Expanding Diversity of Fused Steroid-Quinoline Hybrids by Sequential Amination/Annulation/Aromatization Reactions

Viable alternative approaches to a variety of ring A and ring D-fused steroid-quinoline hybrids, along with ring A, D-fused, and/or ring A-fused, side chain-substituted steroid-bis-quinolines were explored by means of sequential amination/annulation/aromatization reactions of suitable ketosteroids with 2-acyl-substituted anilines. Key factors directing the chemoselective behavior of polyfunctionalized substrates were investigated. Remarkably, the use of TMSOTf as an alternative promoter/catalyst enabled the direct synthesis of the desired hybrids, avoiding the protection/deprotection steps of the conventional procedures when the starting substrates contained labile functional groups.