homoenolates

Homoenolates are enolate equivalents in organic chemistry where the nucleophilic center resides at the gamma carbon relative to a carbonyl group. This location enables carbon–carbon bond formation at the gamma position, effectively providing a one-carbon homologation of carbonyl compounds compared with conventional enolate chemistry, which acts at the alpha position.

Generation and forms of homoenolates can vary. They are commonly described when a gamma-position deprotonation of beta,gamma-unsaturated carbonyl compounds is induced, yielding gamma-lithiated or gamma-activated enolate species. They can also arise from ring-opening processes of cyclopropanols under metal-mediated conditions, producing gamma-functionalizable nucleophiles that behave as homoenolates. In many catalytic contexts, homoenolates appear as metal enolates or as protected gamma-enolate equivalents such as γ-silated or γ-alkoxylated species.

Reactivity of homoenolates centers on gamma-selective bond formation. They participate in gamma-alkylation, gamma-arylation, and gamma-alkenylation reactions with electrophiles such as aldehydes, imines, or allylic electrophiles, delivering gamma-substituted carbonyl products after workup. They can also engage in intramolecular cyclizations and cascade sequences, enabling constructions of more complex architectures. Enantioselective versions have been developed using chiral catalysts to control stereochemistry at newly formed centers, expanding the utility of homoenolate chemistry in asymmetric synthesis.

Overall, homoenolates complement traditional enolate reactivity by enabling gamma-functionalization of carbonyl compounds, with applications in natural product synthesis and medicinal chemistry.