1,3‐Dipolar Cycloaddition Reactions of Nitrile Oxides under “Non‐Conventional” Conditions: Green Solvents, Irradiation, and Continuous Flow

Abstract

The 1,3‐dipolar cycloaddition reactions (DCs) of nitrile oxides (NOs) to alkenes and alkynes are useful methods for the synthesis of 2‐isoxazolines and isoxazoles respectively, which are important classes of heterocyclic compounds in organic and medicinal chemistry. Most of these reactions are carried out in organic solvents and under thermal activation. Nevertheless the use of supercritical carbon dioxide (scCO2) and ionic liquids (Ils) as alternative solvents and the application of microwave (MW) and ultrasound (US) as alternative activation procedures have evident advantages from the “Green Chemistry” point of view. The critical discussion on the applications of these “unconventional” activation methods and reaction conditions in the 1,3‐DCs of NOs is the objective of the present Review.

Convenient Synthesis of Pyrazolo[4′,3′:5,6]pyrano[4,3-c][1,2]oxazoles via Intramolecular Nitrile Oxide Cycloaddition

“…The synthetic strategy that we designed to construct the pyrazolo [4 ,3 :5,6]pyrano [4,3c] [1,2]oxazole ring system employs difunctional substrates (4a-d) that contain an aldoxime unit next to the allyloxy group attached to the pyrazole core and can serve as intermediates for nitrile oxide generation and subsequent cycloaddition (Scheme 1). isoxazoline moiety in a highly regio-and diastereoselective manner [16].…”

“…The synthetic strategy that we designed to construct the pyrazolo[4′,3′:5,6]pyrano [4,3-c] [1,2]oxazole ring system employs difunctional substrates (4a-d) that contain an aldoxime unit next to the allyloxy group attached to the pyrazole core and can serve as intermediates for nitrile oxide generation and subsequent cycloaddition (Scheme 1). As starting materials for the synthesis of compounds 4a-d, we used 1-phenyl-, 1-(4fluorophenyl)-, 1-(4-bromophenyl)-and 1-methylpyrazol-3-ols (1a-d), which are readily accessible from the oxidation of appropriate pyrazolidin-3-ones [34].…”

“…In order to prepare the 3a,4-dihydro-3H,7H-pyrazolo [4 ,3 :5,6]pyrano [4,3-c] [1,2]oxazole derivatives 5a-d by the INOC reaction, aldoximes 4a-d were synthesized by the treatment of 3a-d with hydroxylamine hydrochloride in the presence of sodium acetate [36]. As a result, the synand anti-3-allyloxy-4-pyrazolaldoximes were obtained in total yields of 82-97%.…”

“…We previously investigated the metal-free intramolecular alkyne-azide cycloaddition reaction for the formation of the pyrazolo [4,3-f ] [1,2,3]triazolo [5,1-c] [1,4]oxazepine ring system [26] as well as the synthesis of 2,6-dihydropyrano [2,3-c]pyrazole derivatives by employing the ring-closing metathesis (RCM) reaction [27]. In continuation of our interest in the synthesis and investigation of novel pyrazole-containing polyheterocyclic systems [28][29][30][31][32][33], we report herein the synthesis and structural elucidation of new 3a,4dihydro-3H,7H-and 4H,7H-pyrazolo [4 ,3 :5,6]pyrano [4,3-c] [1,2]oxazole derivatives from appropriate 3-(prop-2-en-1-yloxy)-or 3-(prop-2-yn-1-yloxy)-1H-pyrazole-4-carbaldehyde oximes via the intramolecular nitrile oxide cycloaddition reaction.…”

Shedding Light on the Chemistry and the Properties of Münchnone Functionalized Graphene

“…During the last decade, several groups have pioneered cycloaddition chemistry for the chemical modification of a wide array of carbon-based nanomaterials, including fullerene, carbon nanotubes, graphene, and carbon quantum dots, either in their pristine or functionalized forms [ 1 , 2 , 3 , 4 , 5 ]. The different cycloaddition strategies are an important tool to increase the processability, solubility, and colloid stability of nanostructures, to achieve better control over composition, and to target specific applications [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ].…”