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.