Isoindolinone Synthesis via One‐Pot Type Transition Metal Catalyzed C−C Bond Forming Reactions

Abstract

Isoindolinone structure is an important privileged scaffold found in al argev ariety of naturallyo ccurring as well as synthetic, biologically and pharmaceutically active compounds. Owing to its crucial role in anumber of applications, the synthetic methodologies for accessingt his heterocyclic skeleton have received significant attentiond uring the past decade. In general, the synthetic strategies can be divided into two categories:F irst, direct utilization of phthalimides or phthalimidines as startingm aterials for the synthesis of isoindolinones;a nd second, construction of the lactam and/or aromatic rings by different catalytic methods, including CÀHa ctivation, cross-coupling,c arbonylation, condensation, addition and formal cycloaddition reactions. Especially in the last mentioned, utilization of transition metal catalysts provides access to ab road range of substituted isoindolinones.H erein, the recent advances (2010-2020) in transition metal catalyzed synthetic methodologies via formation of new CÀCbonds for isoindolinones are reviewed.

Recent Advances in the Direct Functionalization of Isoindolinones for the Synthesis of 3,3‐Disubstituted Isoindolinones

“…In this aspect, the Hu group in 2018 has tried to address this issue by developing a three-component reaction between 3-hydroxyisoindolinones, methyl aryldiazoacetates and benzylic alcohols. [25] The integration of 1 mol% of Rh 2 (OAc) 4 Also utilizing α-diazoacetates as nucleophiles, the Singh group later reported a chiral phosphoric acid catalyzed highly enantioselective Mannich-type reaction with in situ formed cyclic N-acyl ketimines. [26] CPA 6 b was identified to be the best for the generation of various isoindolinone-based α-amino diazo esters bearing a tetrasubstituted stereogenic centers (Scheme 24).…”

“…[3c-f] Owing to their importance and versatility in the synthesis of natural products, drugs and related analogues, considerable efforts have been made to develop highly efficient synthetic methodologies including catalytic asymmetric protocols to access 3,3disubstituted isoindolinone frameworks. [4] This subunit includes all kinds of tetrasubstituted carbon centers, [5] all-carbon or heteroatom-containing, spirocyclic or not, providing an ideal platform for the development of new synthetic methods and new catalysts to showcase their power and potential. The past few decades have witnessed a rapid progress in the construction of tetrasubstituted carbon center at the C-3 position of isoindolinones.…”

“…The past few decades have witnessed a rapid progress in the construction of tetrasubstituted carbon center at the C-3 position of isoindolinones. In general, the synthetic strategies can be classified into two major categories, namely, the direct functionalization of parent isoindolinones and the lactam ring formation involved reactions, [4] judging by whether there is a lactam ring formation process or not during the production of the final 3,3-disubstituted isoindolinones. Peng et al in 2019 [4a] summarized the catalytic asymmetric synthesis of isoindolinones via chiral organocatalysis and transition metal catalysis.…”

“…in 2019 [4a] summarized the catalytic asymmetric synthesis of isoindolinones via chiral organocatalysis and transition metal catalysis. Savela recently [4c] highlighted the transition metal catalyzed construction of isoindolinones via the lactam ring formation strategy. However, there lacks a comprehensive review to introduce the direct functionalization of parent isoindolinones to synthesize functionalized isoindolinones, especially the 3,3‐disubstituted isoindolinones, because only catalytic asymmetric utilization of parent isoindolinones as starting materials are included in Peng's review despite both two strategies are introduced.…”

Rhodium(III)-Catalyzed Intramolecular Benzylic C(sp3)–H Amidation for the Synthesis of Isoindolinones

“…During the past decades, transition-metal-catalyzed C-H functionalization has provided simplified and efficient approaches to a large variety of isoindolinone derivatives. 5…”