Synthesis Of Isoxazolines Research Articles

Crown Ether Base: Highly Active, Regioselective and Reusable Catalytic Systems for Double Bond Migration in Allylic Compounds

AbstractThe highly active, reusable and regioselective crown ethers bases catalytic systems, especially 15‐Crown‐5/NaOH, 18‐Crown‐6/KOH, dibenzo‐18‐Crown/6‐t‐BuOK, and 18‐Crown‐6/t‐BuOK, for double bond migration in various allyl and diallyl compounds have been presented. Allyl and/or diallyl: arenes and heteroarenes, ethers, acetal, sulfides, selenide, sulfoxides, imines, phosphine, and phosphine oxide were smoothly converted into their corresponding 1‐propenyl derivatives under very mild conditions. Some of the C,O‐ and O,S‐diallyl compounds were fully regioselectively isomerized to allyl‐(1‐propenyl) derivatives. An unprecedented and significant effect of increasing the reaction rate and shortening the quantitative reaction conversion time without decreasing the selectivity under ultrasound‐assisted conditions was observed. Various solvents, including low‐boiling point ones containing only C, H and/or O atoms, such as DMFL, DME, THF, Et2O, toluene, and 1,4‐dioxane, can be used instead of the most frequently used DMSO. Remarkably highly effective recycling of 18‐Crown‐6/t‐BuOK and dibenzo‐18‐Crown‐6‐t‐BuOK catalytic systems for isomerization of low‐boiling or high‐boiling point allyl compounds respectively and crown ethers from all examined catalytic systems was developed. The opportunity to effectively combine the double bond migration with in situ generation of nitrile oxide and finally 1,3‐DC‐cycloaddition into one pot variant synthesis of isoxazolines from Qallyl has also been announced.

Tert-Butyl Nitrite-Mediated Domino Synthesis of Isoxazolines and Isoxazoles from Terminal Aryl Alkenes and Alkynes.

A sequential construction of C-C, C-O, C═N, and C═O bonds from alkenes leading to the direct synthesis of isoxazolines in the presence of tert-butyl nitrite, quinoline, and the Sc(OTf)3 catalyst in DCE at 80 °C has been accomplished. An unprecedented three consecutive C-H functionalizations of two styrenes are involved in this isoxazoline synthesis. In this radical-mediated reaction, one-half of the aryl alkene is converted into an intermediate 2-nitroketone, which serves as a 1,3-dipolarophile and undergoes cycloaddition with the other half of the unreacted aromatic terminal alkene. The use of an alkyne in lieu of an alkene leads to the formation of isoxazole under identical reaction conditions.

Copper-mediated oxysulfonylation of alkenyl oximes with sodium sulfinates: a facile synthesis of isoxazolines featuring a sulfone substituent.

A novel and efficient Cu(OAc)2-mediated oxysulfonylation of alkenyl oximes with sodium sulfonates was developed. The reactions are easy to conduct, occur under mild conditions, and form a broad range of sulfone-substituted isoxazolines in good yields.

Green Organocatalytic Synthesis of Isoxazolines via a One-Pot Oxidation of Allyloximes.

A green, sustainable, organocatalytic, and efficient synthesis of isoxazolines from allyloximes was developed. A 2,2,2-trifluoroacetophenone-catalyzed oxidation of allyloximes, utilizing H2O2 as the green oxidant, was taken advantage of in order to introduce a cheap and environmentally friendly protocol for the synthesis of substituted isoxazolines. A variety of substitution patterns, both aromatic and aliphatic moieties, are well tolerated, leading to isoxazolines in moderate to excellent yields.

Physicochemical characterization of benzalkonium chloride and urea based deep eutectic solvent (DES): A novel catalyst for the efficient synthesis of isoxazolines under ultrasonic irradiation

Various novel deep eutectic solvents (DESs) have been prepared by combining different molar ratio of benzalkonium chloride and urea, subsequently characterized for some physical and spectroscopic properties. Among newly formed DESs, one of the mixture (1:2) was employed in combination with ultrasound (US), for the synthesis of selective isoxazoline derivatives. The reactions were also performed by nonultrasonic (NUS)/thermal method using conventional solvent system for comparison purposes. Applying DES, as a reaction medium in either of the thermal and ultrasonic assisted methods, an appreciable improvement in the product yield was achieved in a shorter time. The results show some advantages in terms of reaction time and energy consumption when DES and ultrasound combination was used for the synthesis of isoxazolines. Recyclability attributes of DES were also studied which revealed that a marginal decrease in the yield (%) was recorded up-to four runs. The findings of this study support the use of DES in combination with ultrasound technique as a viable green route for the synthesis of isoxazoline derivatives.

Visible-light-mediated generation of nitrile oxides for the photoredox synthesis of isoxazolines and isoxazoles.

Visible-light photoredox catalysis enables the synthesis of biologically relevant isoxazolines and isoxazoles from hydroxyimino acids. The process shows broad functional group compatibility and mechanistic and computational studies support a visible-light-mediated generation of nitrile oxides by two sequential oxidative single electron transfer processes.

Enantioselective Synthesis of Isoxazolines by 1,3-Dipolar Cycloaddition

Enantioselective Synthesis of Isoxazolines by 1,3-Dipolar Cycloaddition

Copper Nitrate Mediated Synthesis of Isoxazolines

Copper Nitrate Mediated Synthesis of Isoxazolines

Synthesis of Isoxazolines and Isoxazoles Inspired by Fipronil

Phenylpyrazoles (or arylpyrazoles) are known to be extremely potent as noncompetitive inhibitors of the GABA-gated chloride channel on the GABA receptor. This project involves the synthesis of novel isoxazole and isoxazoline heterocycles that have similar structural features to the commercially used phenylpyrazole, fipronil. Synthesis of the appropriately substituted styrenes and phenylacetylenes is followed by 1,3-dipolar cycloaddition reaction with several aliphatic nitrile oxides, which are prepared in situ from aldoximes with bleach. Relative reaction rates were determined for these specialized alkene and alkyne dipolarophiles.

Catalytic Asymmetric Synthesis of Isoxazolines from Silyl Nitronates.

1,3-Dipolar cycloadditions of triisopropylsilyl nitronates and 2-alkylacroleins produced isoxazolines bearing a chiral quaternary center in high yields and enantioselectivities with the aid of a chiral oxazaborolidine catalyst. One chiral isoxazoline product was converted to (R)-(+)-Tanikolide in 9 steps in a total yield of 43%.

ChemInform Abstract: An Environmentally Benign Synthesis of Isoxazolines and Isoxazoles Mediated by Potassium Chloride in Water.

Abstract1,3‐Dipolar cycloaddition of nitrile oxides, generated in situ by treatment of aldoximes with KCl and oxone in water, with alkenes or alkynes yields isoxazolines and isoxazoles, respectively.

ChemInform Abstract: One‐Pot Synthesis of Isoxazolines from Aldehydes Catalyzed by Iodobenzene.

A convenient one-pot, three-step procedure for the synthesis of isoxazolines starting from aldehydes has been developed involving catalytic cycloaddition between nitrile oxides and alkenes, in which iodobenzene is used as the catalyst for the in situ generation of a hypervalent iodine intermediate. In this approach, the aldehydes are first transformed with hydroxylamine sulfate into aldoximes, which are then oxidized to nitrile oxides by the in situ generated hypervalent iodine intermediate; finally, a 1,3-dipolar cycloaddition between the nitrile oxides and alkenes occurs to provide the isoxazolines in moderate to good yields.

Highly regio- and diastereoselective, acidic clay supported intramolecular nitrile oxide–alkene cycloaddition on d-ribose derived nitriles: an efficient synthetic route to isoxazoline fused five and six membered carbocycles

An efficient synthetic route to isoxazoline fused carbocycles from carbohydrate scaffolds that comprise of free hydroxyl group(s) is described with high regio- and stereoselectivity. Montmorillonite K-10/chloramine T oxidation and in situ intramolecular nitrile oxide–alkene cycloaddition (INOC) of d-ribose derived oximes have been developed for the diversity oriented synthesis of isoxazoline fused five and six membered carbocycles.

ChemInform Abstract: Organocatalyzed Synthesis of Isoxazolines Initiated by a Chemoselective Oxa‐Michael Reaction of N‐BocNHOH.

ChemInform Abstract: Organocatalyzed Synthesis of Isoxazolines Initiated by a Chemoselective Oxa‐Michael Reaction of N‐BocNHOH.

An environmentally benign synthesis of isoxazolines and isoxazoles mediated by potassium chloride in water

An effective and environmentally benign procedure for the synthesis of isoxazolines and isoxazoles has been developed by a cycloaddition of nitrile oxides with alkenes or alkynes in water. In this approach, potassium chloride is first oxidized into chlorine in water by the environmentally friendly oxidant Oxone®, then aldoximes are oxidized into nitrile oxides by the in situ generated hypochlorous acid, finally a 1,3-dipolar cycloaddition between nitrile oxides and alkenes or alkynes occurs to provide the corresponding isoxazolines and isoxazoles in good yields.

Copper-Catalyzed Oxyazidation of Unactivated Alkenes: A Facile Synthesis of Isoxazolines Featuring an Azido Substituent

A novel and efficient Cu(OAc)2-catalyzed oxyazidation of unactivated alkenes was developed. The reactions are easy to conduct, occur under mild conditions, and form azido-substituted isoxazolines in good yields.

Phosphane‐Catalyzed [4+1] Annulation between Nitroalkenes and Morita–Baylis–Hillman Carbonates: Facile Synthesis of Isoxazoline N‐Oxides by Phosphorus Ylides

A phosphane-catalyzed [4+1] annulation between nitroalkenes and Morita-Baylis-Hillman carbonates has been realized; this provides facile and diastereoselective access to polysubstituted isoxazoline N-oxides in moderate to excellent yields. In the annulation, an in situ formed allylic phosphorus ylide presumably serves as a pivotal active intermediate. This reaction accordingly represents the first example of phosphorus ylide initiated [4+1] cyclization of nitroalkenes to give isoxazoline N-oxides.

Organocatalysed synthesis of isoxazolines initiated by a chemoselective oxa-Michael reaction of N-BocNHOH

An organocatalysed and chemoselective one-pot oxa-Michael-cyclocondensation reaction of N-BocNHOH to unsaturated α-ketoesters is reported which affords an original entry to enantioenriched 3-isoxazoline carboxylate derivatives as biorelevant heterocyclic frameworks.

One-Pot Synthesis of Isoxazolines from Aldehydes Catalyzed by Iodobenzene

A convenient one-pot, three-step procedure for the synthesis of isoxazolines starting from aldehydes has been developed involving catalytic cycloaddition between nitrile oxides and alkenes, in which iodobenzene is used as the catalyst for the in situ generation of a hypervalent iodine intermediate. In this approach, the aldehydes are first transformed with hydroxylamine sulfate into aldoximes, which are then oxidized to nitrile oxides by the in situ generated hypervalent iodine intermediate; finally, a 1,3-dipolar cycloaddition between the nitrile oxides and alkenes occurs to provide the isoxazolines in moderate to good yields.

Synthesis of Isoxazolines and Pyrazolines via Radical C-H Oxidation

Synthesis of Isoxazolines and Pyrazolines via Radical C-H Oxidation