Catalytic Asymmetric Dearomative Cyclizations of Indolyldimethanols via Umpolung Strategy.

The catalytic asymmetric dearomative (CADA) cyclization of indolylmethanols has been achieved via an umpolung strategy. By leveraging C3 umpolung of indolyldimethanols, two CADA cyclizations were realized under asymmetric organocatalysis. These transformations deliver two series of chiral indolenine- or indoline-based polycyclic scaffolds containing two or three adjacent stereogenic centers with high regio-, diastereo-, and enantioselectivity. This work not only provides a practical solution to persistent challenges in the CADA cyclization of indoles and introduces a C3 electrophilicity-based strategy for indole dearomatization, but also offers an efficient and stereoselective route to chiral indolenine- and indoline-fused polycyclic systems. Furthermore, mechanistic insights derived from theoretical calculations elucidate the plausible reaction pathway and account for the high regio- and stereoselectivity observed in the CADA cyclization.