Diversification of ortho-fused cycloocta-2,5-dien-1-one cores and 8 to 6-Ring conversion by sigma bond C-C cleavage

Eccleshare, Lee; Lozada-Rodriguez, Leticia; Cooper, Phillippa; Burroughs, Laurence; Ritchie, John; Lewis, William; Woodward, Simon

Abstract

Sequential treatment of 2-C6H4Br(CHO) with LiC≡CR1 (R1 = SiMe3, tBu), nBuLi, CuBr∙SMe2 and HC≡CCHClR2 [R2 = Ph, 4-CF3Ph, 3-CNPh, 4-(MeO2C)Ph] at -50 oC leads to formation of an intermediate carbanion (Z)-1,2-C6H4{CA(=O)C≡CBR1}{CH=CH(CH–)R2} (4). Low temperatures (-50 oC) favour attack at CB leading to kinetic formation of 6,8-bicycles containing non-classical C-carbanion enolates (5). Higher temperatures ( 10 oC 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) indicates both pathways are viable and of similar energies. Reaction of 6 with H+ affords 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%); while the carboxylic acids readily form amides under T3P® conditions (71-95%).

Citation

Eccleshare, L., Lozada-Rodriguez, L., Cooper, P., Burroughs, L., Ritchie, J., Lewis, W., & Woodward, S. (in press). Diversification of ortho-fused cycloocta-2,5-dien-1-one cores and 8 to 6-Ring conversion by sigma bond C-C cleavage. Chemistry - A European Journal, 22(35), https://doi.org/10.1002/chem.201601970

• Journal Article Type: Article
• Acceptance Date: Jun 21, 2016
• Online Publication Date: Jul 25, 2016
• Deposit Date: Jul 5, 2016
• Publicly Available Date: Jul 25, 2016
• Journal: Chemistry - a European Journal
• Print ISSN: 0947-6539
• Electronic ISSN: 1521-3765
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 35
• DOI: https://doi.org/10.1002/chem.201601970
• Keywords: Annulation, Medium-ring compounds, Synthetic methods, Ring expansion, C-C activation
• Public URL: https://nottingham-repository.worktribe.com/output/799579
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/chem.201601970/abstract
• Additional Information: This is the peer reviewed version of the following article: L. Eccleshare, L. Lozada-Rodriguez, P. Cooper, L. Burroughs, J. Ritchie, W. Lewis, S. Woodward: Diversification of ortho-fused cycloocta-2,5-dien-1-one cores and 8 to 6-Ring conversion by sigma bond C-C cleavage, Chemistry European Journal 2016, v. 35, issue 35 which has been published in final form at http://dx.doi.org/10.1002/chem.201601970. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.