Aza‐oxyallyl Cations and Their Applications in (3+m) Cycloaddition Reactions

Abstract

Aza‐oxyallyl cations, as proposed by Sheehan in the 1960s have garnered significant attention among the synthetic organic community, owing to their diverse reactivity profile for constructing N‐scaffolds of biological interest. During its initial growth, aza‐oxyallyl cations were used effectively as a 3‐unit synthon as 1,3 dipoles to create N‐heterocycles via cycloaddition reactions, wherein aza‐oxyallyl cation served as electrophilic counterpart. Recently, new variations of aza‐oxyallyl cations reactivity have been reported, including its usage as a 1,4 dipole in cycloaddition reactions, domino reactions, and the unique alkylating ability of heteroatoms. This review article provides an update of the recent developments in this area and the prevailing mechanistic insight.

A concise approach to 2-pyrrolin-5-one scaffold construction from α-halohydroxamates and β-keto compounds

“…These findings demonstrated that the electron-donating groups –OBn or other –OR groups could remarkably improve the reaction efficiency. 20 Considering the higher reactivity of non-substituted α-bromohydroxamates than that of α-substituted α-bromohydroxamates and previous reports, 13,15 a a plausible mechanism of the reaction process is proposed in Scheme 1. α-Halohydroxamate was reacted with NaI to yield the corresponding iodide.…”

“…In recent years, α-halohydroxamates have been extensively used as novel building blocks to construct various important N-heterocycles. 13 So far, the application of α-halohydroxamates in a range of [3 + 1], 14 [3 + 2], 15 [3 + 3], 16 and [3 + 4] 17 domino and/or cycloaddition reactions has been well explored with the generation of a variety of four- to seven-membered aza-heterocyclic rings. Specifically, these unique synthons are easily accessible from the corresponding amines.…”

Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders

“…The IN route has been similarly studied for the delivery of nucleotide-based drugs. The importance of oligonucleotide therapy in the treatment of chronic inflammatory respiratory diseases is comprehensively discussed in a review published by Mehta et al where they also emphasised the importance of delivery routes including nasal administration [198]. Many investigations have employed the olfactory pathway to transport oligonucleotides or oligonucleotide-loaded nanoparticles [199][200][201][202][203][204][205][206][207] to the brain.…”

Diastereo- and Enantioselective (3 + 2) Cycloaddition of a New Aza-π-Allylpalladium Zwitterionic Intermediate

“…Dipolar cycloadditions of the crucial C(CO)N synthon’s synthetic equivalents have therefore attracted considerable interest. While the reactivity of α-haloamides has been widely documented, only two enantioselective dipolar cycloadditions have been reported and rely on the activation of the electrophilic cycloaddition partner by a squaramide organocatalyst . The group of Hamada exploited the dipolar properties of acrylamides to design an enantioselective (3 + 2) cycloaddition based on a chiral iminium activation method .…”