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Focused ortho ‐Lithiation and Functionalization of p ‐Bromo‐ and p ‐Iodoanisole
Author(s) -
Slocum D. W.,
Jennings John A.,
Reinscheld Thomas K.,
Whitley Paul E.
Publication year - 2018
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201800616
Subject(s) - metalation , chemistry , substituent , bromine , halogen , medicinal chemistry , aryl , conjugate , surface modification , halogenation , iodine , substrate (aquarium) , stereochemistry , organic chemistry , alkyl , mathematical analysis , oceanography , mathematics , geology
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.