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

Abstract

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 3,3disubstituted 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-formationinvolved 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.

Enantioselective synthesis of α-tetrasubstituted (3-indolizinyl) (diaryl)methanamines via chiral phosphoric acid catalysis

“…7 f Although these strategies enable direct access to asymmetric synthesis of chiral indolizine derivatives, development of new class indolizines is still a formidable target. To continue our efforts 8 on the advancement of chiral phosphoric acid catalysis, 9 we here present the chiral spirocyclic phosphoric acid (SPINOL-PA) catalyzed enantioselective Friedel–Crafts of indolizines with in situ generated cyclic α-diaryl N -acyl imines 10 for the synthesis of chiral α-(3-indolizinyl)(diaryl) methanamines.…”

Efficient synthesis of bioactive isoindolinone derivatives containing continuous quaternary carbons by intermolecular OH transfer

“…Isoindolinones represent an important class of biologically active small molecules and have seen increasing applications in medicinal chemistry. 1,2 It has been reported that isoindolinones exhibit widespread biological activity, 2 including antitumor, anti-inflammatory, antiviral, and anti-addictive effects. Many synthetic pharmaceutical molecules contain isoindolinones, such as MDM2-p53 inhibitors, 3 PI3Kγ inhibitors, 4 RSV inhibitors, 5 HIV-1 reverse transcriptase inhibitors, 6 muscarinic acetylcholine receptor modulators 7 and anticancer agents 8 (Scheme 1).…”

On Route to Diverse Nitrogen‐Bridged Polyhetero‐cycles with an N(acyl), N(aryl)‐acetal Core

“…Nitrogen‐containing heterocycles have been always regarded as privileged targets in organic synthesis due to their central role in pharmaceuticals, agricultural chemicals and materials. Among them, the ones having an oxo‐isoindole nucleus [1a,b] are currently the focus of intense research in order to achieve of valuable C3‐N bridged polyheterocyclic structures [2] …”