ja402058v_si_002.pdf (164.28 kB)
The Cinchona Primary Amine-Catalyzed Asymmetric Epoxidation and Hydroperoxidation of α,β-Unsaturated Carbonyl Compounds with Hydrogen Peroxide
journal contributionposted on 2013-05-01, 00:00 authored by Olga Lifchits, Manuel Mahlau, Corinna M. Reisinger, Anna Lee, Christophe Farès, Iakov Polyak, Gopinadhanpillai Gopakumar, Walter Thiel, Benjamin List
Using cinchona alkaloid-derived primary amines as catalysts and aqueous hydrogen peroxide as the oxidant, we have developed highly enantioselective Weitz–Scheffer-type epoxidation and hydroperoxidation reactions of α,β-unsaturated carbonyl compounds (up to 99.5:0.5 er). In this article, we present our full studies on this family of reactions, employing acyclic enones, 5–15-membered cyclic enones, and α-branched enals as substrates. In addition to an expanded scope, synthetic applications of the products are presented. We also report detailed mechanistic investigations of the catalytic intermediates, structure–activity relationships of the cinchona amine catalyst, and rationalization of the absolute stereoselectivity by NMR spectroscopic studies and DFT calculations.
CinchonaenalNMR spectroscopic studieshydrogen peroxideDFT calculationscinchona amine catalystenantioselectiverelationshipAsymmetricacyclic enonesapplicationWeitzinvestigationCompoundscopeEpoxidationstereoselectivityamineshydroperoxidation reactionsPeroxideUsingrationalizationintermediateoxidantarticlecarbonyl compoundsepoxidationsubstrateCarbonylmemberedUnsaturatedHydroperoxidation