Unlocking a Grignard Cascade: Three-Component Access to Complex Polycyclic Architectures from Quinolines

We report a transition-metal-free, three-component reaction for the direct C2/C3 annulation of quinolines with Grignard reagents and enones. This method unveils a new enone reactivity in [4 + 2] cyclizations, enabling efficient dearomatization to construct hexahydroacridinones with four contiguous stereocenters. This operationally simple protocol exhibits exceptional regio- and stereoselectivity, broad substrate scope, and high atom economy, facilitating the late-stage diversification of complex bioactive molecules.