Development of Chiral, Bifunctional Thio­squar­amides: Enantio­selective Michael Additions of Barbituric Acids to Nitroalkenes

We report a general method for the synthesis of chiral thio­squar­amides, a class of bifunctional catalysts not previously described in the literature. Thio­squar­amides are found to be more acidic and significantly more soluble in nonpolar solvents than their oxo­squar­amide counterparts, and they are excellent catalysts for the unreported, enantio­selective conjugate addition reaction of the barbituric acid pharmacaphore to nitroalkenes, delivering the chiral barbiturate derivatives in high yields and high enantio­selectivities, even with catalyst loadings as low as 0.05 mol%.