Synergistic Construction of Axial and Central Chirality via an Organocatalytic Three-Component Reaction Involving In Situ-Formed α-Functionalized Alcohols

The synergistic construction of both axial and central chirality represents a formidable challenge in asymmetric catalysis. Herein, we report an organocatalytic three-component reaction among N-aryl-2-substituted anilines, 2-oxo-2-arylacetaldehydes, and indoles, which enables the de novo synthesis of axially and centrally chiral N-(2-substituted phenyl)benzo[e]indol-1-ones. This transformation features the in situ formation of α-functionalized alcohols, followed by a 1,2-addition of the resulting iminium species. Notably, the adjacent axially and centrally chiral α-functionalized alcohol serves as a pivotal intermediate that governs the enantioselectivity of the subsequent addition step. This strategy not only expands the synthetic applicability of α-functionalized alcohols but also provides a robust platform for the synergistic construction of both axial and central chirality.