Synthesis of 1-oxaazulan-2-ones and furanotropones from troponoids: a reexamination and extension to colchicinoids

Reactions of [3,5,7-H-2(3)]-2-tosyloxytropone (1b) in DMSO with enolates th at, like sodium ethyl acetoacetate or sodium diethyl malonate, bear a leavi ng 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 th at, like sodium acetylacetonate, do not bear a leaving group. 9-Tosyloxyiso colchicide (15) behaves like 2-tosyloxytropone, giving the product 16 of C- 11 attack, whereas 10-tosyloxycolchicide (17) resists attack at C-8 and onl y a very slow nucleophilic attack at C-10 by the enolate to give 18 is obse rved. Hydroxylic solvents do not allow any of these processes. (C) 2000 Pub lished by Elsevier Science Ltd. All rights reserved.