title: Diversification of ortho-Fused Cycloocta-2,5-dien-1-one Cores and Eight- to Six-Ring Conversion by σ Bond C-C Cleavage.
abstract: Sequential treatment of 2-C6 H4 Br(CHO) with LiC≡CR(1) (R(1) =SiMe3 , tBu), nBuLi, CuBr⋅SMe2 and HC≡CCHClR(2) [R(2) =Ph, 4-CF3 Ph, 3-CNPh, 4-(MeO2 C)Ph] at -50 °C leads to formation of an intermediate carbanion (Z)-1,2-C6 H4 {CA (=O)C≡CB R(1) }{CH=CH(CH(-) )R(2) } (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 R(2) 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: H2 O, D2 O, I2 , allylbromide, S2 Me2 , CO2 and lead to the expected C-E derivatives (E=H, D, I, allyl, SMe, CO2 H) 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® conditions (71-95 %).
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Lee
authors.initials: L
authors.lastname: Eccleshare
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Leticia
authors.initials: L
authors.lastname: Lozada-Rodríguez
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Phillippa
authors.initials: P
authors.lastname: Cooper
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: Laurence
authors.initials: L
authors.lastname: Burroughs
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: John
authors.initials: J
authors.lastname: Ritchie
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK.
authors.forename: William
authors.initials: W
authors.lastname: Lewis
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK. simon.woodward@nottingham.ac.uk.
authors.forename: Simon
authors.identifier: http://orcid.org/0000-0001-8539-6232
authors.initials: S
authors.lastname: Woodward
keywords: C−C activation; annulation; medium-ring compounds; ring expansion; synthetic methods