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

The construction of tetrasubstituted carbon centers (especially chiral ones) represents one of the most challenging and demanding topics in the synthesis of natural products and related drugs. The development of isoindolinones with this feature appears to be of great importance, because 3,3-disubstituted isoindolinones, which feature all kinds of tetrasubstituted carbon centers, also including spirocyclic and all-carbon or heteroatom-containing centers, show a wide spectrum of biological and pharmaceutical activities. Therefore, the synthetic methodologies for preparing these skeletons have received significant attention during the past decade. In general, these strategies can be classified into two major categories, namely the direct functionalization of parent isoindolinones and lactam-ring-formation-involved reactions, depending on whether there is a lactam-ring-formation process or not during the production of the final 3,3-disubstituted isoindolinone. Since the second strategy has been well reviewed, this review mainly summarizes the recent progress in the direct functionalization of parent isoindolinones to construct 3,3-disubstituted isoindolinones via three subdivided strategies.

Automated summary

The construction of tetrasubstituted carbon centers, especially chiral ones, is a challenging topic in the synthesis of natural products and related drugs. Recent focus has been on developing isoindolinones with diverse tetrasubstituted carbon centers, such as spirocyclic and all-carbon or heteroatom-containing centers, due to their wide range of biological and pharmaceutical activities. Research has mainly concentrated on methods for preparing these skeletons, with a distinction between direct functionalization of parent isoindolinones and lactam-ring-formation-involved reactions.