N-(2-formyl-1-methylimidazol-4-yl)-2,2-dimethylpropanamide: a versatile reagent for preparing imidazole-amine ligands with variable second-coordination spheres

Two synthetic pathways to N-(2-formyl-1-methylimidazol-4-yl)-2,2-dimethylpropanamide from 1-methyl-2-carboxaldehyde are described. The reagent serves as a useful synthon for reductive amination reactions with primary and secondary amines in the presence of sodium cyanoborohydride to yield a series of ligands with second coordination sphere functional groups. Protocols for the syntheses of related imidazole synthons functionalized in the 4-position with amino acids, Schiff bases, and other amides are also reported.