Transition-Metal-free Double-Insertive Coupling of Isocyanides with Arylboronic Acids Enabled Diarylmethanamines

Diarylmethanamines as a structural motif are frequently encountered in bioactive molecules, drugs, pharmaceutical candidates, and ligands. However, the existing synthetic methods cannot meet the demand for diarylmethanamines. Here, we report a double-in-sertive coupling reaction of isocyanides with arylboronic acids under transition-metal-free conditions to deliver valuable diarylmethylamines. This coupling reaction features a broad range of substrate scope with good functional group compatibility, and it can also be employed in late-stage modification of bioactive compounds and drug molecules, as well as in ligand synthesis. Density functional theory (DFT) calculations indicate that the reaction is through the formation of boronic anhydride followed by two insertion reactions with isocyanide to access the diarylmethanamine derivatives, instead of direct insertion of isocyanide into arylboronic acid.