-ylidenes and azomethine ylide. The stereochemistry of 1,3-dipolar cycloaddition as well as the stereochemistry of Knoevenagel condensation of benzoisothiazole-2,2-dioxide with aldehydes were studied. [ABSTRACT FROM AUTHOR]

Abstract: Pyrrolidines, piperidines, and azepanes with annulated isoxazole, isoxazoline or isoxazolidine rings were prepared by intramolecular 1,3-dipolar cycloadditions of nitrones or nitrile oxides. The corresponding 1,3-dipoles were obtained from N-Boc-protected and N-allyl-, N-propargyl- or N-(3-butenyl)-substituted 2-aminoethanal or 3-aminopropanal. [Copyright &y& Elsevier]

Abstract: Chiral spiropyrazolinepenicillanates were obtained in a stereoselective fashion via 1,3-dipolar cycloaddition reactions of 6-alkylidenepenicillanates with diphenyldiazomethane, phenyldiazomethane, and diazomethane. Microwave-induced ring contraction of spiro-1-pyrazoline-β-lactams leading to chiral spirocyclopropylpenicillanates is also described. [Copyright &y& Elsevier]

Abstract: The cycloaddition reactions of 4-dimethylamino-1-alkoxycarbonylmethylpyridinium bromides with various 2-oxoindolin-3-ylidene derivatives in ethanol in the presence of triethylamine afforded the unprecedented dispirocyclopentanebisoxindole derivatives in good yields and in high diastereoselectivity. Under similar reaction conditions, the reactions of 1-alkoxycarbonylmethylpyridinium bromides with 3-phenacylideneoxindoles only resulted in 4-oxo-3-(2-oxoindolin-3-ylidene)-4-arylbutanoates. The stereochemistry of the complex spirooxindoles was established by 1H NMR data and single crystal structures. [Copyright &y& Elsevier]

A strategy for the 1,3-dipolar cycloaddition of nitrilimines to δ-allenoates has been developed to provide various 1,3,5-trisubstituted pyrazole-4-carboxylates and pyrazole-4 -carboxamide derivatives, which have excellent anticancer effects. This protocol exhibits characteristics of good yield, mild reaction condition, facile operation process and post-processing steps. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: The first novel protocol of the synthesis of 2-substituted benzo[f]isoindole-4,9-dione framework via the one-pot, 1,3-dipolar cycloaddition of quinones, paraformaldehyde and N-substituted amino ester hydrochlorides in the present of iodine at refluxing acetonitrile was reported. All these reactions proceed with good to excellent yields. The promising results obtained 1,3-dipolar cycloaddition will have the potential application in natural product exhibiting important biological activities. [Copyright &y& Elsevier]

Abstract: Polyhydroxylated pyrrolizidines bearing a methyl group at C-5 have been synthesized by 1,3-dipolar cycloaddition of five membered cyclic nitrones with methyl vinyl ketone followed by a N–O reductive cleavage and in situ intramolecular reductive amination. The stereochemistry of the obtained compounds is examined in relation to the reactions mechanism. [Copyright &y& Elsevier]

Abstract: Reactions of 3-nitro-2-trifluoro(trichloro)methyl-2H-chromenes, including 2-unsubstituted derivatives, with N-alkyl-α-amino acids (sarcosine, proline) and paraformaldehyde proceed diastereoselectively to give 1-benzopyrano[3,4-c]pyrrolidines in good yields as a result of a 1,3-dipolar cycloaddition of the intermediate nonstabilized azomethine ylide at the Δ3-bond of the chromene system. [Copyright &y& Elsevier]

Abstract: Theoretical calculations employed to investigate the diastereoselectivity of isoxazolidines and bicyclic [3,3,0]-isoxazolidines, obtained from the α,α-diphenylprolinol trimethylsilyl ether-catalyzed three-component domino reactions, revealed two different functions of the catalyst. In the synthesis of bicyclic [3,3,0]-isoxazolidine compounds, the catalyst's role was to facilitate the initial Michael reaction, but did not influence the stereochemistry of the bicyclic [3,3,0]-isoxazolidine. In the synthesis of isoxazolidines, the catalyst was involved in controlling the stereogenic centers on the isoxazolidine through hydrogen bonding and steric effects in the 1,3-dipolar cycloaddition step. Insights gained from our mechanistic investigations have enabled us to propose a scheme for the synthesis of bicyclic [3,3,0]-isoxazolidine compounds bearing six stereogenic centers. [Copyright &y& Elsevier]

Abstract: 1,3-Dipolar cycloadditions of dialkyl-substituted 2-benzylidenecyclopropane-1,1-dicarboxylates and a number of C-carbamoyl nitrones proceed with high efficiency and selectivity with the formation of single isomeric spiro[cyclopropane-1,4-isoxazolidine] cycloadduct. Obtained cycloadducts easily undergo cyclopropyl ring opening–cyclization to form new β-lactams fused with isoxazolidine ring in high yields. [Copyright &y& Elsevier]

Abstract: The effect of solvent nature on the reactions of pyridinium ylides with E-1,2-di(alkylsulfonyl)-1,2-dichloroethene was investigated for the first time. It was found, that in aprotic solvents (CHCl3, DMF, CH3CN) these reactions take place as a 1,3-dipolar cycloaddition (1,3-DC) followed by double elimination with the formation of substituted 1,2-di(alkylsulfonyl)indolizines. In a protic solvent (EtOH) in the presence of excess Et3N and heating, the reactions of substituted pyridinium salts with E-1,2-di(alkylsulfonyl)-1,2-dichloroethenes take place simultaneously as a 1,3-DC and as an addition–elimination (AdN–E1,5) and lead to the formation of 1,2-di(alkylsulfonyl)indolizines and 4,5-di(alkylsulfonyl)furans. [Copyright &y& Elsevier]

Abstract: A practical and efficient one-pot method for synthesis of a novel kind of N-attached 1,2,3-triazole-containing bisphosphonates was developed. Michael addition reaction of sodium azide with ethylidene bisphosphonates and 1,3-dipolar click cycloaddition were reasonably integrated into one-pot reaction in the presence of sonication. Vinylidene bisphosphonate, NaN3, and terminal alkyne were employed as the reactants, CuSO4·5H2O sodium ascorbate was employed as the catalyst system, and AcOH/H2O (1:1 v/v) were employed as the solvent system to create an acidic environment to achieve optimal efficiency. [Copyright &y& Elsevier]

A new strategy for the synthesis of 3-aryl-4-methyl-5-O-substituted isoxazolines via tandem catalytic isomerization of O-allyl systems to O-(1-propenyl) systems—1,3-dipolar cycloaddition (1,3-DC) to nitrile oxides is presented. The influence of the heteroatom in Ph-X-CH=CHCH3 (X=O, S, or Se) on the regio- and stereoselectivity of ArCNO 1,3-cycloaddition to these dipolarophiles is analyzed as well. The dipolarophiles were obtained via [RuClH(CO)(PPh3)3]–, [RuH2(CO)(PPh3)]– or base (KOH/18-crown-6)-catalyzed double bond migration in corresponding allyl ethers, O-allyl acetals, PhS– and PhSe–allyl systems. Cycloadditions of nitrile oxides to O-(1-propenyl) systems were fully regioselective whereas in the reactions of ArCNO with the PhS–(1-propenyl) and PhSe–(1-propenyl) systems both possible regioisomers were formed. It was established that within the majority of dipolarophiles of ROCH=CHCH3 type 1,3-DC is concerted, while for some dipolarophiles of RXCH=CHCH3 (X=O and R=Ph3C, 2,3-dihydroxypropyl, tetrahydropyran-2-yl; X=S or Se and R=Ph) type 1,3-DC turns into a two-step reaction with simultaneous rotation about C–C bond. The results of the experiments have been analyzed theoretically using DFT calculations. The results of these calculations agreed well with the experimental data. [Copyright &y& Elsevier]

Abstract: Two regioisomers of 2-arylpyrazolo[3,4-c]quinolin-4(5H)-ones and 2-arylpyrazolo[4,3-c]quinolin-4(5H)-ones were synthesized by utilizing 3-arylsydnones, ethyl 3-bromopropynoate, and 2-aminophenylboronic acid pinacol ester in presence of catalytic agent Pd(PPh3)4. This efficient one-pot synthesis methodology involved 1,3-dipolar cycloaddition, Suzuki coupling reaction, and intramolecular cyclization three sequence steps. [Copyright &y& Elsevier]

Abstract: Chiral spiro-β-lactam derivatives have been prepared via stereoselective 1,3-dipolar cycloaddition of 6-diazopenicillanates. Using dipolarophiles such as acrylonitrile, acrylates or methyl vinyl ketone spiro-2-pyrazoline-β-lactams were obtained, whereas the cycloaddition with N-substituted-maleimides afforded spiro-1-pyrazoline-β-lactams. 6-Diazopenicillanates also reacted with electron-deficient alkynes to give the corresponding spiro-3H-pyrazole-β-lactam as single product. The observed stereoselectivity can be explained considering that the major product results from the addition to the less sterically hindered α-side of the β-lactam. Microwave-induced denitrogenation of spiro-1-pyrazoline-β-lactams allowed the stereoselective synthesis of novel spirocyclopropyl-β-lactams. The rationalization of the observed selectivity was supported by electronic structure calculations. [Copyright &y& Elsevier]