An investigation of imidazole and oxazole syntheses using aryl-substitutedTosMIC reagents

This article describes efficient and mild protocols for preparing polysubst ituted imidazoles in a single pot fi om aryl-substituted tosylmethyl isocya nide (TosMIC) reagents and imines generated in situ. Traditional imine-form ing reactions employing virtually any aldehyde and amine followed by additi on of the TosMIC reagent delivers 1,4,5-trisubstituted imidazoles with pred ictable regiochemistry. Employing chiral amines and aldehydes, particularly those derived from or-amino acids, affords imidazoles with asymmetric cent ers appended to N-1 or C-5 with excellent retention of chiral purity. 1,4-D isubstituted imidazoles are also readily prepared by a simple variant of th e above procedure. Selecting glyoxylic acid as the aldehyde component of th is procedure leads to intermediates such as 48, which readily undergo decar boxylation and elimination oft;he tosyl moiety to deliver 1,4-disubstituted imidazoles in high yields. Alternatively, using NH4OH as the amine compone nt in conjunction with a variety of aldehydes delivers 4,5-disubstituted im idazoles in moderate to good yields in a single pot while avoiding the need for protecting groups. Finally, the facile preparation of mono- and disubs tituted oxazoles from these TosMIC reagents and aldehydes is described.