Catalytic Intermolecular [4+2]-Cycloaddition toward the Stereo­selective C2–C3 Annulation of Indoles

Abstract

AbstractCatalytic dearomative cycloaddition involving the C2–C3 bond of indoles is a powerful strategy for the synthesis of fused indoline scaffolds. Through dearomative cycloaddition/annulation, planar indole substrates can be readily transformed into rigid, three-dimensional polycyclic complex structures in one step. Molecules with architectural complexity are generally considered to have drug-like properties. Hence, annulation products have tremendous potential for discovering therapeutic properties, and this strategy has become an important part of the medicinal chemistry toolbox. Using appropriate catalyst control, desirable stereoselectivity can be achieved. Previous literature reports reveal that [3+2]-cycloadditions of indoles have been extensively studied. In contrast, the catalytic [4+2]-cycloaddition/dearomatization of indoles has been much less investigated. In this short review, we focus specifically on six-membered ring annulations via [4+2]-cycloaddition with the C2–C3 bond of indoles and discuss the various catalytic methods that have been developed toward this objective.1 Introduction2 [4+2]-Cycloaddition/Annulation of Indoles2.1 Electron-Rich Indoles2.1.1 Transition-Metal Catalysis2.1.2 Organocatalysis2.2 Electron-Deficient Indoles2.2.1 Transition-Metal Catalysis2.2.2 Organocatalysis3 Summary and Outlook