Synthesis of 1-Oxaazulan-2-ones and Furanotropones from Troponoids: a Reexamination and Extension to Colchicinoids

Reactions of [3,5,7-2H3]-2-tosyloxytropone (1b) in DMSO with enolates that, like sodium ethyl acetoacetate or sodium diethyl malonate, bear a leaving group, occur at C-7, followed by either sequential protonation at C-2, 1,6-elimination, and intramolecular heterocyclization (to give 1-oxaazulan-2-ones), or sequential sulfinate loss and intramolecular heterocyclization (to give furanotropones). The latter is the exclusive route with enolates that, like sodium acetylacetonate, do not bear a leaving group. 9-Tosyloxyisocolchicide (15) behaves like 2-tosyloxytropone, giving the product 16 of C-11 attack, whereas 10-tosyloxycolchicide (17) resists attack at C-8 and only a very slow nucleophilic attack at C-10 by the enolate to give 18 is observed. Hydroxylic solvents do not allow any of these processes.