Cycloaddition Reactions Of Nitrile Oxides Research Articles

Studies on [2 + 3] cycloaddition reaction of nitrile oxides to linear dipolarophiles bearing multiple double bonds

Site selectivity, regioselectivity, and stereoselectivity of [2 + 3] cycloaddition of benzonitrile oxides to polyunsaturated esters were examined. Site selectivity was correlated with electron charges of unsaturated carbon atoms. Structure of the products has been established by an extensive application of 1H and 13C NMR spectroscopy and electrospray ionization mass spectrometry.

1,3-Dipolar Cycloaddition Reaction of Nitrile Oxides to Isatin Imines

A simple and efficient one-pot route for the synthesis of novel spiro [indolin– oxadiazol] derivativesby 1,3-dipolar cycloaddition reaction of nitrile oxides and isatin imine under classical or microwave irradiation conditions is described.4-amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione was synthesized by cyclization of thiocarbohydrazide and acetic acid. 3-((3-methyl-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)imino)indolin-2-one was prepared by condensation of primary amine of 4-amino-5-methyl-2,4-dihydro-3H-1,2,4-triazole-3-thione with isatin through a single step and 4'-(3-methyl-5-thioxo-1H-1,2,4-triazol-4(5H)-yl)- 3'-(substituted phenyl)-4'-hydro spiro[indolin-3,5'[1,2,4]oxadiazol]-2-one were afforded by the reaction of corresponding Schiff base with hydroximinoyl chloride and their derivatives under basic conditions at room temperature. The products were obtained in good yields. Elemental analysis, IR, 1H NMR, 13C NMR, and Mass spectral data confirmed the structure of newly synthesized compounds.

ChemInform Abstract: A Novel Protocol for the Facile Construction of Tetrahydroquinoline Fused Tricyclic Frameworks via an Intramolecular 1,3‐Dipolar Nitrile Oxide Cycloaddition Reaction.

AbstractThe successful development of an efficient method for the construction of fused tricyclic tetrahydroisoxazoloquinoline scaffolds involving an intramolecular 1,3‐dipolar nitrile oxide cycloaddition reaction utilizing Baylis—Hillman derivatives in good yields is achieved for the first time.

Synthesis of trifluoromethylated isoxazoles and their elaboration through inter- and intra-molecular C-H arylation.

We report conditions for the preparation of a range of trifluoromethylated isoxazole building blocks through the cycloaddition reaction of trifluoromethyl nitrile oxide. It was found that controlling the rate (and therefore concentration) of the formation of the trifluoromethyl nitrile oxide was Critical for the preferential formation of the desired isoxazole products versus the furoxan dimer. Different conditions were optimised for both aryl- and alkyl-substituted alkynes. In addition, the reactivity at the isoxazole 4-position has been briefly explored for these building blocks. Conditions for intermolecular C-H arylation, lithiation and electrophile quench, and alkoxylation were all identified with brief substrate scoping that signifies useful tolerance to a range of functionalities. Finally, complementary processes for structural diversification through either intramolecular cyclisation or intermolecular cross-coupling were developed.

Mechanism and regioselectivity of 1,3-dipolar cycloaddition reactions of bicyclic monoterpenes with aryl and heteroaryl nitrile oxides: a DFT study

The reactivity and regioselectivity of 1,3-dipolar cycloaddition reactions of aryl and heteroaryl nitrile oxides (1a–1c) with bicyclic monoterpenes (R)-(+)-a-pinene (2a) and (S)-(–)-b-pinene (2b) have been investigated by using density functional theory based on reactivity indices and activation energy calculations at the B3LYP/6-31G(d) level of theory in the gas phase. The potential energy surface analyses for both reactions are in agreement with the experimental observations. Moreover, our calculations on the geometries, bond orders, and global electron density transfers at the transition state structures shows that these 1,3- dipolar cycloaddition reactions occur via an asynchronous one-step mechanism.

ChemInform Abstract: Application of Chiral Ligands: Carbohydrates, Nucleoside‐Lanthanides and Other Lewis Acid Complexes to Control Regio‐ and Stereoselectivity of the Dipolar Cycloaddition Reactions of Nitrile Oxides and Esters.

Abstract4R,5S‐ or 4S,5R‐trisubstituted isoxazolines are obtained.

Correction: Application of chiral ligands: carbohydrates, nucleoside-lanthanides and other Lewis acid complexes to control regio- and stereoselectivity of the dipolar cycloaddition reactions of nitrile oxides and esters

Correction for ‘Application of chiral ligands: carbohydrates, nucleoside-lanthanides and other Lewis acid complexes to control regio- and stereoselectivity of the dipolar cycloaddition reactions of nitrile oxides and esters’ by Mirosław Gucma et al., RSC Adv., 2015, 5, 13112–13124.

Application of chiral ligands: carbohydrates, nucleoside-lanthanides and other Lewis acid complexes to control regio- and stereoselectivity of the dipolar cycloaddition reactions of nitrile oxides and esters

Enantioselectivity of the cycloaddition up to 99.8%.

A novel protocol for the facile construction of tetrahydroquinoline fused tricyclic frameworks via an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction.

An efficient method towards the synthesis of quinoline fused tricyclic compounds involving an intramolecular 1,3-dipolar nitrile oxide cycloaddition reaction utilizing Baylis-Hillman derivatives in good yields has been described for the first time. A highly functionalized tricyclic framework was created by forming two rings and two adjacent stereocentres through the formation of two N-C bonds, one C-C bond and one O-C bond in a highly regio and diastereoselective manner.

Asymmetric synthesis of spiro[isoxazolin-3,3'-oxindoles] via the catalytic 1,3-dipolar cycloaddition reaction of nitrile oxides.

A highly enantioselective 1,3-dipolar cycloaddition of nitrile oxides with 3-arylidene-oxindoles was realized by a chiral N,N'-dioxide-nickel(II) complex catalyst under mild reaction conditions. A series of spiro-isoxazoline-oxindole derivatives were obtained in moderate yields (up to 65%) with good regioselectivities (up to 99:1), excellent enantioselectivities (up to 99% ee), and exclusive diastereoselectivity as well.

1,3‐Dipolar Cycloaddition Reaction of Nitrile Oxides Revisited—Unusual Side Products Characterized by 2D NMR

Cycloaddition of (4‐trifluoromethyl)phenylnitrile oxide to N‐(4‐methoxyphenyl)acrylamide afforded bicyclic tetrahydro‐oxazolo‐(3,2‐b)[1,3]oxazine‐2‐carboxamide derivative in result of N‐acylation of the initially formed cycloadduct by the dipolarophile. 2:1 Cycloaddition of the same dipole to N‐(4‐methoxyphenyl)crotonamide yielded dihydro[1,2]‐oxazolo[2,3‐d][1,2,4]oxadiazole‐7‐carboxamide because of the second addition of the dipole to the C═N bond of the first formed 2‐isoxazoline compound. Structures of the products have been elucidated by an extensive application of 1D and 2D NMR spectroscopy.

ChemInform Abstract: Novel Methods for the Synthesis of 4‐(Azol‐5‐yl)isoxazoles.

AbstractThree title compounds of type (V) are prepared by the [3 + 2] cycloaddition reaction of enamines (III) and nitrile oxides generated in situ from hydroxamoyl chlorides.

NMR Studies on 1,3-Dipolar Cycloaddition of Nitrile Oxides to Norbornenes

The 1,3-dipolar cycloaddition reaction of nitrile oxides to norbornenes substituted with an acrylate-derived moiety was examined. Only adducts to norbornene system were formed with a good exo selectivity and complete site-selectivity. Structures of the products were elucidated by an extensive application of electrospray ionization-mass spectrometry (ESI-MS) and 2D 1H and 13C nuclear magnetic resonance (NMR).

Isoxazolylpyrrolidinylpiperazine Ligands, a New Class for Dopamine D3and D4Receptor Antagonists

Since the dopamine receptor system plays an important role in the development of neurological disorders like schizophrenia, extensive efforts have been made to explore potent and selective ligands for dopamine receptors for the discovery of antipsychotic drugs. In connection with search for potent ligands for dopamine receptors, we have studied the construction and biological activities of libraries of arylpiperazine derivatives with isoxazole rings. Recently we reported the design and synthesis of isoxazolylpiperidinylpiperazine derivatives having 6-membered nitrogen heterocycle, piperidine in between piperazine and isoxazole. To investigate the structure-activity relationship, the new isoxazolylpyrrolidinylpiperazine derivatives, which possess 5membered ring system, pyrrolidine in between piperazine and isoxazole, were designed and synthesized. In this paper, we report the construction of a small focused library of isoxazolylpyrrolidinylpiperazines and their binding affinities for dopamine D3 and D4 receptors. The synthesis of isoxazolylpyrrolidinylpiperazine derivatives is shown in Schemes 1, 2 and 3. The key synthetic strategy to these compounds involved coupling between two building blocks 2 and 3 using reductive amination reaction. Preparation of building block 2 is described in Scheme 2. Protection of the amino group of pyrrolidin-2-ylmethanol 4 with (t-Boc)2O in dichloromethane at rt for 1 h provided compound 5 in 90% yield. Oxidation of 5 with PCC and SiO2 in dichloromethane at rt for 3 h gave aldehyde 6 in 71% yield. Reductive amination of the aldehyde 6 with piperazine derivatives 7 using NaBH(OAc)3 in presence of 4 A molecular sieve over 6 h afforded compounds 8 in 60-92% yields. Deprotection of 8 with CF3CO2H in dichloromethane at rt furnished building block 2 in 87-99% yields. Synthesis of building block 3 is shown in Scheme 3. Treatment of aldehydes 9 with hydroxylamine hydrochloride and Na2CO3 at 60 C for 1-6 h gave oximes 10 in 99% yields. Isoxazole ring system was then installed by two-step sequence of nitrile oxide cycloaddition reaction which

KF/Al2O3: Solid-Supported Reagent Used in 1,3-Dipolar Cycloaddition Reaction of Nitrile Oxide

The stereoselective synthesis of 2-isoxazolidine through 1,3-dipolar cycloaddition reaction of nitrile oxide, which is in situ generation from aldoxime in the presence of N-bromosuccinamide and solid-supported reagent KF/Al2O3 at room temperature, is reported. KF/Al2O3 is sufficiently basic such that it can replace organic bases such as Et3N used in typical procedures and it catalyses the reaction to enhance the rate of the reaction.

ChemInform Abstract: Stereoselective Synthesis of Novel Annulated Thiopyrano Indole Derivatives from Simple Oxindole via Intramolecular 1,3‐Dipolar Cycloaddition Reactions of Nitrone and Nitrile Oxide.

AbstractTreatment of the aldehydes (I) with hydroxylamines (II) under basic conditions yields the title skeleton via nitrone formation followed by intramolecular 1,3‐dipolar cycloaddition.

Aryl nitrile oxide cycloaddition reactions in the presence of pinacol boronic acid ester

An aryl substrate with dual functionality consisting of a nitrile oxide and a pinacolyl boronate ester was prepared by mild hypervalent iodine oxidation (diacetoxyiodobenzene) of the corresponding aldoxime, without decomposition of the boronate functionality. The nitrile oxide was trapped in situ with a variety of dipolarophiles to yield aryl isoxazolines with the boronate ester function intact and available for subsequent reaction.

ChemInform Abstract: Application of Chiral Ligands: Carbohydrates, Alkaloids—Lanthanides and Other Lewis Acid Complexes to Control Regio‐ and Stereoselectivity of the Dipolar Cycloaddition Reactions of Nitrile Oxides and Crotonamides and Cinnamides.

AbstractTrisubstituted isoxazolidines are synthesized by cycloaddition of aryl nitrile oxides with secondary α,β‐unsaturated amides in the presence of different catalyst systems.

Solid phase synthesis of isoxazole and isoxazoline-carboxamides via [2+3]-dipolar cycloaddition using resin-bound alkynes or alkenes

An efficient approach for the parallel solid phase synthesis of isoxazole and isoxazoline derivatives has been developed. The isoxazoles and isoxazolines were constructed through a 1,3-dipolar cycloaddition reaction of nitrile oxides, with resin-bound alkynes or alkenes. The cycloaddition reaction conditions performed on solid phase supports was optimized, and an array of resin-bound carboxylic acid building blocks was utilized for distinct conversions. This methodology presents a new alternative to the diversity oriented synthesis of disubstituted isoxazoles and isoxazolines different from existing routes which are limited in structural diversity.

Intramolecular 1,3-Dipolar Nitrile Oxide Cycloaddition Using Baylis-Hillman Derivatives: Stereoselective Synthesis of Tricyclic Chromenoisoxazolines

A novel protocol for the construction of tricyclic chromenoisoxazoline frameworks via an intramolecular 1,3-dipolar nitrile oxide cycloaddition (INOC) reaction using Baylis-Hillman derivatives is described for the first time. The INOC reaction leads to a novel class of angularly substituted fused tricyclic chromenoisoxazolines, with the creation of two rings and two adjacent stereocenters, one of them being an all-carbon quaternary center, in a unique fashion. The tricyclic chromenoisoxazolines are obtained in a highly stereoselective fashion with good yields.