Asymmetric Vinylogous Reactions Catalyzed By L-amino Acid-derived Thiourea Catalysts

1. Highly Enantio-and Diastereoselective Reactions of γ,γ-Substituted Butenolides Through DirectVinylogous Conjugate Additionswe developed highly enantio-and diastereoselective synthesis of γ,γ-butenolide-substituted α-andβ-stereogenic amides via direct vinylogous conJugate addition reactions. The study made an importantbreakthrough in the following aspects:1) The first time for direct asymmetric vinylogous conJugateadditions of both γ-aryl and alkyl-substituted butenolides achieving highly enantio-and diastereoselective;2) The first synthesis of γ,γ-butenolide-substituted α-and β-stereogenic amides;3) L-tert-Leucine-derivedamine-thiourea, which could be easily prepared, was identified as the best catalyst;4) Low catalystloading (1-10mol%) was required, Suitable for industrial production;5) Density functional theory (DFT)calculations were performed to support the importance of the weak non-classical C-H···O hydrogenbonding interaction between the oxalidinone ring and the thiourea catalyst in increasing enantioselectivity2. Direct Asymmetric Vinylogous Aldol Reaction of Allyl Ketones with Isatins: Divergent Synthesisof3-Hydroxy-2-Oxindole DerivativesThe first highly enantioselective vinylogous aldol reaction is mediated by a bifunctional catalyst andleads to E-configured vinylogous aldol products. These products are used as common intermediates in thesynthesis of divergent biologically active3-hydroxy-2-oxindole derivatives. Computational studiesindicated that the observed stereoselectivity is a result of favorable secondary л–л*and H-bondinginteractions in the transition state.