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Asymmetric Nazarov Cyclizations of Unactivated Dienones by Hydrogen‐Bond‐Donor/Lewis Acid Co–Catalyzed, Enantioselective Proton‐Transfer

Jan B. Metternich, Martin Reiterer, Eric N. Jacobsen

2020Advanced Synthesis & Catalysis26 citationsDOIOpen Access PDF

Abstract

We report an enantioselective Nazarov cyclization catalyzed by chiral hydrogen-bond-donors in concert with silyl Lewis acids. The developed transformation provides access to tri-substituted cyclopentenones in high levels of enantioselectivity (up to 95% e.e.) from a variety of simple unactivated dienones. Kinetic and mechanistic studies are consistent with a reversible 4π-electrocyclization C-C bond-forming step followed by rate- and enantio-determining proton-transfer as the mode of catalysis.

Topics & Concepts

ChemistryEnantioselective synthesisCatalysisLewis acids and basesHydrogen bondSilylationProtonChiral Lewis acidCombinatorial chemistryMedicinal chemistryOrganic chemistryStereochemistryMoleculePhysicsQuantum mechanicsAsymmetric Synthesis and CatalysisAxial and Atropisomeric Chirality SynthesisTraditional and Medicinal Uses of Annonaceae