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.