Control of Regio‐ and Enantioselectivity in the Asymmetric Organocatalytic Addition of Acetone to 4‐(Trifluoromethyl)pyrimidin‐2(1H)‐ones

Abstract

AbstractThe reactions of variously substituted 4‐(trifluoromethyl)pyrimidin‐2(1H)‐ones with acetone in the presence of L‐proline or chiral secondary amine organocatalysts were studied. As demonstrated, 4‐(trifluoromethyl)pyrimidin‐2(1H)‐ones unsubstituted at the 6‐position of the heterocyclic ring react with acetone at the endocyclic C=N or C=C bond depending on whether thermodynamic or kinetic control is operative in the addition reaction and also depending on the catalyst used. Racemic kinetically preferred regioisomers, 6‐(2‐oxopropyl)‐4‐(trifluoromethyl)‐3,4‐dihydropyrimidin‐2(1H)‐ones, were found to undergo intermolecular organocatalytic rearrangement into enantioenriched thermodynamically stable products, 4‐(2‐oxopropyl)‐4‐(trifluoromethyl)‐3,4‐dihydropyrimidin‐2(1H)‐ones, with enantiomeric ratios up to 83:17.