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Here described an acid‐controlled regional diverse synthesized process of CF3‐containing ketoimines by the condensation of benzo[b]thiophene‐2,3‐dione and 2,2,2‐trifluoroethlamine. The imines obtained at either the 2‐position or 3‐position can be further used as substrates in asymmetric organocatalyzed [3+2]‐cycloaddition reactions, leading to a library of regiodiverse bispiro‐compounds with 85–96 % yield and 65–99 % ee. [ABSTRACT FROM AUTHOR]

The present minireview provides a survey of literature reports on the application of 3,3,3-trifluoropropene derivatives bearing sulfur-containing functional groups at positions 1 or 2 in the synthesis of functionalized five-membered heterocycles – pyrroles, pyrrolines, pyrrolidines, tetrahydrothiophenes, pyrazoles, pyrazolines, pyrazolidines, isoxazoles, isoxazolines, isoxazolidines, and triazoles via [3+2] cycloaddition reactions with 1,3-dipolarophiles. [ABSTRACT FROM AUTHOR]

In this computational study, density functional theory (DFT) calculations at the M06/6-311G(d,p) level of theory were employed to study the regio-, stereo-, and site-selectivities of 1,3-dipolar cycloadditions of benzonitrile oxide (BNO) with unsymmetrically substituted norbornenes and norbornadienes. The reactions between BNO and unsymmetrically-substituted 2-norbornes and unsymmetrically-substituted 2-norbornadienes proceed with the oxygen of the BNO attacking the more hindered side of the double bond in all cases except when strong EWGs are introduced. For the reaction between BNO and unsymmetrically-substituted 2-norbornadienes, varying degrees of selectivities are observed depending on the substituent, indicating that site-selectivity is largely influenced by nature of substituents. Generally, the regio-isomers in which the oxygen of the BNO is bonded to the more hindered side of the double bond are favored except when strong EWGs are introduced, and exo stereoisomers are generally favored over the endo stereo-isomers. Electrophilic (Pk +) and nucleophilic (Pk -) Parr functions computations are in complete agreement with the selectivity predicted by the activation barrier trends. [ABSTRACT FROM AUTHOR]

Microwave-assisted synthesis of N-methyl-2,3-diferrocenyl-4,4-dicyanopyrrolidine has been accomplished in moderate yields via a facile 1,3-dipolar cycloaddition and its crystal structure was determined by single-crystal X-ray diffraction (CCDC no. 1583719). It crystallizes: C27H25Fe2N3, Mr = 503.20, orthorhombic, P212121, a = 10.4873(9), b = 10.5251(10), c = 20.8587(19) Å, V = 2302.4(4) Å3, ρ = 1.452 g cm−3, Z = 4, T = 298(2) K. [ABSTRACT FROM AUTHOR]

Nitrilium betaine 1,3-dipoles are ubiquitous reagents in organic chemistry, with applications ranging from natural product synthesis to materials science. Given the high reactivity of these zwitterionic motifs, they are invariably generated in situ from a suitable precursor, prior to use. This short review summarises the recent progress in the development of modern approaches towards the formation of these 1,3-dipoles, and their applications within a diverse range of fields. 1 Introduction 2 Nitrile Ylides 2.1 2 H -Azirine Rearrangement 2.2 Addition of Nitriles to Carbenes 3 Nitrile Imines 3.1 2,5-Tetrazole Thermolysis 3.2 2,5-Tetrazole Photolysis 3.3 Diaryl Sydnone Photolysis 4 Nitrile Oxides 4.1 Hypervalent Iodine 4.2 The Nitroso Radical 4.3 Green Chemistry Approaches 4.4 Other Approaches 5 Conclusions [ABSTRACT FROM AUTHOR]

A highly stereoselective 1,3‐dipolar [6+4] cycloaddition towards bridged azabicyclo[4.3.1]decane scaffolds has been developed, reacting aldehydes, 2‐aminomalonates and tropone under mild conditions in the presence of a chiral phosphoric acid catalyst. The scope is demonstrated for a series of aldehydes and 2‐aminomalonates, and the reaction proceeds in high yields, >95:5 d.r. and up to 99 % ee. A series of transformations, as well as a mechanistic proposal, are presented. [ABSTRACT FROM AUTHOR]

Involving the cyano group of N‐cyano sulfoximines in [3+2]‐cycloaddition reactions with 1,3‐dipoles provides practical routes for the construction of 5‐membered heterocycles bearing sulfoximinoyl moieties. An ytterbium‐catalyzed cycloaddition utilizing hydrazonoyl chlorides was developed, as well as a reaction involving imidoyl chlorides proceeding without the aid of a catalyst. Following these protocols, a range of sulfoximines with N‐1,2,4‐triazolyl and N‐1,2,4‐oxadiazolyl substituents was prepared. [ABSTRACT FROM AUTHOR]

The electronic structure of molecules is routinely assessed using a number of methodologies including Bader's Quantum Theory of Atoms in Molecules (QTAIM) and Weinhold's Natural Bond Orbital/Natural Resonance Theory (NBO/NRT). Previously these methods were applied to the study of isothiirane; however, the results obtained were incongruous with one another: the QTAIM analysis suggested an acyclic structure while NRT indicated a cyclic structure. The previous results assume the NRT description to be correct despite limitations in the analysis, while Foroutan‐Nejad et al. (Chem. Eur. J. 2014, 20, 10140) employed a multiple molecular graph analysis to resolve the QTAIM discrepancy. In this work, we re‐examine the electronic structure of isothiirane, employing a detailed NRT analysis and the catastrophe theory model originally described by Bader for the study of three‐membered ring systems; additional analysis is performed using NMR tensor calculations and studying substituent effects. A congruous description of the electronic structure of isothiirane and the substituted versions is achieved using all modes of analysis. These results highlight how the careful application of commonly used methodologies can achieve a unified description of electronic structure. © 2018 Wiley Periodicals, Inc. The electronic structure of isothiirane is studied using a combined QTAIM, NRT, 13C NMR tensor, and substituent effect analysis. The inner workings of the analysis tools used are critically evaluated. In opposition to previous analysis, which was in disagreement on the electronic structure, isothiirane is described as a hybrid of a carbene and zwitterion (1,3‐dipole). The given methodology can be used to determine any molecules electronic structure and isothiirane may be a new moiety for use in cycloaddition chemistry. [ABSTRACT FROM AUTHOR]

Chemistry of nitro groups and nitro compounds has long been intensively studied. Despite their long history, new reactions and methodologies are still being found today. This is due to the diverse reactivity of the nitro group. The importance of nitro chemistry will continue to increase in the future in terms of elaborate synthesis. In this article, we will take a walk through the recent advances in nitro chemistry that have been made in past decades.

This note describes a novel reaction cascade in which a tosylhydrazone derivative of eucarvone undergoes a non-classical dimerization process under basic conditions. The key step in this sequence is a dipolar cycloaddition between a diazo species and a transient cyclopropene. A proposed mechanism for this sequence is presented that is supported by single crystal X-ray analysis of the resulting dimer. We believe this unique transformation is of note as it highlights a neat and efficient entry to complex polycyclic architectures containing an embedded pyrazoline moiety.

The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics.

We describe herein studies on the cycloaddition of phospha-Münchnones and alkenes, and the factors that influence selectivity between 2-pyrrolines and bicyclic products. Coupling this cycloaddition with the formation of the dipoles can provide a one-pot route to synthesize 2-pyrrolines in moderate yield from imines, acid chlorides and alkenes. [ABSTRACT FROM AUTHOR]

Nitrile oxides afford 2-isoxazoline heterocycles through [2 + 3] cycloaddition reactions with alkenes. These heterocycles can be converted to useful intermediates, such as β-hydroxy ketones and γ-amino alcohols, leading to pharmaceutical and agrochemical compounds. However, nitrile oxides directly connected to a carbonyl group show low reactivity owing to the decrease in energy of the dipole HOMO. Furthermore, when dissymmetric internal alkenes are used, regioselective control is difficult. Herein, we have designed nitrile oxides bound to alkenes through the oxime group and demonstrated their intramolecular [2 + 3] cycloaddition reactions. The desired cycloadducts were obtained in high yields and as single regioisomers. Furthermore, face-selective cycloaddition reactions were achieved by introducing a stereocenter into the linker moiety, affording the desired cycloadducts with good diastereoselectivity. [Display omitted] [ABSTRACT FROM AUTHOR]

The coupling of proline- and azetidinone-substituted alkenes to 2-azidobenzoic and 2-azidobenzenesulfonic acid gives precursors that undergo intramolecular azide to alkene 1,3-dipolar cycloadditions to give imine-, triazoline- or aziridine-containing pyrrolo[1,4]benzodiazepines (PBDs), pyrrolo[1,2,5]benzothiadiazepines (PBTDs), and azetidino[1,4]benzodiazepines. The imines and aziridines are formed after loss of nitrogen from a triazoline cycloadduct. The PBDs are a potent class of antitumour antibiotics. [ABSTRACT FROM AUTHOR]

A method based on hydroamination mediated by inorganic base was developed for the synthesis of cyclic nitrones from alkenyl oximes. DFT calculations of the reaction pathway suggested that this hydroamination could proceed through an unprecedented nucleophilic amination of the unactivated alkene by the oxime nitrogen atom. The transition state of this reaction is stabilized by an ionic interaction between a metal cation such as K+ and the oxime oxygen and negatively charged alkene moiety. [ABSTRACT FROM AUTHOR]

Abstract: A facile one-pot synthesis of pyrrolidinyl-spirooxindole grafted 3-nitrochromanes has been accomplished by 1,3-dipolar cycloaddition (1,3-DC) reaction of 3-nitrochromenes with azomethine ylides generated in situ from isatin and secondary amino acids. The regio- and stereochemical outcome of the cycloaddition reaction was ascertained by X-ray crystallographic analysis. [Copyright &y& Elsevier]

New fused tetrazolone derivatives were synthesized using homophthalic and maleic anhydrides. Treatment of anhydrides with trimethylsilyl azide opened the lactone rings and formed the corresponding intermediates, which bore 1,3-dipole and dipolarophile functionalities in ortho positions. The intermediates partially underwent internal 1,3-dipolar cycloaddition to produce fused tetrazolone derivatives. When the carbonyl groups in anhydride were not conjugated with any double bond, then a triazine-fused tetrazolone derivative was formed. [ABSTRACT FROM AUTHOR]

Thermally initiated combined intra-intermolecular criss-cross cycloadditions of substituted nonsymmetrical allenyl azines with isocyanate or isothiocyanate dipolarophiles were investigated. Substituted 1,3,10-triazatricyclo[5.2.1.0]dec-6-en-2-ones or -dec-6-ene-2-thiones were obtained as the main products in moderate to very good yields. The thermal stabilities of the tricyclic adducts in reactions with the competing reactive dipolarophile dimethyl acetylenedicarboxylate were studied and are discussed. In some cases, substituted 5,6-dihydro-4 H-pyrrolo[1,2- b]pyrazoles were found as side products. This reaction showed high atom economy and in all cases we observed the presence of one diastereoisomer and regioisomer only, which was clearly revealed by crystallographic analysis. Graphical abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: Radiofluorination via [3+2]-nitrone-alkene cycloaddition was studied using the model reaction between 18F-labeled C-(4-fluorophenyl)-N-phenyl nitrone ([18F]1) and substituted maleimides 2a–c. [18F]1 was prepared in RCY of 73.6±5.8% and radiochemical purity of >95%. Cycloaddition of [18F]1 to 2a in toluene at 80°C and in EtOH at 110°C gave the respective isoxazolidine [18F]5a in >80% RCY at 10min reaction time. Reaction between [18F]1 and 2b, c also went smoothly to afford the respective cycloaddition products in high radiochemical yields. [Copyright &y& Elsevier]

Abstract: An efficient and highly diastereoselective synthesis of highly substituted tetrahydrofurans from the reaction of a vicinal t-butyldiphenylsilylmethyl-substituted cyclopropyl diester with aldehydes and ketones has been developed. The 2,5-cis-disubstitution predominates over the 2,5-trans-disubstitution by as much as 12:1. The reaction with cyclic ketones generates spiro-fused tetrahydrofurans in good yields. [Copyright &y& Elsevier]

Abstract: The transition metal catalyzed reaction of α-diazo carbonyl compounds has found numerous applications in organic synthesis, and its use in either heterocyclic or carbocyclic ring formation is well precedented. In contrast to other catalysts that are suitable for carbenoid reactions of diazo compounds, those constructed with the dirhodium(II) framework are most amenable to ligand modification that, in turn, can influence reaction selectivity. The reaction of rhodium carbenoids with carbonyl groups represents a very efficient method for generating carbonyl ylide dipoles. Rhodium-mediated carbenoid–carbonyl cyclization reactions have been extensively utilized as a powerful method for the construction of a variety of novel polycyclic ring systems. This article will emphasize some of the more recent synthetic applications of the tandem rhodium carbenoid cyclization/cycloaddition cascade for natural product synthesis. Discussion centers on the chemical behavior of the rhodium metal carbenoid complex that is often affected by the nature of the ligand groups attached to the metal center. [Copyright &y& Elsevier]

The [3+2] and [1+2] cycloaddition pathways between ethene and a series of 13 nitrilimines (R1CNNR2) have been examined by density functional theory [PBE0/6-311++G(2df,pd)] calculations. All reactions have low barriers ranging from 14.14 (R1 = CH3, R2 = H) to 1.01 (R1 = R2 = F) kcal mol–1, and large reaction exothermicities consistent with the transient nature of nitrilimines. The [3+2] and [1+2] transition-state structures are very similar, mainly differing in the relative orientation of their fragments and the newly forming C—C bond distance, and exhibit only minor deviations from the structures of the reactants. Both reaction pathways are concerted and asynchronous, but the [1+2] reaction has a greater degree of asynchronicity. Examination of the frontier molecular orbitals reveals that both the [3+2] and [1+2] barrier heights are related to two sets of orbital interactions, with the interaction between the lowest unoccupied molecular orbital π of nitrilimine and the highest occupied molecular orbital of ethene in common. The second interaction in both cases is carbene-like. A relationship between the weights of the 1,3-dipolar resonance contribution in the various nitrilimines and the corresponding [3+2] barrier heights was not found, but a good correlation could be found between the [1+2] barrier heights and both the 1,3-dipolar and carbene contributions. Inspection of the potential energy surface in the vicinity of the two transition states for the reaction between unsubstituted nitrilimine and ethene suggests that the observed [3+2] product is a result of an initial carbene-like approach of the two fragments followed by a ridge bifurcation that leads to the [3+2] product minimum. [ABSTRACT FROM AUTHOR]

A series of novel N-methyl spiropyrrolidines have been synthesized in good yield by the cycloaddition reaction of azomethine ylides generated by a decarboxylative route from sarcosine and paraformaldehyde with conformationally locked s-trans enone functionality present in the (E)-3-arylidene-4-chromanone as dipolarophiles. The structure of the title compound was established by spectroscopic techniques. [ABSTRACT FROM AUTHOR]

Abstract: The 1,3-dipolar cycloaddition of an azomethine ylide, generated from isatin and benzylamine by a 1,5-prototopic shift route with various p-substituted 2,6-bis(arylmethylidene)cyclohexanones under different conditions, proceeded regioselectively to give novel dispiroheterocycles. The product on subsequent annulation with hydrazine hydrate afforded 4-aryl-5-phenyl(spiro[2.3″]oxindole)3′-aryl-3′,3a′,4′,5′,6′,7′-hexahydro-2H-indazolospiro[7′.3]pyrrolidines in good yield. [Copyright &y& Elsevier]

In the reactions of cobaltadithiolene complexes [CpCo(S2C2Z2)] (Z=CN, COOMe, Ph, Me) with aryl azides, two types of substitution reactions occurred. One is the replacements of the sulfur of cobaltadithiolene by arylimido groups and the other is the replacements of the S&z.sbnd;CZ&z.dbnd6;CZ moiety of cobaltadithiolene. The product of latter reaction was also formed by the reactions of the metal cluster complex [Cp4Co4S6] with aryl azides. The azides with electron-donating substituents gave these products in higher yields than those with electron-withdrawing substituents. In these reactions, arylnitrenes as intermediates were predictable. The reactions of [CpCo(dmit)] (dmit=C3S5) with phenyl azide and tosyl azide led to the replacements of the terminal sulfur (C&z.dbnd6;S) of the dmit ligand by imido groups to give novel imine complexes [CpCo(S2C2S2C&z.dbnd6;NR)] (R=Ph, Ts). [Copyright &y& Elsevier]