Synthesis of Endothiopeptides via Ugi Reaction and their Conversion to Thiazoles

Significance

The venerable Ugi reaction is used in a four-component format for the synthesis of endothiopeptides from thiocarboxylic acids, primary amines, aldehydes or ketones, and isonitriles in moderate to good yields. The reaction involves, as the last step, a S- to N-transacetylation process. Under Lewis or Brønsted acid catalyzed conditions, the products 1 are converted into thiazolidines 2 which, upon treatement with TMSI, undergo elimination to the corresponding thiazoles 3. Under microwave conditions, the last conversion proceeds faster, cleaner, and with fewer side reactions to give products in up to 91% yields.