The aim of this project was to attempt to find a method for introducing the cis-dihydroxyl substitution at the A/B-ring junction of model compounds related to the saquayamycins. The Diels-Alder reactions of maleic anhydride and bromomaleic anhydride with 5,5-dimethyl-3-vinylcyclohexa-1,2-dienyl acetate gave the two required endo-adducts in good yield, namely (+/-)-7,7-dimethyl-1,3-dioxo-1,3,3a,4,6,7,9a, 9b-octahydrobenzo[e]isobenzofuran-9-yl acetate (6) and (+/-)- 9b-bromo-7,7-dimethyl-1,3-dioxo-1,3,3,3a, 4,6, 7,9a, 9b-octahydrobenzo[ e] isobenzofuran-9-yl acetate (9). Each of these was converted into the B-ring mono-epoxide, namely (+/-)-3,3-dimethyl-7,9-dioxo-3,5a,6,6a,7,9,9b-octahydro-4H-benzo[e]oxireno-2,3-furan-1-yl acetate (7) and a mixture of two racemic diastereoisomers of 9a-bromo-3,3-dimethyl-7,9-dioxoperhydrobenzo[e]oxireno[2,3-f]isobenzofuran-1-yl acetate (12), respectively. It was then hoped to deprotonate both (7) and (12) at the 9a position in order to effect migration of the 8, 9 double bond to the 9, 9a position. Reaction of (7) with a mild base (pyridine) did not effect any reaction. Similar treatment of (12) did remove the 9a proton, but it also effected ring opening of the epoxide, followed by dehydration and dehydrobromination to give an excellent (but unwanted) yield of the aromatized system (+/-)-7,7-dimethyl-1,3-dioxo-1, 3,5,7-tetrahydrobenzo[e]isobenzofuran-9-yl acetate. Dehydrobromination of (9), and deprotonation of the 9a position, similarly formed the aromatic system (+/-)- 7,7-dimethyl-1,3-dioxo-1,3,6,7,8,9-hexahydrobenzo[e]isobenzofuran-9-yl acetate (11) in good yield.
Apponyi, M. A., Bowie, J. H., Skelton, B., & White, A. (2002). Model Compounds Related to Saquayamycin. Attempts to Oxygenate the A/B-Ring Junction. Australian Journal of Chemistry, 55(n/a), 343-348. https://doi.org/10.1071/CH02040