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Insights into the Mechanism of Enantioselective Copper‐Catalyzed Ring‐Opening Allylic Alkylation of Cyclopropanols

Akito Kitabayashi, Sho Mizushima, Kosuke Higashida, Yuto Yasuda, Y. Shimizu, Masaya Sawamura

2022Advanced Synthesis & Catalysis15 citationsDOI

Abstract

Abstract Enantioselective copper‐catalyzed ring‐opening allylic alkylation of a cyclopropanol with an allyl phosphate was developed using a phenol‐NHC chiral ligand. DFT calculations indicated that a copper homoenolate is formed via Li−Cu bimetallic activation of a cyclopropoxide and that syn ‐S N 2’ attack of the Cu center of the homoenolate to the allyl phosphate followed by facile C−C bond formation affords the β‐allylated ketone. Noncovalent interaction analysis showed that the enantiocontrol is achieved by the synergy of electrostatic interactions among Cu, Li, and O atoms, C−H⋅⋅⋅O interactions, and C−H/π London dispersions. magnified image

Topics & Concepts

ChemistryEnantioselective synthesisBimetallic stripAllylic rearrangementCopperTsuji–Trost reactionAlkylationRing (chemistry)CatalysisMedicinal chemistryKetoneLigand (biochemistry)StereochemistryCombinatorial chemistryOrganic chemistryReceptorBiochemistryCyclopropane Reaction MechanismsAsymmetric Hydrogenation and CatalysisN-Heterocyclic Carbenes in Organic and Inorganic Chemistry