Mechanochemical Single-Carbon Insertion into (Iso)quinolines

(Iso)quinolines are among the most common heterocycles in US Food and Drug Administration approved drugs, whereas benzoazepines are underrepresented in drug discovery libraries, primarily because of the lack of efficient preparation routes. Therefore, an efficient method of converting (iso)quinolines to benzoazepines by leveraging the chemistries unique to (iso)quinolines to access diverse benzoazepines should be valuable. Herein, we report a mechanochemical skeletal editing protocol for use in carbon-atom insertion into (iso)quinolines to afford the corresponding benzoazepines. This reaction proceeds readily under ambient conditions without the need for metal additives, bulk solvent, or complicated pre-activation processes. Using this user-friendly protocol, we investigate substrate scope, and reaction mechanism. Moreover, benzoazepines undergo light-induced cycloaddition to yield cyclobutene-fused indolines, which can be converted to indoles by selectively removing carbon atoms. The utility of this skeletal transform is further demonstrated through the skeletal editing of pharmaceutically relevant (iso)quinolines. Benzoazepines are underrepresented in drug discovery libraries, primarily because of the lack of efficient preparation routes. Here, the authors report a mechanochemical skeletal editing protocol for use in carbon-atom insertion into (iso)quinolines to afford the corresponding benzoazepines.