Synthesis of Substituted 2-Aminoimidazoles

Significance

Looper and co-workers described a three-step synthesis of highly substituted 2-aminoimidazoles. The first step consists of the preparation of propargyl cyanamides by copper(I)-­catalyzed addition of an iminium generated from condensation of aldehydes (R^² = alkyl or aryl) with secondary amines. Without further purification, the resulting tertiary amines are subjected to a von Braun reaction. The use of 4-methoxybenzyl-, 2,4- and 3,4-dimethoxybenzyl-substituted propargyl amines lead to the propargyl cyanamides in good yields whereas symmetric N,N-dialkylpropargyl amines give exclusively propargyl bromide. Screening of catalysts led to the use of La(OTf)₃ for the final addition-hydroamination step. Both acyclic and cyclic secondary amines generated guanidine intermediates which underwent cyclization to the alkyne to afford 2-aminoimidazoles in good yields.