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

Sequential treatment of 2-C6H4Br(CHO) with LiCCR1 (R-1=SiMe3, tBu), nBuLi, CuBrSMe2 and HCCCHClR2 [R-2=Ph, 4-CF3Ph, 3-CNPh, 4-(MeO2C)Ph] at -50 degrees C leads to formation of an intermediate carbanion (Z)-1,2-C6H4{C-A(=O)CCBR1}{CH=CH(CH-)R-2} (4). Low temperatures (-50 degrees C) favour attack at C-B leading to kinetic formation of 6,8-bicycles containing non-classical C-carbanion enolates (5). Higher temperatures (-10 degrees C to ambient) and electron-deficient R-2 favour retro sigma-bond C-C cleavage regenerating 4, which subsequently closes on C-A 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, I-2, 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; R-1=SiMe3, tBu; R-2=Ph) are versatile starting materials for NaBH4 and Grignard C=O additions, desilylation (when R-1=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 (R) conditions (71-95%).