Enantioselective synthesis of hydantoins by chiral acid-catalysed condensation of glyoxals and ureas

Hydantoins are important scaffolds in natural products and pharmaceuticals, with only a few synthetic strategies available for their asymmetric preparation. We herein describe a single-step enantioselective synthesis of 5-monosubstituted hydantoins via condensation of glyoxals and ureas in the presence of a chiral phosphoric acid at room temperature. Products were formed in up to 99% yield and 98 : 2 e.r. Using mechanistic and kinetic studies, including time course H-1 NMR monitoring, we revealed that the reaction likely proceeds via face-selective protonation of an enol-type intermediate.

Automated summary

We report a single-step enantioselective synthesis of 5-monosubstituted hydantoins via condensation of glyoxals and ureas in the presence of a chiral phosphoric acid at room temperature. The products were obtained in up to 99% yield and 98:2 enantiomeric ratio. Mechanistic and kinetic studies revealed that the reaction likely proceeds via face-selective protonation of an enol-type intermediate.