Recent Advances in the Generation of Nitrilium Betaine 1,3-Dipoles

Abstract

Nitrilium betaine 1,3-dipoles are ubiquitous reagents in organic chemistry, with applications ranging from natural product synthesis to materials science. Given the high reactivity of these zwitterionic motifs, they are invariably generated in situ from a suitable precursor, prior to use. This short review summarizes the recent progress in the development of modern approaches towards the formation of these 1,3-dipoles, and their applications within a diverse range of fields.

Strategies and Methods for the Synthesis of 2‐Pyrazolines: Recent Developments (2012–2022)

“…The most common precursors are hydrazonyl halides [10] and 2,5tetrazoles [11] (Scheme 1), but more modern approaches have also been discovered. [12] In the following sections, the nitrile imine methodologies towards pyrazolines are included and divided by the NI precursor (whether it is hydrazonyl halide or another) and then by the dipolarophile employed. Since Huisgen's reports, [5,13] the reactions between NIs and α,β-enones, or other electron-deficient alkenes have received extensive examination; the post-2012 reports will be discussed in the following sections.…”

“…Since NIs are unstable, they are typically generated in situ using an appropriate precursor. The most common precursors are hydrazonyl halides [10] and 2,5‐tetrazoles [11] (Scheme 1), but more modern approaches have also been discovered [12] . In the following sections, the nitrile imine methodologies towards pyrazolines are included and divided by the NI precursor (whether it is hydrazonyl halide or another) and then by the dipolarophile employed.…”

Electrochemically‐Assisted in situ Generation of Hydrazonoyl Halides for the Synthesis of 3H‐1,2,4‐Triazol‐3‐ones

“…The synthesis of 3 H ‐1,2,4‐triazole‐3‐one derivatives starting from hydrazonoyl halides have been extensively studied compared to those with hydrazones as substrate [34] . Nevertheless, the activation of hydrazones, especially under the action of electrodes obviate the harsh multistep synthetic routes utilizing expensive and hazardous reagents for the preparation of hydrazonoyl halides [35] . Although, some efforts have been made for the electrosynthesis of 1,2,4‐triazole scaffolds, studies focusing on electrochemical synthesis of these valuable systems are still infrequent [36–38] …”

“…[34] Nevertheless, the activation of hydrazones, especially under the action of electrodes obviate the harsh multistep synthetic routes utilizing expensive and hazardous reagents for the preparation of hydrazonoyl halides. [35] Although, some efforts have been made for the electrosynthesis of 1,2,4-triazole scaffolds, studies focusing on electrochemical synthesis of these valuable systems are still infrequent. [36][37][38] The drawback of alternative synthetic approaches for the synthesis of 1,2,4-triazole-3-ones made us to envisage an innovative mild electrochemical pathway to reach our targeted products.…”

Environmentally Benign and User-Friendly In Situ Generation of Nitrile Imines from Hydrazones for 1,3-Dipolar Cycloaddition

“…Not surprisingly, nitrile imines have found wide applications in medicinal chemistry, bioorthogonal chemistry, and materials chemistry . However, nitrile imines are unstable and usually require in situ generation from one of the two precursors: hydrazonyl halide or 2,5-disubstituted tetrazole (Scheme ). Although thermolysis/photolysis of 2,5-tetrazole generates nitrile imine without exogenous reagents, the limitations regarding the availability and/or preparation of 2,5-disubstituted tetrazoles and high temperature and specific UV light constrain its substrate scope.…”