DFT-Assisted Atroposelective Construction of Indole-Fused N-Heteroaromatic Frameworks through Palladium-Catalyzed C–H Imidoylation

On the basis of density functional theory (DFT) calculations, we designed an asymmetric synthesis method for axially chiral biaryls through C(sp²)–H imidoylative cyclization of isocyanides. Building on this, we successfully synthesized axially chiral compounds containing indole-fused N-heteroaromatic frameworks via palladium-catalyzed C–H imidoylation to achieve high yields and enantioselectivity. Various efficient cyclization pathways facilitated the synthesis of indole-fused ring derivatives with either C–C or C–N axial chirality. This not only provides an efficient and diverse strategy for the synthesis of axially chiral compounds but also demonstrates that DFT-assisted design is a reliable tool for accurately predicting reaction stereoselectivity and effectively reducing the workload of chemical experiments.