Halogen effect on tandem [4+2] cycloaddition/aromatization sequence of allenyl 2-halo-3-vinylcyclohex-2-enyl ether

Steric and enthalpic effects of substituents on diene moieties play a crucial role in intramolecular cycloaddition reactions. Allenyl 2-halogenated-3-vinylcyclohex-2-enyl ethers underwent a tandem [4+2] cycloaddition/aromatization reaction to afford the corresponding tetrahydro-3H-naphtho[1,8-bc]furan compound in high yield.     

An expedient diastereoselective synthesis of pyrrolidinyl spirooxindoles fused to sugar lactone via [3+2] cycloaddition of azomethine ylides

Synthesis of pyrrolidinyl-spirooxindoles fused to sugar lactone has been achieved by a one pot three component 1,3-dipolar cycloaddition (1,3-DC) reaction. A unique dipolarophile (α,β-unsaturated lactone) derived from d-glucose/d-galactose reacted with azomethine ylide generated in situ from isatin/N-substituted isatin and secondary amino acids (sarcosine/proline/piperidine-2-carboxylic acid) to give the corresponding cycloadducts in good yield. The cycloaddition was found to be highly regio- and diastereoselective.     

Nucleophilic phosphine-catalyzed [3+2] cycloaddition of allenes with N-(thio)phosphoryl imines and acidic methanolysis of adducts N-(thio)phosphoryl 3-pyrrolines: a facile synthesis of free amine 3-pyrrolines

In this report, the dipolarophile imines with easily removable activating group O,O-diethyl(thio)phosphoryl have been investigated in the nucleophilic phosphine-catalyzed [3+2] cycloaddition reaction of electron-deficient allenes. Under the catalysis of a tertiary phosphine, N-(thio)phosphorylimines readily undergo the [3+2] cycloaddition reaction with ethyl 2,3-butadienoate or ethyl 2,3-pentadienoate, affording the corresponding N-(thio)phosphoryl 3-pyrrolines in moderate to high yields with good diastereoselectivity. Removal of the (thio)phosphoryl group from the adducts has been successfully achieved via the acidic methanolysis of the P-N bond, giving the free amine 3-pyrrolines in fair to good yields without severe aromatization. Thus, a facile synthesis of N-unsubstituted 3-pyrrolines is established from the phosphine-catalyzed [3+2] cycloaddition reaction of allenes with imines.     

The Synthesis of 3-pyrazinyl-pyrazolo [1,5-a] pyridines from an enol ether

The synthesis of 3-(6-chloropyrazin-2-yl)pyrazolo[1,5-a]pyridine from an enol ether and 4-substituted 1-aminopyridinim iodides via a 3+2 cycloaddition is presented. A high throughput reaction screen was used to optimize the yield of the cycloaddition. This protocol is operationally simple, scalable, proceeds at room temperature, and the reaction profiles are very clean.     

AgNO3 catalyzed synthesis of 5-substituted-1H-tetrazole via [3+2] cycloaddition of nitriles and sodium azide

An efficient one-pot, convenient catalysis for the synthesis of 5-substituted-1H-tetrazoles is reported. The [3+2] cycloaddition involves various nitriles, sodium azide in refluxing DMF and AgNO₃ as catalyst to give corresponding 5-substituted-1H-tetrazoles in good to excellent yields. It is expected that the reaction proceeds via in situ formation of a silver azide species, which participates in coordination of nitrile moiety followed by cycloaddition of azide ion to give tetrazole.     

An expedient approach for the regio- and stereoselective synthesis of novel spiroindolizidines via [3+2] cycloaddition

A new series of spiroindolizidines was synthesized by one-pot, three-component condensation of azomethine ylides, generated from 1,2,3,4-tetrahydroisoquinoline with ninhydrin or isatin derivatives by a 1,5-prototropic shift route, with various derivatives of trans-β-nitrostyrene in a regio- and stereoselective manner. X-ray crystal structure analysis and NMR spectroscopic data confirmed the structure outcome of the cycloaddition reaction.     

A theoretical investigation on the regioselectivity of the [3+2] cycloaddition of nitrile oxide and N-vinylpyrrole

Theoretical calculations were performed on the [3+2] cycloaddition (32CA) reaction of nitrile oxide and N-vinylpyrrole. The regiochemistry of the reaction has been studied based on potential energy surface analysis and global and local reactivity indices of the reactants. The global electron density transfer (GEDT) calculations at the possible transition states revealed that this cycloaddition has a nearly non-polar character. The ELF topological analyses of the selected structures involved in the intrinsic reaction coordinate (IRC) of TS1a suggests that this 32CA reaction takes place through a two-stage one-step mechanism.     

Synthesis of acridinedione derived mono spiro-pyrrolidine/pyrrolizidine derivatives—a facile approach via intermolecular [3+2] cycloaddition reaction

A facile synthesis of acridinedione derived mono spiro-pyrrolidine and pyrrolizidine derivatives has been accomplished by 1,3-dipolar cycloaddition reaction. The O-acryloylacridinediones, as dipolarophiles reacted with azomethine ylide derived from di-/tri-ketones and sec-amino acids to give acridinedione derived mono spiropyrrolidine/pyrrolizidine derivatives in good yield.     

Convenient and efficient access to tri- and tetra-substituted 4-fluoropyridines via a [3 + 2]/[2 + 1] cyclization reaction

A [3 + 2]/[2 + 1] cycloaddition reaction of gem?difluorocyclopropenes is presented, offering a mild and efficient approach to accessing tri- and tetra-substituted 4-fluoropyridines in moderate to good yields with excellent regioselectivity. Multiple synthetic applications, including process-scale reactions, modification of bioactive molecules, derivatization reactions and synthesis of the analogue of the PKM2 modulator, are subsequently described.     

Preparation of cis-2-aminocyclopropanol: [2+1] cycloaddition reaction of bis(iodozincio)methane with α-ketoimine

A reaction of α-ketoimine with bis(iodozincio)methane gave a cis-2-aminocyclopropanol derivative via [2+1] cycloaddition. The reaction proceeded via a sequential nucleophilic attack of bis(iodozincio)methane to a couple of carbonyl groups in the substrate, which was fixed into s-cis conformation with a couple of zinc atoms in the reagent. The reaction proceeded with high diastereoselectivity.     

Copper-catalyzed synthesis of 5-substituted 1H-tetrazoles via the [3+2] cycloaddition of nitriles and trimethylsilyl azide

The [3+2] cycloaddition between various nitriles and trimethylsilyl azide proceeds smoothly in the presence of a Cu^I catalyst in DMF/MeOH, to give the corresponding 5-substituted 1H-tetrazoles in good to high yields. The reaction most probably proceeds through the in situ formation of a copper azide species, followed by a successive [3+2] cycloaddition with the nitriles.     

One-pot reaction of ortho-acylphenols and terminal alkynoates for synthesis of 2-alkyl-substituted chromanones

A facile synthesis of 2-alkyl-substituted chromanones from ortho-acylphenols and terminal alkynoates is described. The method contains two consecutive processes in one-pot reaction through a DABCO-catalyzed condensation reaction and a KOBu^t-mediated intramolecular cycloaddition to afford the desired products.     

Synthesis of substituted imidazolines via [3+2]-cycloaddition of aziridines with nitriles

An efficient synthesis of 2,4-disubstituted 1H-imidazolines from aziridines and nitriles in the presence of BF₃-Et₂O or triethyloxonium tetrafluoroborate has been described. The reaction proceeds via a [3+2]-cycloaddition reaction. Most of the nitriles successfully underwent cycloaddition reactions with aziridines even at room temperature in a very short time.     

Inverse‐electron demand [π2 + σ2 + σ2] cycloaddition reaction of dimethyl oxaquadricyclane‐2,3‐dicarboxylate with cyclooctyne

A first example of an inverse‐electron demand [_π2 + _σ2 + _σ2] cycloaddition reaction of dimethyl oxaquadricyclane‐2,3‐dicarboxylate was reported: cyclooctyne underwent cycloaddition with dimethyl oxaquadricyclane‐2,3‐dicarboxylate to afford the corresponding adducts one of whose structure was confirmed by a single crystal X‐ray analysis.     

Enantioselective synthesis of homocarbocyclic-2′-oxo-3′-azanucleosides

The enantioselective synthesis of homocarbocyclic-2′oxo-3′-azanucleosides has been performed by cycloaddition reaction of the N-glycosyl nitrones with allyl nucleobases. The use of nitrones originated from two different carbohydrates, the N-ribosyl nitrone and the N-mannosyl nitrone, proceeded in a stereocontrolled and predictable manner with a good degree of enantioselectivity, so allowing an easy entry to both enantiomers.     

Synthesis of novel spiropyrrolidines through [3+2] cycloaddition reactions with Baylis-Hillman adducts as dipolarophiles

The synthesis of a series of novel spiropyrrolidines and polycyclic heterocycles has been accomplished by 1,3-dipolar cycloaddition reactions with Baylis-Hillman adducts. The reaction also yielded novel furo[3,4-b]pyrrole in some cases by an unusual cyclization.     

Cycloaddition of hydrazones and 1, 2-diarylalkynes promoted by t-BuOK/DMF: A convenient synthesis of tetraarylpyrazoles

A facile synthesis of tetraarylpyrazoles has been developed via t-BuOK/DMF promoted intermolecular cycloaddition of hydrazones and 1,2-diarylalkynes.     

3-Thiolated 2-azetidinones: synthesis and in vitro antibacterial and antifungal activities

A series of 3-thiolated β-lactams were synthesized by [2+2] ketene-imine cycloaddition reaction from S-substituted mercaptoacetic acids and Schiff bases. Then, some of the 3-methylthio β-lactams were converted to 3-(methylsulfinyl) β-lactams and 3-(methylsulfonyl) β-lactams using m-CPBA under different reaction conditions. All the compounds were characterized by spectral data and elemental analyses and were evaluated for their in vitro antibacterial and antifungal activities against pathogenic strains including Staphylococcus aureus (Methicillin resistant strain). The preliminary screening results indicated that some of these compounds demonstrated moderate to very good antibacterial and antifungal activities.     

Asymmetric synthesis of β-lactams by [2+2] cycloaddition using 1,4:3,6-dianhydro-d-glucitol (isosorbide) derived chiral pools

Highly diastereoselective synthesis of cis-β-lactams via [2+2] cycloaddition reactions of imines derived from a chiral bicyclic aldehyde and ketenes is described. The chiral bicyclic aldehyde as well as chiral acids were prepared from commercially available inexpensive isosorbide. The cycloaddition reaction was found to be highly diastereoselective; in some cases giving a single diastereomer of cis-azetidin-2-one in very good yields. A moderate diastereoselectivity was observed with chiral ketenes derived from isosorbide.     

An efficient synthesis of (±)-panduratin A and (±)-isopanduratin A, inhibitors of dengue-2 viral activity

Panduratin A and its regioisomer isopanduratin A are synthesized in four steps from (E)-ocimene, [(E)-3,7-dimethyl-1,3,6-octatriene] via a Diels-Alder cycloaddition reaction.