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Application of molecular electron density theory (MEDT) to investigate the [5+2] cycloaddition reaction between oxidopyrylium and ethervinylether, we discovered that oxidopyrylium is an electrophile and ethervinylether is a nucleophile by an examination of conceptual DFT indices. Analysis of energetical parameters shows clearly that this cycloaddition is both regio- and stereoselective, which is extremely consistent with the experience. Topological analysis of the electron localization function (ELF) has shown that this [5+2] cycloaddition is achieved by a two-step, single-step mechanism along the most favored route. Aside from that, docking outcomes show that the (1–20) oxabicyclo[3.2.1]octene derivatives have a significant anti-HIV potential. [ABSTRACT FROM AUTHOR]

The given text is a scientific research article that explores the synthesis and characterization of various compounds using different reactions and starting materials. The compounds synthesized include isoxazolines, pyrazolines, isoxazolidines, cinnamyl- and indenyl-linked moieties, and 2-phosphorylated 2,5-dihydrofurans. The document provides detailed information on the reaction conditions, yields, physical properties, and spectroscopic data of the synthesized compounds. The information presented can be useful for researchers studying the synthesis and characterization of these compounds. [Extracted from the article]

Comprehensive Summary: A new family of dibenzoullazine derivatives was synthesized through 1,3‐dipolar cycloaddition of polycyclic aromatic azomethine ylides with alkynylbenziodoxoles followed by oxidation. The benziodoxole moiety in the resulting products was used as a versatile linchpin for the synthesis of structurally diverse functional dibenzoullazines that are difficult to access by other synthetic methods. [ABSTRACT FROM AUTHOR]

An asymmetric 1,3‐dipolar cycloaddition of β‐fluoroalkylated α,β‐unsaturated 2‐acyl imidazole with nitrones or N,N'‐cyclic azomethine imines to construct chiral α‐fluoroalkylated γ‐amino alcohols or chiral α‐fluoroalkylated 1,3‐diamino compounds has catalyzed by chiral‐at‐metal rhodium complexes is reported. The corresponding products with three contiguous tertiary stereocenters were obtained in 62%–98% yields with stereoselectivities up to >20:1 dr and 99% ee. Remarkably, as low as 0.06 mol% of chiral‐at‐metal rhodium complex can promote a gram‐scale reaction with nitrones or N,N'‐cyclic azomethine imines. [ABSTRACT FROM AUTHOR]

The manuscript presents an efficient method for the synthesis of various cis-azetidin-2-ones with high regio- and diastereoselectivity. This approach utilizes Kinugasa reaction involving diverse functionalized nitrones, including diaryl nitrones and α,β-unsaturated nitrones, in conjunction with acetylenic alcohols. Copper (I) serves as a catalyst to facilitate the transformation. [ABSTRACT FROM AUTHOR]

The reaction of 1-(3-(furan-2-yl)-5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl)ethan-1-one 1 with dimethylformamide dimethyl acetal (DMF-DMA) afforded 3-(dimethylamino)-1-(3-(furan-2-yl)-5-methyl-1-(4-nitrophenyl)-1H-pyrazol-4-yl)prop-2-en-1-one 2. Then the treatment of enaminone 2 with the appropriate hydrazonoyl halides 3a–f in chloroform in the presence of triethylamine at reflux gave novel bipyrazolyl methanone derivatives 4a–f. The novel bipyrazole derivatives 4a–c and 4d–f reacted with hydrazine hydrate in ethanol at reflux to give the corresponding pyrazolopyridazinones 9a–c and pyrazolopyridazines 10d–f, respectively. Stirring of hydroximoyl chlorides 11a,b with enaminone 2 in chloroform in the presence of triethylamine at room temperature afforded isoxazole derivatives 12a,b. The reaction of isoxazoles 12a,b with hydrazine hydrate in refluxing ethanol gave the corresponding isoxazolopyridazines 14a,b. [ABSTRACT FROM AUTHOR]

Herein, we have synthesized multifunctionalized 2‐oxa‐3‐azabicyclo[3.1.1]heptanes, which are considered potential bioisosteres for meta‐substituted arenes, through Eu(OTf)3‐catalyzed formal dipolar [4π+2σ] cycloaddition of bicyclo[1.1.0]butanes with nitrones. This methodology represents the initial instance of fabricating bicyclo[3.1.1]heptanes adorned with multiple heteroatoms. The protocol exhibits both mild reaction conditions and a good tolerance for various functional groups. Computational density functional theory calculations support that the reaction mechanism likely involves a nucleophilic addition of nitrones to bicyclo[1.1.0]butanes, succeeded by an intramolecular cyclization. The synthetic utility of this novel protocol has been demonstrated in the concise synthesis of the analogue of Rupatadine. [ABSTRACT FROM AUTHOR]

Herein, we have synthesized multifunctionalized 2‐oxa‐3‐azabicyclo[3.1.1]heptanes, which are considered potential bioisosteres for meta‐substituted arenes, through Eu(OTf)3‐catalyzed formal dipolar [4π+2σ] cycloaddition of bicyclo[1.1.0]butanes with nitrones. This methodology represents the initial instance of fabricating bicyclo[3.1.1]heptanes adorned with multiple heteroatoms. The protocol exhibits both mild reaction conditions and a good tolerance for various functional groups. Computational density functional theory calculations support that the reaction mechanism likely involves a nucleophilic addition of nitrones to bicyclo[1.1.0]butanes, succeeded by an intramolecular cyclization. The synthetic utility of this novel protocol has been demonstrated in the concise synthesis of the analogue of Rupatadine. [ABSTRACT FROM AUTHOR]

This article discusses the synthesis of hybrid molecules using natural building blocks in medicinal chemistry. The authors focus on lappaconitine and talatisamine, two diterpene alkaloids with broad physiological activities. They explore the use of sulfolane and its derivatives as pharmacologically significant fragments, highlighting their various pharmacological effects and low toxicities. The article presents the synthesis of previously unreported isoxazolidines using microwave irradiation and provides NMR spectral data for the obtained products. The authors acknowledge the support of a research project focused on the synthesis of biologically active compounds based on natural compounds. [Extracted from the article]

Herein, we report a new synthetic route to 1,4-epoxy-2-aryltetrahydro-1-benzazepine derivatives with high efficiency, namely the Rh(III)-catalyzed C–H allylation of nitrones with allyl precursors, followed by subsequent intramolecular 1,3-dipolar cycloaddition, to deliver the title compounds. This reaction is regio- and stereo-selective, generating the cis-isomer with a broad substrate scope and good functional group tolerance. [ABSTRACT FROM AUTHOR]

Design of spirocyclic scaffolds, which are able for direct interaction with biological targets, is a developing trend in medicinal chemistry. In continuation of the previous work on HIV‐1 inhibitors, a synthetic approach towards spiro[imidazole‐4,3′‐pyrrolo[1,2‐a]quinolin]‐5‐ones via 1,3‐dipolar cycloaddition of quinolinium ylides with arylydeneimidazol‐4‐ones was outlined. Derivatives with various substitution pattern were prepared in 42–86 % yields. Use of 2,2,2‐trifluoroethanol as a solvent is crucial for successful preparation of the derivatives, its role is sought as prolonging lifetime of the cycloadducts. [ABSTRACT FROM AUTHOR]

A novel approach for the synthesis of unsaturated 7-membered lactones by Pd-catalyzed [5+2] dipolar cycloaddition of vinylethylene carbonates (VECs) and C5-substituted Meldrum's acid derivatives has been developed. Various Meldrum's acid derivatives worked well in this reaction under mild reaction conditions. A variety of 7-membered lactones can be accessed in a facile manner in moderate to good yields by employing easily prepared Meldrum's acid derivatives. [ABSTRACT FROM AUTHOR]

Cycloheptatrienyl (tropyl) molecules are representative non‐alternant hydrocarbons that offer interesting chemistry because of their unique structures and properties. However, there have been a limited number of polycyclic aromatic tropyl cations and radicals reported in the literature. Herein, we report the synthesis of a series of azahomocorannulene derivatives, where the key reactions are a 1,3‐dipolar cycloaddition of polycyclic aromatic azomethine ylides with dibenzotropone and a subsequent palladium‐catalyzed cyclization. X‐ray diffraction analysis revealed that the obtained azahomocorannulenyl cation and radical adopt planar structures and exhibit unique packing structures. Their electronic and optical properties were investigated experimentally and theoretically to reveal their aromatic character. [ABSTRACT FROM AUTHOR]

N‐Selective carbamoylation reaction of oximes with isocyanates generates nitrones, which undergo 1,3‐dipolar cycloaddition with various dipolarophiles to afford diverse isoxazolidines. Notably, combinations of highly electron‐rich oxime and highly electron‐deficient dipolarophile exhibited high reactivity, with product yields of up to 94 %. The substituent on the isoxazolidine‐nitrogen atom could be successfully removed without loss of the cyclic structure. Computational studies have also elucidated the mechanism of the reaction and origin of stereoselectivity. [ABSTRACT FROM AUTHOR]

Cycloheptatrienyl (tropyl) molecules are representative non‐alternant hydrocarbons that offer interesting chemistry because of their unique structures and properties. However, there have been a limited number of polycyclic aromatic tropyl cations and radicals reported in the literature. Herein, we report the synthesis of a series of azahomocorannulene derivatives, where the key reactions are a 1,3‐dipolar cycloaddition of polycyclic aromatic azomethine ylides with dibenzotropone and a subsequent palladium‐catalyzed cyclization. X‐ray diffraction analysis revealed that the obtained azahomocorannulenyl cation and radical adopt planar structures and exhibit unique packing structures. Their electronic and optical properties were investigated experimentally and theoretically to reveal their aromatic character. [ABSTRACT FROM AUTHOR]

Highly stereoselective 1,3-dipolar cycloaddition allowed the synthesis of the original stable TN antigen mimic presenting a constraint on the amino acid part. Two main conformations of the GalNAc moiety were detected by molecular modelling and NMR. A ligand/protein interaction study was performed by saturation transfer difference NMR analyses using two GalNAc-specific model lectins highlighting that the constrained C-glycoside analog was recognized by these proteins as well as the TN antigen derivative. [ABSTRACT FROM AUTHOR]

This article explores the synthesis of vinyloxaziridines from conjugated nitrones using visible-light-promoted cycloisomerization. Previous attempts to synthesize oxaziridines under photochemical conditions have been unsuccessful, but the authors of this study discovered a successful method using benzaldehyde and benzylhydroxylamine hydrochloride. Further optimization of the reaction led to high yields of vinyloxaziridines. The study also found that substituted cinnamaldehydes and enals were ideal for the reaction, and changing the electronic nature of the cinnamyl ring did not affect the efficiency. The research provides valuable insights into the synthesis of complex nitrogen-containing heterocycles and suggests potential for further research in this area. [Extracted from the article]

Isoxazolidine derivatives were designed, synthesized, and characterized using different spectroscopic techniques and elemental analysis and then evaluated for their ability to inhibit both α-amylase and α-glucosidase enzymes to treat diabetes. All synthesized derivatives demonstrated a varying range of activity, with IC50 values ranging from 53.03 ± 0.106 to 232.8 ± 0.517 μM (α-amylase) and from 94.33 ± 0.282 to 258.7 ± 0.521 μM (α-glucosidase), revealing their high potency compared to the reference drug, acarbose (IC50 = 296.6 ± 0.825 µM and 780.4 ± 0.346 µM), respectively. Specifically, in vitro results revealed that compound 5d achieved the most inhibitory activity with IC50 values of 5.59-fold and 8.27-fold, respectively, toward both enzymes, followed by 5b. Kinetic studies revealed that compound 5d inhibits both enzymes in a competitive mode. Based on the structure–activity relationship (SAR) study, it was concluded that various substitution patterns of the substituent(s) influenced the inhibitory activities of both enzymes. The server pkCSM was used to predict the pharmacokinetics and drug-likeness properties for 5d, which afforded good oral bioavailability. Additionally, compound 5d was subjected to molecular docking to gain insights into its binding mode interactions with the target enzymes. Moreover, via molecular dynamics (MD) simulation analysis, it maintained stability throughout 100 ns. This suggests that 5d possesses the potential to simultaneously target both enzymes effectively, making it advantageous for the development of antidiabetic medications. [ABSTRACT FROM AUTHOR]

This article provides a comprehensive overview of the synthesis and characterization of luminescent substances containing azole motifs, specifically focusing on pyrazole derivatives. The authors explore different synthetic routes and reactions with hydrazines to develop more efficient methods for the synthesis of ethynylpyrazoles and ethynylpyrazolines. They also discuss the potential applications of the synthesized compounds in medicinal, agricultural, and materials science fields. The article includes experimental results, discusses reaction mechanisms, and provides data to support their findings. This resource is valuable for library patrons conducting research on azole compounds and their applications. [Extracted from the article]

The reaction of 1-vinyl-4,5-dihydro-1H-benzo[g]indole with C-aryl-N-methylnitrones in the presence of nickel (II) perchlorate proceeds regioselectively to form a mixture of diastereomeric adducts of formal (3+3) cycloaddition, whereas the main products of the reaction with C,N-diarylnitrones are dipyrromethanes. [ABSTRACT FROM AUTHOR]

Isoxazolidine, isoxazole, and isoquinolinone rings are present in the structure of several natural products and/or pharmaceutically interesting compounds. In this work, facile and efficient pathways have been developed for the preparation of fused frameworks bearing those heterocycles. The successful approaches for both isoxazolidine/isoquinolinone and isoxazole/isoquinolinone hybrid syntheses relied initially on 1,3-dipolar cycloadditions of nitrones and nitrile oxides to indenone and 2-propargylbenzamide, respectively. The construction of the isoquinolinone lactam system followed by performing a selective Schmidt reaction for isoxazolidine derivatives (two steps overall), whereas the isoxazole lactams were reached via an Ullmann-type cyclisation (three steps overall). Key observations were made regarding the stereo- and regioselectivities of the reactions employed, and small libraries of the targeted hybrids were prepared, demonstrating the general applicability of these strategies. [ABSTRACT FROM AUTHOR]

Metal‐free cycloaddition reactions between a diazido‐diborane and alkynes are used to synthesize new ditriazolyl‐diborane molecules, a bis(ferrocenyl‐1,2,3‐triazolyl)‐diborane and a bis(2‐pyridyl‐1,2,3‐triazolyl)‐diborane. Then, the bis(2‐pyridyl‐1,2,3‐triazolyl)‐diborane was used as polydentate ligand for the synthesis of larger architectures. Reaction with ditriflato‐diborane yielded a tetracationic hexaboron compound, and reaction with metal salts yielded dicationic ring compounds with two hexacoordinate metal atoms and two integrated diborane units. [ABSTRACT FROM AUTHOR]

1‐Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO2S−NCO, to give spirocyclic β‐lactams. Reduction of the β‐lactam ring with alane produced 1‐azaspiro[3.3]heptanes. Incorporation of this core into the anesthetic drug bupivacaine instead of the piperidine fragment resulted in a new patent‐free analogue with high activity. [ABSTRACT FROM AUTHOR]

1‐Azaspiro[3.3]heptanes were synthesized, characterized, and validated biologically as bioisosteres of piperidine. The key synthesis step was thermal [2+2] cycloaddition between endocyclic alkenes and the Graf isocyanate, ClO2S−NCO, to give spirocyclic β‐lactams. Reduction of the β‐lactam ring with alane produced 1‐azaspiro[3.3]heptanes. Incorporation of this core into the anesthetic drug bupivacaine instead of the piperidine fragment resulted in a new patent‐free analogue with high activity. [ABSTRACT FROM AUTHOR]

A two-step, one-pot synthesis of 3-substituted 1H-dibenzo[e,g]indazoles in good to high yields via a LiOtBu-promoted intramolecular 1,3-dipolar cyclization of 2′-alkynyl-biaryl-2-aldehyde N-tosylhydrazones was developed. The N-Ts-hydrazones used were prepared in situ via the reactions of 2′-alkynyl-biaryl-2-aldehydes and TsNHNH2 (p-methylbenzenesulfonohydrazide). Two types of signals related to the hydrogen bonds, forming in several products, were observed in the 1H NMR spectra recorded in DMSO-d6, assigned to N-H bonds in their dimeric species of product and tautomer. [ABSTRACT FROM AUTHOR]

Herein we have reported an expedient di‐functionalization of such versatile scaffolds. By harnessing an under explored reactivity of N‐aminopyridinium ylides, we have developed an aminopyridylation of N‐substituted maleimides and 1, 4‐quinones at room temperature in 2‐methyl THF without any external reagents. The [3+2] cycloaddition of N‐aminopyridinium ylides generate the corresponding cycloadduct with various maleimides and 1, 4‐quinone substrates, which rapidly undergoes oxidation at the alkene moiety under open air, inducing a considerable driving force, thermodynamically, to facilitate aromatisation of the pyridine and a subsequent homolytic cleavage of the N−N bond to generate the desired 2, 3‐aminopyridylated products in good to excellent yield. Experimental and computational studies clarify the reaction mechanism. [ABSTRACT FROM AUTHOR]

The stereodivergent asymmetric synthesis of 2,5‐trans/cis pyrrolidines by 1,3‐dipolar cycloaddition using two different types of activated alkenes is described. When ylidene‐isoxazolones were employed as dipolarophiles, the Ag/(S,Sp)‐iPr‐FcPHOX‐catalyzed asymmetric [3+2] cycloaddition of imino lactones proceeded with 2,5‐trans selectivity. Subsequent decarboxylation of the isoxazolone rings produced pyrrolidines with 2,5‐trans stereoretention. In the reaction using acyclic enones as activated alkenes, the Ag/(R,Sp)‐ThioClickFerrophos complex‐catalyzed asymmetric [3+2] cycloaddition afforded 2,5‐cis substituted pyrrolidines in high yields and enantioselectivities. Therefore, these methods can be considered as a formal stereodivergent synthesis of 2,5‐cis/trans pyrrolidines. [ABSTRACT FROM AUTHOR]

δ,ϵ‐Unsaturated oximes, on heating with O‐alkyl S‐(pyridin‐2‐yl)carbonothioates (PySCO2R) in refluxing toluene, undergo intramolecular cycloaddition to give N‐alkoxycarbonylated multi‐cyclic compounds. Mechanistic studies indicate that the reaction involves direct generation of N‐alkoxycarbonyl nitrones followed by cycloaddition, instead of intramolecular oxime‐olefin cycloaddition (IOOC) followed by alkoxycarbonylation. DFT calculation indicates that N‐alkoxycarbonylation of oxime with PySCO2R is a concerted reaction. The reaction of oxime with a chiral alkoxycarbonylation reagent exhibits a reasonably high diastereo‐face selectivity. [ABSTRACT FROM AUTHOR]

Readily available hydroxamic acids were leveraged to access challenging nitrones in the presence of H3PO4 as a Brønsted acid catalyst and engaged in an intramolecular (3+2) annulation reaction to make valuable cyclopentane-fused isoxazolidines with high yields and excellent diastereoselectivity. The products were further utilized in a unique base-promoted benzilic amide rearrangement to provide cyclopentane-fused γ-lactams bearing three contiguous stereocenters as a single diastereomer. [ABSTRACT FROM AUTHOR]

The 1,3-dipolar cycloaddition of 1H-pyrrole-2,3-diones to azomethine ylides generated in situ by the condensation of L-proline and arylcarbaldehydes proceeds regio- and diastereoselectively to form substituted ethyl 1,2,5',6',7',7a'-hexahydro-3'H-spiro[pyrrole-3,2'-pyrrolo[2,1-b]oxazole]-4-carboxylates. The structure of the synthesized ethyl (3R*,3'R*,7a'S*)-3'-(4-bromophenyl)-2-oxo-1,5-diphenyl-1,2,5',6',7',7a'-hexahydro-3'H-spiro[pyrrole-3,2'-pyrrolo[2,1-b]oxazole]-4-carboxylate was confirmed by single crystal X-ray analysis. [ABSTRACT FROM AUTHOR]

4, 4'-(Bicyclo (2.2.1) hept-5-en-2 yl methylene) bis (2-methoxyphenol) (BPA-NB) was utilized as a step-growth monomer for the synthesis of (co)poly(ether ether ketone)s (PEEK-NBs) via nucleophilic aromatic substitution polycondensation. A homo and five PEEK-NBs were synthesized by polycondensation of 4, 4'-difluorobenzophenone with BPA-NB and various compositions of BPA-NB and bisphenol-A, respectively. 1H NMR spectroscopy confirmed the chemical structure and composition of PEEK-NBs. Inherent viscosity and number-average molecular weight values of PEEK-NBs were in the range 0.64 to 0.78 dL g−1 and 62,670 to 84,470 g mol−1, respectively, indicating the formation of polymers of reasonably high molecular weight. It was easy to dissolve PEEK-NBs in common organic solvents such as chloroform, dichloromethane, and tetrahydrofuran. Tough, transparent, and flexible films of PEEK-NBs could be cast from chloroform solution. X-Ray diffraction studies indicated amorphous nature of PEEK-NBs. Glass transition temperature (Tg) values, determined by DSC analysis, of PEEK-NBs were in the range 163 to190 °C and Tg values increased with the increase in mol % of BPA-NB. The post-polymerization modification of a representative PEEK-NB was demonstrated using two azido compounds, namely, 4-(azidomethyl)-7-methoxy-2H-chromen-2-one and 9-(azidomethyl)anthracene, via metal-free azide-alkene 1,3-dipolar cycloaddition reaction to obtain copoly(ether ether ketone)s appended with coumarinyl and anthracenyl moieties, respectively. [ABSTRACT FROM AUTHOR]

Hydrogen bonding greatly influences rates and equilibrium positions of chemical reactions, conformations, and sometimes even stereochemistry. This study reports on tetranitrofluorenone oximate, a novel dye capable of naked‐eye detection of hydrogen‐bond donating species (HBDs) and of rapid determination of H‐bond donation strength by hypsochromic shift monitoring. In addition, the molecule possesses atropisomeric conformations, of M and P configuration, as evidenced in solid and solution state studies by X‐ray diffraction and electronic circular dichroism (ECD), respectively. In the latter case, enantiopure bis‐thioureas were the most effective HBDs to promote a chiral induction (diastereoselective recognition, Pfeiffer effect); the ECD results being rationalized by time‐dependent density functional theory (TDDFT) calculations. Based on these experiments, bis‐thioureas were used as chiral reagents in asymmetric 1,3‐dipolar cycloadditions of structurally‐related nitrones; the ECD sensing of the stereoinduction between bis‐thioureas and the oximate serving as an indirect method of selection of the most effective HBD for asymmetric synthesis. [ABSTRACT FROM AUTHOR]

Gold‐catalyzed cascade reactions between 1,5‐diyn‐3‐ols and nitrones to deliver carbazole derivatives are described. Such cascade reactions are applicable to facile synthesis of polyaromatic compounds containing carbazole subunits. Notably, the reaction mechanism involves unexpected oxoarylations, rather than oxidative Mannich reactions as known for but‐1‐yn‐4‐ols. Our control experiments indicate that the presence of a second alkyne as in 1,5‐diyn‐3‐ols enables such oxoarylations due to a weak bonding between gold and this alkyne, rending the tethered alcohol less conformationally flexible. [ABSTRACT FROM AUTHOR]

Tropane alkaloids constitute a compound‐class which is structurally defined by a central 8‐azabicyclo[3.2.1]octane core. A diverse bioactivity profile combined with an unusual aza‐bridged bicyclic framework has made tropanes molecules‐of‐interest within organic chemistry. Enantioselective examples of (5+2) cycloadditions between 3‐oxidopyridinium betaines and olefins remain unexplored, despite 3‐oxidopyridinium betaines being useful reagents in organic synthesis. The first asymmetric (5+2) cycloaddition of 3‐oxidopyridinium betaines is reported, affording tropane derivatives in up to quantitative yield and with excellent control of peri‐, regio‐, diastereo‐, and enantioselectivity. The reactivity is enabled by dienamine‐activation of α,β‐unsaturated aldehydes combined with in situ formation of the pyridinium reaction‐partner. A simple N‐deprotection protocol allows for liberation of the tropane alkaloid motif, and synthetic elaborations of the cycloadducts demonstrate their synthetic utility to achieve highly diastereoselective modification around the bicyclic framework. DFT computations suggest a stepwise mechanism where regio‐ and stereoselectivity are defined during the first bond‐forming step in which the pyridinium dipole exerts critical conformational control over its dienamine partner. In the second bond‐forming step, a kinetic preference toward an initial (5+4) cycloadduct was identified; however, a lack of catalyst turn‐over, reversibility, and thermodynamic bias favoring a (5+2) cycloadduct rendered the reaction fully periselective. [ABSTRACT FROM AUTHOR]

A stereo‐, regio‐ and chemoselective synthesis of a series of structurally diverse novel oxobenzothiophene embedded spirooxindolopyrrolidine/pyrrolizidine hybrid heterocycles were achieved in excellent yields by multicomponent 1,3‐dipolar cycloaddition reaction process. The 1,3‐dipole component employed was generated in situ from isatin and N‐methylglycine/L‐proline while the dipolarophile, ethyl 2‐(3‐oxobenzo[b]thiophen‐2(3H)‐ylidene)acetate was prepared from thiophenol in two good yielding steps. The formation of spiroheterocyclic hybrids occurred through the formation of two C=C and one C−N bonds in a single synthetic transformation. The compounds formed consists of three adjacent stereocenters, out of which two are spirocarbons. The synthesized spiro compounds were assayed for their AChE/BChE inhibitory activity and most of the spirocompounds showed promising cholinesterase inhibitory activity. Among them, spiropyrrolidine that substituted with chlorine atom on the oxindole ring displayed significant activity (4.16±0.09 μM) with respect to standard drug, galantamine (2.09±0.11 μM). Molecular modelling simulation was explored for the most potent compound that revealed interesting binding templates to the active site of enzyme. [ABSTRACT FROM AUTHOR]

Generally, the potential reactive "olefin pairs" in the molecular crystals satisfying Schmidt's criteria could undergo topological [2+2] cycloaddition. In this study, another factor that affects the photodimerization reactivity of chalcone analogues was found. The cyclic chalcone analogues of (E)‐2‐(2,4‐dichlorobenzylidene)‐2,3‐dihydro‐1H‐inden‐1‐one (BIO), (E)‐2‐(naphthalen‐2‐ylmethylene)‐2,3‐dihydro‐1H‐inden‐1‐one (NIO), (Z)‐2‐(2,4‐dichlorobenzylidene)benzofuran‐3(2H)‐one (BFO), and (Z)‐2‐(2,4‐dichlorobenzylidene)benzo[b]thiophen‐3(2H)‐one (BTO) have been synthesized. While the geometrical parameters for the molecular packing of the above four compounds did not exceed Schmidt's criteria, [2+2] cycloaddition did not occur in the crystals of BIO and BTO. The single crystal structures and Hirshfeld surface analyses revealed that interactions of C=O⋅⋅⋅H (CH2) existed between adjacent molecules in the crystal of BIO. Therefore, the carbonyl and methylene groups linked with one carbon atom in carbon‐carbon double bond were tightly confined in the lattice, acting as a tweezer to inhibit free movement of the double bond and suppressing [2+2] cycloaddition. In the crystal of BTO, similar interactions of Cl⋅⋅⋅S and C=O⋅⋅⋅H (C6H4) prevented free movement of the double bond. In contrast, the intermolecular interaction of C=O⋅⋅⋅H only exists around the carbonyl group in the crystals of BFO and NIO, leaving the C=C double bonds to move freely and allowing the occurrence of [2+2] cycloaddition. Driven by photodimerization, the needle‐like crystals of BFO and NIO displayed evident photo‐induced bending behavior. This work demonstrates that the intermolecular interactions around carbon‐carbon double bond affect the [2+2] cycloaddition reactivity except for Schmidt's criteria. These findings provide valuable insights into the design of photomechanical molecular crystalline materials. [ABSTRACT FROM AUTHOR]

Activation of nitromethane to endow new reactivity is an interesting and meaningful but also challenging topic. Herein, we report an electrochemical activation of nitromethane to serve as both the heterocyclic skeleton and oxime sources for the construction of isoxazoline aldoximes. The isoxazoline aldoximes that are prepared by four steps with the reported strategy are synthesized in a single step from low‐cost and readily available nitromethane and olefins with moderate to excellent yields under our electrochemical conditions. The reaction also takes advantage of high atom‐economy and E‐selectivity. Moreover, the mechanism is studied by control experiments, a kinetic isotope effect (KIE) study, cyclic voltammogram (CV) experiments, and density functional theory (DFT) calculations. The mechanistic results reveal that nitromethane may be activated under electrochemical conditions to deliver a 1,2,5‐oxadiazole 2‐oxide intermediate, which undergoes [3+2] cycloaddition with olefins to yield isoxazoline aldoximes. [ABSTRACT FROM AUTHOR]

Activation of nitromethane to endow new reactivity is an interesting and meaningful but also challenging topic. Herein, we report an electrochemical activation of nitromethane to serve as both the heterocyclic skeleton and oxime sources for the construction of isoxazoline aldoximes. The isoxazoline aldoximes that are prepared by four steps with the reported strategy are synthesized in a single step from low‐cost and readily available nitromethane and olefins with moderate to excellent yields under our electrochemical conditions. The reaction also takes advantage of high atom‐economy and E‐selectivity. Moreover, the mechanism is studied by control experiments, a kinetic isotope effect (KIE) study, cyclic voltammogram (CV) experiments, and density functional theory (DFT) calculations. The mechanistic results reveal that nitromethane may be activated under electrochemical conditions to deliver a 1,2,5‐oxadiazole 2‐oxide intermediate, which undergoes [3+2] cycloaddition with olefins to yield isoxazoline aldoximes. [ABSTRACT FROM AUTHOR]

We have prepared a ligand library based on a ferrocenyl aziridinyl methanol core unit (simply called FAM) having a phenyl group, a cyclohexyl group, and a naphthyl group to be used in 1,3‐dipolar cycloaddition (1,3‐DC) reactions for the synthesis of chiral pyrrolidines. These chiral ligands were used with AgOAc in 1,3‐DC reactions taking place between the aryl‐substituted azomethine ylides and N‐methylmaleimide as the dipolarophile. In each case, the expected aryl‐substituted pyrrolidines were obtained in good to excellent yields with acceptable enantioselectivities favoring only the endo product. The chiral catalyst system CFAM4–AgOAc was also used in 1,3‐DC reaction with different dipolarophiles such as dimethyl maleate, tert‐butyl acrylate, methyl acrylate, trans‐chalcone, and vinyl sulfone. In each case, the cycloadducts were obtained in acceptable yields albeit with low ee. Fortunately, it was possible to increase the ee up to >99% upon crystallization. [ABSTRACT FROM AUTHOR]

1-Ethyl-3-methyl 6-phenylindolizine-1,3-dicarboxylate (7b) Pale yellow solid powder obtained from reaction between 3-phenylpyridinium salt B 3a b and ethyl propiolate, yield 77%, mp 120-22 °C, SP 1 sp H NMR (400 MHz CDCl SB 3 sb ): I i (ppm) 1.42 (t, 3H, SP 3 sp J SB HH sb = 7.2 Hz, 1-CO SB 2 sb CH SB 2 sb I CH SB 3 sb i ), 3.93 (s, 3H, 3-CO SB 2 sb CH SB 3 sb ), 4.38 (q, 2H, SP 3 sp J SB HH sb = 7.2 Hz, 1 B - b CO SB 2 sb CH SB 2 sb ), 7.40 (dd, 2H, SP 3 sp J SB HH sb = 8.8, 7.2 Hz, I m i B - b H), 7.47 (t, 1H, SP 3 sp J SB HH sb = 7.2 Hz, I p i B - b H), 7.58 (dd, 2H, SP 3 sp J SB HH sb =8.8 Hz, SP 4 sp J SB HH sb =1.6 Hz, I o i B - b H), 7.64 (d, 1H, SP 3 sp J SB HH sb = 9.6 Hz, 8-H), 7.99 (s, 1H, 2-H), 8.37 (d, 1H, SP 3 sp J SB HH sb = 9.6 Hz, 7-H), 9.77 (s, 1H, 5-H). B 6n b : 1.40 (t, 3H, SP 3 sp J SB HH sb = 7.2 Hz, 1-CO SB 2 sb CH SB 2 sb I CH SB 3 sb i ), 4.44 (q, 2H, SP 3 sp J SB HH sb = 7.2Hz, 1-CO SB 2 sb I CH SB 2 sb i ), 5.61 (s, 2H, 3-CO SB 2 sb CH SB 2 sb ), 7.36-7.63 (m, 12H, 2-H, 6-H and C SB 6 sb H SB 5 sb groups), 8.77 (d, 1H, SP 3 sp J SB HH sb = 8.8 Hz, 7-H), 10.54 (s, 1H, 5-H). 3-(tert-Butyl) 1,2-dimethyl 6-phenylindolizine-1,2,3-tricarboxylate (7f) Cream colored solid powder obtained from reaction between 3-phenylpyridinium salt B 3c b and DMAD, yield 79%, mp 266-70 °C, SP 1 sp H NMR (400 MHz CDCl SB 3 sb ): I i (ppm) 1.57(s, 9H, -OC(CH SB 3 sb ) SB 3 sb ), 3.90 (s, 3H, 1-CO SB 2 sb CH SB 3 sb ), 3.98 (s, 3H, 2-CO SB 2 sb CH SB 3 sb ), 7.39 (t, 1H, SP 3 sp J SB HH sb = 7.2 Hz, I p i -H), 7.46 (t, 2H, SP 3 sp J SB HH sb = 7.6 Hz, I m i -H), 7.60-7.62 (unresolved m, 3H, I o i -H, 8-H), 8.34 (d, 1H, SP 3 sp J SB HH sb = 9.2 Hz, 7-H), 9.74 (s, 1H, 5-H). [Extracted from the article]

A concise asymmetric total synthesis of (−)‐quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3‐dipolar cycloaddition reaction of N‐heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio‐, exo‐ and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a RhIII‐catalyzed C−H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline‐pyrrolidine tetracyclic core unit of quinocarcin. [ABSTRACT FROM AUTHOR]

A concise asymmetric total synthesis of (−)‐quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3‐dipolar cycloaddition reaction of N‐heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio‐, exo‐ and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a RhIII‐catalyzed C−H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline‐pyrrolidine tetracyclic core unit of quinocarcin. [ABSTRACT FROM AUTHOR]

A highly efficient multigram synthesis of spirocyclic and fused isoxazoline building blocks is described. Isoxazoline‐3‐carboxylates were synthesized via a regioselective 1,3‐dipolar cycloaddition reaction of 2‐chloro‐2‐(hydroxyimino)acetate and carbo‐ or heterocyclic alkenes bearing endo‐ or exocyclic C=C double bonds, resulting in fused or spirocyclic isoxazolines, respectively. The preparation of up to 300 g of these compounds was achieved in a single run. The ester group of isoxazolines was then subjected to common synthetic transformations for the synthesis of corresponding building blocks, including alcohols, chlorides, azides, amines, aldehydes, carboxylic acids, amino acids and their derivatives, difluoromethyl‐substituted compounds, and bicyclic γ‐lactones. Additionally, a direct cycloaddition‐based approach to the synthesis of aminoalkyl‐ and chloromethyl‐substituted isoxazolines was proposed to improve their preparation. The described isoxazoline building blocks are expected to be valuable tools for drug discovery. [ABSTRACT FROM AUTHOR]

[3 + 2] Cycloaddition reactions of heteroaromatic N-ylides with electron-deficient olefins have been developed. The heteroaromatic N-ylides, in situ generated from N-phenacylbenzothiazolium bromides, can smoothly react with maleimides under very mild conditions, affording fused polycyclic octahydropyrrolo[3,4-c]pyrroles in good-to-excellent isolated yields. This reaction concept could also be extended to 3-trifluoroethylidene oxindoles and benzylidenemalononitriles as electron-deficient olefins for accessing highly functionalized polyheterocyclic compounds. A gram-scale experiment was also carried out to verify the practicability of the methodology. [ABSTRACT FROM AUTHOR]

In the present study, cellulose-supported Schiff base Cu(II) catalyst [(Cell-ThP-Cu(II))] has been developed, synthesized, and characterized by TGA, XRD, FT-IR, SEM, EDS, ICP-OES, XPS, and BET/BJH techniques. The catalytic performance of Cell-ThP-Cu(II) was investigated for one-pot Chan-Lam coupling followed by Huisgen 1,3-cycloaddition. As a result, various 1-aryl-1,2,3-triazoles were prepared using arylboronic acids, sodium azide, and phenyl acetylenes. The notable merits of the proposed approach are low catalyst loading (0.072 mol%), high TONs (up to 1041–1347) and TOFs (up to 190–224), catalyst reusability (up to 5 cycles) and the use of a green solvent at room temperature. [ABSTRACT FROM AUTHOR]

Hydrazonoyl chlorides react with β‐nitrostyrenes in ethanol under the clean action of ultrasonic irradiation. The reaction proceeds at room temperature via 1,3‐dipolar cycloadditions of in situ generated nitrile imine with β‐nitrostyrenes with concurrent elimination of HCl and HNO2 to afford 1,3,4‐trisubstituted pyrazoles with good to high yields and excellent regioselectivity in a short time. [ABSTRACT FROM AUTHOR]

Oximes cause photo‐promoted, copper‐catalyzed N‐selective arylation with diaryl iodonium salts to produce nitrones, which in turn undergo intra‐ or intermolecular 1,3‐dipolar cyclization with olefins to afford N‐aryl isoxazolidines. Hypervalent iodine reagents substituted with either electron‐rich or electron‐deficient groups afford the corresponding N‐aryl isoxazolidines in 26–95% yields. This method offers a faster reaction rate, lower catalyst loading and broader substrate scope of oxime than similar nitrone syntheses employing Chan‐Lam‐Evans coupling. The reaction involves via a radical/single electron transfer (SET) pathway, and does not proceed in the absence of photoirradiation. [ABSTRACT FROM AUTHOR]