Diversification of ortho-Fused Cycloocta-2,5-dien-1-one Cores and Eight- to Six-Ring Conversion by [sigma] Bond C-C Cleavage

Sequential treatment of 2-C6H4Br(CHO) with LiCCR1 (R1=SiMe3, tBu), nBuLi, CuBrSMe2 and HCCCHClR2 [R2=Ph, 4-CF3Ph, 3-CNPh, 4-(MeO2C)Ph] at -50°C leads to formation of an intermediate carbanion (Z)-1,2-C6H4{CA(=O)CCBR1}{CH=CH(CH-)R2} (4). Low temperatures (-50°C) favour attack at CB leading to kinetic formation of 6,8-bicycles containing non-classical C-carbanion enolates (5). Higher temperatures (-10°C to ambient) and electron-deficient R2 favour retro σ-bond C-C cleavage regenerating 4, which subsequently closes on CA providing 6,6-bicyclic alkoxides (6). Computational modelling (CBS-QB3) indicated that both pathways are viable and of similar energies. Reaction of 6 with H+ gave 1,2-dihydronaphthalen-1-ols, or under dehydrating conditions, 2-aryl-1-alkynylnaphthlenes. Enolates 5 react in situ with: H2O, D2O, I2, allylbromide, S2Me2, CO2 and lead to the expected C-E derivatives (E=H, D, I, allyl, SMe, CO2H) in 49-64% yield directly from intermediate 5. The parents (E=H; R1=SiMe3, tBu; R2=Ph) are versatile starting materials for NaBH4 and Grignard C=O additions, desilylation (when R1=SiMe) and oxime formation. The latter allows formation of 6,9-bicyclics via Beckmann rearrangement. The 6,8-ring iodides are suitable Suzuki precursors for Pd-catalysed C-C coupling (81-87%), whereas the carboxylic acids readily form amides under T3P conditions (71-95%).