Pure and Applied Chemistry

Abstract: Several highly substituted imidazoles have been under investigation at GlaxoSmithKline as potential therapies for the treatment of rheumatoid arthritis and have spawned the need for a general synthetic method for their preparation on a multikilogram scale. We describe herein the optimization of a general method for the preparation of aryl-substituted TosMIC reagents and the ease with which they undergo [3+2] cycloadditions with a host of imines, prepared in situ, to generate densely functionalized imidazoles with various substitution patterns in a completely regioselective manner.