Isoprene-Mediated Lithiation of 1-Alkylimidazoles: Chiral Induction of the Alkyl Substituent

Abstract

The isoprene-mediated lithiation of imidazoles bearing a secondary alkyl substituent at the nitrogen (7, 8 and 13) and the subsequent nucleophilic addition to different electrophiles allows the preparation of the corresponding 2- functionalized imidazoles 10, 11 and 14. The presence of a stereogenic center in the alkyl substituent induces diastereoselection during the nucleophilic addition step with a prochiral electrophile (i.e. pivalaldehyde), producing the expected imidazole derivative with excellent overall yield, but low de (up to 26%). Keywords: Isoprene-mediated lithiation, imidazole derivatives, nucleophilic addition, lithium