Executive Summary : | Fused indolines featuring a C3 all-carbon quaternary stereocentre have a high 3D character and are encountered in numerous bioactive natural products, pharmaceuticals, and synthetic compounds which display a broad range of biological properties. In view of this, the need for synthesizing indoline-based small organic compounds has been increasing continuously and tremendous efforts have been devoted into the development of effective ways to prepare such compounds, with the indole-ring dearomatizing cascade approaches among the most popular. However, all the existing dearomatizing cascade reactions of 3-substituted indoles almost always deliver 2,3-fused indolines. In contrast, construction of C3 all‐carbon quaternary stereocenter bearing 3,4-fused indolines by cascade reactions of 3,4-disubstituted indoles has remarkably little (only one) precedent. Herein, we propose to synthesize natural product-like, new classes of 3,4-fused polycyclic indolines bearing multiple stereogenic centers including a C3 all‐carbon quaternary stereocenter via dearomatizing, tandem double intramolecular cyclization of 3,4-disubstituted indoles. The proposed key mechanistic steps are intramolecular and C3 selective (i) Pd-catalyzed arylation, (ii) KOtBu/Et3B-mediated alkylation, (iii) Michael-type addition and (iv) Friedel-Crafts alkenylation of indole C4-tethered electrophiles, concomitantly followed by intramolecular trapping of the resulting imine/iminium moiety by an indole C3-tethered nucleophile. The compounds will be synthesized in chemo‐, regio‐, and diastereoselective fashions. Moreover, wherever applicable, asymmetric versions of the proposed syntheses will be executed using chiral catalysts. Overall, the proposed methods have the potential to access complex polycyclic 3,4-fused indoline scaffolds of high interest for synthetic and medicinal chemistry. |