Asymmetric Synthesis of Cyclohexane‐Fused Drug‐Like Spirocyclic Scaffolds Containing Six Contiguous Stereogenic Centers via Organocatalytic Cascade Reactions

Abstract

AbstractDrug‐like spirocyclic scaffolds have been prepared asymmetrically by fusing fully functionalized cyclohexanes with medicinally important pyrazolone, rhodanine, barbituric acid or indandione moieties. This approach utilizes an organocatalytic tandem Michael–Michael–aldol reaction that yields diverse chiral spirocyclic backbones containing six contiguous stereogenic centers and multiple functional groups. The target compounds are generated in good yield and with high stereoselectivity (up to 99 % ee and 95:5 dr). Intriguingly, diastereocontrol of the spiro‐products changes depending on the substrate.magnified image