Synthesis of Bicyclo[2.1.0]pentanes and Vinylcyclopropanes Using Palladium Carbenes: Ligand-Controlled Carbene Reactivity.

ABSTRACT: Once physical organic curiosities, bicyclo[2.1.0]pentanes (colloquially termed housanes) are useful strain-release reagents and are unique structural motifs for medicinal chemistry campaigns because of their high Fsp³ content. Despite this, methods to synthesize housanes are lacking due to their highly strained nature. Herein, we report an intramolecular cyclopropanation strategy to obtain functionalized housanes using palladium carbenes (20 substrates, up to 89% yield). Key to the success of this reaction was the insight that the reactivity of Pd(0) carbenes is controlled by the supporting ligand. Strongly donating N-heterocyclic carbene ligands promote cyclopropanation reactivity, while some π-accepting phosphoramidite ligands (e.g., rac-MonoPhos) afford C-H inse

SUBMITTER: Eckart-Frank IK 

PROVIDER: S-EPMC12801349 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature