A simple and effective one-pot cascade procedure to provide 2,4-disubstituted thiazoles
and symmetrical dimeric thiazoles directly from commercially available acid chlorides
and β-azido disulfides in moderate to high yields is described. This cascade transformation
consists of disulfide cleavage, thiocarbonylation, phosphine-promoted intramolecular
Staudinger/aza-Wittig reaction and dehydrogenation to form the corresponding thiazoles.
The application of our methodology is demonstrated by the concise two-step synthesis
of anticancer agent SMART and its O-linked dimer in 64% and 46% overall yields, respectively.
This directed cascade reaction could be easily handled and scaled up under mild conditions,
enabling the construction of focused thiazole derivatives for further pharmacological
evaluation.
Key words
one-pot reaction - 2,4-disubstituted thiazole - dimeric thiazole - acid chloride -
SMART
