Use of ketene dithioacetal as a latent carboxylic acid in the macrolactonization applicable to the synthesis of dilactonic pyrrolizidine alkaloids

Acid 5a (or 5b) bearing the ketene dithioacetal moiety functioned as an equivalent of a dicarboxylic acid. Use of the ketene dithioacetal in the formation of 11-membered dilactones is demonstrated. Compound 5a (or 5b) was converted to an acid imidazolide which reacted regioselectively with retronecine at the allylic position. Mild acidic hydrolysis of the ketene dithioacetal moiety led to a thioester, which underwent macrocyclization with the secondary hydroxyl group mediated by silver(I) trifluoroacetate to give derivatives of the pyrrolizidine alkaloids.