Focused ortho ‐Lithiation and Functionalization of p ‐Bromo‐ and p ‐Iodoanisole

By use of the strategy for ortho ‐lithiation (DoM) that conceptually diminishes the p K A difference between the ortho ‐H of the substrate and the conjugate acid of the metalating agent, effective metalation of bromine and iodine bearing aryl substrates can be carried out. As a set of prototypes, p ‐bromoanisole ( p ‐BrA) and p ‐iodoanisole ( p ‐IA) have been successfully ortho ‐metalated in promoted hydrocarbon media using ortho ‐lithiodimethylbenzylamine ( o ‐LiDMBA) as the metalating agent. No hint of exchange of either halogen was noted using these conditions. These studies add to the emerging evidence of a hitherto unidentified acidifying effect on the proton(s) ortho ‐ to a directing metalation group (DMG) by both a p ‐iodo and a p ‐bromo substituent.