CYCLOADDITION CHEMISTRY OF ANHYDRO-4-HYDROXY-1,3-THIAZOLIUM HYDROXIDES (THIOISOMUNCHNONES) FOR THE SYNTHESIS OF HETEROCYCLES

A series of alpha,alpha-disubstituted thioisomunchnones were prepared by treating acyclic or cyclic thioamides with bromoacetyl chloride in the presence of triethylamine. The resulting mesoionic dipole was foun d to undergo bimolecular 1,3-dipolar cycloaddition with several differ ent dipolarophiles. When a hydrogen atom is present in the alpha-posit ion of the thioamide, the initially formed N-acyl iminium ion undergoe s proton loss to produce a S,N-ketene acetal at a faster fate than thi oisomunchnone formation. The cycloaddition behavior of several substit uted thioisomunchnones which possess a tethered alkene were also exami ned. The stereochemical outcome of the intramolecular reaction is the consequence of an endo cycloaddition of the neighboring pi-bond across the transient thioisomunchnone dipole. Molecular mechanics calculatio ns reveal that the endo diastereomers are significantly lower in energ y than the corresponding exo isomers. Attempts to cycloadd the thioiso munchnone dipole across a tethered indolyl ring were unsuccessful. Ins tead, products derived by nucleophilic cyclization of the indolyl ring onto the thio N-acyl iminium ion were formed in good yield.