Regioselective Formation of Imidazol-2-yllithium, Imidazol-4-yllithium, and Imidazol-5-yllithium Species

Article abstract of DOI:10.1021/jo00013a042

Representative imidazol-2-yllithium, imidazol-4-yllithium, and imidazol-5-yllithium species have been prepared via halogen-metal exchange, and the propensity of the latter two to undergo isomerization and quench by electrophilic reagents has been studied.The C2-unsubstituted imidazol-5-yllithium species 3 is generated within 10 min at -78 degC from 1-<(benzyloxymethyl)>-4,5-diiodoimidazole (1b) and affords the C5-formyl product 4 upon reaction with DMF, but gives the isomeric C2-formyl product 6 if allowed to equilibrate to the imidazol-2-yllithium species 5 for an additional 35 min at -78 degC before quench.The less reactive electrophile diethyl carbonate is unable to trap 3 and instead reacts with 5 to afford tris<1-<(benzyloxy)methyl>-4-iodo-2-imidazolyl>carbinol (7).In contrast, 1-<(benzyloxy)methyl>-4-iodoimidazole-5-carboxaldehyde ethylene acetal (10) metalates to give the C2-unsubstituted imidazol-4-yllithium species 13, which undergoes a very rapid conversion to its imidazol-2-yllithium isomer 14, even at -100 degC, giving the 2,5-dicarboxaldehyde 5-ethylene acetal 16 or the 2-deuterio-5-carboxaldehyde ethylene acetal 15 upon quench with DMF or D2O, respectively.Thus, in the presence of C2 unsubstitution, C5 functionalization could be accomplished when the electrophile was sufficiently reactive, while C4 functionalization could not.Short- and long-range 1H- 13C heteronuclear (Hetcor) 2D NMR spectroscopic analyses were instrumental in the structural assignments of key compounds.