A formal total synthesis of (+/-)-homogynolide-B

A formal total synthesis of (+/-)-homogynolide-B, a sesquiterpene containin g an alpha-spiro-beta-methylene-gamma-butyrolactone moiety spirofused to a bicyclo[4.3.0]nonane framework, is described. Thus, Hagemann's ester 11 was converted into the allyl alcohol 16 in three steps. One-pot Claisen rearra ngement of the allyl alcohol 16 and 2-methoxypropene in the presence of a c atalytic amount of propionic acid afforded a 3:2 epimeric mixture of the ke tone 15 and further rearranged product 19. Ozonolysis followed by intramole cular aldol condensation and hydrogenation transformed the enones 15a,b int o the key intermediate keto ketals 13a and 13b. Methoxymethylene Wittig rea ction followed by bromoacetalisation converted the keto ketal 13a into the radical precursor bromo acetal 22a. The 5-exo-dig radical cyclisation of th e bromo acetal 22a, followed by acid catalysed hydrolysis and oxidation, le d to the keto spirolactone 12, Greene's precursor of homogynolide-B. The sa me sequence transformed the keto ketal 13b into a 3:2 mixture of the spirol actones 12 and 25, which on equilibration furnished the spirolactone 12. Th e stereostructure of the keto spirolactone 12 was unambiguously established by single-crystal X-ray diffraction analysis.