Catalytic Asymmetric Synthesis of Quaternary Barbituric Acids

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.