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

Abstract

Catalytic dearomative cycloaddition with C2-C3 bond of indoles is a powerful strategy for the synthesis of fused indoline scaffolds. By dearomative cycloaddition/annulation, planar indole substrates can be readily transformed into rigid, three-dimensional polycyclic complex structures in one step. Architectural complexity of molecules is generally considered as drug-like properties. Thus, the annulation products have tremendous potential in discovering therapeutic properties. This strategy has become an important part of the medicinal chemistry toolbox. Using appropriate catalyst control, desirable stereoselectivity can be achieved in the reaction. Previous literature reports indicate that [3+2]-cycloaddition of indoles has been extensively studied. On the contrary, catalytic [4+2]-cycloaddition/dearomatization of indoles has been much less investigated. In this review, we aim to focus specifically on the six- membered ring annulation via [4+2]-cycloaddition with C2-C3 bond of indoles and discuss on various catalytic methods that have been developed toward this direction.