Dual-Functional Enone-Directing Group/Electrophile for Sequential C–C Bond Formation with α-Diazomalonates: A Short Synthesis of Chiral 3,4-Fused Tricyclic Indoles

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.