Despite a growing body of studies on directing-group (DG)-assisted C–H activation strategies, efficient exploitation of the used DG remains underexplored. We developed a rhodium-catalyzed C–H functionalization of indoles at the C4 position using α,β-unsaturated enones as versatile DGs. Combined experimental and theoretical analyses revealed that the C–H activation process was reversible and the course of Rh-carbene generation controlled the overall site-selectivity of the C–H functionalization. The introduced malonate unit and the used enone DG were cyclized in a further C–C bond forming process to assemble 3,4-fused tricyclic indoles in an asymmetric manner. Telescoping the two reaction sequences provided rapid entry into this densely functionalized indole architecture from readily available chemical feedstock.

Hydrocarbazolones are a key structural unit in many natural bioactive compounds and are thus a valuable synthetic target. A rhodium‐catalyzed C−H functionalization reaction with acceptor/acceptor diazo compounds was developed for synthesizing 2,3‐fused indole variants. An α,β‐unsaturated enone was utilized as a directing group for site‐selective C−H activation and as an electrophile for the subsequent cyclization. Overall, the developed annulation enabled the rapid assembly of synthetically valuable hydrocarbazolones from readily available indoles. Additionally, computational investigations were conducted to elucidate the reaction pathway and rationalize the experimentally observed site‐selectivity.

No abstract

A dearomative spirocyclization of diazo‐functionalized indoles was developed under metal‐free conditions. Although the spiroindolenine architecture with a tertiary alkyl substituent at the 2‐position is a privileged scaffold of bioactive molecules, a general synthetic strategy has remained elusive. In this study, a dual catalyst system comprising maleic acid and Schreiner's thiourea was used to construct a spiroindolenine core that was inaccessible by rhodium or silver catalysis. Computational studies revealed a unique macrocyclic transition state consisting of the substrate, maleic acid, and thiourea cocatalyst, which lowered the activation energy of spirocyclization through multipoint mutual interactions.

No abstract