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.