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Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids

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journal contribution
posted on 2017-10-12, 00:00 authored by Sandra del Pozo, Silvia Vera, Mikel Oiarbide, Claudio Palomo
The catalytic asymmetric α-functionalization of prochiral barbituric acids, a subtype of pseudosymmetric 1,3-diamides, to yield the corresponding 5,5-disubstituted (quaternary) derivatives remains essentially unsolved. In this study 2-alkylthio-4,6-dioxopirimidines are designed as key 1,3-diamide surrogates that perform exceedingly in amine-squaramide catalyzed C–C bond forming reactions with vinyl ketones or Morita–Baylis–Hillmann-type allyl bromides as electrophiles. Mild acid hydrolysis of adducts affords barbituric acid derivatives with an in-ring quaternary carbon in unprecedented enantioselectivity, offering valuable materials for biological evaluations.