2-Protecting groups for 5-lithiation in the syntheses of imidazoles

Abstract

Various substituents have been examined as possible 2-protecting groups against organolithium reagents in the syntheses of imidazoles on the basis of the ease of decarboxylation of imidazole-2-carboxylic acids and cleavage of the C(2)–Si bond. The tertiary amido function and t-butyldimethylsilyl (TBDMS) group at the 2-position permit quantitative 5-lithiation of N-substituted imidazoles. Deprotection of the amido function occurs under alkaline conditions while the TBDMS group is removed by several reagents. The TBDMS substituent is stable to butyl-lithium at temperatures up to –10 °C.