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

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.