De Novo Access to Persubstituted Benzene-Fused Benzosilacyclohexanes via Organocatalytic Benzannulation of 4-Dicyanomethylene-1,1-Disubstituted Silacyclohexanes

Abstract We report an organocatalytic domino benzannulation strategy for the facile synthesis of persubstituted benzene-containing quinoline-fused silacyclohexanes and sila-tetrahydronaphthalenes using 4-dicyanomethylene-1,1-disubstituted silacyclohexanes as silicon-containing building blocks. The utility of this methodology was further demonstrated by a gram-scale synthesis, diverse transformations, and the promising antiproliferative activity against HCT-116 cells, along with the ability to modulate lysosome-associated pathways and mitigate the level of proteotoxic aggregation. This work provides a modular route to previously inaccessible persubstituted benzene-fused silacyclohexanes, offering new opportunities for silicon-containing functional molecules in drug discovery and materials science.