Experimental and Computational Studies on Interrupted Nazarov Reactions: Exploration of Umpolung Reactivity at the α‑Carbon of Cyclopentanones

• Published in: Journal of the American Chemical Society Vol. 136; no. 42; pp. 14903 - 14911
• Main Authors: Wu, Yen-Ku, Dunbar, Christine R, McDonald, Robert, Ferguson, Michael J, West, F. G
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22.10.2014
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja507638r

A set of densely substituted, α-functionalized cyclopentanones can be generated by a two-component, domino reaction sequence entailing the Nazarov electrocyclization of divinyl ketones and nucleophilic addition of the resulting 2-oxidocyclopentenyl cations by selected trapping modalities. Bypassing the typical eliminative termination, Nazarov oxyallyl species can react with carbon π-nucleophiles through cycloadditions (or formal cycloadditions), in which bridged bicyclic systems are established, or nucleophilic trappings whereby one terminal carbon of the oxyallyl intermediate is subjected to carbon–carbon bond formation. A detailed investigation of reaction parameters to explicitly control the course of the “interrupted” Nazarov reactions is described. This methodology allows for facile installation of α-quaternary centers bearing allyl, alkynyl, and heteroaryl groups in an umpolung fashion. In addition, the trapping event of a Nazarov intermediate with furan was studied by DFT computations, in conjunction with experimental data, offering a rationale for the observed reaction pattern and diastereoselectivity.