Approaches to the Formation of Condensed Isoindolones

Abstract

Both direct and multistep reactions, involving the application of carbonyl compounds, e. g. oxoacids, phthalimides, 2-iodobenzamides or acylhalides, have been developed as novel synthetic routes for the preparation of 3substituted 2,3-dihydro-1H-isoindol-1-ones, which are reviewed here. Alternatively, reductive or acid-catalyzed rearrangements of certain heterocycles lead to the formation of 3-substituted isoindolones. Asymmetric syntheses too have been described. R 2 = alkyl, Bzl, Ph 17 18 48-51% Advanced Methods for the Synthesis of 3-Substituted Current

Continuous Flow Photochemical and Thermal Multi-Step Synthesis of Bioactive 3-Arylmethylene-2,3-Dihydro-1H-Isoindolin-1-Ones

“…Due to their broad biological activities, the synthesis of 3-arylmethylene-2,3-dihydro-1H-isoindolin-1-ones has been widely studied [1,2]. Among the many synthetic pathways developed, the photodecarboxylative benzylation of phthalimides represents a mild and efficient access to these important target compounds [3,4].…”

A Concise and Flexible Diastereoselective Approach to Heteroring-Fused Isoindolinones

“…3 Alternatively, the isoindolinone ring can be fused with constitutionally diverse heterocyclic moieties, and this class of compounds has recently attracted considerable attention due to their profound physiological and chemotherapeutic properties. 4 The representative compounds 1-4 fall into this class of compounds ( Figure 1). Thus, the tricyclic g-lactams 1, with heteroatomic substituents at the 3-position, have been studied as selective non-nucleosidic HIV reverse transcriptase inhibitors, 5 and 2 has also been shown to have a promising antibacterial activity.…”

“…9 Organic chemists have at their disposal a great number of synthetic methods for the preparation of substituted isoindolinones, 10 but few flexible and general methods are available for the construction of highly heterofused models with structural variability. 4 In this re-gard, we have aimed to develop new and convergent approaches to rapidly achieve molecular complexity in a highly efficient manner. We have assumed that the presence of heteroatoms in the cyclic moieties embedded in the compact molecular framework could retain the bioactivity of the models and lead to a new generation of SAR studies.…”

Practical Outcome of Azaphthalimide Reduction with Zn/AcOH at Various Temperatures

“…Additionally, there seem to be no reports in the literature on the reductive manipulation of 5azaphthalimides. Herein we report the results of our studies on the reduction of azaphthalimides 1 and 2 with Zn dust in acetic acid-the set of conditions widely used for production of isoindolinones from phthalimides [14] but, to the best of our knowledge, never tested for the aza analogs of the latter [15]. conversion to the 3-hydroxy-4-azaisoindolin-1-ones 3, which were isolated in high yield by filtration, evaporation of the volatiles, and simple crystallization of the residue from ether or aqueous ethanol ( Table 1) [17], whereas the same treatment of 2 resulted in mixtures consisting predominantly of 6-azaisoindolin-1-ones 6 with <30% of the partially reduced 3-hydroxy-6-azaisoindolin-1-ones 4 still present, according to 1 H NMR analysis of the crude reaction mixture (Scheme 1) [18].…”