Isoprene-mediated lithiation of imidazole derivatives: mechanism considerations

The isoprene-mediated lithiation, with lithium metal, of different imidazole derivatives is an interesting methodology for their functionalization. Studies of different possible intermediates involved in the reaction employing density functional theory calculations, at the B3LYP/6-311++G(d,p) level are considered. A plausible mechanism is described, in which isoprene is reduced, to the corresponding radical anion, in the presence of Li(s), acting then as a base deprotonating N-methylimidazole (NMI) and producing the 1,1-dimethylallyl radical. This radical is further reduced by the excess of lithium proceeding once more as a base. This final step produces stable final products that compensate the previous equilibriums, making favourable the whole process.

This work was generously supported by the Spanish Ministerio de Educación y Ciencia [CTQ2004-01261, CTQ2007-65218, and CONSOLIDER INGENIO 2010 (CSD2007-00006)], the Generalitat Valenciana (GRUPOS 03/135, GV05/52, GV/2007/036, GVPRE/2008/278 and PROMETEO 2009/039) and the Universidad de Alicante.